Mustanski 2004 Reseña de investigación biológica sobre OS

Annual Review of Sex Research:

Una reseña crítica de la investigación biológica reciente sobre orientación sexual humana

Mustanski, Brian S

Brian S. Mustanski Indiana University

Meredith L. Chivers Northwestern University

J. Michael Bailey Northwestern University

El apoyo para la preparación de este manuscrito fue provisto por una beca para investigación de graduados de la Fundación Nacional de la Ciencia [National Science Foundation Graduate Research Fellowship] a Brian S. Mustanski. La correspondencia relativa a este artículo debe ser dirigida a Brian Mustanski, Departamento de

Sicología de la Universidad de Indiana, 1101 East 10th Street, Bloomington, IN 47405.

(bmustans@indiana.edu)

Este artículo provee una reseña y crítica comprensiva de la investigación biológica sobre orientación sexual publicada a lo largo de la última década. Cubrimos la investigación que indaga en (a) la teoría neurohormonal de la orientación sexual (siconeuroendocrinología, estrés prenatal, asimetría cerebral, neuroanatomía, emisiones otoacústicas y antropometría), (b) influencias genéticas, (c) efectos fraternales de orden de nacimiento y (d) un rol putativo de inestabilidad de desarrollo.

A pesar de los resultados inconsistentes a través de ambos estudios y rasgos, se some support for the neurohormonal theory is garnered, but mostly in men. Genetic research using family and twin methodologies has produced consistent evidence that genes influence sexual orientation, but molecular research has not yet produced compelling evidence for specific genes. Although it has been well established that older brothers increase the odds of homosexuality in men, the route by

which this occurs has not been resolved. We conclude with an examination of the limitations of biological research on sexual orientation, including measurement issues (paper and pencil, cognitive, and psychophysiological), and lack of research on women.

 

Key Words: birth order, developmental instability, genetic, homosexuality, hormones, phallometry, sexual orientation, vaginometry

Ya ha pasado más de una década desde que la primera reseña de la evidencia de una base biológica de la orientación sexual fue publicada en esta revista (Gooren,

Fliers, & Courtney, 1990). El foco de aquella reseña estaba en el papel desempeñado por las hormonas en la explicación de variaciones intrasexuales de la orientación sexual. Más recientemente Bailey y Pillard (1995) reseñaron los datos existentes extant data relativos a las influencias genéticas sobre lla orientación sexual. Desde aquellas reseñas ha habido una considerable expansión de la evidencia que da apoyo a la existencia de influencias biológicas. Estos estudios han explorado las diferencias genéticas, neuroanatómicas, endocrinas y morfológicas basadas en la orientación sexual. Dada la acumulación de datos nuevos desde las últimas reseñas, parece un momento apropiado para evaluar la evidencia en esta área. El foco de esta reseña está en la evidencia reciente (de los últimos 10 años) en relación con el rol putativo de los factores biológicos que influyen en la orientación sexual. Cuando es necesario se incluye investigacióin menos contemporánea para contextualizar la evidencia más nueva. Los artículos se identificaron buscando en PubMed y PsychInfo términos comunes relativos a la orientación sexual (i.e., homosexualidad, gay, etc.) junto con términos biológicos relevantes (genética, cerebro, etc.), permitiendo solamente que se buscasen artículos publicados en los últimos 10 años. Se les preguntó a los autores que habían presentado papers relevantes en el Simposio Internacional de Desarrollo comportamental reunido por Lee Ellis en el 2000, que se había concentrado en la base biológica de la orientación sexual, si tenían alguna investigación reciente que debiera ser incluida en la reseña. Finalmente, se colocó un aviso en SEXNET, una servidor de listas de e-mail para investigadores que estudian el comportamiento sexual, pidiendo Referencias de artícules recientemente publicados o todavía sin publicar.

Muchos de lose studios que se reseñan en este artículo han provocado intenso interés tanto en el scenario científico como en el escenario popular. Algo de este interés con toda probabilidad puede haber resultado de la equivocada creencia de que varias explicaciones etiológicas de la orientación sexual deben tener implicaciones sociales y éticas que difieran (véase Greenberg & Bailey, 1993, para una discusión). Such thinking confuses several related but distinct concepts, such as genetic versus environmental, voluntary versus compelled, innate versus acquired, immutable versus changeable, and moral versus immoral (see Bailey & Pillard, 1995, for a discussion). Similarly, the term biological is frequently misunderstood and misused due to it being somewhat amorphous, given that all human behaviors are enacted by the brain and thus are in some sense biological. Rather than asking if sexual orientation is biological, we believe it is more fruitful to consider whether differences in sexual orientation primarily reflect differences in social experiences, differences in biologic factors unrelated to social experiences, or both. The ultimate goal of such research will be to understand the timing and mechanism of various etiological factors that influence sexual orientation.

Empirical researchers exploring the basis of biological influences acting on

sexual orientation have traditionally used two approaches. In the first, a wide

array of methodology to explore the role that hormones play in influencing

sexual orientation has been used. Such research is generally based on the

“neurohormonal theory” (Ellis & Ames, 1987) positing that homosexuality is

caused by atypical sex hormone levels in utero with concomitant sex-atypical

neural differentiation. The second approach, behavioral genetics, is focused on

identifying the source and magnitude of genetic influences on sexual

orientation. Two more recent approaches are focused on developmental instability

as measured by fluctuating asymmetry and nonright-handedness (Lalumiere,

Blanchard, & Zucker, 2000; Mustanski, Bailey, & Kaspar, 2002), and the relation

between sexual orientation and number of older brothers (Blanchard, 1997). There

have been relatively few attempts to synthesize the results from these varying

approaches, although they are not inherently mutually exclusive. For example,

having several older brothers may increase the effects of genes that influence

sexual orientation, thereby producing changes in hormone activity in the brain.

An inestimable number of additional interactions are imaginable, although at

this point insufficient understanding of the biological factors influencing

sexual orientation hampers their specification. Consequently, we review each

area of study individually, and conclude with a discussion of the limitations of

the current research.

Neurohormonal Influences

The most influential theory about the origins of homosexuality implicates

sex-atypical androgen action during gestation (Ellis & Ames, 1987), making this

a logical starting place for such a review. A now classic paper by Phoenix, Goy,

Gerall, and Young (1959), in which the differential organizational and

activational influences of sex steroids were demonstrated, initiated this line

of research. In this study, Phoenix and colleagues injected pregnant guinea pigs

with testosterone propionate during gestation and gonadectomized them after

birth. At birth, the treated female offspring had masculinized external

genitalia that were nearly identical to those of normal male offspring. When the

offspring were sexually mature, they were injected with various doses of

estradiol benzoate. En comporación con los controles hembras, las hembras prenatalmente androgenizadas mostraron una duración reducida de la lordosis que no fue significativamente diferente de la de los controles machos. Las hembras tratadas también tenían más probabilidad de mostrar más conductas de monta que los controles hembras. De este modo, los descubrimientos de Phoenix y sus colegas demostraron que la testosterone, cuando es administrada durante períodos sensibles de desarrollo, tiene una acción masculinizadota sobre el tejido neural involucrado en la conducta de apareamiento. Este efecto organizador de las hormonas sexuales en hembras y machos parece ser cierto en la mayoría de las especies mamíferas (I. L. Ward & 0. B. Ward, 1985).

Aunque la investigación animal no humana es heurísticamente útil, hay varios problemas con su uso para informar de la orientación sexual humana, Beach (1979)

Comentó que simplemente que los mismos términos descriptivos se usen a través de las especies no garantiza que los conceptos subyacentes sean idéntico. Los comportamiento específicos de la especie (i.e., lordosis o monta en las ratas) no alcanzan a capturer la pintura total de la orientación sexual humana. Un segundo problema que tiene usar literatura sobre animales en apoyo de la teoría neurohormonal es que los datos no proveen apoyo inequívoco para los efectos de organización, especialmente para las mujeres (Meyer-Bahlburg, 1984).

Por ejemplo, Dorner (1976) mostró que solamente después de gonadectomía y administración de testosterona en la adultez las ratas hembras expuestas tempranamente al andrógeno demostraban comportamientos sexuales típicos del macho. Si las gónadas de las ratas del experimento no eran extirpadas, los animales mostraban un claro predominio del comportamiento sexual de la hembra y solamente un aumento leve en los comportamientos típicos del macho. Se han encontrado resultados similares en primates no humanos hembras (Eaton, Goy, & Phoenix, 1973). Additionally, the fact

that experimental hormone manipulations can influence sexual orientation in a

laboratory does not prove that they do so in normal populations. Meyer-Bahlburg

(1984) pointed out a final inadequacy of the animal literature: Hormonal

manipulations result not only in a shift of sex-dimorphic behavior, but also in

alterations of the genitals. In contrast, homosexual people usually have normal

genitalia. Based on these limitations, it is clear that although the animal

literature can be extremely useful in developing hypotheses and testing ideas

not possible with human participants, only data from human studies can

definitely establish what role sex hormones play in human sexual orientation.

Estudios Humanos

Los investigadores más tempranos de la relación entre hormonas sexuales y la orientación sexual humana exploraron la hipótesis de que algunos varones gays tuvieran niveles disminuidos de testosterona en circulación. Esta investigación ya ha sido extensamente reseñada en otra parte (véase Meyer-Bahlburg, 1984) y sugiere poca o ninguna diferencia entre hombres gays y heterosexuales en niveles de andrógeno circulante. Adicionalmente, las manipulaciones experimentales de andrógenos de varón parecen afectar la magnitud de la libido y no la dirección de la orientación sexual (Barahal, 1940).

Results from research on activational hormone effects in women have been less

consistent. Gartrell, Loriaux, and Chase (1977) and Loraine, Adamopoulos,

Kirkham, Ismail, and Dove, (1971) found lesbians to have higher levels of

testosterone than heterosexual women, but Dancey (1990) and Downey, Erhardt,

Schiffman, Dyrenfurth, and Becker (1987) found no differences. In two studies,

Pearcey, Docherty, and Dabbs (1996) and Singh, Vidaurri, Zambarano, and Dabbs

(1999) compared two putative subtypes of lesbian women, those who either

self-identified or were rated as “butch” with those who were “femme.” “Butch” is

a colloquial term used to refer to a masculine woman, and “femme” is the term

used for a more feminine lesbian woman. In both studies significant differences

were found in salivary testosterone levels among lesbian women, but these

studies must be interpreted with caution because of their failure to

consistently control for the phase of the menstrual cycle and their reliance on

indirect measures of plasma hormone levels. Thus, research exploring the

activational role of hormones on adult sexual orientation, although not directly

measuring hormone activity in critical areas, seems to suggest no effect in men.

Additional research will be needed examining hormone levels in butch and femme

lesbian women and heterosexual women. Future researchers in this area should

make every attempt to control for differences in lifestyle and behavior that

could explain group differences in hormone activity such as diet, drug use, and

exercise.

Another route through which hormones could influence sexual orientation is

through prenatal, organizational action. We begin our review of this evidence by

suggesting a thought experiment, representing an ideal test of the neurohormonal

hypothesis. This thought experiment begins with complete sex reassignment of a

random sample of newborn males, along with rearing by adoptive parents unaware

of their child’s birth sex. Follow up in adulthood indicating that these

children were sexually attracted to females would strongly suggest that sexual

orientation was programmed prenatally into the developing neural circuitry.

Obviously, this study would never be conducted for ethical reasons.

Nevertheless, it is worth keeping in mind the ideal experiment in order to judge

how closely available data approach it.

The best approximation of our thought experiment is based on studies of children

without any known prenatal hormonal abnormalities who, for a variety of reasons,

are sexually reassigned shortly after birth. Such procedures rarely occur, but

are most often performed for one of two reasons: sufficient damage to a male

infant’s penis to require its removal (ablatio penis), or genetic males born

with cloacal exstrophy (described below). In neither of these cases is the

approximation perfect. First, the child is not adopted by parents unaware of the

sex reassignment. This is an important limitation, as the psychosexual

developmental effects of parental knowledge of discordance between genetic and

rearing sex have not been studied. Second, the sex reassignment is not perfect

because of medical limitations. Nevertheless, these cases are the closest

approximation of our ideal experiment.

Table 1 contains case reports and studies of prenatally normal males sexually

reassigned near birth, and followed up after the onset of sexual maturity. As

seen in Table 1, three cases of ablatio penis have been reported in the

literature, all consequences of circumcision accidents. In only two of these

cases was sexual orientation explicitly reported, and in both, sexual

orientation was either fully or partially directed toward women. Also reported

in Table 1 are 36 cases of genetic males who were sex reassigned because of

cloacal exstrophy, a disorder of embryogenesis that causes, among other

problems, poor differentiation of the genitals. In one report (Vates et al.,

1999), the patient maintained a female identity and reported sexual attraction

toward males. For the larger study (Reiner, personal communication, February 3,

2002) the vast majority of the patients rejected their assigned gender and

reported sexual attraction toward females. Interpretation of these data must be

accompanied by consideration of the many associated medical issues experienced

by these children. Comparisons of the psychosexual outcome between children with

cloacal extrophy and a similar medical condition may help control for the

possible effects of extensive medical treatment during development. Bladder

exstrophy-epispadias is a similar disorder of embryogenesis, but the penis is

not similarly effected, making sexual reassignment rare. One study of 14 males

over the age of 14 reports 100% sexual orientation toward females, but a number

of psychosexual and physical dysfunctions (Reiner, Gearhart, & Jeffs, 1999). In

both of these approximations of our ideal thought experiment, the results

vis-avis sexual orientation suggest that whether sex reassigned or not,

attraction to females is nearly universal. Such results are consistent with the

predictions of the neurohormonal hypothesis because, despite sex reassignment at

birth, the male typical hormone levels en utero seem to have produced sexual

attraction toward females.

In addition to the evidence provided by hormonally normal male infants assigned

to a female gender, several hormonally-induced congenital intersex syndromes

have been proposed as models for understanding the organizational role of

hormones in sexual orientation differentiation, including congenital adrenal

hyperplasia (CAH) (Ehrhardt, Evers, & Money, 1968; Money, Schwartz, & Lewis,

1984; Zucker et al., 1996), androgen insensitivity syndrome (AIS) (Money et al.,

1984; Wisniewski et al., 2000), and 5-alpha reductase deficiency (SARD)

(Imperato-McGinley, Guerrero, Gaultier, & Peterson, 1974). Because genetic males

with 5ARD have been studied without formal or rigorous assessment of sexual

orientation, this condition will not be discussed in this review. Readers

interested in further details about these conditions should see one of the above

references.

As described by Zucker (1999), CAH is a genetically recessive defect in which

the synthesis of cortisol is disrupted and, in its place, the adrenal glands

secrete androstenedione, which is metabolized into testosterone and eventually

into dihydrostosterone, both active components of masculinization (Brown et al.,

1993). In genetically female fetuses, increased androgen levels result in

genital masculinization ranging from mild clitoral enlargement to a fully formed

penis and empty scrotum (Migeon, 1979; New, Ghizzoni, & Speiser, 1996). In

extreme cases, if the diagnosis is not established neonatally, the child may be

assigned a male gender and subsequently raised as a boy (Money & Dalery, 1976).

When the condition is correctly diagnosed, the genitals are surgically altered

to appear female (Allen, Hardy, & Churchill, 1982), cortisol-replacement therapy

is initiated to prevent postnatal virilization (New & Josso, 1988), and a female

gender is assigned and the infant is raised as a girl. This second case of CAH

has been described as a “model experiment of nature” (Zucker & Bradley, 1995, p.

140) because it allows an examination of the role of prenatal androgens on

sexual orientation, while partially controlling for the psychosexual rearing

environment.

The sexual orientation of adult women with CAH has been examined in eight

studies with at least 10 participants. Two of these studies took place before

the availability of cortisol-replacement therapy, thus the participants did not

receive the treatment until late in life (Ehrhardt et al., 1968; Lev-Ran, 1974).

Of the remaining studies, only three employed concurrent non-CAR controls

(Dittmann, Kappes, & Kappes, 1992; Money et al., 1984; Zucker et al., 1996).

Thus, these will be the only ones reviewed.

Money et al. (1984) compared 30 CAH patients to 15 AIS patients and 12 patients

with Mayer-Rokitansky-Kister Syndrome (MRKS; the 46, XX counterpart to AIS; see

Griffin, Edwards, Madden, Harrod, & Wilson, 1976, for a description). Of those

participants who were willing or able to describe their sexual orientation, 48%

of the CAH girls reported same-sex arousal imagery and 22% reported same-sex

partner sexual contact compared to 7% and 4%, respectively, for the AIS/MRKS

groups, and 15% and 10%, respectively, based on the original Kinsey female data

(Kinsey, Pomeroy, Martin, & Gebhard, 1953). The relative elevation in

bisexual/homosexual fantasy has been replicated by Zucker et al. (1996) in a

study of 31 CAH females who were compared to unaffected sisters and cousins (N =

15), and by Dittmann et al. (1992) in a sample of 34 CAH females and 14 control

sisters.

The contrast between the AIS and CAH females is particularly powerful, as they

represent opposite extremes of androgenization. CAH females have

greater-than-typical androgen levels, whereas AIS individuals are, to varying

degrees, insensitive to androgens. Because of this X-linked genetic mutation,

AIS genetic males possess female external genitalia, undescended testes, and

feminine body features, and are typically raised as female (Brinkmann, 2001).

Wisniewski et al. (2000), in a sample of 46, XY women (N = 14) with complete

AIS, produced results similar to the Money et al. (1984) study mentioned above.

Sexual attractions to men were reported by 100% of the women during adolescence,

and by 93% during adulthood, suggesting that lack of prenatal androgen action

biases sexual attraction toward men. Interpretation of the AIS results is

limited by the fact that rearing sex is confounded with hormonal activity. This

condition deviates from our thought experiment because AIS children are both

reared as female and are insensitive to the masculinizing effects of androgens.

Additional evidence for the role of prenatal excesses of androgens in females

comes from the effects of diethylstilbestrol (DES), a nonsteroidal estrogen that

has masculinizing effects similar, but not of the same magnitude, as those seen

in CAR DES attained widespread use to treat at-risk pregnancies during the

1940s-1960s until its use was halted because of adverse physical effects such as

increased risk for cancer. Because DES is a less potent masculinizing agent than

CAH, and was administered late in the pregnancy, the genitalia are not

masculinized in female children, thus partially ruling out the possibility of

differential socialization based on abnormal genitalia. In several studies of

DES-exposed women, relative increases in homosexual fantasies have been shown

(Ehrhardt et al., 1985; Meyer-Bahlburg et al., 1995), thus providing further

support for the role of prenatal androgens in determining sexual orientation.

The results of these various approximations of our thought experiment have been

interpreted by some to be consistent with animal research demonstrating the

influence of prenatal sex hormones on sexually dimorphic reproductive behaviors.

Such interpretations have been met with criticism and attempts at generating

alternative explanations to the idea that prenatal hormones hard wire sexual

orientation into fetal brains (Bleier, 1984, pp. 97-101; Fausto-Sterling, 1985,

pp. 133138). For example, it has been suggested that parental response to

ambiguous genitalia can have uncharacterized psychosocial implications that

increase the likelihood of homosexual or bisexual fantasies occurring. Another

criticism implicates homosexuality as a possible side effect of one of the many

medications that these individuals often take to treat their medical conditions.

Money et al. (1984) also present the possibility that a child may avoid

developmentally appropriate peer sexual experiences because of internalized

anxiety about the appearance of their genitalia, resulting in an altered

psychosexual development. Although such alternative explanations are possible,

the relatively consistent result across these various conditions, that prenatal

androgen activity potentiates attraction to females and the absence of such

activity potentiates attraction to males, is strongly suggestive of prenatal

neurohormonal effects in determining sexual orientation.

Prenatal Stress

Because the vast majority of homosexual individuals do not have one of the

endocrine disorders mentioned above, a major weakness of the neurohormonal

theory is the lack of evidence for a proximal mechanism that might impinge on

prenatal sex hormone levels. If there is a neurohormonal event linked to sexual

orientation, what produces that neurohormonal event? One animal paradigm that

has been considered a potential etiological model for this mechanism is based on

evidence that maternal stress demasulinizes and feminizes the sexual behavior of

male rat progeny (I. L. Ward, 1972; 0. B. Ward, Denning, Hendricks, & French,

2002) via a delay of the testosterone surge critical for sexual differentiation

of the brain (I. L. Ward & Weisz, 1980). Although external genitalia remain

unaltered, the size of the sexually dimorphic nucleus of the preoptic area

(discussed later) is feminized (0. B. Ward, 1992). This model is by no means

ideal because of inconsistencies in the animal and human literature. Chapman and

Stem (1978) found no morphological or behavioral differences between offspring

of stressed and nonstressed rats, whereas Sachar and Clement (1980) stated that

the human adrenal response to stress is attenuated in comparison to rats.

Several researchers have explored the effects of prenatal maternal stress on

human sexual orientation, with mixed results. One study compared the number of

men registered by “venerologists” as homosexual (N = 865) per the total number

of male births in East Germany, and found significant differences between

cohorts born during and after World War 11 compared to those before the war

(Dorner et al., 1980), the assumption being that women who were pregnant during

and immediately after the war were more likely to experience stress. Dorner,

Schenk, Schmiederl, and Ahrens (1983) replicated these results by asking 100

bisexual/gay men and 100 heterosexual men about stressful events that might have

occurred during their mother’s pregnancy. Ellis, Peckham, Ames, and Burke (1988)

surveyed a small sample of mothers about stress during each trimester of

pregnancy. A marginally significant trend for increased stress during the second

trimester was found for mothers of gay offspring. As pointed out by LeVay

(1996), the results are difficult to interpret given that a significant

difference was also found for a 3-month period a year before they became

pregnant. In a more recently reported study conducted between 1988 and 1998 in

the U.S., over 7,500 offspring and their mothers provided retrospective

information regarding the offspring’s sexual orientation and the mother’s

stressful experiences and use of alcohol and nicotine during pregnancy (Ellis &

Cole-Harding, 2001). The inclusion of maternal drug use as a variable in this

study is justified, based on animal studies in which it has been demonstrated

that the administration of drugs to pregnant females has effects on the sexual

behavior of offspring similar to the effects of prenatal stress (0. B. Ward,

1992). Findings from this study suggested that prenatal stress has a small, but

significant, effect on sexual orientation in males, alcohol has no effect, and

nicotine significantly increases the probability of homosexuality in females.

These studies have been criticized on the methodological grounds that there were

no reliability checks for independent and dependent variables, the possibility

of demand characteristics (mothers and sons looking for an explanation for

homosexuality), and lack of consideration of alternative explanations (e.g.,

higher paternal absence; Bailey, Willerman, & Parks, 1991). In addition, in one

study this effect was not replicated: Mothers’ recall of stress during pregnancy

correlated close to zero with their son’s Kinsey scale ratings of sexual

orientation (Bailey et al., 1991). One possible explanation for the inconsistent

results across studies may be the small effect size of the phenomenon, such that

it is only detectable with massive samples. Additionally, the reliance on

retrospective reporting may blur any detectable effect. Although difficult to

perform, prospective studies would provide more convincing evidence of the

existence of a maternal stress effect on sexual orientation.

En ausencia de tecnología que permita la determinación directa de acción hormonal prenatal específica de tejidos en seres humanos, otra metodología de investigación ha sido la comparación de sujetos homosexuales y heterosexuales en rasgos de los que se cree que están influidos por la hormonas sexuales prenatales. Esto es consistenco con una de las predicciones principales de la hipótesis neurohormonal: que los individuos homosexuales deberían tener una frecuencia más alta de características del otro sexo [cross-sex characteristics] que los individuos heterosexuales (Ellis & Ames, 1987). Esta idea ha sido explorada en una variedad de rasgos medidos usando técnicas biológicas, incluyendo asimetría cerebral, estructuras neuroanatómicas, emisiones otoacústicas y características antropométricas.

Marcadores Neurosicológicos de Asimetría Cerebral Funcional

Functional cerebral asymmetry (FCA) refers to the division of labor between the

hemispheres of the brain for the processing of language and spatial abilities.

Despite inconsistent results across studies, narrative reviewers of the

literature have suggested that men show a modest increase in functional

asymmetry compared to women, meaning that the hemispheres of men are more

specialized (Hiscock, Inch, Jacek, Hiscockkalil, & Kalik, 1994; McGlone, 1980).

Zucker and Bradley (1995) provided a comprehensive review of studies exploring

sexual orientation differences in FCA and reported largely inconsistent results.

Given the depth of their review, we focus only on studies published since that

time.

Sanders and Wright (1997) found gay men lacked a male-typical left visual field

advantage on a dot detection task. In another study, gay men and lesbian women

did not show the association between hand preference and the magnitude of

perceptual asymmetry on a dichotic listening task found among heterosexuals

(McCormick & Witelson, 1994). Reite, Sheeder, Richardson, and Teale (1995) found

gay men had a female typical pattern of decreased cerebral laterality when

measured with a magnetoencephalogrpham during an auditory task. Alexander and

Sufka (1993) found gay men’s EEG patterns resembled the patterns recorded from

heterosexual women during various verbal and spatial tasks (for a replication

see Wegesin, 1998). In the only study to include lesbian women Wegesin (1998)

found no sexual orientation effects. Although these studies seem to suggest a

different pattern of FCA dependent on sexual orientation in men, the limited

number of studies and their reliance on small convenience samples require

replications with larger samples before any definitive conclusion can be drawn.

One trait shown to be an indirect index of FCA is an individuals handedness

(Geshwind & Galabura, 1985). In order for handedness to be relevant to sexual

orientation under the prenatal neurohormonal theory, its development should be

canalized prenatally and be dependent upon androgens. Little is definitively

known about the ontogeny of handedness, but indirect evidence, such as increased

rates of nonrighthandedness among males, is consistent with both prenatal

canalization and hormonal influences (see Lalumiere et al., 2000; Mustanski et

al., 2002, for a review of the data).

Narrative reviews of the literature on the association between handedness and

sexual orientation have disagreed about the existence of a correlation (Halpern

& Haviland, 1997; Zucker & Bradley, 1995). A recent meta-analysis of 20 studies

examined the rates of nonright-handedness based on sexual orientation (Lalumiere

et al., 2000). Overall, homosexual participants had 39% greater odds of being

nonrighthanded than heterosexuals, with 34% odds for men and 91% for women. As

mentioned earlier, the most parsimonious neurohormonal hypothesis specifies that

male homosexuality depends on low prenatal androgen action and that female

homosexuality depends on high prenatal androgen action (Ellis & Ames, 1987). In

terms of handedness findings, this theory would predict increased

left-handedness in lesbians compared to heterosexual women and decreased

left-handedness in gay men compared to heterosexual men (i.e., a sex-atypical

pattern for homosexual subjects). Lesbian women demonstrated this pattern,

whereas gay men did not. The fact that these data are both consistent with the

neurohormonal hypothesis in women but not men, and that women show a larger

effect size is suggestive of several considerations. First, there may be

different influences impinging on sexual orientation in males and females (we

return to this shortly). Second, given that the male data is inconsistent with

the neurohormonal hypothesis as specified, alternative theories should be

considered.

Neuroanatomía

En 1976, Dorner formuló su teoría clásica del “centro dual de apareamiento” sobre el papel de regions cerebrales específicas en el comportamiento sexual. Basándose en un modelo de ratas, Corner implicó a la región medial preoptico anterior hipotalámica [medial preoptic-anterior hypothalamic region] (mPOA) as being

involved in the regulation of male-typical sexual behaviors and the ventromedial

nucleus in the regulation of female sexual behavior. The extremely limited

research in humans on these areas and how they relate to sex and sexual

orientation will be summarized below. Table 2 was created to help organize the

findings and clarify that multiple terms have been used for the same structure.

To help navigate the pattern of replications and failed replications, the table

is laid out to describe which studies have produced positive and negative

findings for sex and sexual orientation differences in each brain structure.

Allen, Hines, Shryne, and Gorski (1989) stated that the preoptic area (mPOA) is

the most likely to show a sex difference in humans because this area shows the

most consistently replicated sex difference in nonhumans. Within the preoptic

area, a particular region termed the sexually dimorphic nucleus (SDN) was found

to be approximately 2.5 times larger in human men than women, and to contain 2.2

times as many cells (Hofman & Swaab, 1989; Swaab & Fliers, 1985). A difference

based on sexual orientation was investigated in a sample of 34 subjects who

varied on sex, sexual orientation, and AIDS serostatus (Swaab & Hofman, 1990).

Using morphometric analysis of the SDN, no difference in either volume or cell

number based on sexual orientation was found. However, another hypothalamic

nucleus located in the immediate vicinity of the SDN, the suprachiasmatic

nucleus (SCN), was found to be 1.7 times larger in gay versus heterosexual men,

and contained 2.1 times as many cells. The fact that the SDN was not found to be

associated with sexual orientation is inconsistent with Dorner’s hypothesis

(1976). The fact that a difference was found in the SCN, a nucleus not known to

be sexually dimorphic (Hofman, Fliers, Goudsmit, Swaab, & Partiman, 1988; Swaab,

Fliers, & Partiman, 1985), makes interpretation of these data difficult without

replication.

Other regions in the preoptic area that have been found to be sexually dimorphic

are the second and third interstitial nuclei of the anterior hypothalamic (INAH)

(Allen et al., 1989). Allen et al. argued that the region labeled INAH-1 most

likely corresponds to the SDN identified by Swaab and Fliers (1985), but

methodological differences accounted for the lack of sexual dimorphism in their

research. Specifically, Swaab and Fliers (1985) found an interaction between sex

and age for the INAH-1 region, introducing the possibility that age differences

between the two samples may explain the inconsistent results. However, more

recent researchers have failed to replicate this interaction effect, while

replicating the sex difference in the INAH-3 region (Byne et al., 2000).

Additionally, cytoarchitectonic comparisons between the INAH-3 region in humans

with similar hypothalamic structures in monkeys and rats suggest that it may be

the best candidate for homology with the mPOA (Byne, 1998).

Based on the reported sex differences in INAH-2 and INAH-3 (Allen et al., 1989),

LeVay (1991) measured these regions in the autopsied brains of 19 gay men who

died of AIDS, 16 presumably heterosexual men (6 died of AIDS), and 6 presumably

heterosexual women (1 had died of AIDS). A heterosexual orientation was presumed

in those brains that were not specifically provided by deceased individuals who

were known to be gay based on medical records. In this sample, no sex difference

in the INAH-1, INAH-2, and INAH-4 was observed. As shown in Table 2, the lack of

a sex differences in INAH-1 and INAH-4 is consistent with other studies (Allen

et al., 1989; Byne et al., 2000), whereas the lack of a difference in INAH-2 is

consistent with the findings of some researchers (By-ne et al., 2000), but not

others (Allen et al., 1989). The finding of a larger INAH-3 in males compared to

females is consistent with all previous studies (Allen et al., 1989; Byne et

al., 2000), making it the most theoretically relevant location to look for a

sexual orientation difference. This study found a comparable cell volume in the

INAH-3 between heterosexual women and gay men, both of which were significantly

smaller than the heterosexual men (LeVay, 1991). Comparisons that only included

the heterosexual participants who died of AIDS (n = 6) were robust in producing

the effect. Recently, Byne et al. (2001) reported a nonsignificant trend toward

INAH-3 occupying a smaller volume in gay men (N = 14) than in heterosexual men

(N = 34), with no difference in the number of neurons within the nucleus. None

of these studies have included lesbian women.

Although no researchers have explored sexual orientation effects in the anatomy

of the ventromedial nucleus, the hypothalamic region posited by Dorner (1976) to

be related to female sexual behavior, two investigators have explored the

anterior commissure (AC). The AC is a fibrous tract located within the

hypothalamus connecting the two hemispheres of the brain. In one study, Demeter,

Ringo, and Doty (1988) found the cross-sectional area of this tract to be larger

in men. In two studies Allen and Gorski (1991, 1992) found it to be larger in

women. Lasco, Jordan, Edgar, Petito, and Byne (2002) found no difference and

Highley et al. (1999) found no difference in area but did find differences in

fiber number and type. The putative increased size of the AC in females has been

posited as an explanation for the modest decrease in functional cerebral

lateralization (FCL) possibly found in women (Allen & Gorski, 1991). Some

evidence for sexual orientation differences in FCL has been shown to exist.

Thus, research on this structure seems theoretically appropriate. Allen and

Gorski (1992) examined the ACs of 30 gay men, 30 presumably heterosexual men,

and 30 presumably heterosexual women, matched for age. The gay men in their

sample had ACs that were 34% larger than those of the heterosexual men. Analyses

suggested no significant difference between men who did and did not die of AIDS.

Lasco et al. (2002), however, failed to find any variation in the size of the AC

with sexual orientation in a sample of 120 participants.

Taken together, the results of these studies suggest that brain differences may

be related to sexual orientation and implicate brain centers both believed

(POA/INAH) and unproven (SCN, AC) to influence sexual behavior. As shown in

Table 2, despite some variability in the evidence supporting the existence of

sex differences in various hypothalamic nuclei, one consistent finding emerges

from these studies: The region that consistently evidences a sex difference, the

INAH-3, also shows the best evidence for a sexual orientation effect. One

limitation of these studies is the subjective nature of identifying the borders

between brain regions. The fact that in all studies raters blind to the sexual

orientation of their subjects were used helps to prevent systematic rater

biases. Some studies also included multiple independent raters of the traces of

relevant regions, an important step when relying on a subjective measure.

Independent replication is essential before any of these findings can be

accepted, especially because initial positive reports are likely come from

studies in which many areas were examined and several statistical tests were

performed on nonindependent measures, usually without a correction for the

number of comparisons. Replication is especially important for those areas where

there is little reason, a priori, to expect a sexual orientation effect because

no sex difference exists (e.g., SCN & AC). Another major criticism is the

potential confound of AIDS serostatus as reductions in testosterone levels have

been documented in late-stage HIV infections (Byne & Parsons, 1993). The fact

that each of these studies included HIV positive heterosexual male controls, and

produced no evidence of AIDS having an effect on the results, reduces but does

not eliminate this criticism, because different disease courses could vary by

sexual orientation. A final limitation of these studies is that they have not

included lesbian women.

Otoacoustic Emissions

Click-evoked otoacoustic emissions (CEOAEs) are echo-like waveforms that are

emitted by the inner ear in response to brief sounds (McFadden & Pasanen, 1998).

CEOAEs show individual differences, are highly heritable, and are generally

stable throughout life (McFadden & Pasanen, 1998). Support for a hormonal role

in CEOAEs comes from two lines of evidence. First, sex differences exist in both

newborns and adults, with women having stronger CEOAEs and both sexes

experiencing increased magnitude in the right ear (see McFadden, 2002 for a

review). Second, McFadden, Loehlin, and Pasanen, (1996) reported that female

dizygotic twins with male cotwins had CEOAEs that are more typical of men. In

lower animals, females with male litter mates may be exposed to increased levels

of androgens via diffusion across the amniotic fluids (vom Saal, 1989). Evidence

for cross-twin hormone exposure in human twin studies is mixed (e.g. Loehlin et

al., 2000), but the existence of sex differences does lend support to the

hypothesis that androgens may play a role in the development of these emissions.

Research examining the CEOAEs of women whose mothers took DES and females

affected with CAH is currently underway to further investigate the association

between prenatal hormones and CEOAEs (McFadden, 2002).

In a sample of 237 subjects, McFadden and Pasanen (1998) replicated the

previously mentioned sex and ear differences. In comparisons based on sexual

orientation, no difference was found in men. For women, a main effect for sexual

orientation was demonstrated, with lesbian and bisexual women emitting lower

(i.e., more male typical) CEOAEs than heterosexual women. Researchers exploring

brain waves in response to click stimuli, called auditory evoked potentials

(AEPs), have found similar male-typical results in women (McFadden & Champlin,

2000). For men, these results are less clear, as the nonheterosexual men were

shifted even further from the heterosexual women than were the heterosexual men,

suggesting to the authors evidence for hypermasculiniation of nonheterosexual

men and women. McFadden and Pasanen proposed that the most parsimonious and

theoretically supported explanation for the above results is a graded

progression of exposure to prenatal androgens that influences both sexual

orientation and the peripheral auditory system. Sexual orientation differences

in behavior that could have confounded the results (e.g., gay men may be more

likely to attend loud concerts than heterosexual men) were tested for but are

not supported by the currently available evidence (McFadden, 2002). Replications

by independent laboratories are needed to substantiate these results.

Anthropometrics

Several anthropometric characteristics have been explored in relation to sexual

orientation: finger length, dermatoglyphics, weight, height, body morphology,

and penis length. The relation between sexual orientation and these

characteristics is hypothesized to be the result of nonspecific effects of

prenatal sex-atypical hormonal action. If sexual orientation is related to

perturbations in prenatal hormone environments, the effects of these

perturbations should be observable in sexually dimorphic traits other than

sexual orientation (Money, 1987).

Several lines of evidence suggest that finger length ratio may be a window into

the prenatal hormone milieu. The trait is sexually dimorphic; in women the index

finger (21) is nearly equal in length to the ring finger (41)), whereas in men

2D is shorter on average than 41), and this ratio is established by 2 years of

age (Manning, Scutt, Wilson, & Lewis-Jones, 1998). The sex difference in finger

length ratio is small, however, approximately one-third of a standard deviation

(Williams et al., 2000). According to Williams et al. (2000, p. 445) “because

all nongonadal somatic sex differences in humans appear to be the result of

fetal androgens masculinizing males (Breedlove, Cooke, & Jordan, 1999), the sex

difference in 2D:4D probably reflects the prenatal influence of androgens on

males.” Based on this idea, smaller 2D:4D ratios are believed to index greater

levels of prenatal androgen exposure. Indeed, the 2D:4D ratio is negatively

correlated with adult androgen levels (Manning et al., 1998), but the

relationship between prenatal and adult androgen levels is unknown at this time.

Additionally, differences have been found in finger length ratios in lesbians

based on self-identification as “butch” or “femme” (Brown, Finn, Cooke, &

Breedlove, 2001), a dichotomy with some evidence of hormonal underpinnings

(Singh et al., 1999). Perhaps the strongest evidence that finger length ratios

are indicative of prenatal androgen levels comes from a recent study reporting

that the 2D:4D ratios in children with CAH were smaller than control subjects,

regardless of sex (Brown, Hines, Fane, & Breedlove, 2001).

In a sample of 720 adults attending a public street fair in San Francisco,

Williams and colleagues (2000) replicated the higher 2D:4D ratio in women, with

the additional observation that the sex difference was greater on the right

hand. The authors interpreted this as evidence that the right-hand 2D:4D ratio

is more sensitive to fetal androgens than the left. Analyses of these data

indicated that the right-hand 2D:4D ratio was significantly smaller in lesbian

women (i.e., more masculine) compared to heterosexual women, and not

significantly different from that of heterosexual men. The 2D:4D ratio was not

significantly different, based on sexual orientation, in men for either hand.

However, when the sample was segregated into gay men with and without older

brothers, gay men with older brothers had smaller 2D:4D finger ratios (i.e.,

more masculine).

Robinson and Manning (2000) reported lower 2D:4D ratios in a sample of gay men,

independent of the number of older brothers. In the largest sample to date (N =

2,000), Lippa (2002) reported significantly more feminine 2D:4D ratios among gay

men, a finding in conflict with earlier reports. This finding was also robust

against ethnic group differences, a factor known to influence this ratio

(Robinson & Manning, 2000). Lippa found no significant difference between

lesbian and heterosexual women after controlling for ethnicity. Considering

these conflicting results, further research in this area is needed before it

will be possible to evaluate its support for the neurohormonal hypothesis. In

such research, investigators should make sure to collect a large and ethnically

diverse enough sample so that the proven effects of ethnicity on 2D:4D ratio can

be controlled. As noted by Lippa, without such controls, difference in ethnic

representation across samples could induce spurious results.

Another anthropometric phenomenon that has been studied in relation to sexual

orientation is dermatoglyphic asymmetry. Skin ridges, or dermatoglyphics, are

found on the palms and soles of all primates, and in humans, are determined

between the 8th and 16th week of fetal life (Holt, 1968). After birth, the ridge

patterns are not affected by development or the environment, and can only be

altered by severe mechanical damage (Cummins & Midlo, 1961), making them a good

source of information about the timing of prenatal events correlated with their

eventual pattern (Mustanski et al., 2002).

In order for dermatoglyphics to be relevant to the neurohormonal hypothesis,

their development must be related to prenatal androgens. Jamison, Jamison, and

Meier (1994) suggested a mechanism whereby prenatal testosterone might influence

dermatoglyphic variation via its relationship with nerve growth factor and

epidermal growth factor. Empirical evidence based on studies of nonhuman and

human primates provide moderate support for an association between androgens and

dermatoglyphic patterns (see Mustanski et al., 2002, for a review).

In a sample of 182 heterosexual men and 66 gay men, Hall and Kimura (1994)

reported a significantly greater incidence of leftward asymmetry in gay men,

defined as two or more ridges on the left hand. In two more recent studies of

the same size or larger, this effect was not replicated (El-Hani et al., in

press; Mustanski et al., 2002). In addition, no difference was found for total

ridge count or continuous leftward asymmetry (the continuous counterpart of the

arbitrary dichotomization used by Hall & Kimura). Several researchers have also

explored this phenomenon in transsexuals (Green & Young, 2000; Slabbekoorn, van

Goozen, Sanders, Gooren, & Cohen-Kettenis, 2000) and twins (Hall, 2000a, 2000b)

with conflicting results. As discussed by Mustanski et al. (2002), large-scale

studies that either employed less-reliable dichotomizations of the dependent

measure, or reported multiple tests, were the only ones to return positive

results. Those studies in which the more reliable and statistically appropriate

continuous measure was employed, and in which multiple tests on the data were

not conducted, consistently produced no association between sexual orientation

and dermatoglyphics (El-Hani et al., in press; Mustanski et al., 2002;

Slabbekoorn et al., 2000).

Weight and height, additional sources of anthropometric data, are sex-dimorphic

somatic characteristics with men, on average, being taller and heavier than

women. Differences between heterosexual and homosexual men and women on these

somatic traits could be, under a biological model, attributable to sex-atypical

organization of sex-dimorphic brain structures responsible for physical growth

(i.e., hypothalamic-pituitary-gonadal axis) (Blanchard & Bogaert, 1996a). In the

past, this literature has been problematic to interpret because of small sample

sizes, lack of control of confounding variables (e.g., controlling for age and

height when examining difference in weight), and the failure to test a

directional hypothesis adequately (Blanchard & Bogaert, 1996a). The results of

three studies designed to address these factors showed gay men reported being

lighter and shorter, compared to heterosexual men (Blanchard & Bogaert, 1996;

Blanchard, Dickey, & Jones, 1995; Bogaert & Blanchard, 1996a), whereas in others

with adequate sample sizes no weight (Siever, 1994; Yager, Kurtzman, Landsverk &

Wiesmeier, 1988) or height differences (Evans, 1972) have been found.

Studies examining height and weight differences in lesbian and heterosexual

women are less numerous. In his analysis of 275 lesbian and 5,201 heterosexual

women’s case histories recorded by the Kinsey Institute, Bogaert (1998) showed

that lesbians reported being, on average, heavier and taller than heterosexual

women did. The weight difference reported by Bogaert replicated differences

reported by other researchers (see Bogaert, 1998, for a review). The difference

in height reported by Bogaert contradicts that of Perkins (1981), who reported

no significant differences between a large sample of lesbian women and

population norms.

Factors other than those that are neurohormonal in origin may account for the

differences observed in weight. For example, gay men may be relatively more

concerned about slimness compared to heterosexual men and thus report being

lighter (a similar argument could be made for heterosexual women compared to

lesbian women). However, there is little evidence to support these hypotheses

(Bogaert, 1998; Bogaert & Blanchard, 1996). One large methodological weakness in

this literature is the use of self-reported weight in these studies; objective

weight measurement is preferable to eliminate systematic reporting biases.

Examining differences in height as an index of somatic sex-atypicality is

particularly appealing because, unlike weight, final adult height is unlikely to

be influenced by environmental, psychological, or medical factors (Bogaert &

Blanchard, 1996). The differences in height reported in the most rigorous

studies to date are small; 1.5 cm for men (adjusted for maternal and paternal

height) (Bogaert & Blanchard, 1996), and 89 mm for women (Bogaert, 1998). In

both studies analyses were based on self-reported height, reducing the

reliability of the values. Again, replication of these effects must be attempted

using objective morphometric measures rather than collecting data through

self-report.

Related to the issue of weight and height is the study of body morphology. In

females, the pubertal surge in estrogens enlarges the pelvis and facilitates fat

deposits in the buttocks and thighs. This, in combination with the inhibition of

fat deposition in the abdomen, results in a waistto-hip ratio (WHR) in the range

of .67-.80 (Singh, 1993). In men, the pubertal increase in androgen production

facilitates fat deposition in a fashion nearly opposite to women, resulting in a

WHR in the range of .85-.95 (Singh, 1995). In the only study to-date exploring

WHR and sexual orientation, self-described “butch” and “femme” lesbians were

compared to each other and a sample of heterosexual women (Singh et al., 1999).

WHR was measured by the participants based on instructions provided by the

researchers. Butch lesbians were found to have higher (i.e., more masculine) WHR

than either the femme lesbians or heterosexual women, even after controlling for

age and body mass differences. After rejecting lifestyle choices as an

explanation for these results, Singh et al. (1999) concluded that the evidence

suggests differences in the current hormonal milieu by sexual orientation and

degree of masculinity.

The rationale for examining pubertal timing in relation to sexual orientation is

similar to that cited for anthropometric measures; sex differences in pubertal

onset are evident, with boys reaching puberty later than girls (Reiter &

Rosenfeld, 1998). Gay men would resemble heterosexual women (i.e., reach puberty

earlier than heterosexual men) because relevant sex-dimorphic brain structures

involved in the timing and regulation of puberty would be shifted toward a

female-typical pattern (Blanchard & Bogaert, 1996a). Similarly, lesbians would

resemble heterosexual men, reaching puberty later than heterosexual women

(Bogaert, 1998). Based on multiple physical indices of puberty, (i.e., first

ejaculation, pubic hair) gay men have been shown to reach puberty earlier than

heterosexual men (Blanchard & Bogaert, 1996a; Bogaert & Blanchard, 1996; Kinsey,

Pomeroy, & Martin, 1948) and researchers using behavioral indices of puberty

have found similar results (see Bogaert & Blanchard, 1996, for a review).

Conversely, using physiological markers for onset of puberty (i.e., age of first

menarche), Bell, Weinberg, and Hammersmith (1981), Tenhula and Bailey (1998),

and Bogaert (1998) reported no significant difference in pubertal onset between

lesbian and heterosexual women. Pubertal timing is measured via retrospective

reports of discrete physiological events, but puberty is not a discrete event,

it is a series of ongoing physical changes. Therefore, these results should be

regarded with some skepticism. Furthermore, it is possible that men’s recall of

puberty is less reliable than women’s because men have no significant discrete

event to recall, whereas women do (i.e., menarche).

Putative early androgen differences between gay and heterosexual men could cause

subtle differences in penile differentiation, and, thus, penis size and sexual

orientation has been examined in two studies. Bogaert and Hershberger (1999) and

Nedoma and Freund (1961) have both reported gay men to have larger penises than

heterosexual men, both in erect length (Cohen’s d = .41 and .78, respectively)

and circumference. Although penile length and circumference were self-assessed

in Bogaert and Hershberger’s sample, their results replicate those of Nedoma and

Freund, in which penile measurements were recorded by the researchers.

Additionally, Bogaert and Hershberger’s sample was large (n = 813 and n = 3,417

for gay and heterosexual men, respectively) and analyses included controls for

differences in education, height, and weight between gay and heterosexual men.

These results have yet to be replicated in a representative sample using

objective measures.

The evidence concerning the neurohormonal hypothesis is extremely heterogeneous in several respects. In synthesizing this body of data, it is important to take

into consideration that some data are more directly relevant to the hypothesis

than other data. For example, the outcome of genetic males with cloacal

exstrophy who have been reared as girls is almost an ideal test of the

neurohormonal hypothesis. In contrast, the ontogeny of other biological markers

is not well understood and is imperfectly related to prenatal androgen level.

Thus, the rather uniform findings for the cloacal cases, which favor the

neurohormonal hypothesis, are more important than the mixed findings for other

traits. With this consideration in mind, we review the consistency of different

research areas related to the neurohormonal hypothesis.

Three research areas have produced consistent results upon independent

replication or meta-analysis: the clinical evidence, pubertal development in

men, and FCA/handedness. Within these domains, both the clinical and pubertal

development data are supportive of the neurohormonal hypothesis. The recent

meta-analysis of the handedness data (Lalumiere et al., 2000) produced results

that are incompatible for males with the theory as described by Ellis and Ames

(1987). The results for females are compatible with the theory. Evidence

consistent with the INAH-3 differences described by LeVay (1991) has been

reported in one study (Byne et al., 2001), and these results are compatible with

the neurohormonal theory. Independent replications have yet to be published for

some indices (otoacoustic emissions and body morphology), whereas for other

areas replication has produced mixed results (prenatal stress, dermatoglyphics,

height, weight, and finger length). As in other areas of science, two factors

will likely lead to greater understanding of the role hormones play in sexual

orientation. Replication by independent laboratories will lead to a clearer

picture of the relationship between sexual orientation and many of these

putative biological markers of prenatal hormone status. Additionally,

technological advances in behavioral endocrinology may allow more powerful tools

to be used in the investigation of target tissue hormone sensitivity in humans.

Until that time it is difficult to make any definitive conclusions about the

soundness of the neurohormonal hypothesis.

Genetic Influences

Research hypothesizing genetic influences on sexual orientation began over 60

years ago, motivated by the idea that gay men are genetically female (Lang,

1937, 1940). Techniques for identifying the sex chromosomes discredited this

hypothesis (Pare, 1956). Without evidence for clear chromosomal abnormalities

among homosexual subjects, researchers turned to three other methods for

exploring the genetic nature of sexual orientation: family studies, to explore

the frequency and pattern of the familiality of homosexuality; twin and adoption

studies, to partition the population variance in sexual orientation into genetic

and environmental components; and molecular genetics studies, to identify

specific genes that influence an individuals sexual orientation.

Estudios de Familia

Most family studies of sexual orientation have recruited male and female

probands through newspaper advertisements that do not mention the nature of the

study (Bailey & Bell, 1993; Bailey & Benishay, 1993; Bailey & Pillard, 1991;

Bailey, Pillard, Neale, & Agyei, 1993; Bailey et al., 1991; Dawood, Pillard,

Horvath, Revelle, & Bailey, 2000; Pillard, 1990; Pillard & Weinrich, 1986).

Bailey et al. (1999) used more assiduous ascertainment of two samples, one

recruited through consecutive admissions at an HIV outpatient center and the

other from a gay pride festival. Such recruitment decreases the chance that

siblings will self-select for participation based on their concordance for

homosexuality. The median rate of homosexuality in brothers of gay men is

approximately 9% (reviewed in Bailey & Pillard, 1995), a figure well above

recent population base rates of homosexuality (Laumann, Gagnon, Michael, &

Michaels, 1994).

Female homosexuality also appears to run in families, although estimates of

homosexuality among sisters of lesbians vary widely, ranging from 6% to 25%

(Bailey & Pillard, 1995). Although both male and female homosexuality appears to

run in families, it remains unclear whether it runs in the same families. When

comparing across studies, there is modest evidence that opposite-sex siblings of

homosexual probands (i.e., sisters of gay men and brothers of lesbians) have

increased rates of homosexuality compared with controls, although statistical

genetic techniques have not been utilized to provide a more definitive answer to

this question. One major limitation of these family studies is that often the

rates of homosexuality are based on the subject’s ratings of their siblings’

sexual orientation. As discussed later, relying on subjects to identify the

sexual orientation of their family members is likely to introduce significant

error into the study (see Kirk, Bailey, & Martin, 1999 for discussion).

Estudios de mellizos

Family studies cannot disentangle whether a trait’s familiality is due to

genetic or common environmental effects because siblings do not just share

common genes but usually also share their rearing environment. Twin studies

allow the variance in a trait within a population to be partitioned into

heritable effects and influences explained by the shared and nonshared sibling

environment. Heritability refers to the proportion of variance in a trait within

the population that is due to genetic effects. Shared environmental effects, as

defined in twin studies, refer to environmental influences that make siblings

more similar to each other. Nonshared environmental influences are factors that

tend to make siblings different from each other. For a thorough review of these

concepts see Turkheimer and Waldron (2000).

The earliest twin studies of sexual orientation reported extraordinarily high

heritability estimates (Kallmann, 1952). This and other early studies have been

criticized because of their reliance on mentally ill gay men, poor zygosity

determination, unusually high MZ concordance rates, and possible ascertainment

bias toward concordance (e.g., Rosenthal, 1970). Recent samples of twins

ascertained via advertisements in homophile publications or via moderate-sized

twin registries suggest that the familial nature of homosexuality is due largely

to genetic influences (Bailey & Pillard, 1991; Bailey et al., 1993; Buhrich,

Bailey, & Martin, 1991; Whitam, Diamond, & Martin, 1993, but see also King &

McDonald, 1992). It is important to note, however, that the validity of these

studies is questionable for reasons related to sampling. Identifying

participants through homophile publications and word-or-mouth may result in a

concordance-dependent ascertainment bias for twins concordant for homosexuality

(Kendler & Eaves, 1989). This bias will not likely result in inflated

heritability estimates, however. Heritability estimates would be inflated if MZ

twins from concordant pairs were more likely to be ascertained than DZ twins

from concordant pairs. There is no evidence that this occurred in any study,

although the possibility cannot be excluded (Bailey & Pillard, 1995).

All studies before 1991 and by Whitam et al. (1993) only report concordance

rates by zygosity. More sophisticated quantitative genetic techniques, which use

structural equation modeling with model fit based on maximum-likelihood, allow

much more precise estimation of the various sources of variance and also allow

significance testing on each parameter (Neale & Cardon, 1992). Additionally,

multivariate models have also been used to explore the source of covariation

between sexual orientation and related traits (i.e., sex-dimorphic behaviors)

while increasing the power of the parameter estimates.

Table 3 contains recent twin studies that have employed genetic modeling

techniques to estimate the proportion of variance in sexual orientation due to

heritable, as well as environmental sources of variation. The table also shows

the method of twin ascertainment and how the dependent variables were measured.

One study reported by Hershberger (1997) is not included in the table because an

atypical sampling strategy, involving recruiting twins from a volunteer twin

registry based on their concordance for being married or never-married, makes it

difficult to interpret the parameter estimates. The studies reported by Bailey,

Dunne, and Martin, (2000), Kirk, Bailey, Dunne, and Martin, (2000), and Kendler,

Thornton, Gilman, and Kessler (2000) deserve special attention because of their

population-based ascertainment strategies. Population-based samples of twins

overcome many of the selection biases endemic to the previously cited

literature. The first of two studies based on the large population-based sample

of Australian twins is unique because both univariate estimates of sexual orientation and two covariates, childhood gender nonconformity (CGN) and continuous gender identity (CGI), are included along with a multivariate model incorporating all three (Bailey, Dunne, & Martin, 2000). Univariate analyses of the sexual orientation variable resulted in evidence for familial influences, but genetic and common environmental contributions could not be disentangled without the addition of the previously mentioned covariates. The results of

multivariate analyses suggested significant and moderate genetic and nonshared

environmental contributions for sexual orientation and its covariates. The

second report based on the Australian twin data included a multivariate model

that incorporated measures of both behavioral and psychological sexual

orientation (Kirk et al., 2000). Significant heritable and nonshared

environmental influences were reported for the latent sexual orientation

variable indicated by multiple measures of sexual orientation. Kendler et al.

(2000) also used a population-based sample, but, because of the low prevalence

of nonheterosexuality, they had insufficient power to separately model the data

for males and females. Qualitative comparisons of their data indicated that

concordance rates were higher in the female-female pairs than the male-male

pairs, but the data were not reported in a quantitative fashion. Together, these

studies suggest the existence of both genetic and nonshared environmental

influences on sexual orientation. As seen in Table 3, and based on the

preponderance of evidence, it also appears that genes influence sexual

orientation more strongly in males than females.

Estudios Moleculares

En un esfuerzo de identificar genes particular que contribuyan a la naturaleza heredable de la orientación sexual, se ha conducido una cantidad limitada de estudios tanto de vinculación como de asociación. Los estudios de vinculación buscan regions cromosómicas específicas que se transmiten dentro de las familias, junto con un fenotipo (i.e., la orientación sexual) en niveles de probabilidad mayores que la casualidad (50% para hermanos de cualquier sexo).

Association studies look at the relationship between variation at a specific

locus of a gene, and phenotypic variation. Hamer, Hu, Magnuson, Hu, and

Pattatucci (1993a) reported the first linkage study in 40 families of gay men.

In the initial pedigree analysis, the researchers noted increased rates of

homosexuality in maternal male relatives. This result implicates the X

chromosome because, except in very unusual cases, a male inherits his X

chromosome from his mother. Using a genetic linkage methodology, Hamer and

colleagues examined 22 DNA markers on the X chromosome. Thirtythree of 40 pairs

of gay brothers shared chromosomal region Xq28, which is significantly different

from the expected number of 20 (50%) (Hamer et al., 1993a).

Sin embargo, los resultados del estudio de Hamer et al. (1993a) fueron cuestionados. Risch, Squires-Wheeler y Keats (1993) argumentaron que las tasas incrementadas de parientes maternos gays podría deberse simplemente a las tasas disminuidas de reproducción entre hombres gays. En otras palabras, es improbable que un gene gay sea heredado de un padre gay, porque para empezar es improbable que un hombre gay tenga hijos. En segundo lugar, Risch et al. disputed Hamer et al.’s (1993a) calculation of the prevalence of gay firstdegree family members relative to the general population rate. Although this parameter, ,, has never been estimated in an epidemiologically valid manner, Risch et al. correctly noted that the larger it is estimated to be, the more significant the results produced by Hamer et al. (1993a). Hamer and his

colleagues (1993b) responded to many of these criticisms and concluded that, as

with many scientific findings, replication will be the ultimate arbiter.

Se han informado tres intentos de replicación de este estudio de vinculación. Hu et al. (1995) informaron una replicación con éxito de sus resultados temprano de Xq28 y extendieron el estudio para incluir hermanos heterosexuales. Su informe de una tasa de compartición [sharing rate] de Xq28 del 22% en hermanos discordantes por su orientación sexual fue significativamente menos que el 50% de compartición [sharing] esperado por azar. Este valor, en adición al marcador de compartición del 67% para la región Xq28 entre hermanos concordantes, representa una replicación positiva de los resultados tempranos. El estudio también incluyó 36 pares de hermanas lesbianas pero no se encontró evidencia para el exceso de compartición de marcadores. Se descubrió también un 66% de nivel de compartición para Xq28 en una muestra independiente de 54 pares de hermanos gays (Sanders et al., 1998 [tal como se los cita en Hamer, 1999]). Sin embargo, Rice, Anderson, Risch yinformaron una replicación fallida de la vinculación a la  Xq28 en una muestra de 52 pares de hermanos varones gays de familias canadienses. A diferencia del grupo de Hamer, sin embargo, no seleccionaron familias consistentes con la transmisión materna, con lo que disminuyeron la probabilidad de encontrar vinculación con el cromosoma X. Se puede encontrar una discusión más a profundo de los temas metodológicos que pueden explicar las discrepancias en los resultados, así como un metanálisis de los resultados a las fechas, en Bailey (1995), Hamer (1999), y Rice, Risch,

and Ebers (1999).

In one candidate gene association study of male sexual orientation, DNA sequence

variation in the androgen receptor gene has been explored (Macke et al., 1993).

The selection of this gene was based on neurohormonal evidence implicating

prenatal androgen levels in determining sexual orientation. No significant

differences in the distribution of mutations based on sexual orientation were

observed. An additional linkage analysis was performed, demonstrating that

sibling pairs concordant for homosexuality did not show increased sharing of

specific androgen receptor alleles.

Si lose studios de mellizos previamente citados están en lo cierto en que las influencias genéticas en verdad explican una porción de la variación en orientación sexual, entonces eventualmente las técnicas moleculares deberían permitir la identificación de genes específicos. Los avantes recientes en genética molecular, junto con los marcadores adicionales provistos por el Proyecto Genoma Humano, deberían facilitar esta búsqueda. No obstante estos avances, una cantidad de factores limitan la aplicabilidad de las metodologías genéticas de investigación moleculares tradicionales para hacer investigación en rasgos complejos como la orientación sexual y otros fenotipos comportamentales.

First, principles of genetic epidemiology must be considered, such as the fact

that familial recurrence patterns of homosexuality are not attributable to

common major genes (Bailey & Bell, 1993; Bailey et al., 2000; Bailey & Pillard,

1991; Bailey et al., 1999; Bailey et al., 1993). If sexual orientation is

polygenic, many genes exerting a small effect, they will be difficult to

identify because of low power (Stoltenberg & Burmeister, 2000).

Second, behavior genetic analyses have found that nonshared environmental

influences do play a role in sexual orientation; such factors have not been

specifically identified by including them in biometric twin models. The

relationship between environmental and genetic factors has also not yet been

explicated. Gene X environment interactions are just one likely possibility; in

this case the magnitude of genetic effects vary depending on the environment in

which they are expressed. For example, genes that predispose toward

heterosexuality can only be active in environments in which opposite sex

individuals are present. It is also unclear whether nongenetic etiological

factors are capable of producing a homosexual orientation on their own. In other

words, can environmental influences produce homosexuality independently of

genetic factors (when this occurs in a trait known to have genetic influences it

is known as a phenocopy)? If the answer is yes, the potential for

environmentally produced phenocopies exist and, therefore, potentially confound

molecular genetic research on this phenotype. Phenocopies reduce the power to

detect linkage because, from a genetics perspective, environmentally produced

phenotypes are false positives.

Third, traditional approaches to linkage are limited with behavioral phenotypes

because of the possibility that some combinations of dispositional genes will

not produce effects sufficient to cause the expression of the complete

phenotype. In terms of genetic research on sexual orientation, this means that

pedigree members may possess dispositional genes in subthreshold numbers,

causing them not to express the full homosexual phenotype. If sexual orientation

were dichotomized, then such individuals would be labeled heterosexual and would

be false negatives from a genetic perspective. Researchers have thus far largely

avoided this issue by using “affected” sib-pair designs that only include

sib-pairs in which both are gay, but these approaches lose power because the

whole pedigree cannot be included and dichotomizations can surrender a lot of

information. One partial solution to these problems would be to identify

indicators of processes that mediate between dispositional genes and the sexual

orientation phenotype. Such factors have been termed “endophenotypes” and are

considered more sensitive markers of underlying liability status (Gottesman,

McGruff, & Farmer, 1987). Endophenotypes are selected for being closer to the

mechanism of gene action than most qualitative categories and thus should be

more sensitive to degree of genetic liability among both affected and

nonaffected pedigree members. Therefore, endophenotypes would increase power by

allowing the inclusion of all pedigree members and also by avoiding the need for

dichotomization.

Linkage studies of alcoholism that have included both traditional diagnostic

information (i.e., DSM diagnosis) and an endophenotype (i.e., P300 amplitude)

have provided evidence for the usefulness of such techniques (Lunetta, Wilcox,

Smoller, & Neuberg, 1999). Bailey et al. (2000) have suggested childhood gender

nonconformity and its adult form, continuous gender identity, as psychometric

(meaning not assessed using a biological measure) endophenotypes for sexual

orientation. An explicit examination of whether these traits meet the

requirements for an endophenotype, as defined by Hesselbrock, Begleiter,

Porjesz, O’Connor, and Bauer (2001), has yet to be provided.

Despite all of the limitations mentioned above, the intense interest in

uncovering specific dispositional genes for homosexuality will likely lead to

additional research efforts. Such research will be aided by the identification

of new markers and genetic techniques identified through the Human Genome

Project. The payoff for finding such genes is enormous, but not for social or

moral reasons, as we believe such thinking is simpleminded (see Greenberg &

Bailey, 1993 for a discussion). Instead, locating such genes will be a large

step forward in identifying the more proximal mechanisms through which sexual

orientation is determined.

Fraternal Birth-Order Effect

Perhaps the most replicated finding in sexual orientation research is that gay

men are born later in their sibships, compared with heterosexual men.

Furthermore, recent studies have clarified that this effect is primarily due to

older brothers, who increase the probability of homosexuality in later-born

males (Blanchard, 1997). In at least 14 samples, gay men had significantly more

older brothers compared with heterosexual men but did not have a greater number

of older sisters, once the number of older brothers has been controlled (see

Blanchard, 2001, for a review). This fraternal birth-order effect has been shown

to be robust beyond gay men attracted to other adult men. The probability of

genetic males being attracted to men increases with the number of older brothers

in samples of male-to-female transsexuals (Blanchard, Zucker, Cohen-Kettenis,

Gooren, & Bailey, 1996; Green, 2000), pedophiles (Blanchard et al., 2000;

Bogaert, Bezeau, Kuban, & Blanchard, 1997), and nonpedophilic sex offenders

(Blanchard & Bogaert, 1998). The magnitude of this effect may be larger in

markedly feminine gay men (Blanchard & Scheridan, 1992). Despite several studies on women, no consistent tendency toward early or late births or atypical sibling

sex ratios has been detected (Blanchard, 1997).

Based on statistical analyses of selected samples, Cantor, Blanchard, Paterson,

and Bogaert (2002) estimated that between 14.8% and 15.2% of gay men can

attribute their homosexuality to the fraternal birthorder effect, based on

population base rates of homosexuality of 1% and 4% respectively. Additional

statistical evidence suggests that each additional older brother increases the

odds of same-sex attraction by 33% (Blanchard & Bogaert, 1996b).

Several hypothetical mechanisms have been posited to explain the fraternal

birth-order effect, some psychological and some biological. As the focus of this

paper is on biological influences, readers interested in putative psychosocial

explanations for this effect should consult Blanchard’s (1997) extensive review.

In terms of biological theories, traditional genetics cannot explain these

results because purely genetic phenomena do not show birth-order effects. Some

researchers have suggested the birth-order effect may be an artifact of advanced

maternal or paternal age, which then results in increased gametic mutations

(Raschka, 1995). Such explanations have been ruled out by multivariate analyses

demonstrating the robustness of the effect after controlling for maternal and

paternal age (Blanchard & Bogaert, 1996b). Blanchard and Bogaert have

hypothesized that a maternal immune response, provoked by male fetuses, becomes

stronger with each male pregnancy, thereby allowing the mother’s immune system

to act as the meter by which fraternal birth order is recorded, The first

antigen thought to influence sexual orientation via the maternal antibody

response was testosterone (MacCulloch & Waddington, 1981), but this theory was

subsequently discredited because steroid hormones are not normally antigenic

(Blanchard, 1997). Another proposed antigen is the Y-linked minor

histocompatiblity antigen (H-Y) (Blanchard, 2001). Thus far, the only empirical

evidence for the role of this antigen comes from research demonstrating that

male mice whose mothers are immunized to H-Y prior to pregnancy are less likely

to successfully mate with receptive females (Singh & Verma, 1987). Use of these

data as support of the H-Y antigen hypothesis are limited by the fact that

decreased mating among male rats is a poor proxy for homosexuality in human

males. Further research should be conducted in this area before maternal immune

response to the H-Y antigen can be considered a serious candidate as a mechanism

in the fraternal birth-order effect.

Whatever the precise mechanism, recent evidence suggests that the fraternal

birth-order effect is related to prenatal events. In two studies, based on large

samples, it has been demonstrated that gay males with older brothers weigh less

at birth than heterosexual males with older brothers (Blanchard & Ellis, 2001;

Blanchard et al., 2002). Because birth weight is clearly a prenatal phenomenon,

the fact that it is predicted by the interaction between sexual orientation and

the number of older brothers is strongly suggestive of a prenatal determinant

for both the fraternal birth-order effect and sexual orientation itself. In

another study by Lalumiere, Harris, and Rice (1999), it was found that a man’s

number of older brothers was a significant predictor of fluctuating asymmetry

(discussed in greater detail below), one marker of developmental perturbations

that could possibly have resulted from a maternal immune response. Although the

investigators did not directly assess sexual orientation, the results do provide

further evidence that the number of older brothers does have implications for

later born male offspring.

Developmental Instability

As mentioned in several of the earlier sections of this article, the

neurohormonal theory of sexual orientation differentiation does not adequately

explain several of the empirical findings (e.g., handedness, finger length). An

alternative mechanism, developmental instability (DI), has recently been

suggested as another possibility for explaining these associations (Lalumiere et

al., 2000; Mustanski et al., 2002). Developmental instability refers to an

organism’s inability to form an “ideal” (e.g., bilaterally symmetrical)

phenotype under varying levels of perturbations (Palmer, 1994). Developmental

perturbations during gestation could result from maternal illness, infection,

chemical use or exposure, and any number of other random factors. If

homosexuality results from a fetus’s inability to fully buffer against

developmental and/or environmental agents, then homosexual people should show

other markers of DI. Two commonly used markers are nonright-handedness (Yeo &

Gangestad, 1993; Yeo, Gangestad, & Daniels, 1993) and fluctuating asymmetry

(Palmer, 1994).

Nonright-handedness has been established as a marker of DI via its association

with a number of traits thought to result from developmental perturbations, such

as autism, stuttering, dyslexia (Geshwind & Galabura, 1985), neural tube

defects, and schizophrenia (Yeo & Gangestad, 1993, 1998). Fluctuating asymmetry

is an index of deviation from bilateral symmetry obtained by measuring the left-

and right-side of various physical sites, and taking the absolute value of the

difference. High indices indicate greater discrepancy between left- and

right-side measurements (i.e., greater asymmetry) and are believed to result

when an organism’s developmental plan is not expressed equivalently on both

sides of the body (Markow & Gottesman, 1989). Dermatoglyphic fluctuating

asymmetry, one of the most commonly used indices of developmental instability,

is indicated when either a left- or right-hand finger has more ridges than its

counterpart on the other hand. Increased levels of dermatoglyphic fluctuating

asymmetry have been observed in a variety of disorders believed to be the result

of developmental perturbations such as cleft-lip/palate, dyslexia,

schizophrenia, and minor physical abnormalities (e.g., Adams & Niswander, 1967;

Green, Bracha, Satz, & Christenson, 1994; Qazi, Masakawa, McGann, & Woods,

1980).

DI theorists would predict homosexuality to be the result of a perturbated

developmental process because, from the perspective of reproductive fitness, the

“ideal” phenotypic outcome of sexual orientation differentiation is likely to be

heterosexuality. In evolutionary terms, an organism that includes reproduction

in its developmental plan is more “fit.” Indeed, gay men have fewer offspring on

average than heterosexual men (Bell & Weinberg, 1978). DI theorists would

predict that gay men and lesbian women would show characteristics demonstrated

to be markers of DI, such as increased nonright-handedness and increased

fluctuating asymmetry compared to heterosexual men and women. Support for the DI

hypothesis is, at this time, limited. In only one study has any kind of

fluctuating asymmetry in homosexual participants been measured. Mustanski et al.

(2002) explored the relationship between dermatoglyphic fluctuating asymmetry

and sexual orientation and found no significant effects. Both male and female

homosexuality have been linked to increased incidence of nonright-handedness

(Lalumiere et al., 2000), a marker of DI. Therefore, these results could be

construed as supportive of the DI model. The application of DI theory to sexual

orientation is speculative and certainly less well articulated than the

neurohormonal theory. It is possible, however, that the DI and neurohormonal

hypotheses are related (e.g., the effects of an altered prenatal hormonal

environment may be manifestations of developmental instability). Future research

should focus on assessing multiple physical indicators of fluctuating asymmetry

in the same participant.

Impedimentos para la Identificación de Factores Biológicos

Despite the extensive research on the biological basis of sexual orientation,

methodological limitations impede the clear identification of etiological

factors. Many of these issues are relevant to all research on sexual

orientation, whereas others are more specific to biological research. General

criticisms include lack of a precise and commonly agreed upon definition and

measurement of sexual orientation and the exclusion of women from research.

Definition and Measurement of Sexual Orientation

One obstacle in research on sexual orientation is a lack of consensus on the

definition of sexual orientation and in methods used to operationalize this

construct. Although a myriad of definitions of sexual orientation have been

proposed (see Sell, 1997, for a review), most include a psychological (i.e.,

sexual fantasy/attraction) and/or a behavioral component(s). Self-definition as

gay, lesbian, or heterosexual is also used as another method of defining sexual

orientation. Therefore, three indices of sexual orientation can be considered:

sexual behavior, sexual fantasy and/or attraction, and self-definition.

Paper and pencil measures. The most commonly used instrument for assessing

sexual orientation is the Kinsey Scale, unidmensional 0 to 6 scales of

attraction, fantasy, and behavior to same- and opposite-sexed persons (Kinsey,

Pomeroy, & Martin, 1948). Less frequently used is the Klein Sexual Orientation

Grid, a multidimensional scale assessing sexual attraction, sexual behavior,

sexual fantasies, emotional preferences, social preferences, self-identification

and homosexual/heterosexual lifestyle choice (Klein, Sepekoff, & Wolf, 1985).

More recently, researchers have also included items measuring attitudes toward

sameand opposite-sex sexual activity as an additional measure of sexual

orientation (Kirk et al., 2000).

What is most problematic about using these measures in research is a lack of

consensus on methods of deriving a composite “sexual orientation score” based on

the data gathered. In general, there is a strong relationship between sexual

attraction/fantasy and behavior in gay men (Diamond, 1993). Thus, collapsing

these variables is likely not problematic.

Whether this is true for women, however, is doubtful. Bailey et al. (2000)

reported correlations between sexual fantasy and sexual attraction for men and

women (.92 vs. .67) demonstrating less overlap in women on measures of same-sex

interest. Recent research has helped to partially solve this definitional

dilemma by demonstrating that additive genetic factors that influence measures

of feelings, attitudes, and number of same-sex partners are primarily the same

for men and women (Kirk et al., 2000). Additionally, one latent “homosexuality”

factor appears to explain most of the variation in these measures (Kirk et al.,

2000). Based on these data, it seems appropriate to conclude that all of these

measures are tapping into the same construct, indicating they are all

appropriate for use in biological research on sexual orientation. However, using

certain dimensions of the Kinsey scales, such as sexual behavior, in isolation

is unadvisable as factors unrelated to sexual orientation, such as opportunity,

may influence the occurrence of same-sex sexual activity

Assigning individuals to groups based on sexual orientation scores can also be

problematic. Typically, Kinsey scores of 0 or 1 are considered heterosexual, 2

though 4 bisexual, and 5, 6 homosexual. Trichotomization, although intuitively

appealing, may not be ideal. For example, there is evidence that individuals

with composite Kinsey scores of 1 show elevations on traits related to sexual

orientation (e.g., childhood gender nonconformity), suggesting that Kinsey ls

should not be considered heterosexual (Bailey et al., 2000). Some researchers,

mostly those studying men, may dichotomize the Kinsey scale, including men

indicating bisexual interest/behavior in the homosexual group. The rationale for

dichotomizing is likely the belief that bisexual men are truly homosexual, but

this a priori assumption may be problematic, as varying degrees of same- and

opposite-sex interest will likely be represented in a homosexual group. One

method of avoiding the conundrum of assigning individuals to groups is to

perform analyses using sexual orientation measures as continuous variables.

Defining sexual orientation using self-identity is problematic for women because

of the potential heterogeneity in same- and opposite-sex sexual interest amongst

women who identify as lesbian. Base-rate estimates of same-sex sexual

orientation evinced from large probability samples have shown exclusive same-sex

attraction and self-identification as gay versus lesbian to be less common

amongst women (2.4% of men vs. .3% of women; 2.0% in men vs. .9% in women,

respectively) (Laumann et al., 1994). These data show a greater percentage of

women reporting a lesbian identity versus exclusive same-sex attraction, a

pattern that is not seen in men. Similarly, lesbian women consistently report

more heterosexual experiences than gay men do (Kinsey et al., 1953) and, after

self-identifying as lesbian, report some degree of opposite-sex attraction

(Rust, 1992). We advise researchers to use several other indices of sexual

orientation, such as attraction and behavior, in addition to self-reported

identity as gay, lesbian, bisexual, or heterosexual.

Cognitive and other methods. Recently, psychologists have become interested in

applying performance assessment developed by cognitive scientists as a method of

measuring various traits. For example, Treat, McFall, Viken, and Kruschke (2001)

demonstrated the utility of using such methods to study the role of social

information processing in the perpetration of sexually coercive behavior.

Recently, Wright and Adams (1999) used reaction time to slides of nude and

non-nude males and females in a choice discrimination task as a cognitive

measure of sexual orientation. Latency to reaction time in the nude condition

was shown to correctly identify 90% of the heterosexual men and 75% of the gay

men. Other cognitive paradigms, such as priming and categorization tasks, should

be explored for their efficacy in providing information about sexual

orientation. If future researchers are able to replicate the results of Wright

and Adams (1999), then such cognitive measures may be an appropriate

endophenotype for studying the genetic, or more broadly the biological, basis of

sexual orientation.

Other methods of assessing sexual orientation, such as responses from family,

friends, and sexual partners about the proband’s sexual attractions and

behaviors may also be beneficial information, with concordance from cotwin

sexual orientation assessments estimated at 97.5% (Bailey & Pillard, 1991;

Pillard & Weinrich, 1986). However, such high concordance rates have not been

shown in all studies. Kirk, Bailey, and Martin (1999) found concordance rates of

50% for sibling assessment of sexual orientation. Additionally, ethical

limitations of this approach may prohibit its use as a method of sexual

orientation assessment.

Sexual orientation can be considered a multifaceted construct; assessing several

factors in this construct should, in theory, help to define an individual’s

sexual orientation more accurately. Information about self-reported attractions

and behavior, self-identity, sexual fantasies, adult and childhood gender

identity, sexual excitement and disgust at the thought of sex with same and

opposite sex individuals, subjective and genital responses to male and female

sexual stimuli, and collateral information from informed individuals could be

analyzed to extract a general factor or analyzed to examine the factor

components of the construct. In any case, researchers are strongly urged to

measure sexual orientation using multiple methods as no single measure gives the

“true” answer to an individual’s sexual preferences or identity. The magnitude

of the agreement between factors in the sexual orientation construct differs for

men and for women, as will be further demonstrated in the sections to follow.

Sexual Arousal Assessment in Men and Women

Phallometry. One very promising objective measure of male sexual orientation is

physiological sexual arousal (penile response) to male and female sexual stimuli

or, in other words, phallometric assessment of gender preference. This technique

involves measuring changes in penile circumference or volume in response to

visual or audiovisual sexual stimuli depicting either men or women, with penile

response interpreted as sexual attraction to male or female sexual partners.

Both forms of penile plethysmography (i.e., circumferential and volumetric

methods) are reliable and valid measures of sexual arousal in men (Janssen,

Vissenberg, Visser, & Everaerd, 1997; Zuckerman, 1971). Discriminant validity

has been demonstrated for both forms of penile plethysmography; heterosexual and

homosexual men are easily differentiated on the basis of penile responses to

male and female sexual stimuli (Barr & McConaghy, 1971; Freund, 1963, Freund et

al., 1973; Freund, Langevin, Cibiri, & Zajac, 1974; Mavissakalian, Blanchard,

Abel, & Barlow, 1975; McConaghy & Blaszczynski, 1991; Sakkeim, Barlow, Beck, &

Abrahamson, 1985; Tollison, Adams, & Tollison, 1979).

Some researchers dispute the discriminant validity of circumferential

measurement of penile responses (McConaghy, 1989, 1999) and psychometric rigor

of phallometric testing in general (Marshall & Fernandez, 2000; see ATSA

Professional Issues Committee, 2001, for an opposing view). McConaghy (1989)

argued that homosexual and heterosexual men have not been adequately

differentiated using circumferential methods of sexual arousal assessment. He

noted that circumferential and volumetric methods of penile plethysmography are

not equivalent measures of penile erection, although the measures are highly

correlated (Kuban, Blanchard, & Barbaree, 1999; Wheeler & Rubin, 1987);

circumferential devices assess magnitude of erection, whereas volumetric devices

assess haemodynamic changes associated with the early development of erection.

This subtle difference is important because of the physiological implications

inherent to using either method. When using a circumferential device to assess

sexual orientation, stimuli must be of sufficient length (several minutes,

McAnulty & Adams, 1992) and intensity (i.e., audiovisual stimulus vs. visual or

audio alone) to provoke significant changes in penile girth. Conversely,

volumetric assessment is a more sensitive measure, able to register responses

using shorter and less sexually intense stimuli (i.e., still photographs of

nudes).

The ability of subjects to manipulate their responses in a phallometric test is

problematic and challenges the validity of the measure. There is evidence that

individuals can suppress (but not enhance) their response (Money, 1987)

presumably through shifting of attentional focus during stimulus presentation.

Several researchers have investigated methods of preventing or identifying

faking, with mixed results (Freund et al., 1988; Langevin, Stanford, & Block,

1975; Proulx, Cote, & Achille, 1993; Quinsey & Chaplin, 1988; Wilson, 1998).

According to McConaghy (1999), penile volume assessment is less prone to

response manipulation than circumferential measures because changes in penile

volume are unconscious and involuntary. Data are lacking to support this

supposition. Concern about response manipulation is greatest under conditions in

which subjects are likely to attempt to manipulate test results, such as

forensic settings.

Phallometric assessment is, in general, a psychometrically sound and objective

measure of sexual preference in men, and because the data are dimensional versus

categorical, sexual arousal patterns could be considered viable candidates for

an endophenotype for sexual orientation. To date, no researchers have explored

this option.

For a more detailed critical review of phallometric assessment in forensic

settings see ATSA Professional Issues Committee, 2001. For a critical review of

laboratory methods of sexual arousal assessment see Rowland (1999), as well as

articles by Seto and by McConaghy previously cited in this review. Vaginometry.

Sexual arousal to male or female sexual stimuli is less promising as an

objective measure of sexual orientation for women. The relationship between

sexual arousal and sexual orientation in women is less clear, and research is

less abundant than for men. Sexual arousal assessment using vaginometry (vaginal

photoplethysmography) and/or ratings of subjective sexual arousal to male and

female sexual stimuli does not differentiate between heterosexual and lesbian

women (Chivers & Bailey, 2000; Laan, Sonderman, & Janssen, 1995). These

conclusions are based on two studies (Chivers & Bailey, 2000; Laan, Sonderman, &

Janssen, 1995) including approximately 150 women participants. The results have

recently been replicated in subsequent research based on an additional 90 women

(Chivers, Reiger, Latty & Bailey, 2002; Laan, Sonderman, & Janssen, 2002).

Using sexual arousal patterns as an endophenotype for sexual orientation in

women seems unlikely and theoretically unsupported, given the data cited above.

Moreover, given the lack of discrimination between male and female sexual

stimuli in women with adult sexual preferences, vaginometric assessment of women

in forensic settings appears equally dubious. To date, research examining

vaginometric assessment of women offenders is very rare and includes only one

study of seven women offenders against children (Brinton, 1999) and a single

case design (Cooper, Swaminath, Baxter, & Poulin, 1990). These two studies

provide limited support for using vaginometry in forensic settings.

Forensic scientists keen to use the measure are encouraged to consider first

conducting research to validate the measure before applying the testing in

forensic assessment of women sex offenders. Even so, vaginometric assessment

using a photoplethysmograph is impractical with potentially uncooperative or

nonadmitting participants (women offenders) as the device is quite sensitive to

movement artifacts and could easily be spoiled by voluntary pubococcygeal muscle

contractions.

Given the seeming “panpotential” nature of genital arousal in women, describing

a woman’s sexual orientation based solely upon this aspect of her sexuality

would not only contradict her self-report, but would rely on the potentially

erroneous assumption that female sexual orientation must be defined in part by

genital arousal. Again, we encourage and support multidimensional assessment of

the sexual orientation construct in order to avoid making simplistic judgments

of an individual’s sexual orientation. Because of the increased flexibility of

women’s sexual (compared to that of men), this point becomes even more

important. Given that the male model of sexual orientation has been rejected in

women for many factors (e.g., lower agreement between sexual attraction and

sexual behavior, lack of differentiated sexual arousal patterns to male and

female sexual stimuli), the challenge of defining sexual orientation in women

and understanding how biological influences function in women remains to be

adequately addressed by sexuality researchers.

Limited Research on Women

The body of research examining the biological basis of sexual orientation in

women is less extensive than for men. There are approximately twice the number

of published articles about sexual orientation that are related to men compared

to those related to women. Although it is only a rough estimate, searching

MEDLINE for the term “homosexuality” limited to human research from 1990-2002

returned 5,098 articles when a “male” limit is placed and 2,611 when a “female”

limit is placed. Although only a small percentage of these articles are likely

to be empirical studies of the etiology of sexual orientation, we believe the

magnitude of the difference is likely to be representative.

Some researchers have commented that women have been relatively ignored in

research on the biological (as well as psychological) basis of sexual

orientation (Mustanski et al., 2002; Peplau, Spaulding, Conley, & Veniegas,

1999). Our review makes apparent that, more often than not, women have been

included in preliminary investigations of the majority of biological traits

related to sexual orientation. In some cases, as in the investigation of birth

order, null effects are observed in women and the line of research is no longer

pursued. In other cases, promising insights, such as increased waist-to-hip

ratios and circulating testosterone levels in masculine (but not feminine)

lesbians (Singh et al., 1999), indicate that meaningful biological markers of

sexual orientation may exist for women.

Another possible explanation for the isparity between male anti female sexual

orientation research may lie in the expectation that biological factors

influencing sexual orientation in men and women are essentially mirror

opposites. For example, the neurohormonal hypothesis postulates that

homosexuality is the result of a similar mechanism in men and women: excesses

(in women) or deficits (in men) of androgens in the prenatal environment.

Accumulated knowledge about male and female sexual orientation has shown that

sexual orientation may not be a parallel phenomenon in men and women. For

example, the distribution patterns, bimodal for men and unimodal for women

(Bailey et al., 2000), and the prevalence of homosexuality and bisexuality

(Laumann et al., 1994) differ between men and women. Additionally, researchers

examining the development of sexual identity suggest important gender

differences in same-sex attractions and sexual activity; young women typically

experienced these milestones in emotionally oriented contexts (i.e., crushes,

sexual contact within a romantic relationship) versus the sexually oriented

context (i.e., anonymous sexual encounters) experienced by young men

(Savin-Williams & Diamond, 2000). Several authors, such as Baumeister (2000) and

Peplau et al. (1999), have also commented on the degree of flexibility or

plasticity of several facets of female sexuality when compared to male

sexuality, including sexual orientation.

As noted by Peplau et al. (1999), the relationship between sexual plasticity and

sexual orientation in women has yet to be explored. One potential manifestation

of female sexual plasticity is the weak relationship between sexual arousal to

male and female sexual stimuli and sexual orientation in women observed by

Chivers and colleagues (2000, 2002) and by Laan and colleagues (1995, 2002).

Given the differences observed, it may prove more fruitful to examine male and

female sexual orientation with separate models and hypotheses in the future

(Bailey et al., 2000; Peplau, Garnets, Spalding, Conley, & Veniegas, 1998).

Conclusion

Based on the data summarized in this review, it should be clear that sexual

orientation is influenced by biological factors to some degree. Hopefully, we

have also made apparent that the degree to which biological factors influence

sexual orientation is likely to differ between men and women. The puzzling and

outstanding question is how and when these biological factors act and to what

degree these factors influence sexual orientation in women and in men.

Although the ontogeny of sexual orientation is not entirely explicated by the

extant research, it is possible to make several tentative conclusions based on

the evidence reviewed herein. First, biological factors seem to exert a portion

of their influence before birth. Evidence from the cloacal exstrophy and ablatio

penis cases, the handedness research, the older brother phenomenon, and several

other seemingly correlated biological traits that are canalized prenatally, are

all supportive of this conclusion. Secondly, genetic factors appear to explain

the familial variance in sexual orientation. Contrary to popular belief, this

does not prove that sexual orientation is canalized prenatally, as genes

influence a host of traits that are not expressed until after birth. Similarly,

it does not preclude the possibility of a prenatal canalization of sexual

orientation. Although precise genetic mechanisms have yet to be definitively

specified, these are likely to be identified in the future. Third, although

further replications are needed, brain anatomy and neuropsychological measures

all point to structural and functional brain differences related to sexual

orientation in women and in men. Finally, it is apparent from the data

summarized that women’s and men’s sexual orientation are very different

phenomena. Women’s sexual orientation, and indeed women’s sexuality, must be

studied from a perspective that tests the applicability of a male model, rather

than assuming it’s applicability, in order to develop a comprehensive model of

women’s sexuality.

References

1. Adams, M. S., & Niswander, J. D. (1967). Developmental “noise” and a congenital malformation. Genetic Research, 10, 313-317.
2. Alexander, J. E., & Sufka, K. J. (1993). Cerebral lateralization in homosexual males: A preliminary EEG investigation. International Journal of Psychophysiology, 15, 269-274.
3. Allen, L. E., Hardy, B. E., & Churchill, B. M. (1982). The surgical management of the enlarged clitoris. Journal of Urology, 128, 351-354.
4. Allen, L. S., & Gorski, R. A. (1991). Sexual dimorphism of the anterior commissure and massa intermedia of the human brain. Journal of Comparative Neurology, 34, 895-903. Allen, L. S., & Gorski, R. A. (1992). Sexual orientation and the size of the anterior commissure in the human brain. Proceedings of the National Academy of Sciences of the US, 89, 7199-7202.
5. Allen, L. S., Hines, M., Shryne, J. E., & Gorski, R. A. (1989). Two sexually dimorphic cell groups in the human brain. Journal of Neuroscience, 9, 497-506. ATSA Professional Issues Committee [Seto, M. C., Adkerson, D. L., Hindman, J., Jensen, S. H., Peters, J. M., & Peterson, K. D.]. (2001). Practice standards and guidelines for members of the Association for the Treatment of Sexual Abusers (3rd ed.). Beaverton, OR: Association for the Treatment of Sexual Abusers.
6. Bailey, J. M. (1995). Sexual orientation revolution. Nature Genetics, 11, 353-354.
7. Bailey, J. M., & Bell, A. P. (1993). Familiality of female and male homosexuality. Behavior Genetics, 23, 313-322.
8. Bailey, J. M., & Benishay, D. S. (1993). Familial aggregation of female sexual orientation. American Journal of Psychiatry, 150, 272-277.
9. Bailey, J. M., Dunne, M. P., & Martin, N. G. (2000). Genetic and environmental influences on sexual orientation and its correlates in an Australian twin sample. Journal of Personality and Social Psychology, 78, 524-536.
10. Bailey, J. M., & Pillard, R. C. (1991). A genetic study of male sexual orientation. Archives of General Psychiatry, 48, 1089-1096.
11. Bailey, J. M., & Pillard, R. C. (1995). Genetics of human sexual orientation. Annual Review of Sex Research, 6, 126-150.
12. Bailey, J. M., Pillard, R. C., Dawood, K., Miller, M. B., Farrer, L. A., Trivedi, S., & Murphy, R. L. (1999). A family history study of male sexual orientation using three independent samples. Behavior Genetics, 29, 79-86.
13. Bailey, J. M., Pillard, R. C., Neale, M. C., & Agyei, Y. (1993). Heritable factors influence sexual orientation in women. Archives of General Psychiatry, 50, 217-223.
14. Bailey, J. M., Willerman, L., & Parks, C. (1991). A test of the maternal stress theory of human male homosexuality. Archives of Sexual Behavior, 20, 277-293.
15. Barahal, H. S. (1940). Testosterone in psychotic male homosexuals. Psychiatric Quarterly, 14 319-329.
16. Barr, R. F., & McConaghy, N. (1971). Penile volume changes to appetitive and aversive stimuli in relation to sexual orientation and conditioning performance. British Journal of Psychiatry, 119, 377-383.
17. Baumeister, R. F. (2000). Gender differences in erotic plasticity: The female sex drive as socially flexible and responsive. Psychological Bulletin, 126, 347-374.
18. Beach, F. A. (1979). Animal models for human sexuality. In R. Porter & J. Whelan (Eds.), Sex, hormones, and behavior (pp. 113-143). Amsterdam: Excerpta Medica.
19. Bell, A. P, & Weinberg, M. S. (1978). Homosexualities: A study of diversity among men and women. New York: Simon and Schuster.
20. Bell, A. P., Weinberg, M. S., & Hammersmith, S. K. (1981). Sexual preference: Its development in men and women. Bloomington: Indiana University Press.
21. Blanchard, R. (1997). Birth order and sibling sex ratio in homosexual versus heterosexual males and females. Annual Review of Sex Research, 8, 27-67.
22. Blanchard, R. (2001). Fraternal birth order and the maternal immune hypothesis of male homosexuality. Hormones Bt Behavior, 40, 105-114.
23. Blanchard, R., Barbaree, H. E., Bogaert, A. F., Dickey, R., Klassen, P., Kuban, M. E., & Zucker, K. J. (2000). Fraternal birth order and sexual orientation in pedophiles. Archives of Sexual Behavior, 29, 463-478.
24. Blanchard, R., & Bogaert, A. F.(1996a). Biodemographic comparisons of homosexual and heterosexual men in the Kinsey interview data. Archives of Sexual Behavior, 25, 551-579.
25. Blanchard, R., & Bogaert, A. F. (1996b). Homosexuality in men and number of older brothers. American Journal of Psychiatry, 153, 27-31.
26. Blanchard, R., & Bogaert, A. F. (1998). Birth order in homosexual versus heterosexual sex offenders against children, pubescents, and adults. Archives of Sexual Behavior, 27, 595-603.
27. Blanchard, R., Dickey, R. & Jones, C. L.(1995). Comparison of height and weight in homosexual versus nonhomosexual gender dysphorics. Archives of Sexual Behavior, 24, 543-554.
28. Blanchard, R., & Ellis, L. (2001). Birth weight, sexual orientation, and the sex of preceding siblings. Journal of Biosocial Science, 33, 451-467.
29. Blanchard, R., & Scheridan, P. M. (1992). Sibship size, sibling sex ratio, birth order, and parental age in homosexual and nonhomosexual gender dysphorics. Journal of Nervous & Mental Disease, 180, 40-47.
30. Blanchard, R., Zucker, K. J., Cavacas, A., Allin, S., Bradley, S. J., & Schachter, D. C. (2002). Fraternal birth order and birth weight in probably prehomosexual feminine boys. Hormones and Behavior, 41, 321-327
31. Blanchard, R., Zucker, K. J., Cohen-Kettenis, P, T., Gooren, L. J. G., & Bailey, J. M. (1996). Birth order and sibling sex ratio in two samples of Dutch gender-dysphoric homosexual males. Archives of Sexual Behavior, 25, 495-514.
32. Bleier, R. (1984). Science and gender: A critique of biology and its theories of women. New York: Pergamon Press.
33. Bogaert, A. F. (1998). Physical development and sexual orientation in women Height, weight, and age of puberty comparisons. Personality and Individual Differences, 24, 115-121.
34. Bogaert, A. F., & Blanchard, R. (1996). Physical development and sexual orientation in men: Height, weight and age of puberty differences. Personality and Individual Differences, 21, 77-84.
35. Bogaert, A. F., Bezeau, S., Kuban, M., & Blanchard, R. (1997). Pedophilia, sexual orientation, and birth order. Journal of Abnormal Psychology, 106, 331-335.
36. Bogaert, A. F., & Hershberger, S. (1999). The relation between sexual orientation and penile size. Archives of Sexual Behavior, 28, 213-221.
37. Bradley, S. J., Oliver, G. D., Chernick, A. B., & Zucker, K. J. (1998). Experiment of nurture: Ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood. Pediatrics, 102, 132-134.
38. Breedlove, S. M., Cooke, B. M., & Jordan, C. L. (1999). The orthodox view of sexual differentiation of the brain. Brain, Behavior, and Evolution, 54, 8-14.
39. Brinkmann, A. 0. (2001). Molecular basis of androgen insensitivity. Molecular and Cellular Endocrinology, 179, 105-109.
40. Brinton, C. (1999, June 23-26). Arousal patterns of female sex offenders compared with nonoffenders. Paper presented at the annual meeting of the International Academy of Sex Research, Stony Brook, NY.
41. Brown, W. M., Finn, C. J., Cooke, B. M., & Breedlove, S. M. (2001). Differences in finger length ratios between self-identified “butch” and “femme” lesbians. Archives of Sexual Behavior, 31, 117-121.
42. Brown, T. R., Scherer, P. A., Chang, Y T., Migeon, C. J., Ghirri, P., Murono, K., & Zhou, Z. (1993). Molecular genetics of human androgen insensitivity. European Journal of Pediatrics, 152, S62-69.
43. Brown, W. M., Hines, M., Fane, B., & Breedlove, S. M. (2001). Masculinized finger length ratios in humans with congenital adrenal hyperplasia (CAH). Hormones & Behavior, 39, 325.
44. Buhrich, N., Bailey, J. M., & Martin, N. G. (1991). Sexual orientation, sexual identity, and sex-dimorphic behaviors in male twins. Behavior Genetics, 21, 75-96.
45. Byne, W. (1998). The medial preoptic and anterior hypothalamic regions of the rhesus monkey: Cytoarchitectonic comparison with the human and evidence for sexual dimorphism. Brain Research, 793, 346-350.
46. Byne, W., Lasco, M. S., Kemether, E., Shinwari, A., Edgar, M. A., Morgello, S., Jones, L. B., & Tobet, S. (2000). The interstitial nuclei of the human anterior hypothalamus: An investigation of sexual variation in volume and cell size, number and density. Brain Research, 856, 254-258.
47. Byne, W., & Parsons, B. (1993). Human homosexuality: The biological theories reappraised. Archives of General Psychiatry, 50, 228-239.
48. Byne, W., Tobet, S., Mattiace, L., Lasco, M. S., Kemether, E., Edgar, M. A., Morgello, S., Buchsbaum, M. S., & Jones, L. B. (2001). The interstitial nuclei of the human anterior hypothalamus: An investigation of variation within sex, sexual orientation and HIV status. Hormones & Behavior, 40, 86-92.
49. Cantor, J. M., Blanchard, R., Paterson, A. D., & Bogaert, A. F. (2002). How many gay men owe their sexual orientation to fraternal birth order? Archives of Sexual Behavior, 31, 5765.
50. Chapman, R. H., & Stern, J. M. (1978). Maternal stress and pituitary-adrenal manipulations during pregnancy in rats: Effects on morphology and sexual behavior of male offspring. Journal of Comparative and Physiological Psychology, 92, 1074-1083.
51. Chivers, M. L., & Bailey, J. M. (2000). Genital and subjective sexual arousal in heterosexual, bisexual and lesbian women. Unpublished masters thesis, Northwestern Universit Evanston IL.
52. Chivers, M. L., Reiger, G., Latty, E., & Bailey, J. M. (2002, June 19-23). Men’s sexual arousal is target-specific. Women’s sexual arousal is bisexual. Paper presented at the annual meeting of the International Academy of Sex Research, Hamburg, Germany.
53. Cooper, A. J., Swaminath, S., Baxter, D., & Poulin, C. (1990). A female sex offender with multiple paraphilias: A psychologic, physiologic (laboratory sexual arousal) and endocrine case study. Canadian Journal of Psychiatry, 35, 334-337.
54. Cummins, H., & Midlo, C. (1961). Finger prints, palms, and soles. New York: Dover. Dancey, C. P. (1990). Sexual orientation in women: An investigation of hormonal and personality variables. Biological Psychology, 30, 251-264.
55. Dawood, K., Pillard, R. C., Horvath, C., Revelle, W., & Bailey, J. M. (2000). Familial aspects of male homosexuality. Archives of Sexual Behavior, 29, 155-163.
56. Demeter, S., Ringo, J. L., & Doty, R. W. (1988). Morphometric analysis of the human corpus callosum and anterior commissure. Human Neurobiology, 6, 219-226.
57. Diamond, M. (1993). Homosexuality and bisexuality in different populations. Archives of Sexual Behavior, 22, 291-310.
58. Diamond, M., & Sigmundson, H. K. (1997). Sex reassignment at birth: Long-term review and clinical implications. Archives of Pediatrics and Adolescent Medicine, 151, 298-304.
59. Dittmann, R. W., Kappes, M. E., & Kappes, M. H. (1992). Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia. Psychoneuroendocrinology, 17, 153-170.
60. Dorner, G. (1976). Hormones and brain differentiation. Amsterdam: Elsevier.
61. Dorner, G., Geiser, T., Ahrens, L., Krell, L., Munz, G., Sieler, H., Kittner, E., & Muller, H. (1980). Prenatal stress and possible aetiogenetic factor homosexuality in human males. Endokrinologie, 75, 365-368.
62. Dorner, G., Schenk, B., Schmiederl, B., & Ahrens, L. (1983). Stressful events in prenatal life of bi- and homosexual men. Experimental and Clinical Endocrinology, 81, 83-87.
63. Downey, J., Ehrhardt, A. A., Schiffman, M., Dyrenfurth, I., & Becker, J. (1987). Sex hormones in lesbian and heterosexual women. Hormones and Behavior, 21, 347-357. Eaton, G. G., Goy, R. W., & Phoenix, C. H. (1973). Effects of testosterone treatment in
64. adulthood on sexual behavior of female pseudohermaphrodite rhesus monkeys. Nature, 242, 119-120.
65. Ehrhardt, A. A., Meyer-Bahlburg, H. F., Rosen, L. R., Feldman, J. F., Veridiano, N. P., Zimmerman, I., & McEwen, B. S. (1985). Sexual orientation after prenatal exposure to exogenous estrogen. Archives of Sexual Behavior, 14, 57-77.
66. Ehrhardt, A. A., Evers, K., & Money, J. (1968). Influence of androgen and some aspects of sexually dimorphic behavior in women with the late-treated adrenogenital syndrome. Johns Hopkins Medical Journal, 123, 115-122.
67. El-Hani, C. N., Moreira, L. M. d. A., Souza, A. L. V., Silva, M. S., Forastieri, V., & Andrade, C. P. (in press). Evidence against a relationship between dermatoglyphic asymmetry and male sexual orientation. Human Biology.
68. Ellis, L., & Ames, M. A. (1987). Neurohormonal functioning and sexual orientation: A theory of homosexuality/heterosexuality. Psychological Bulletin, 101, 233-258.
69. Ellis, L., & Cole-Harding, S. (2001). The effects of prenatal stress, and of prenatal alcohol and nicotine exposure, on human sexual orientation. Physiology & Behavior, 74, 213-226.
70. Ellis, L., Peckham, W, Ames, M. A., & Burke, D. (1988). Sexual orientation of human offspring may be altered by severe maternal stress during pregnancy. The Journal of Sex Research, 25, 152-157.
71. Evans, R. B.(1972). Physical and biochemical characteristics of homosexual men. Journal of Consulting and Clinical Psychology, 39, 140-147.
72. Fausto-Sterling, A. (1985). Myths of gender: Biological theories about women and men. New York: Basic Books.
73. Freund, K. (1963). A laboratory method for diagnosing predominance of homo- or heteroerotic interest in the male. Behaviour Research and Therapy, 1, 85-93.
74. Freund, K. R., Langevin, R., Cibiri, S., & Zajac, Y. (1973). Heterosexual aversion in homosexual males. British Journal of Psychiatry, 122, 163-169.
75. Freund, K., R. Langevin, Cibiri, S., & Zajac, Y. (1974). Heterosexual aversion in homosexual males: A second experiment. British Journal of Psychiatry, 125, 177-180.
76. Freund, K., Watson, R., & Rienzo, D. (1988). Signs of feigning in the phallometric test. Behavior Research & Therapy, 26, 105-112.
77. Gartrell, N. K., Loriaux, L., & Chase, T. N. (1977). Plasma testosterone in homosexual and heterosexual women. American Journal of Psychiatry, 134, 1117-1119.
78. Gearhart, J. P., & Rock, J. A. (1989). Total ablation of the penis after
79. circumcision with electrocautery: A method of management and long term
80. follow-up. The Journal of Urology, 142, 799-801.
81. Geshwind, N., & Galabura, A. M. (1985). Cerebral lateralization: Biological
82. mechanisms, association and pathology: A hypothesis and program for research.
83. 1-111. Archives of Neurology, 43, 428-459, 521-552, 634-654.
84. Gooren, L., Fliers, E., & Courtney, K. (1990). Biological determinants of sexual
85. orientation. Annual Review of Sex Research, 1, 175-195.
86. Gottesman, I. I., McGruff, P, & Farmer, A. (1987). Clinical genetics as clues to
87. the “real” genetics of schizophrenia: A decade of modest gains while playing for
88. time. Schizophrenia Bulletin, 13, 23-47.
89. Green, M. F., Bracha, H. S., Satz, P., & Christenson, C. D. (1994). Preliminary evidence for an association between minor physical anomalies and second trimester neurodevelopment in schizophrenia. Psychiatric Research, 53, 119-127.
90. Green, R. (2000). Birth order and ratio of brothers to sisters in transsexuals. Psychological Medicine, 30, 789-795.
91. Green, R., & Young, R. (2000). Fingerprint asymmetry in male and female transsexuals. Personality and Individual Differences, 29, 933-942.
92. Greenberg, A. S., & Bailey, J. M. (1993). Do biological explanations of homosexuality have moral, legal, or policy implications? The Journal of Sex Research, 30, 245-251.
93. Griffin, J. E., Edwards, C., Madden, J. D., Harrod, M. J., & Wilson, J. D. (1976). Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Annals of Internal Medicine, 85, 224-236.
94. Hall, J. A. Y., & Kimura, D. (1994). Dermatoglyphic asymmetry and sexual orientation in men. Behavioral Neuroscience, 108, 1203-1206.
95. Hall, L. S. (2000a). Dermatoglyphic analysis of monozygotic twins discordant for sexual orientation. In N. M. Durham, K. M. Fox, & C. C. Plato (Eds.), The state of dermatoglyphics-The science of finger and palm prints (Vol. 2, pp. 123-165). Lewiston, NY The Edwin Mellen Press.
96. Hall, L. S. (2000b). Dermatoglyphic analysis of total ridge count in female monozygotic twins discordant for sexual orientation. The Journal of Sex Research, 37, 315-320.
97. Halpern, D. F., & Haviland, M. G. (1997). The correlates of left-handedness: Moderating variables in the epidemiology of left-handedness. Annals of Epidemiology, 7, 165-166.
98. Hamer, D. (1999). Genetics and male sexual orientation. Science, 285, 803.
99. Hamer, D., Hu, S., Magnuson, V, Hu, N., & Pattatucci, A. M. (1993a). A linkage between DNA markers on the X chromosome and male sexual orientation. Science, 261, 321-327.

100.  Hamer, D., Hu, S., Magnuson, V., Hu, N., & Pattatucci, A. M. L. (1993b). Male sexual orientation and genetic evidence [Technical comments]. Science, 262, 2065.

101.  Hershberger, S. L. (1997). A twin registry study of male and female sexual orientation. The Journal of Sex Research, 34, 212-222.

102.  Hesselbrock, V, Begleiter, H., Porjesz, B., O’Connor, S., & Bauer, L. (2001). P300 eventrelated potential amplitude as an endophenotype of alcoholism–evidence from the collaborative study on the genetics of alcoholism. Journal of Biomedical Science, 8, 77-82.

103.  Highley, J. R., Esiri, M. M., McDonald, B., Roberts, H. C., Walker, M. A., & Crow, T. J. (1999). The size and fiber composition of the anterior commissure with respect to gender and schizophrenia. Biological Psychiatry, 45, 1120-1127.

104.  Hiscock, M., Inch, R., Jacek, C., Hiscockkalil, C., & Kalik, K. M. (1994). Is there a sex difference in human laterality: An exhaustive survey of auditory laterality studies from 6 neuropsychology journals. Journal of Clinical and Experimental Neuropsychology, 16, 423-435.

105.  Hofman, M. A., Fliers, E., Goudsmit, E., Swaab, D. F., & Partiman, T. S. (1988). Morphometric analysis of the suprachiasmatic and paraventricular nuclei in the human brain: Sex differences and age-dependent changes. Journal of Anatomy, 160, 127-143.

106.  Hofman, M. A., & Swaab, D. F. (1989). The sexually dimorphic nucleus of the preoptic area in the human brain: A comparative morphometric study. Journal of Anatomy, 164,55-72.

107.  Holt, S. B. (1968). The genetics of dermal ridges. Springfield, IL: Charles C Thomas.

108.  Hu, S., Pattatucci, A., Patterson, C., Li, L., Fulker, D., Cherny, S., Kruglyak, L., & Hamer, D. (1995). Linkage between sexual orientation and chromosome Xq28 in males but not females. Nature Genetics, 11, 248-256.

109.  Janssen, E., Vissenberg, M., Visser, S., & Everaerd, W. (1997). An in vivo comparison of two circumferential penile strain gauges: The introduction of a new calibration method. Psychophysiology, 34, 717-720.

110.  Imperato-McGinley, J., Guerrero, L., Gaultier, T., & Peterson, R. E. (1974). Steroid 5alpha-reductase deficiency in man: An inherited form of male pseudohermaphrotism. Science, 186, 1213-1215.

111.  Jamison, C. S., Jamison, P., & Meier, R. (1994). Effects of prenatal testosterone administration on palmar dermatoglyphic intercore ridge counts of rhesus monkeys (Macaca mulatta). American Journal of Physical Anthropology, 94, 409-419.

112.  Kallmann, F. J. (1952). Twin and sibship study of overt male homosexuality. American Journal of Human Genetics, 4, 136-146.

113.  Kendler, K. S., & Eaves, L. J. (1989). The estimation of probandwise concordance in twins: The effect of unequal ascertainment. Acta Geneticae Medicae et Gemellologiae, Twin Research. 38 253-270.

114.  Kendler, K. S., Thornton, L. M., Gilman, S. E., & Kessler, R. C. (2000). Sexual orientation in a U.S. national sample of twin and nontwin sibling pairs. The American Journal of Psychiatry, 157, 1843-1846.

115.  King, M., & McDonald, E. (1992). Homosexuals who are twins: A study of 46 probands. British Journal of Psychiatry, 160, 407-409.

116.  Kinsey, A. C., Pomeroy, W. B., & Martin, C. E. (1948). Sexual behavior in the human male. Philadelphia: W. B. Saunders.

117.  Kinsey, A. C., Pomeroy, W. B., Martin, C. E., & Gebhard, P. H. (1953). Sexual behavior in the human female. Philadelphia: W. B. Saunders.

118.  Kirk, K. M., Bailey, J. M., Dunne, M. P, & Martin, N. G. (2000). Measurement models for sexual orientation in a community twin sample. Behavior Genetics, 30, 345-356.

119.  Kirk, K. M., Bailey, J. M., & Martin, N. G. (1999). How accurate is the family history method for assessing siblings’ sexual orientation? Archives of Sexual Behavior, 28, 129137.

120.  Klein, F., Sepekoff, B., & Wolf, T. J. (1985). Sexual orientation: A multi-variable dynamic process. Journal of Homosexuality, 11, 35-49.

121.  Kuban, M., Barbaree, H. E., & Blanchard, R. (1999). A comparison of volume and circumference phallometry: Response magnitude and method agreement. Archives of Sexual Behavior, 28, 345-359.

122.  Laan, E., Sonderman, M., & Janssen, E. (1995). Straight and lesbian women’s sexual responses to straight and lesbian erotica: No sexual orientation effects. Paper presented at the annual meeting of the International Academy of Sex Research, Provincetown, MA.

123.  Laan, E., Sonderman, M., & Janssen (2002). Straight and lesbian women:s responses to straight and lesbian erotica: No sexual orientation effects. Manuscript in preparation.

124.  Lalumiere, M. L., Blanchard, R., & Zucker, K. J. (2000). Sexual orientation and handedness in men and women: A meta-analysis. Psychological Bulletin, 126, 575-592. Lalumiere, M. L., Harris, G. T., & Rice, M. E. (1999). Birth order and fluctuating asymmetry: A first look. Proceedings of the Royal Society of London Series B-Biological Sciences, 266, 2351-2354.

125.  Lang, T. (1937). Weiterer Beitrag zur Frage nach der genetischen Bedingtheit der Homosexualitaet [Further contribution to the question of the genetic determination of homosexuality]. Zeitschrift fuer die Gesamte Neurologie and Psychiatrie, 157, 557-574.

126.  Lang, T. (1940). Studies in the genetic determination of homosexuality. Journal of Nervous and Mental Disease, 92, 55-64.

127.  Langevin, R., Stanford, A., & Block, R. (1975). The effect of relaxation instructions on erotic arousal in homosexual and heterosexual males. Behavior Therapy, 6, 453-458. Lasco, M. S., Jordan. T. J., Edgar, M. A., Petito, C. K., & Byne, W (2002). A lack of dimorphism of sex or sexual orientation in the human anterior commissure(I). Brain Research, 936, 95-98.

128.  Laumann, E. O., Gagnon, J. H., Michael, R. T., & Michaels, S. (1994). The social organization of sexuality: Sexual practices in the United States. Chicago: University of Chicago Press.

129.  LeVay, S. (1991). A difference in hypothalamic structure between heterosexual and homosexual men. Science, 253, 1034-1037.

130.  LeVay, S. (1996). Queer science: The use and abuse of research into homosexuality. Cambridge, MA: MIT Press.

131.  Lev-Ran, A. (1974). Sexuality and educational levels of women with the late-treated adrenogenital syndrome. Archives of Sexual Behavior, 3, 27-32.

132.  Lippa, R. A. (2002). Are 2D:4D finger-length ratios related to sexual orientation? Yes for men, no for women. Manuscript submitted for publication.

133.  Loehlin, J. C., Martin, N. G., Harris, J. A., Vernon, P. A., Boomsma, D. I., Henderson, B. A., Berenbaum, S. A., Miller, E. M., & Martin, N. (2000).

134.  Dimensions of psychological masculinity-femininity in adult twins from opposite-sex and same-sex pairs. Behavior Genetics, 30, 19-28.

135.  Loraine, J. A., Adamopoulos, D. A., Kirkham, K. E., Ismail, A. A. A., & Dove, G. (1971). Patterns of hormone excretion in male and female homosexuals. Nature, 234, 552-555.

136.  Lunetta, K. L., Wilcox, M., Smoller, J., & Neuberg, D. (1999). Exploring linkage for alcoholism using affection status and quantitative event related potential phenotypes. Genetic Epidemiology, 17, S241-246.

137.  MacCulloch, M. J., & Waddington, J. L. (1981). Neuroendocrine mechanisms and the aetiology of male and female homosexuality. British Journal of Psychiatry, 139, 341-345.

138.  Macke, J. P., Hu, N., Hu, S., Bailey, M., King, V L., Brown, T., Hamer, D., & Nathans, J. (1993). Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation. American Journal of Human Genetics, 53, 844-852.

139.  Manning, J., Scutt, D., Wilson, J. D., & Lewis-Jones, D. I. (1998). The ratio of the 2nd to 4th digit length: A predictor of sperm number and concentrations of testosterone, luteinizing hormone and oestrogen. Human Reproduction, 13, 3000-3004.

140.  Markow, T. A., & Gottesman, I. I. (1989). Fluctuating dermatoglyphic asymmetry in psychotic twins. Psychiatric Research, 29, 37-43.

141.  Marshall, W. L., & Fernandez, Y. M. (2000). Phallometric testing with sexual offenders: Limits to its value. Clinical Psychology Review, 20, 807-822.

142.  Mavissakalian, M., Blanchard, E. B., Abel, G. C., & Barlow, D. H. (1975). Responses to complex erotic stimuli in homosexual and heterosexual males. British Journal of Psychiatry, 126, 252-257.

143.  McAnulty, R. D., & Adams, H. E. (1992). Validity and ethics of penile circumference measures of sexual arousal: A reply to McConaghy. Archives of Sexual Behavior, 21, 177-186.

144.  McConaghy, N. (1989). Validity and ethics of penile circumference measures of sexual arousal: A critical review. Archives of Sexual Behavior, 18, 357-369.

145.  McConaghy, N. (1999). Unresolved issues in scientific sexology. Archives of Sexual Behavior, 28, 285-318.

146.  McConaghy, N., & Blaszczynski, A. (1991). Initial stages of validation by penile volume assessment that sexual orientation is distributed dimensionally. Comprehensive Psychiatry, 32, 52-58.

147.  McCormick, C. M., & Witelson, S. F. (1994). Functional cerebral asymmetry and sexual orientation in men and women. Behavioral Neuroscience, 108, 525-531.

148.  McFadden, D. (2002). Masculinization effects in the auditory system. Archives of Sexual Behavior, 31, 93-105.

149.  McFadden, D., & Champlin, C. A. (2000). Comparison of auditory evoked potentials in heterosexual, homosexual, and bisexual males and females, Journal of the Association for Research in Otolaryngololoy, 1, 89-99.

150.  McFadden, D., Loehlin, J. C., & Pasanen, E. G. (1996). Additional findings on heritability and prenatal masculinization of cochlear mechanisms: Click-evoked otoacoustic emissions. Hearing Research, 97, 102-119.

151.  McFadden, D., & Pasanen, E. G. (1998). Comparison of the auditory system of heterosexuals and homosexuals: Click-evoked otoacoustic emissions. Proceedings of the National Academy of Sciences, 95, 2709-2713.

152.  McGlone, J. (1980). Sex differences in human brain asymmetry: A critical survey. Behavioral and Brain Sciences, 3, 215-263.

153.  Meyer-Bahlburg, H. F. L. (1984). Psychoendrocrine research on sexual orientation. Current Status and future options. In G. J. DeVries, J. P. C. D. Bruin, H. M. B. Uylings, & M. A. Corner (Eds.), Progress in brain research (Vol. 61, pp. 375-398). Amsterdam: Elsevier. Meyer-Bahlburg, H. F. L., Ehrhardt, A. A., Rosen, L. R., Gruen, R. S., Veridiano, N. P., Vann, F. H., & Neuwalder, H. F. (1995). Prenatal estrogens and the development of homosexual orientation. Developmental Psychology, 31, 12-21.

154.  Migeon, C. J. (1979). Diagnosis and treatment of androgenital disorders. In L. J. DeGroot, G. F. C. Jr., L. Martini, D. H. Nelson, W. D. Odell, J. T. P. Jr., E. Steinberger, & A. I. Winegrad (Eds.), Endocrinology (Vol. 2, pp. 1203-1224). New York: Grune & Stratton.

155.  Money, J. (1987). Sin, sickness, or status? Homosexual gender identity and psychoneuroendocrinology. American Psychologist, 42, 384-399.

156.  Money, J., & Dalery, J. (1976). Iatrogenic homosexuality: Gender identity in seven 46,XX chromosomal females with hyperadrenocortical hermaphroditism born with a penis, three reared as boys, four reared as girls. Journal of Homosexuality, 1, 357-371.

157.  Money, J., Schwartz, M., & Lewis, V. G. (1984). Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46,XX Congenital Virilizing Adrenal Hyperplasia and 46, XY Androgen-Insensitivity Syndrome compared. Psychoneuroendocrinology, 9, 405-414.

158.  Mustanski, B. S., Bailey, J. M., & Kaspar, S. (2002). Dermatoglyphics, handedness, sex, and sexual orientation. Archives of Sexual Behavior, 31, 107-116.

159.  Neale, M. C., & Cardon, L. R. (1992). Methodology for genetic studies of twins and families. Boston: Kiuwer Academic.

160.  Nedoma, K., & Freund, K. (1961). Somatosexual findings in homosexual men. Ceskoslovenska Psychiatre, 57, 100-103.

161.  New, M. I., Ghizzoni, L., & Speiser, P. W. (1996). Update on congenital adrenal hyperplasia. In F. Lifshitz (Ed.), Pediatric endocrinology (Vol. 3, pp. 305-320). New York: Marcel Dekker.

162.  New, M. I., & Josso, N. (1988). Disorders of gonadal differentiation and congenital adrenal hyperplasia. Endocrinology and Metabolism Clinics of North America, 17, 339-366. Palmer, A. R. (1994). Fluctuating asymmetry analyses: A primer. In T. A. Markow (Ed.), Developmental instability: Its origins and evolutionary implications (pp. 335-364). Dordrecht, Netherlands: Kluwer.

163.  Pare, C. M. B. (1956). Homosexuality and chromosomal sex. Journal of Psychosomatic Research, 1, 247-251.

164.  Pearcey, S. M., Docherty, K. J., & Dabbs, J. M., Jr. (1996). Testosterone and sex role identification in lesbian couples. Physiology and Behavior, 60, 1033-1035.

165.  Peplau, T. A., Garnets, L. D., Spalding, L. R., Conley, T. D., & Veniegas, R. C. (1998). A critique of Bem’s “Erotic Becomes Exotic” theory of sexual orientation. Psychological Review, 105, 387-394.

166.  Peplau, T. A., Spaulding, L. R., Conley, T. D., & Veniegas, R. C. (1999). The development of sexual orientation in women. Annual Review of Sex Research, 10, 71-99.

167.  Perkins, M. W. (1981). Female homosexuality and body build. Archives of Sexual Behavior, 10, 337-345. Phoenix, C. H., Goy, R. W., Gerall, A. A., & Young, W. C. (1959). Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology, 65, 369-382.

168.  Pillard, R. C. (1990). The Kinsey Scale: Is it familial? In D. P. McWhirter, S. Sanders, & J. M. Reinisch (Eds.), Homosexuality/heterosexuality: Concepts of sexual orientation. The Kinsey Institute series (Vol. 2, pp. 88-100). New York: Oxford University Press.

169.  Pillard, R. C., & Weinrich, J. D. (1986). Evidence of familial nature of male homosexuality. Archives of General Psychiatry, 43, 808-812.

170.  Proulx, J., Cote, G., & Achille, P. A. (1993). Prevention of voluntary control of penile response in homosexual pedophiles during phallometric testing. The Journal of Sex Research, 30, 140-147.

171.  Qazi, Q. H., Masakawa, A., McGann, B., & Woods, J. (1980). Dermatoglyphic abnormalities in the fetal alcohol syndrome. Teratology, 21, 157-160.

172.  Quinsey, V. L., & Chaplin, T. C. (1988). Preventing faking in phallometric assessments of sexual preference. Annals of the New York Academy of Sciences, 528, 49-58.

173.  Raschka, L. B. (1995). On older fathers [Letter to the editor]. American Journal of Psychiatry, 152, 1404.

174.  Reiner, W. G., Gearhart, J. P., & Jeffs, R. (1999). Psychosexual dysfunction in males with genital anomalies: Late adolescence, Tanner stages IV to VI. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 865-872.

175.  Reite, M., Sheeder, J., Richardson, D., & Teale, P. (1995). Cerebral laterality in homosexual males: Preliminary communication using magnetoencephalography. Archives of Sexual Behavior, 24, 585-593.

176.  Reiter, E. O., & Rosenfeld, R. G. (1998). Normal and aberrant growth. In J. D. Wilson, U. W. Foster, H. M. Kronenberg, & P. R. Larsen, (Eds.), Williams textbook of endocrinology (9th ed., pp. 1427-1509). Philadelphia: W. B. Saunders.

177.  Rice, G., Anderson, C., Risch, N., & Ebers, G. (1999). Male homosexuality: Absence of linkage to microsatellite markers at Xq28. Science, 284, 665-667.

178.  Rice, G., Risch, N., & Ebers, G. (1999). Response: Genetics and male sexual orientation. Science, 285, 803.

179.  Risch, N. J., Squires-Wheeler, E., & Keats, B. J. B. (1993). Male sexual orientation and genetic evidence. Science, 262, 2063-2065.

180.  Rosenthal, D. (1970). Genetic theory and abnormal behavior. New York: McGraw-Hill. Robinson, S. J., & Manning, J. (2000). The ratio of 2nd to 4th digit length and male homosexuality. Evolution and Human Behavior, 21, 333-345.

181.  Rowland, D. L. (1999). Issues in the laboratory study of human sexual response: A synthesis for the nontechnical sexologist. The Journal of Sex Research, 36, 3-15.

182.  Rust, P. C. (1992). The politics of sexual identity: Sexual attraction and behavior among lesbian and bisexual women. Social Problems, 39, 366-386.

183.  Sachar, G., & Clement, U. (1980). Hormonal changes in stress and mental illness. In D. T. Krieger & E. J. Sachar (Eds.), Neuroendocrinology (pp. 177-183). New York: H.P. Publishing.

184.  Sakheim, D. K., Barlow, D. H., Beck, J. G., & Abrahamson, D. J. (1985). A comparison of male heterosexual and male homosexual patterns of sexual arousal. The Journal of Sex Research, 21, 183-198.

185.  Sanders, G., & Wright, M. (1997). Sexual orientation differences in cerebral asymmetry and in the performance of sexually dimorphic cognitive and motor tasks. Archives of Sexual Behavior, 26 463-480.

186.  Savin-Williams, R. C., & Diamond, L. M. (2000). Sexual identity trajectories in sexual minority youth: Gender comparisons. Archives of Sexual Behavior, 29, 607-628.

187.  Sell, R. L.(1997). Defining and measuring sexual orientation: A review. Archives of Sexual Behavior, 26, 643-658.

188.  Siever, M. D. (1994). Sexual orientation and gender as factors in socioculturally acquired vulnerability to body dissatisfaction and eating disorders. Journal of Consulting and Clinical Psychol 62, 252-260.

189.  Singh, D. (1993). Adaptive significance of female physical attractiveness: Role of waist-tohip ratio. Journal of Personality and Social Psychology, 65, 293-307.

190.  Singh, D. (1995). Female judgment of male attractiveness and desirability for relationships: Role of waist-to-hip ratio and financial status. Journal of Personality and Social Psychology, 69, 1089-1101.

191.  Singh, J., & Verma, I. C. (1987). Influence of major histo(in)compatability complex on reproduction. American Journal of Reproductive Immunology and Microbiology, 15, 150-152.

192.  Singh, D., Vidaurri, M., Zambarano, R. J., & Dabbs, J. M., Jr. (1999). Lesbian erotic role identification: Behavioral, morphological, and hormonal correlates. Journal of Personality and Social Psychology, 76, 1035-1049.

193.  Slabbekoorn, D., van Goozen, S. H., Sanders, G., Gooren, L. J., & Cohen-Kettenis, P. T. (2000). The dermatoglyphic characteristics of transsexuals: Is there evidence for an organizing effect of sex hormones. Psychoneuroendocrinology, 25, 365-375.

194.  Stoltenberg, S. F., & Burmeister, M. (2000). Recent progress in psychiatric genetics-some hope but no hype. Human Molecular Genetics, 9, 927-935.

195.  Swaab, D. F., & Fliers, E. A. (1985). A sexually dimorphic nucleus in the human brain. Science, 228, 1112-1115.

196.  Swaab, D. F., Fliers, E., & Partiman, T. S. (1985). The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Research, 342, 37-44. Swaab, D. F., & Hofman, M. A. (1990). An enlarged suprachiasmatic nucleus in homosexual men. Brain Research, 537, 141-148.

197.  Tenhula, W. N., & Bailey, J. M. (1998). Female sexual orientation and pubertal onset. Developmental Neuropsychology, 14, 369-383.

198.  Tollison, C. D., Adams, H. E., & Tollison, J. W. (1979). Cognitive and physiological indices of sexual arousal in homosexual, bisexual, and heterosexual males. Journal of Behavioral Assessment, 1, 305-314.

199.  Treat, T. A., McFall, R. M., Viken, R. J., & Kruschke, J. K. (2001). Using cognitive science methods to assess the role of social information processing in sexually coercive behavior. Psychological Assessment, 13, 549-565.

200.  Turkheimer, E., & Waldron, M. (2000). Nonshared environment: A theoretical, methodological, and quantitative review. Psychological Bulletin, 126, 79-108.

201.  Votes, T. S., Fleming, P., Leleszi, J. P., Barthold, J. S., Gonzalez, R., & Perlmutter, A. D. (1999). Functional, social and psychosexual adjustment after vaginal reconstruction. Journal of Urology, 162, 182-187.

202.  vom Saal, F. S. (1989). Sexual differentiation in litter-bearing mammals: Influence of sex of adjacent fetuses in utero. Journal of Animal Science, 67, 1824-1840.

203.  Ward, I. L. (1972). Prenatal stress feminizes and demasculinizes the behavior of males. Science, 175, 328-329.

204.  Ward, I. L. & Ward, 0. B. (1985). Sexual behavior differentiation: Effects of prenatal manipulations in rats. In N. Adler, D. Pfaff, & R. W. Goy (Eds.), Handbook of behavioral neurobiology: Reproduction (Vol. 7, pp. 77-98.) New York: Plenum.

205.  Ward, I. L., & Weisz, J. (1980). Maternal stress alters plasma testosterone in fetal males. Science, 207, 328-329.

205.Ward, 0. B. (1992). Fetal drug exposure and sexual differentiation of males. In A. Gerall, H. Moltz, & I. L. Ward (Eds.), Handbook of behavioral neurobiology: Vol. 11. Sexual differentiation (pp. 181-219). New York: Plenum.

206.  Ward, 0. B., Ward, I. L., Denning, J. H., Hendricks, S. E., & French, J. A. (2002). Hormonal mechanisms underlying aberrant sexual differentiation in male rats prenatally exposed to alcohol, stress, or both. Archives of Sexual Behavior, 31, 9-16.

207.  Wegesin, D. J. (1998). Event-related potentials in homosexual and heterosexual men and women: Sex-dimorphic patterns in verbal asymmetries and mental rotation. Brain and Cognition, 36, 73-92.

208.  Wheeler, D., & Rubin, H. 13. (1987). A comparison ot volumetric and circumterential measures of penile erection. Archives of Sexual Behavior, 16, 289-299.

209.  Whitam, F. L., Diamond, M., & Martin, J. (1993). Homosexual orientation in twins: A report on 61 pairs and three triplet sets. Archives of Sexual Behavior, 22, 187-206. Williams, T. J., Pepitone, M. E., Christensen, S. E., Cooke, B. M., Huberman, A. D., Breedlove, N. J., Breedlove, T. J., Jordan, C. L., & Breedlove, S. M. (2000). Fingerlength ratios and sexual orientation. Nature, 404, 455-456.

210.  Wilson, R. J. (1998). Psychophysiological signs of faking in the phallometric test. Sexual Abuse: Journal of Research and Treatment, 10, 113-126.

211.  Wisniewski, A. B., Migeon, C. J., Meyer-Bahlburg, H. F., Gearhart, J. P., Berkovitz, G. D., Brown, T. R., & Money, J. (2000). Complete androgen insensitivity syndrome: Longterm medical, surgical, and psychosexual outcome. Journal of Clinical Endocrinology and Metabolism, 85, 2664-2669.

212.  Wright, L. W., & Adams, H. E. (1999). The effects of stimuli that vary in erotic content on cognitive process. The Journal of Sex Research, 36, 145-151.

213.  Yager, J., Kurtzman, F., Landsverk, J., & Wiesmeier, E. (1988). Behaviors and attitudes related to eating disorders in homosexual male college students. American Journal of Psychiatry, 145, 495-497.

214.  Yeo, R. A., & Gangestad, S. W. (1993). Developmental origins of variation in human hand preference. Genetica, 89, 281-296. Yeo, R. A., & Gangestad, S. W. (1998). Developmental instability and phenotypic variation in neural organization. In N. Raz (Ed.), The other side of the error term (pp. 1-51). New York: Elsevier Science.

215.  Yeo, R. A., Gangestad, S. W., & Daniels, W. F. (1993). Hand preference and developmental instability. Psychobiology, 21, 161-168.

216.  Zucker, K. J. (1999). Intersexuality and gender identity differentiation. Annual Review of Sex Research, 10, 1-69.

217.  Zucker, K. J., & Bradley, S. J. (1995). Gender identity disorder and psychosexual problems in children and adolescents. New York: Guilford.

218.  Zucker, K. J., Bradley, S. J., Oliver, G., Blake, J., Fleming, S., & Hood, J. (1996). Psychosexual development of women with congenital adrenal hyperplasia. Hormones & Behavior, 30, 300-318.

219.  Zuckerman, M. (1971). Physiological measures of sexual arousal in the human. Psychological Bulletin, 75, 297-329.