Arch Sex Behav (2008) 37:85–99
DOI 10.1007/s10508-007-9265-1
ORIGINAL PAPER: MINOT SPECIAL ISSUE
Sexual Orientation in Women with Classical or Non-classical
Congenital Adrenal Hyperplasia as a Function of Degree
of Prenatal Androgen Excess
Heino F. L. Meyer-Bahlburg Æ Curtis Dolezal Æ
Susan W. Baker Æ Maria I. New
Published online: 22 December 2007
Ó Springer Science+Business Media, LLC 2007
Abstract 46,XX individuals with classical congenital adre-
nal hyperplasia (CAH) due to deficiency of the enzyme,
21-hydroxylase, show variable degrees of masculinization of
body and behavior due to excess adrenal androgen production.
Increased bisexuality and homosexuality have also been
reported. This article provides a review of existing reports of the
latter and presents a new study aimed at replicating the previous
findings with detailed assessments of sexual orientation on
relatively large samples, and at extending the investigation to
the mildest form, non-classical (NC) CAH. Also, this is the first
study to relate sexual orientation to the specific molecular
genotypes of CAH. In the present study, 40 salt-wasters (SW),
21 SV (simple-virilizing), 82 NC, and 24 non-CAH control
women (sisters and female cousins of CAH women) were
blindly administered the Sexual Behavior Assessment Sche-
dule (SEBAS-A, 1983 ed.; H. F. L. Meyer-Bahlburg & A. A.
Ehrhardt, Privately printed). Most women were heterosexual,
but the rates of bisexual and homosexual orientation were
increased above controls not only in women with classical
CAH, but also in NC women, and correlated with the degree of
prenatal androgenization. Classifying women by molecular
genotypes did not further increase the correlation. Diverse
aspects of sexual orientation were highly intercorrelated, and
principal components analysis yielded one general factor.
H. F. L. Meyer-Bahlburg (&)
C. Dolezal
New York State Psychiatric Institute & Department of
Psychiatry, Columbia University, 1051 Riverside Drive,
NYSPI Unit 15, New York, NY 10032, USA
e-mail: meyerb@childpsych.columbia.edu
S. W. Baker
M. I. New
Department of Pediatrics, Mount Sinai School of Medicine,
New York, NY, USA
Bisexual/homosexual orientation was (modestly) correlated
with global measures of masculinization of non-sexual behav-
ior and predicted independently by the degree of both prenatal
androgenization and masculinization of childhood behavior.
We conclude that the findings support a sexual-differentiation
perspective involving prenatal androgens on the development
of sexual orientation.
Keywords Congenital adrenal hyperplasia

Sexual orientation
Homosexuality
Androgen effects

Disorders of sex development
Hermaphroditism
Introduction
Sexual orientation is a trait with very large differences between
men and women. For instance, Hines (2004, p. 11) reported an
effect size d = 6.0, one of the largest for any gender-related
behavior or trait (although the distribution of sexual orientation
scores in terms of the widely used Kinsey scale raises some
doubts about the appropriateness of the usual statistical measure
of effect size, which assumes a Gaussian distribution). The
demonstration of familiality and heritability of homosexuality
(e.g., Pillard & Bailey, 1998) has led to numerous attempts to
provide genetic explanations. Given the focus of evolution-
ary theory on reproduction and survival of the offspring, a
sexual orientation of women to men and of men to women is
eminently plausible. It is much more difficult to come up
with a compelling evolutionary raison d’être for homosex-
uality and bisexuality. A number of non-endocrine explana-
tory hypotheses have been formulated. In the framework of
evolutionary theory, overdominance (Miller, 2000), kin
altruism (Pillard & Bailey, 1998), and sexually antagonistic
selection (Hamer & Copeland, 1994) have been suggested as
potential mechanisms explaining the gene polymorphism
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that is presumed to underlie homosexuality, and mathemat-
ical models have recently been formulated that should
facilitate their empirical testing (Gavrilets & Rice, 2006).
However, the variability of homosexual behavior across
vertebrate species has not led to a consensus on an expla-
nation in terms of evolutionary theory (Sommer & Vasey,
2006), and the demonstration of learning mechanisms in the
acquisition of sexual preferences in animal models (Pfaus,
Kippin, & Coria-Avila, 2003) has further complicated the
issue. Identification of specific genes has not yet led to
consistent success (Hamer, Hu, Magnuson, Hu, & Pattatucci,
1993; Mustanski et al., 2005; Rice, Anderson, Risch, &
Ebers, 1999), but new findings on extreme skewing of
X-inactivation by DNA-methylation in mothers of gay men
have added additional genetic possibilities (Bocklandt,
Horvath, Vilain, & Hamer, 2006).
Bearman and Brückner (2002) provided a strong meth-
odological critique of much of the existing genetic literature
and presented new data from the AddHealth project that
(indirectly) supported a social-influence hypothesis explain-
ing same-sex attractions in adolescents. Other non-genetic
explanations include the progressive immunization hypoth-
esis, which is derived from the well-replicated association of
homosexuality in males with the number of older brothers in
the sibship and assumes that successive pregnancies with
male fetuses leads in some mothers to the development of
male-specific antigens (Blanchard, 2004; Blanchard &
Lippa, 2007). The developmental instability theory explains
homosexuality as a perturbance of the complex processes of
prenatal brain development by exogenous influences and
was originally stimulated by findings of increased non-right
handedness among homosexuals of both sexes (Lalumière,
Blanchard, & Zucker, 2000), but attempts at finding an
association of homosexuality with fluctuating asymmetry as
a broader index of developmental instability have been
unsuccessful (Rahman, 2005).
The most commonly offered theory places sexual orien-
tation in the context of the sexual differentiation of brain and
behavior in general, with a focus on the role of pre- and
perinatal sex hormones in this process (e.g., Ellis & Ames,
1987; Rahman & Wilson, 2003). This approach was pre-
sumably prompted by the association of human homosex-
uality with gender-atypical (non-sexual) behavior and goes
back to the mid-19th century, when scientific embryology
began focusing on the development of the sex-dimorphic
reproductive tract and its disorders. Such research yielded
medical explanations of somatic hermaphroditism, and
analogous medical concepts were applied to the explanation
of homosexuality (Ulrichs, 1862, 1868, as cited in Hirsch-
feld, 1906; see also Kennedy, 1988, Ch. 5). In this context,
homosexuality was often categorized as an inversion (of
gender roles). With the rapidly advancing techniques of
measurement and synthesis of sex hormones in the second
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Arch Sex Behav (2008) 37:85–99
half of the 20th century, behavioral-endocrinology research
in non-primate mammals demonstrated the profound
‘‘organizational’’ influence of sex hormones during early
developmental periods on later mating behavior and sexual
orientation, with perinatal androgens and estrogens (derived
by aromatization of androgens within brain cells) supporting
the development of masculine behavior, and estrogens
supporting the defeminization of behavior, followed by
‘‘activating’’ effects of sex-specific hormones from puberty
on (Arnold, 2002; Wallen & Baum, 2002). The analogous
processes in primates may be limited to androgen effects, but
the determinants of sexual orientation in primates are not yet
clear (Baum, 2006; Wallen & Baum, 2002). Early attempts to
identify sex hormone abnormalities in human homosexuality
were unsuccessful in men (Meyer-Bahlburg, 1977) and only
partially successful in women (Meyer-Bahlburg, 1979). In
the absence of systemic hormone abnormalities and of any
signs of somatic intersexuality in human homosexuality,
some investigators have suggested that causal endocrine
abnormalities might be limited to the central nervous system
(‘‘CNS-limited pseudohermaphroditism,’’ Dörner, 1976),
which is compatible with the recently growing evidence of
tissue specificity of hormone production and/or metabolism
and of hormone receptors. During the last two decades,
advances in genetics have broadened the focus of research on
sexual differentiation to include the many genes involved in
the sexual differentiation of the gonads (Fleming & Vilain,
2005) and, possibly, of the brain (Arnold, 2002, 2004;
Gatewood et al., 2006). Although research on the specific
genetic mechanisms involved in the brain is still in its early
stages, the recent use of cellular-biology techniques to
unravel the chain of mechanisms involved in the hormone-
based sexual differentiation of specific sex-dimorphic nuclei
of the limbic system and the amygdala in the neonatal
(Burks, Wright, & McCarthy, 2007; Todd, Schwarz, &
McCarthy, 2005; Todd, Schwarz, Mong, & McCarthy, 2007)
and pubertal (Zehr, Todd, Schulz, McCarthy, & Sisk, 2006)
periods of development is likely to contribute in a major way
to the identification of genes with specific functions in these
processes.
Recent quite large-scale behavioral data on humans
continue to support the ‘‘inversion’’ perspective regarding
homosexuality (e.g., Lippa, 2005), and the attempts to find a
hormonal cause continue. Considerable efforts have been
made to identify somatic markers of prenatal sex hormone
effects, such as shifts in the second to fourth finger length ratio
(2D:4D) in homosexuals of both sexes (Manning, 2002); the
findings are suggestive, but far from uniform (Manning,
Churchill, & Peters, 2007; Rahman, 2005). Another such
marker may be the reduction of spontaneous otoacoustic
emissions in lesbians (McFadden, 2002), which is awaiting
replication by independent teams. Clearly, more direct evi-
dence of prenatal sex hormone effects would be desirable.
Arch Sex Behav (2008) 37:85–99
However, experimental variations of the prenatal sex-hor-
mone milieu solely for behavioral research purposes cannot
be ethically justified. Money’s team at Johns Hopkins intro-
duced as an alternative the behavioral study of syndromes of
intersexuality, which represent naturally occurring extreme
variations of the sex-hormone milieu (Ehrhardt, Evers, &
Money, 1968). Classical (prenatal-onset) congenital adrenal
hyperplasia (CAH) in 46,XX individuals is the most prevalent
of the classical intersex syndromes and by far the most thor-
oughly investigated in terms of endocrinology and psychol-
ogy. About 90% of CAH patients suffer from the deficiency of
the enzyme, 21-hydroxylase (Grumbach, Hughes, & Conte,
2003). As one of several endocrine consequences, 46,XX
fetuses with CAH are exposed to unusually high levels of
androgens during fetal development, which variably mascu-
linize the genitalia and presumably also the brain and later
behavior.
If sexual orientation is sexually differentiated in a similar
fashion, 46,XX women with classical CAH should show an
increase in bisexuality and homosexuality. Table 1 presents 18
studies on sexual orientation in 46,XX women with classical
CAH that were published between 1968 and 2007. The data
suggest several conclusions. Most women with classical CAH
are heterosexual, but where control groups or population
data are used for comparisons, bisexual and homosexual
orientation appear increased in CAH women (although four
studies did not find such increases: Kühnle, Bullinger, &
Schwartz, 1995; Lev-Ran, 1974; Müller, Bidlingmaier, Förster,
& Knorr, 1982; Slijper et al., 1992). In 11 studies that sepa-
rately assessed both erotic/romantic imagery and the gender
of actual sex partners, increased bisexuality and homosexu-
ality were seen more commonly in imagery (Ehrhardt, 1979;
Ehrhardt et al., 1968; Gastaud et al., 2007; Guth, Witchel,
Witchel, & Lee, 2006; Horn, 1997; May, Boyle, & Grant,
1996; Money, Schwartz, & Lewis, 1984; Stikkelbroeck
et al., 2003; Zucker et al., 1996), although the differences
did not always reach statistical significance, and in two studies
(Lev-Ran, 1974; Müller et al., 1982), no CAH woman was
positive for bisexuality or homosexuality on either variable.
The methodology of this research is, however, largely
unsatisfactory. Most studies employed relatively small sam-
ples, many also lacked a control group, and two (Johannsen
et al., 2006; Kühnle et al., 1995) even included non-classical
(NC) women in their CAH sample and did not analyze them
separately, although NC women become clinically symp-
tomatic only years after birth. Many studies limited their
data to the gender of actual sex partners or provided only
quite limited detail on imagery, in both cases often without
employing systematic assessment methods. In addition,
studies differed in sample composition regarding the per-
centages of mild and severe cases of CAH women and their
age distribution. Thus, it is difficult to derive solid estimates
87
of population prevalence figures of bisexual and homosex-
ual orientation in CAH women from these data.
Even if the majority of the findings listed support an
association of classical CAH with bisexual or homosexual
orientation in women, a causative interpretation of these
findings in terms of androgen effects on sexual orientation is
not as compelling as would be findings from randomized
control trials of androgen treatment. Human studies of this
kind only use ‘‘quasi-experimental designs’’ with, in the best
case, ‘‘patched-up controls’’ (Kazdin, 2002). One could
strengthen the case for the role of androgens by demonstrating
a dose–response relationship between the degree of prenatal
androgen exposure and the degree of later sexual orientation.
Ideally, we would measure prenatal hormone levels repeat-
edly over the course of fetal development and derive from such
measurements an index of the degree of prenatal androgen
exposure. However, the health risks of even one-time cross-
sectional determinations of androgen levels in the amniotic
fluid, for instance, can be justified only if there are compelling
medical indications for the procedures involved. A relatively
crude alternative is the demonstration of dose–response rela-
tions on the group level using the clinical-endocrine or
molecular-genetics classification of CAH subtypes that differ
in severity, i.e., degree of 21-hydroxylase deficiency and,
thereby, degree of androgen excess. Within classical CAH,
commonly two major subtypes are distinguished, the more
severe salt-wasting (SW) variant and the simple virilizing
(SV) variant, and several studies have shown that bisexuality
and homosexuality are increased more in the SW than the SV
variant (Dittmann et al., 1992; Horn, 1997; Mulaikal et al.,
1987; Zucker et al., 1996) or in CAH women with higher
Prader stages of genital masculinization at birth, which are
also (moderately) correlated with CAH severity (Gastaud
et al., 2007); the earlier finding by our team that CAH-SW
women with gender dysphoria are gynecophilic fits in with the
other data (Meyer-Bahlburg et al., 1996).
Our current study had several goals: (1) To replicate the
published findings on sexual orientation in a relatively large
sample of adult women with classical CAH using a sys-
tematic assessment of multiple aspects of sexual orientation,
and to establish at which age the women reach the respective
romantic/erotic milestones; (2) to extend the dose–response
approach to the mildest form of CAH, the non-classical (NC)
variant, which becomes clinically symptomatic (in somatic
terms) only after birth, in childhood or adolescence; (3) to
examine to what extent sexual orientation and global mea-
sures of gender behavior other than sexual orientation are
correlated; (4) to test whether the prediction of the behavioral
phenotype from the endocrine phenotype can be enhanced
by the molecular-genetics classification; (5) to answer the
question how commonly CAH women see themselves as
men in their romantic/erotic imagery; and (6) to perform a
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Table 1 Sexual orientation in women with CAH: Published data

Reference Country Sample

123
Descriptiona N Age (yrs) Imagery Actual partners Imagery & partners
Range M SD % Hetb % Bi/Hoc No datad % Hetb % Bi/Hoc No datad % Hetb % Bi/ Hoc No datad

Ehrhardt et al. (1968) USA CAH: late-treated 23 19–55 32.3 39.1 43.5 17.4 52.2 17.4 30.4
Lev-Ran (1974) USSR CAH: late-treated 18 13–43 26 77.7 0.0 23.3 38.8 0.0 62.2
Ehrhardt (1979) USA CAH: early-treated 13 11–24 16.8 15.4e 7.7
f
Müller et al. (1982) Germany CAH: 2 SW, (rest SV?) 14 18–30 21 64.3 0.0 35.7 78.6 0.0 21.4
Money et al. (1984) USA CAH: 30 17–26 21g 40.0 37.0 23.0 40.0 13.3 46.7 40.0 36.7 23.3
Controls: 15 AIS, 12 MRKS 27 16–? 66.7 3.7 29.6 92.6 7.4 0.0
Mulaikal, Migeon, USA CAH: 40 SW, 40 SV 80 18–69 33.0 57.5 5.0 37.5
and Rock (1987)
Dittmann, Kappes, Germany CAH: 12 SW, 20 SV 34 11–41 20.0h/
and Kappes (1992) 2 no info 26.5i
Subgroup 9 21–41 22.2 55.6
Controls: Sisters 14 11–31 0.0h/
0.0i
Slijper et al. (1992) Netherlands CAH: 10 16–33 20.8 20.0 0.0 80.0 100.0 0.0 0.0
Kühnle et al. (1995) Germany CAH: 20 SW, 17 SV, 8 NC 45 27.0 6.6 4.4k
Controls: Hospital 46 26.3 5.4 2.2k
staff & families
May et al. (1996) UK CAH: 19 18–37 26.1 5.6 26.5e,l 10.5
Controls: Diabetics 17 18–34 27.0 5.3 0.0m
Zucker et al. (1996)n Canada CAH: 19 SW, 12 SV 31 24.4 6.7 66.7 26.7 6.7 80.0 3.3 16.7
Controls: Sisters, fem. cousins 15 25.6 5.5 100.0 0.0 0.0 100.0 0.0 0.0
Horn (1997) Germany CAH: 17 SW, 12 SV 29 17–36 23.3 5.1 27.6 3 27.6
Stikkelbroeck et al. (2003) Netherlands CAH: All SW 8o 18–29 22.8 50.0 0.0
Hines, Brook, UK CAH: 14 SW, 2 no info 16 23.6 6.7 31p
and Conway (2004) Controls: Sisters, fem. cousins 15 22.7 3.4 0.0q
Morgan, Murphy, Lacey, UK CAH: 18 18–36 22.2r
and Conway (2005)
Johannsen, Ripa, Mortensen, Denmark CAH: 21 SW, 33 17–51 30.3 12.1s
and Main (2006) 6 SV, 5 NC, 1 no info
Controls: Civil Registry 33 17–51 0.0s
Guth et al. (2006) USA CAH: 5 23–34 27 80.0 20.0 0.0 80.0 0.0 20.0
Arch Sex Behav (2008) 37:85–99
 Table 1 continued
Reference Country Sample
Descriptiona N Age (yrs) Imagery Actual partners Imagery & partners
Range M SD % Hetb % Bi/Hoc No datad % Hetb % Bi/Hoc No datad % Hetb % Bi/ Hoc No datad

Gastaud et al. (2007) France CAHt: 4 P-I, 6 P-II, 11 P-III, 35 18–43 29.5 20.0 5.8
11 P-IV, 3 P-V
Controls: Healthy 69 19–45 30.0 5.7
hospital-staff families
Arch Sex Behav (2008) 37:85–99

a
‘‘CAH’’ refers to classical CAH (SW, SV, excluding NC) unless otherwise specified
b
‘‘% Het’’ percentage of women with exclusively heterosexual imagery/experience
c
‘‘%Bi/Ho’’ percentage of women with bisexual or exclusively homosexual imagery/experience
d
‘‘No data’’ combines ‘‘no sexual imagery/partner experience’’ and ‘‘missing information’’
e
‘‘Including the women with actual same-sex partner experience
f
Median
g
According to Zucker and Bradley (1995), p. 143
h
‘‘Had or wishes to have long-term/steady relationship with F partner’’
i
At least one positive item on a 10-item HOM scale indicating homosexual fantasies, wishes, or experiences
k
‘‘Being lesbian and living with a female partner’’
l
‘‘Strong sense of sexual appreciation of females’’
m
‘‘Sexual interest in other women’’
n
Lifetime data
o
Sexual orientation is based on only 6 of the 8 women
p
For the past 12 months
q
‘‘None rated themselves as bisexual or homosexual; all indicated their behavior had been exclusively or mainly heterosexual’’
r
Self-categorization as homosexual or bisexual; partner experience was not specified
s
‘‘Present relationships’’
t
Prader stage of genital development at birth
89

123
90
methodological study of the interrelationship of the sexual
orientation variables.
Method
Participants
The current study is part of a comprehensive long-term follow-
up project of women with CAH. Selection and recruitment of
participants were described in detail elsewhere (Meyer-
Bahlburg, Dolezal, Baker, Ehrhardt, & New, 2006) and will be
only briefly summarized here. During an initial pilot phase of
this project, a small number of women with CAH was
recruited from two pediatric endocrine clinics in New York
City. Subsequent data collection for the main study was lim-
ited to the senior endocrine author’s (M.I.N.) clinic, but data
from both study phases were combined for the final analysis.
Eligible were all adult women with CAH due to 21-hydrox-
ylase deficiency for whom the molecular genetics of the 21-
hydroxylase gene had been determined and who spoke Eng-
lish. Geographically, the participating women were spread
over the entire United States and other continents. Transpor-
tation reimbursement was provided for women within the
continental US.
The total analysis sample for CAH women in this report
included 40 SW women, 21 SV women, and 82 NC women.
Almost all CAH women were on glucocorticoid replace-
ment treatment at the time of the study. A total of 24 non-
CAH control women (labeled COS) consisted of sisters and
female cousins of participating CAH women. Ages ranged
from 18–61 years (subgroup means, 28.8–34.7 years). Not
included in this count are two SW women: one patient
because he had changed to living as a man and was therefore
not administered questionnaires and interviews designed for
women, the other because of cognitive limitations which
interfered with the standard administration of assessment
instruments; the latter was also seriously considering gender
change to male at the time of the examination.
In addition to the control group of sisters and female
cousins, we included for selected comparisons and illus-
trations two control groups (labeled COD) from our
preceding project on the long-term behavioral after effects
of prenatal diethylstilbestrol (DES) exposure (Meyer-
Bahlburg et al., 1995; Pillard et al., 1993), which had used
the same assessment instrument for sexual behavior and
sexual orientation: 67 DES-unexposed female controls and
60 DES-unexposed male controls, of comparable age ranges
and subgroup means.
Study procedures were approved by the appropriate
institutional review boards, and all participants gave written
informed consent.
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Arch Sex Behav (2008) 37:85–99
Measures and Procedure
All women underwent an 8–10 h protocol (often spread out
over several days) of standard self-report questionnaires,
psychometric tests, physical examinations, and systematic
interviews. Sexual orientation was assessed as part of the
Sexual Behavior Assessment Schedule (SEBAS-A, 1983
ed.; H. F. L. Meyer-Bahlburg & A. A. Ehrhardt, Privately
printed), a comprehensive sexual-history interview schedule
that covers psychosexual milestones, sexual orientation,
sexual activity level, and sexual dysfunctions. Its adminis-
tration takes approximately 1 h. The SEBAS-A was placed
late in the overall protocol in order to facilitate rapport
development between interviewer and interviewee and,
thereby, increase disclosure of sensitive information, and
the SEBAS-A instructions to the interviewee emphasized
the importance of accuracy to enhance the participants’
motivation. All SEBAS-A interviews (as well as most other
study interviews) with women were conducted by female
interviewers in order to facilitate self-disclosure. Inter-
viewers were clinical psychologists who were specifically
trained for sexual research interviewing. Procedures were
introduced to keep the interviewers from identifying the
group membership of the study participants along with
instructions for the women against the disclosure of their
medical histories to the interviewers. All interviews were
audiotaped to permit monitoring of interviewer perfor-
mance. Excellent interrater reliability of the SEBAS-A has
been demonstrated (Meyer-Bahlburg et al., 1995).
SEBAS-A variables pertinent to sexual orientation covered
masturbation fantasies, masturbation erotica, romantic/erotic
fantasies during sexual relations with a partner, romantic/sexual
daydreams, romantic/sexual nightdreams, sexual attractions,
‘‘Total Imagery,’’ actual sex partners (‘‘Actual Partners’’), and
overall sexual responsiveness (‘‘Overall Kinsey’’). The first six
variables addressed ‘‘current’’ sexual orientation, with ‘‘cur-
rent’’ defined as the 12 months prior to interview, and each was
preceded by a question concerning its frequency (e.g., ‘‘How
often did you have romantic or sexual nightdreams during the
past 12 months?’’). The remaining three aspects were rated
separately for the past 12 months and for lifelong (‘‘Lifetime’’)
patterns (thus, yielding six variables), with lifelong defined as
‘‘since puberty’’ (for ‘‘Total Imagery’’ and overall sexual res-
ponsiveness), or as ‘‘since becoming sexually active, excluding
prepubertal sexual activities’’ (for sexual relations); both defi-
nitions of lifelong included the past 12 months.
For each sexual-orientation variable, interviewers’ ratings
used the Kinsey Rating Scale (Kinsey, Pomeroy, Martin,
& Gebhard, 1953) with the following formulations: 0 =
entirely heterosexual; 1 = largely heterosexual but inci-
dentally homosexual; 2 = largely heterosexual but also
distinctly homosexual; 3 = equally heterosexual and homo-
sexual; 4 = largely homosexual but also distinctly hetero-
Arch Sex Behav (2008) 37:85–99
sexual; 5 = largely homosexual but incidentally heterosex-
ual; and 6 = entirely homosexual. Since the Kinsey team
had not defined ‘‘distinct,’’ ‘‘a distinct’’ homosexual history
(Kinsey score 2 or ‘‘K2’’) was rated when the woman had
experiences such as homosexual dreams or fantasies over a
period of at least 1-year recurring with some regularity (not
less than ‘‘about once a month’’). Whenever a subscale was
rated ‘‘K2,’’ the corresponding global score could not be
rated less than ‘‘K2.’’
The variables on actual sex partners were based on
detailed structured interview sections concerning diverse
romantic and sexual activities, separately for male and
female partners. The definition of sexual relations as used
here for actual sex partners required genital contact including
but not limited to penile–vaginal intercourse; it did not
require orgasm. Total Imagery was a global rating encom-
passing the preceding six variables on imagery and attrac-
tions and taking into consideration the frequencies of the
respective experiences as reported by the interviewee.
Overall sexual responsiveness was a global rating based on
Total Imagery and Actual Partners.
Data Analysis
The study groups were compared on all sexual-behavior and
sexual-orientation variables by overall standard parametric
procedures (ANOVA), and then, for exploratory purposes,
pairwise by independent-samples t-test. If, for a given
comparison, any of the demographic variables (age; ethnic-
ity; and mean parental education as an index of socioeco-
nomic status) significantly differed between the study groups
and was correlated with the outcome variable in the control
group, the potentially confounding influence of the demo-
graphic variable was controlled for by including it in a
regression analysis. If study groups differed significantly in
variability of the outcome variables on Levene’s test for the
Table 2 Homosexual milestones
COS (n = 22) NC (n = 81)
Number (%) of participants with the experience
Crush 3 (14%) 13 (16%)
Love (yes or maybe versus no) 0 (0%) 4 (5%)
Genital sex 0 (0%) 9 (11%)
Mean age (SD) in years
First crush 15.5 (–b) 15.0 (4.9)
First love – (–) 18.8 (2.1)
First genital sex – (–) 23.2 (4.7)
a
Unordered Row by Column Table Test (Stat Xact) for the top three variables; ANOVA (NC, SV, SW) for age at first crush; t-test (NC, SW) for the
remaining two variables
b
No SD (n = 1)
91
equality of variances, weighted least square (WLS) regres-
sions were performed for analyses requiring demographic
controls; otherwise, t-tests with equal variances not assumed.
In addition, we also followed the wide-spread practice of
dichotomizing the Kinsey-format scales for statistical tests
so as to contrast the number of K0-1 women (exclusively or
almost exclusively heterosexual) with the number of K2-6
women. Four-group and two-group comparisons of these
dichotomized variables were performed by way of Fisher’s
Exact test and its extension to multiple groups. In view of the
modest sample sizes of women with the rare syndrome of
CAH, both conventionally (p < .05) and marginally (p <
.10) significant results were listed. Effect sizes (Cohen’s d) of
differences between CAH groups and controls were calcu-
lated using the variance of the controls, because of the
commonly increased variance of CAH samples on outcome
variables. All statistical analyses were conducted using SPSS
for Windows Release 13.01 (December 12, 2004) or
StatXact, 4.0.1 (2000).
Results
Psychosexual Milestones
Table 2 shows findings on selected items from the SEBAS-
A section, Psychosexual Milestones. Substantial minorities
of women in all groups experienced same-sex crushes, while
fewer women experienced same-sex love and same-sex
genital sex. CAH women were increased above control
women in all three categories, and SW women were highest
(the differences reached significance in several pair com-
parisons [data not shown]). The NC group was higher than
the COS group on all 3 variables (significantly so for genital
sex and marginally significantly for love [data not shown]).
The ages at first occurrence of these states or events
appeared to be relatively late. However, as Table 3 shows,
SV (n = 21) SW (n = 39) pa
6 (29%) 15 (38%) .033
1 (5%) 7 (18%) .048
1 (5%) 6 (15%) n.s.
21.8 (7.6) 13.6 (5.6) (.057)
18.5 (–b) 19.1 (3.8) n.s.
13.5 (–b) 19.8 (7.5) n.s.
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92 Arch Sex Behav (2008) 37:85–99

this does not indicate a general delay of psychosexual
milestones (heterosexual and homosexual combined) in
CAH. Rather, among those women with a history of both
heterosexual and homosexual experiences, the first experi-
ence tended to be heterosexual. For instance, the number of
such women who first had a heterosexual crush as compared
to those who first had a homosexual crush breaks down as
follows: COS 1:0; NC 8:1; SV 6:0; and SW 9:4. The same
holds true of the female COD group (DES-unexposed con-
trols) with 5:3. (For the other milestone categories, women
with both heterosexual and homosexual experiences were
too few for statistical analysis.)
Sexual Orientation: Lifetime
As can be seen on Table 4, four-group comparisons on the
three lifetime Kinsey variables are highly significant. The
data show a rather consistent progression of Kinsey score
means (and also SDs), except for the SV group on Actual

Table 3 Psychosexual milestones (homo- and heterosexual combined): Mean age (SD) in years
COS NC SV SW p (ANOVA)

First crush 10.6 (2.3) 9.4 (2.9) 10.3 (3.0) 10.8 (2.9) (.093)
Menarche 13.4 (1.1) 13.1 (2.1) 14.1 (2.4) 14.1 (2.9) n.s.
First masturbation 13.9 (6.0) 13.5 (4.4) 14.2 (4.3) 15.4 (5.8) n.s.
First genital sexa 17.6 (2.7) 17.6 (4.3) 17.3 (3.8) 18.3 (3.8) n.s
First orgasmb 18.4 (4.5) 17.3 (5.2) 18.9 (4.2) 18.3 (6.5) n.s.
First love 19.4 (5.3) 18.0 (3.6) 17.9 (3.6) 20.2 (4.3) (.094)
a
With a partner, any mode
b
With or without a partner, any mode

Table 4 Lifetime Kinsey-scale scores by subgroup: Means (SDs) and distributions

COS NC SV SW p
M (SD) n M (SD) n M (SD) n M (SD) n

Total Imagery 0.2 (0.5) 21 0.7 (1.1) 79 1.1 (1.8) 21 1.8 (2.2) 38 <.001a
K0–1 20 60 14 20
K2–6 1 19 7 18
No imagery 1 1 0 1
Total 22 80 21 39
K2–6/(K0-1 + K2-6) 5% 24% 33% 47% .003b
Actual Partners 0.0 (0.0) 18 0.2 (0.6) 77 0.1 (0.4) 20 1.1 (2.3) 28 .001a
K0-1 18 74 19 22
K2-6 0 3 1 6
No partners 4 4 1 11
Total 22 81 21 39
K2-6/(K0-1 + K2-6) 0% 4% 5% 21% .017b
Overall Kinsey 0.2 (0.5) 22 0.7 (0.9) 80 0.6 (1.0) 21 1.7 (2.1) 39 <.001a
K0-1 21 60 15 23
K2-6 1 20 6 16
No sexual responsiveness 0 0 0 0
Total 22 80 21 39
K2-6/(K0-1 + K2-6) 5% 25% 29% 41% .014b
a
ANOVA
b
Unordered Row by Column Table Test (StatXact) for K2-6 versus KO-1 across 4 subgroups

123
Arch Sex Behav (2008) 37:85–99 93

Partners and Overall Kinsey, and of K-2-6% for all three

variables with increasing degree of androgenization in terms
6 of 21-OHD severity, although of the 18 respective two-group
comparisons of Kinsey scores only 12 were conventionally
5 and 1 marginally significant, and of the 18 two-group com-
Overall Kinsey, Lifetime

parisons of the dichotomized Kinsey scales only 7 were

4 conventionally and 3 marginally significant (data not shown).
Figure 1 shows the Overall Kinsey scores for lifetime sexual
3 orientation, which combines both imagery and actual partner
experience (using reverse scoring for the male COD group to
2 facilitate comparisons). Effect sizes d for the Kinsey-score
differences between the COS and the CAH subgroups were
1 1.0 for NC, .9 for SV, 3.0 for SW, and 2.3 for women with
classical CAH (SV and SW combined). The effect size for the
0
difference between the male and female DES-unexposed
control groups (COD-F and COD-M) from our preceding
DES study was 6.7 with the combined SD used as reference
N= 63 22 80 21 39 60 (8.1 with the women’s SD used as reference).
COD-F COS NC SV SW COD-M The K2-6% for women with classical CAH (SV and SW
combined) was 42% for Total Imagery, 15% for Actual
Fig. 1 Overall sexual responsiveness, lifetime, as a function of CAH
severity. To facilitate comparisons of the CAH effects with the usual Partners, and 37% for the Overall Kinsey rating. The NC
sex difference, DES-unexposed female controls (COD-F) from our group was significantly higher than the COS group on all
preceding DES project have been added on the left and DES- three Kinsey scores (p B .003, B .006, and B .002, respec-
unexposed male controls (COD-M; reverse-scored) on the right. Both
tively). The table also shows that the Kinsey scores for
individual values (graphed with jitter-function software) and means
and SDs are shown lifetime Total Imagery were higher than for lifetime Actual

Table 5 Homosexual partner experience, lifetime: Mean (SD) frequency category and frequency distributions
COS (n = 22) NC (n = 80) SV (n = 21) SW (n = 38) p (ANOVA)

Same-sex sex partners 0.0 (0.0) 0.2 (0.45) 0.1 (0.2) 0.5 (1.5) .037
None 22 71 20 32
1 6 1 1
2–3 3 2
4–6 1
7–10
11–19 1
20–29
30+ 1
% Any 0% 11% 5% 16%
Same-sex sex occasions 0.0 (0.0) 0.4 (1.3) 0.4 (1.7) 1.1 (2.6) (.086)
None 22 71 20 32
1 3
2–3 3
4–6 1 1
7–10
11–19
20–29 1
30–49
50+ 2 1 4

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94 Arch Sex Behav (2008) 37:85–99

Partners. According to Table 5, the number of women with
any actual same-sex partner experience was relatively small,
and the number of those with considerable experience in
terms of same-sex partner numbers or same-sex occasions
was even smaller. In interpreting these data, one has to take
into consideration that women with classical CAH, and
especially those with the SW variant, had significantly lower
lifetime actual-partner numbers and lower total lifetime sex
occasions (heterosexual and homosexual combined in both
variables) than the other groups (data not shown).
Sexual Orientation: Current (Past 12 Months)
The current data on sexual orientation also show Kinsey
scores for all three CAH subgroups in an apparent dose–
response fashion (Table 6). The gradual increase in Kinsey
scores from non-CAH controls to the most severe SW variant
applied to all variables, and was highly significant for all
categories except for fantasies during partner sex. Again, the
NC group had higher Kinsey scores than the COS group on all
9 variables (5 differences were conventionally significant and
1 marginally so), the SW group was significantly higher than
the two other CAH variants (versus SV with conventional
significance on 1 variable and marginal significance on 2;
versus NC with conventional significance on 8 variables), but
the difference between SV and NC women reached con-
ventional and marginal significance on only 1 variable each.
Sexual Orientation and Non-sexual Gender-related
Behavior
The global lifetime and 12 months Kinsey scores were
correlated with selected global variables of gender-related
behavior (not including sexual orientation), as listed in
Meyer-Bahlburg et al. (2006). The expected correlations
were significant and in the predicted direction, but of modest
size, and stronger for childhood measures than adulthood
measures. For instance, the Overall Kinsey score for lifetime
correlated r = -.40 with the Gender scale of the Recalled
Childhood Gender Questionnaire-Revised (RCGQ-R), but
the Overall Kinsey score for the past 12 months correlated
only r = -.27 with the (adult) Hobby Preferences Scale
(the high end on both gender scales is feminine).
Cross-gender Imagery
At the end of the imagery section, the participant was asked
about the frequency with which they saw themselves as ‘‘a
person of the opposite sex’’ in their erotic imagery, sepa-
rately for the past 12 months and lifetime (since puberty,
excluding the past 12 months). As Table 7 shows, all groups
except SV included some women with such experience. The
percent of women with such experience and the frequency of
having that experience, especially for lifetime, was signifi-
cantly increased in the SW subgroup above all other groups.

Table 6 Mean Kinsey scores (SD) for the past 12 months by subgroup
COS NC SV SW p (ANOVA)

Masturbation erotica 0.8 (1.5) 0.9 (1.3) 3.0 (2.4) 3.4 (2.3) .004
Masturbation fantasies 0.3 (0.8) 0.9 (1.3) 1.7 (1.9) 2.5 (2.4) .000
Fantasies during partner sex 0.3 (0.7) 0.8 (1.3) 1.0 (2.0) 2.4 (3.0) (.069)
Daydreams 0.0 (0.0) 0.6 (1.3) 1.0 (1.8) 2.4 (2.8) .000
Nightdreams 0.1 (0.3) 0.5 (1.1) 1.2 (2.1) 3.2 (2.9) .000
Attractions 0.1 (0.3) 0.3 (0.9) 0.9 (1.3) 1.6 (2.2) .000
Total Imagery 0.2 (0.5) 0.7 (1.1) 1.1 (1.6) 1.9 (2.3) .000
Actual Partners 0.0 (0.0) 0.1 (0.7) 0.05 (0.2) 1.4 (2.6) .000
Overall Kinsey score 0.2 (0.5) 0.5 (0.8) 0.9 (1.3) 1.8 (2.3) .000
Note that the n’s vary somewhat between items because not all women have experience with all of them

Table 7 Seeing self as man during romantic/erotic imagery, by subgroup

COS NC SV SW p (ANOVA or
Exact Test)

Mean frequency (categorized), lifetime 0.1 (0.3) 0.1 (0.5) 0.0 (0.0) 0.4 (0.8) .024
Mean frequency (categorized), past 12 months 0.1 (0.4) 0.1 (0.4) 0.0 (0.0) 0.3 (0.8) (.074)
% Women, lifetime 10% 6% 0% 21% .030
% Women, past 12 months 5% 6% 0% 16% n.s.

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Arch Sex Behav (2008) 37:85–99
Predicting Sexual Orientation from Prenatal
Androgenization and Gender Variables
Using hierarchical stepwise regression, we tried to predict the
Overall Kinsey Score for the past 12 months successively
from the degree of prenatal androgenization in terms of the
four CAH-severity groups, childhood gender-related behav-
ior (the Gender scale of the RCGQ-R), adult gender-related
behavior (the sum score of the Hobby Preferences Scale), and
Seeing Self as Man during Romantic/Erotic Imagery, Fre-
quency: Lifetime (Excluding the Past 12 Months). Prenatal
androgenization and RCGQ-R Gender contributed signifi-
cantly to the variance accounted for and were significant in
the final model, but Hobby Preferences and Seeing Self as
Man was not (Table 8).
Role of the Molecular Genotype
Finally, we wanted to test whether the CAH subtypes as
defined by endocrine criteria or their classification by
molecular genotype is more closely associated with sexual
orientation. We employed the widely used severity classi-
fication of molecular genotypes of the 21-OH gene (White &
Speiser, 2000), which is based on the in-vitro synthesis of
21-OH expressed as % of synthesis by the intact genotype. It
yields four groups, listed here in ascending severity and with
the major molecular genotypes: (1) Genotypes V281L or
P30L (20–50% or 30–60% 21-OH; all patients are NC); (2)
Table 8 Prediction of overall Kinsey score (past 12 months) from
degree of prenatal androgenization and gender variables, using step-
wise hierarchical regression
R2 change
a,b
Degree of prenatal androgenization .130
RCGQ-R Gender scaleb .062
b relation matrix of all 12-month Kinsey variables. All of the
Hobby Preferences scale .015
Seeing Self as Man During Romantic/Erotic
Imagery, lifelong (excluding past 12 months)c .014
Final model
b p
a,b
Degree of prenatal androgenization -.219
b
RCGQ-R Gender scale -.386
Hobby Preferences scaleb .167
Seeing Self as Man During Romantic/ .118
Erotic Imagery, lifelong
(excluding the past 12 months)c
a
Degree of prenatal androgenization coded SW = 1, SV = 2,
NC = 3, COS = 4
b
High score = feminine
c
High score = masculine
95
Table 9 Prediction of overall Kinsey score (past 12 months) from
endocrinea and geneticb classification of CAH, using stepwise hierar-
chical regression
R2 change p
Genetic entered first, clinical second
Genetic .100 .000
Clinical .007 .356
Clinical entered first, genetic second
Clinical .102 .000
Genetic .004 .453
a
Endocrine classification coded SW = 1, SV = 2, NC = 3
b
Genetic classification coded by molecular genotypes: V281L or
P30L = 1; I172N = 2, I2 splice = 3, Gene deleted = 4
I172N (1+% 21-OH; 10% of patients are SW); (3) I2 splice
(0+% 21-OH; most patients are SW); (4) ‘‘Null’’/gene
deleted (0% 21-OH; all patients are SW). In compound
heterozygotes the classification is based on the allele with
the milder mutation. We had severity-classifiable genotypes
for 28 SW women, 17 SV women, and 79 NC women. Using
stepwise hierarchical regression, we either entered the mole-
cular genotype classification first, and the clinical endocrine
classification second, or vice versa. As Table 9 shows, nei-
ther procedure indicated that the variable entered second
added significant predictive variance to sexual orientation
outcome. Thus, the two classifications did not differ in their
association with the Kinsey score. In this particular sub-
sample, the endocrine and genetic classifications correlated
Pearson r = .90 with each other, i.e., there was little room
for divergence between molecular genotype and endocrine
phenotype.
p Intercorrelations among Sexual Orientation Variables
.000
For methodological purposes, we constructed an intercor-
.002
.115
Kinsey variables were quite highly intercorrelated, with
Pearson r ranging from .50 to .92 (median = .78). A prin-
.135
cipal components analysis of all these variables (except for
Masturbation Erotica which had too few women with the
relevant experience and excluding the two global variables,
Total imagery and Overall Kinsey score) yielded one gen-
.028 eral factor accounting for 77.2% of the variance. The factor
.001 loadings for the individual variables were: Daydreams .96,
.144 Attractions .93, Masturbation Fantasies .92, Fantasies Dur-
.135 ing Partner Sex .88, Night Dreams .81, and Actual Partners
.76. On the basis of the principal components analysis, we
constructed a 6-item unit-weighted scale of sexual orienta-
tion. This scale was correlated with the interviewer rating of
overall sexual responsiveness during the past 12 months (at
the end of the sexual-orientation section) with Pearson
r = .94 (p < .001).
123
96
Discussion
Our data clearly showed increased sexual orientation
towards females (i.e., bisexuality and homosexuality) in
women with classical CAH (SV and SW combined) com-
pared to non-CAH controls. Note that our data constitute
underestimates: The two 46,XX individuals with SW-CAH
who were excluded from analysis for technical reasons were
both living with female partners at the time of the evaluation
and had a history of sexual responsiveness to females. Thus,
our study corroborates earlier findings on sexual orientation
in CAH. We also clearly replicate earlier demonstrations of
increased bisexual/homosexual orientation in SW women
compared to SV women, and earlier reports indicating that
these shifts are more strongly accentuated in romantic/erotic
imagery than actual sex-partner experiences.
More surprising is the finding of increased bisexual/
homosexual orientation in NC women above controls in the
diverse variables evaluated here. This finding is in line with
our earlier report on mild, but significant shifts of the same
NC women towards masculinized gender-related behavior
other than sexual orientation (Meyer-Bahlburg et al., 2006).
In the endocrine literature, NC is usually described as a
syndrome characterized by onset of clinical (somatic, phy-
siological) symptoms of androgen excess after birth, in
childhood or later. Since there is consensus that the mas-
culinization of gender-related behavior in classical CAH is
due to the effect of prenatal androgens on the developing
brain, these behavioral shifts in NC women were not
expected. The finding raises the question whether the mild
androgen excess that is likely to be present in NC fetuses
from the first trimester on, but is insufficient to noticeably
affect the sexual differentiation of the genitalia, is never-
theless sufficient to slightly affect the sexual differentiation
of the brain. Alternatively, the data suggest an unexpected
postnatal effect of mild but persistent androgen excess on
brain and gender-related behaviors. Our study does not
provide data that would help us to argue in favor of one or
the other explanation.
In conjunction with the other CAH subgroups and the
control women, our NC data further strengthen the notion of
a dose–response relationships of androgens with sexual
orientation, at least on the subgroup level, given that the
other hormone abnormalities seen in the CAH syndrome
(e.g., deficiency of cortisol and aldosterone, excess of ACTH
and 17-hydroxyprogesterone) are not known to be associ-
ated with masculinization of gender-related behavior in
animals or humans (although specific studies of this kind are
yet to be conducted). As we had found analogous relation-
ships with CAH severity for non-sexual gender-related
behavior (Meyer-Bahlburg et al., 2006), we also could
confirm significant, but modest-sized correlations of sexual
orientation scores with non-sexual gender-related behaviors,
123
Arch Sex Behav (2008) 37:85–99
which had been shown by others (e.g., Hines et al., 2004).
Such findings are also in line with an understanding of sexual
orientation in the context of sexual differentiation. Given the
many differences in sexual orientation and associated vari-
ables between men and women, the question arises, whether
the increased sexual orientation towards females associated
with CAH severity in 46,XX individuals is a model of the
role of androgens in sexual-orientation development in
males rather than lesbian women. Early developmental
research on non-sexual sex-dimorphic behavior in animals
sought to explain sex differences in behavior (e.g., Beatty,
1979), and experimental manipulations of pre- and perinatal
androgen levels served to show to what extent one could
create male-typical behavior in females so treated. Later,
such findings were also used to explain interindividual
variations of gender-related behavior among females (e.g.,
Hines, 2004), and there is some supportive evidence for this
approach in humans. That this may apply also to sexual
orientation in at least a subgroup of women is suggested by
the fact that earlier research has repeatedly shown that about
one third of homosexual women have (modestly) increased
levels of androgens (Meyer-Bahlburg, 1979).
One of the major limitations of the interpretation of
findings in classical CAH in relation to animal studies is the
hormone treatment that females with classical CAH typi-
cally receive throughout postnatal life. The classical animal
study of sexual differentiation of brain and behavior exposes
the female fetus to androgen treatment during the known
early hormone-sensitive period of sexual differentiation of
the brain and then again around the time of puberty/young
adulthood. That combination tends to maximize the devel-
opment of cross-gender sexual behaviors, especially when
ovariectomy after puberty preceded the treatment with tes-
tosterone propionate, as shown by Dörner (1976, p. 164) in
the rat. By contrast, human 46,XX individuals with CAH are
initially exposed to excess, endogenous androgens from
their adrenals during the presumed hormone-sensitive pre-
natal period of sexual differentiation of the brain, and in the
severe variants at even higher levels than normal males and
more chronically so (Carson et al., 1982; Pang, Levine,
Chow, Faiman, & New, 1979; Pang et al., 1980, 1985;
Wudy, Dörr, Solleder, Djalali, & Homoki, 1999); however,
from birth on, the excess androgen levels are suppressed by
glucocorticoid replacement therapy (sometimes to levels
even lower than is normal for healthy females), the ovaries
are left in place, and female puberty is induced by an
endogenous, largely normal female hormonal milieu.
Unfortunately, there are no behavioral studies of non-human
primates that mimic the androgen history of 46,XX humans
with CAH, so that we cannot be sure if we should expect to
see much more bisexuality and homosexuality in 46,XX
individuals without postnatal androgen suppression. The
early study by Ehrhardt et al. (1968) on late-treated women
Arch Sex Behav (2008) 37:85–99
with CAH who did not have glucocorticoid treatment
available before later adolescence or adulthood does not
show massive increases in bisexuality or homosexuality
compared to our data, but most of those early studied women
must have had milder (non-SW) variants of CAH implying
relatively less prenatal androgen excess, or they would not
have survived. Also the fact that the effect size for sexual
orientation in SW as the most severe CAH variant does not
reach even half the effect size for the sex difference despite
chronically high prenatal androgen levels may be related to
the other male-atypical features of 46,XX CAH develop-
ment and/or reflect the absence of Y-based genes in the
46,XX brain, which are suspected of participating in the
sexual differentiation of the brain in other vertebrates
(Arnold, 2002; Gatewood et al., 2006).
Another potentially confounding factor is the fact that
insufficient glucocorticoid replacement or treatment inter-
ruptions lead to virilization, i.e., somatic symptoms of and-
rogen excess, and, if occurring early enough during childhood
development, also to stunting of growth, while overtreatment
brings about variable degrees of obesity, all of which may
reduce attractivity to men and romantic approaches by men,
and to related body-image concerns of the CAH women. This
raises the question whether associated inhibition of romantic
practice in adolescence, perhaps also supported by less-ster-
eotypic feminine leisure time activities and, at least for some
CAH women, relative isolation in the peer group, might
increase the chance of bisexual/homosexual development
rather than exclusively a direct effect of androgens on brain
circuits that regulate sexual behavior. If so, this might be an
example of the interaction of social and biological factors in
the development of bisexuality/homosexuality, for which
Bearman and Brückner (2002) argued.
In our data set, the clinical-endocrine classification of
CAH was highly correlated with the classification based on
molecular genetics, and knowledge of one did not add to the
predictive power of the other in terms of gender outcome.
Thus, there is no suggestion that the molecular-genetic
defect influences sexual-orientation outcome through any
other physiological route than the hormonal abnormalities
caused by the degree of enzyme deficiency.
It is noteworthy that our data suggest an influence of CAH
severity on cross-gender identity in sexual situations. Our
data here again represent an underestimate because of the
exclusion of two SW patients from the current data analysis,
one having undergone gender change to male, the other
considering it (see above). Perhaps, gender-atypicality in
non-sexual behavior along with later emerging atypical
sexual orientation facilitate in some CAH women an iden-
tification with selected aspects of the male role, which may
subsequently broaden and thereby lead to late overall gender
identity change, as it has been documented to occur in some
46,XX individuals with CAH (Meyer-Bahlburg et al., 1996).
97
Our data show that current sexual orientation is not only
predicted from the degree of prenatal androgen exposure as
indicated by the CAH-severity classification, but in addi-
tion also from the degree of masculinization of gender-
related behavior during childhood. The latter variable
could reflect variable brain responsiveness to prenatal
androgens as well as postnatal psychosocial influences,
provided retrospective reporting bias can be ruled out. This
study does not provide an opportunity to decide between
these options.
The association of CAH severity with outcome appears in
all aspects of sexual orientation assessed in our protocol and
plausibly explains the strong general factor that emerged
from the principal-component analysis. This finding, along
with the high correlation of the resulting summary scale
with the global interviewer rating of overall sexual
responsiveness, suggests the feasibility of a simplified self-
report version of a multi-item sexual orientation assessment.
The current data set on sexual orientation suffers from the
same overall limitations as the previous one on gender
development (Meyer-Bahlburg et al., 2006), namely, small
sample size, questionable representativeness, and cross-
sectional design. However, our findings on a dose–response
relationship of androgens and sexual orientation appear
even stronger than for non-sexual gender-related behavior
and make a persuasive case for the extension of this asso-
ciation to women with NC CAH. Overall, our findings
support a sexual-differentiation perspective involving pre-
natal androgens on the development of sexual orientation.
Acknowledgments The project described was supported in part by
USPHS Grants HD-38409, RR06020 (GCRC), and by Grant Number
U54 RR01-9484 from the National Center for Research Resources
(NCRR), a component of the National Institutes of Health (NIH). Its
contents are solely the responsibilities of the authors and do not nec-
essarily represent the official views of NCRR or NIH. We thank the
study women for their participation in this research. Ms. Rhoda Gruen
served as interviewer trainer. Ms. Patricia Connolly assisted in word
processing.
References
Arnold, A. P. (2002). Concepts of genetic and hormonal induction of
vertebrate sexual differentiation in the twentieth century, with
special reference to the brain. In D. W. Pfaff, A. P. Arnold, A. M.
Etgen, S. E. Fahrbach, & R. T. Rubin (Eds.), Hormones, brain,
and behavior (Vol. 4, pp. 105–135). Amsterdam: Academic Press
(Elsevier Science).
Arnold, A. P. (2004). Sex chromosomes and brain gender. Nature
Reviews Neuroscience, 5, 701–708.
Baum, M. J. (2006). Mammalian animal models of psychosexual
differentiation: When is ‘translation’ to the human situation
possible? Hormones and Behavior, 50, 579–588.
Bearman, P. S., & Brückner, H. (2002). Opposite-sex twins and
adolescent same-sex attraction. American Journal of Sociology,
107, 1179–1205.
123
98
Beatty, W. W. (1979). Gonadal hormones and sex differences in
nonreproductive behaviors in rodents: Organizational and acti-
vational influences. Hormones & Behavior, 12, 112–163.
Blanchard, R. (2004). Quantitative and theoretical analyses of the
relation between older brothers and homosexuality in men.
Journal of Theoretical Biology, 230, 173–187.
Blanchard, R., & Lippa, R. A. (2007). Birth order, sibling sex ratio,
handedness, and sexual orientation of male and female partici-
pants in a BBC internet research project. Archives of Sexual
Behavior, 36, 163–176.
Bocklandt, S., Horvath, S., Vilain, E., & Hamer, D. H. (2006). Extreme
skewing of X chromosome inactivation in mothers of homosexual
men. Human Genetics, 118, 691–694.
Burks, S. R., Wright, C. L., & McCarthy, M. M. (2007). Exploration of
prostanoid receptor subtype regulating estradiol and prostaglan-
din E2 induction of spinophilin in developing preoptic area
neurons. Neuroscience, 146, 1117–1127.
Carson, D. J., Okuno, A., Lee, P. A., Stetten, G., Didolkar, S. M., &
Migeon, C. J. (1982). Amniotic fluid steroid levels. Fetuses with
adrenal hyperplasia, 46,XXY fetuses, and normal fetuses. Amer-
ican Journal of Diseases of Children, 136, 218–222.
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.
Dörner, G. (1976). Hormones and brain differentiation. Amsterdam:
Elsevier/North-Holland Biomedical Press.
Ehrhardt, A. A. (1979). Psychosocial adjustment in adolescence in
patients with congenital abnormalities of their sex organs. In H. L.
Vallet & I. H. Porter (Eds.), Genetic mechanisms of sexual
development (pp. 473–483). New York: Academic Press.
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.
Ellis, L., & Ames, M. A. (1987). Neurohormonal functioning and
sexual orientation: A theory of homosexuality–heterosexuality.
Psychological Bulletin, 101, 233–258.
Fleming, A., & Vilain, E. (2005). The endless quest for sex
determination genes. Clinical Genetics, 67, 15–25.
Gastaud, F., Bouvattier, C., Duranteau, L., Brauner, R., Thibaud, E.,
Kutten, F., et al. (2007). Impaired sexual and reproductive
outcomes in women with classical forms of congenital adrenal
hyperplasia. Journal of Clinical Endocrinology and Metabolism,
92, 1391–1396.
Gatewood, J. D., Wills, A., Shetty, S., Xu, J., Arnold, A. P., Burgoyne,
P. S., et al. (2006). Sex chromosome complement and gonadal sex
influence aggressive and parental behaviors in mice. Journal of
Neuroscience, 26, 2335–2342.
Gavrilets, S., & Rice, W. R. (2006). Genetic models of homosexuality:
Generating testable predictions. Proceedings of the Royal Society
B, 273, 3031–3038.
Grumbach, M. M., Hughes, I. A., & Conte, F. A. (2003). Disorders of
sex differentiation. In P. R. Larsen, H. M. Kronenberg, S.
Melmed, & K. S. Polonsky (Eds.), Williams textbook of endocri-
nology (10th ed., pp. 842–1002). Philadelphia: W. B. Saunders.
Guth, L. J., Witchel, R. I., Witchel, S. F., & Lee, P. A. (2006).
Relationships, sexuality, gender identity, gender roles, and self-
concept of individuals who have congenital adrenal hyperplasia:
A qualitative investigation. Journal of Gay & Lesbian Psycho-
therapy, 10, 57–75.
Hamer, D., & Copeland, P. (1994). The science of desire: The search
for the gay gene and biology of behavior. New York: Simon &
Schuster.
Hamer, D. H., Hu, S., Magnuson, V. L., Hu, N., & Pattatucci, A. M. L.
(1993). A linkage between DNA markers on the X-chromosome
and male sexual orientation. Science, 261, 321–327.
123
Arch Sex Behav (2008) 37:85–99
Hines, M. (2004). Brain gender. New York: Oxford University
Press.
Hines, M., Brook, C., & Conway, G. S. (2004). Androgen and
psychosexual development: Core gender identity, sexual orienta-
tion, and recalled childhood gender role behavior in women and
men with congenital adrenal hyperplasia (CAH). Journal of Sex
Research, 41, 75–81.
Hirschfeld, M. (1906). Vom Wesen der Liebe. Zugleich ein Beitrag zur
Lösung der Frage der Bisexualität. Jahrbuch für Sexuelle
Zwischenstufen, 8, 1–284.
Horn, P. (1997). Sexualverhalten, psychosexuelle Orientierung und
Orgasmuserleben junger Frauen mit kongenitalem adrenogeni-
talem Syndrome. Unpublished doctoral thesis, Universität
Leipzig, Leipzig.
Johannsen, T. H., Ripa, C. P. L., Mortensen, E. L., & Main, K. M.
(2006). Quality of life in 70 women with disorders of sex
development. European Journal of Endocrinology, 155, 877–885.
Kazdin, A. E. (2002). Research design in clinical psychology (4th ed.).
Boston: Allyn & Bacon.
Kennedy, H. (1988). Ulrichs: The life and works of Karl Heinrich
Ulrichs, pioneer of the modern gay movement. Boston: Alyson
Publications.
Kinsey, A. C., Pomeroy, W. B., Martin, C. E., & Gebhard, P. H. (1953).
Sexual behavior in the human female. Philadelphia: Saunders.
Kühnle, U., Bullinger, M., & Schwarz, H. P. (1995). The quality of life
in adult female patients with congenital adrenal hyperplasia: A
comprehensive study of the impact of genital malformation and
chronic disease on female patients’ life. European Journal of
Pediatrics, 154, 708–716.
Lalumière, M. L., Blanchard, R., & Zucker, K. J. (2000). Sexual
orientation and handedness in men and women: A meta-analysis.
Psychological Bulletin, 126, 575–592.
Lev-Ran, A. (1974). Sexuality and educational levels of women with
the late-treated adrenogenital syndrome. Archives of Sexual
Behavior, 3, 27–32.
Lippa, R. A. (2005). Sexual orientation and personality. Annual Review
of Sex Research, 16, 119–153.
Manning, J. T. (2002). Digit ratio: A pointer to fertility, behavior and
health. New Brunswick, NJ: Rutgers University Press.
Manning, J. T., Churchill, A. J. G, & Peters, M. (2007). The effects of
sex, ethnicity, and sexual orientation on self-measured digit ratio
(2D:4D). Archives of Sexual Behavior, 36, 223–233.
May, B., Boyle, M., & Grant, D. (1996). A comparative study of
sexual experiences: Women with diabetes and women with
congenital adrenal hyperplasia. Journal of Health Psychology,
1, 479–492.
McFadden, D. (2002). Masculinization effects in the auditory systems.
Archives of Sexual Behavior, 31, 99–111.
Meyer-Bahlburg, H. F. L. (1977). Sex hormones and male homosex-
uality in comparative perspective. Archives of Sexual Behavior, 6,
297–325.
Meyer-Bahlburg, H. F. L. (1979). Sex hormones and female homo-
sexuality: A critical examination. Archives of Sexual Behavior, 8,
101–119.
Meyer-Bahlburg, H. F. L., Dolezal, C., Baker, S. W., Ehrhardt, A. A.,
& New, M. I. (2006). Gender development in women with
congenital adrenal hyperplasia as a function of disorder severity.
Archives of Sexual Behavior, 35, 667–684.
Meyer-Bahlburg, H. F. L., Ehrhardt, A. A., Rosen, L. R., Gruen, R. S.,
Veridiano, N. P., Vann, F. H., et al. (1995). Prenatal estrogens and
the development of homosexual orientation. Developmental
Psychology, 31, 12–21.
Meyer-Bahlburg, H. F. L., Gruen, R. S., New, M. I., Bell, J. J.,
Morishima, A., Shimshi, M., et al. (1996). Gender change from
female to male in classical congenital adrenal hyperplasia.
Hormones and Behavior, 30, 319–332.
Arch Sex Behav (2008) 37:85–99
Miller, E. M. (2000). Homosexuality, birth order, and evolution:
Toward an equilibrium reproductive economics of homosexual-
ity. Archives of Sexual Behavior, 29, 1–34.
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. Psychoneuroendo-
crinology, 9, 405–414.
Morgan, J. F., Murphy, H., Lacey, J. H., & Conway, G. (2005). Long
term psychological outcome for women with congenital adrenal
hyperplasia: Cross sectional survey. British Medical Journal, 330,
340–341.
Mulaikal, R. M., Migeon, C. J., & Rock, J. A. (1987). Fertility rates in
female patients with congenital adrenal hyperplasia due to 21-
hydroxylase deficiency. New England Journal of Medicine, 316,
178–182.
Müller, M., Bidlingmaier, F., Förster, C., & Knorr, D. (1982).
Psychosexuelles Verhalten von Frauen mit adrenogenitalem
Syndrom. Helvetica Paediatrica Acta, 37, 571–580.
Mustanski, B. S., DuPree, M. G., Nievergelt, C. M., Bocklandt, S.,
Schork, N. J., & Hamer, D. H. (2005). A genomewide scan of
male sexual orientation. Human Genetics, 116, 272–278.
Pang, S., Levine, L. S., Cederqvist, L. L., Fuentes, M., Riccardi, V. M.,
Holcombe J. H., et al. (1980). Amniotic fluid concentrations of
delta 5 and delta 4 steroids in fetuses with congenital adrenal
hyperplasia due to 21-hydroxylase deficiency and in anencephalic
fetuses. Journal of Clinical Endocrinology and Metabolism, 51,
223–229.
Pang, S., Levine, L. S., Chow, D. M., Faiman, C., & New, M. I. (1979).
Serum androgen concentrations in neonates and young infants
with congenital adrenal hyperplasia due to 21-hydroxylase
deficiency. Clinical Endocrinology, 11, 575–584.
Pang, S., Pollack, M. S., Loo, M., Green, O., Nussbaum, R., Clayton,
G., et al. (1985). Pitfalls of prenatal diagnosis of 21-hydroxylase
deficiency congenital adrenal hyperplasia. Journal of Clinical
Endocrinology and Metabolism, 61, 89–97.
Pfaus, J. G., Kippin, T. E., & Coria-Avila, G. (2003). What can animal
models tell us about human sexual response? Annual Review of
Sex Research, 14, 1–63.
Pillard, R. C., & Bailey, J. M. (1998). Human sexual orientation has a
heritable component. Human Biology, 70, 347–365.
Pillard, R. C., Rosen, L. R., Meyer-Bahlburg, H. F. L., Weinrich, J. M.,
Feldman, J. F., Gruen, R. S., & Ehrhardt, A. A. (1993).
Psychopathology and social functioning in men prenatally
exposed to diethylstilbestrol (DES). Psychosomatic Medicine,
55, 485–491.
Rahman, Q. (2005). Fluctuating asymmetry, second to fourth finger
length ratios and human sexual orientation. Psychoneuroendo-
crinology, 30, 382–391.
Rahman, Q., & Wilson, G. D. (2003). Born gay? The psychobiology of
human sexual orientation. Personality and Individual Differences,
34, 1337–1382.
99
Rice, G., Anderson, C. A., Risch, N., & Ebers, G. (1999). Male
homosexuality: Absence of linkage to microsatellite markers at
Xq28. Science, 284, 665–667.
Slijper, F. M. E., van der Kamp H. J., Brandenburg, H., de Muinck
Keizer-Schrama S. M. P. F., Drop, S. L. S., & Molenaar, J. C.
(1992). Evaluation of psychosexual development of young
women with CAH: A pilot study. In W. Bezemer, P. Cohen-
Kettenis, K. Slob, & N. van Son-Schoones (Eds.), Sex matters (pp.
47–50). Amsterdam: Elsevier Science Publishers B.V.
Sommer V., & Vasey P. L. (Eds.). (2006). Homosexual behavior in
animals. An evolutionary perspective. Cambridge: Cambridge
University Press.
Stikkelbroeck, N. M. M. L., Beerendonk, C. C. M., Willemsen, W. N.
P., Schreuders-Bais, C. A., Feitz, W. F. J., Rieu, P. N. M. A., et al.
(2003). The long term outcome of feminizing genital surgery for
congenital adrenal hyperplasia: Anatomical, functional and
cosmetic outcomes, psychosexual development, and satisfaction
in adult female patients. Journal of Pediatric and Adolescent
Gynecology, 16, 289–296.
Todd, B. J., Schwarz, J. M., & McCarthy, M. M. (2005). Prostaglandin-
E2: A point of divergence in estradiol-mediated sexual differen-
tiation. Hormones and Behavior, 48, 512–521.
Todd, B. J., Schwarz, J. M., Mong, J. A., & McCarthy, M. M. (2007).
Glutamate AMPA/kainate receptors, not GABAA receptors,
mediate estradiol-induced sex differences in the hypothalamus.
Developmental Neurobiology, 67, 304–315.
Wallen, K., & Baum, M. J. (2002). Masculinization and defeminization
in altricial and precocial mammals: Comparative aspects of
steroid hormone action. In D. W. Pfaff, A. P. Arnold, A. M. Etgen,
S. E. Fahrbach, & R. T. Rubin (Eds.), Hormones, brain, and
behavior (Vol. 4. pp. 385–423). Amsterdam: Academic Press
(Elsevier Science).
White, P. C., & Speiser, P. W. (2000). Congenital adrenal hyperplasia
due to 21-hydroxylase deficiency. Endocrine Reviews, 21, 245–
291.
Wudy, S. A., Dörr, H. G., Solleder, C., Djalali, M., & Homoki, J.
(1999). Profiling steroid hormones in amniotic fluid of midpre-
gnancy by routine stable isotope dilution/gas chromatography-
mass spectrometry: Reference values and concentrations in
fetuses at risk for 21-hydroxylase deficiency. Journal of Clinical
Endocrinology & Metabolism, 84, 2724–2728.
Zehr, J. L., Todd, B. J., Schulz, K. M., McCarthy, M. M., & Sisk, C. L.
(2006). Dendritic pruning of the medial amygdala during pubertal
development of the male Syrian hamster. Journal of Neurobiol-
ogy, 66, 578–590.
Zucker, K. J., & Bradley, S. J. (1995). Gender identity disorder and
psychosexual problems in children and adolescents. New York:
Guilford Press.
Zucker, K. J., Bradley, S. J., Oliver, G., Blake, J., Fleming, S., & Hood,
J. (1996). Psychosexual development of women with congenital
adrenal hyperplasia. Hormones and Behavior, 30, 300–318.
123
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