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J. Biosoc. Sci., (2017) 49, 527–535, © Cambridge University Press, 2016
doi:10.1017/S0021932016000584 First published online 7 Nov 2016
BIRTH ORDER AND ANDROPHILIC
DOUG P. VANDERLAAN*†
, RAY BLANCHARD‡, KENNETH J. ZUCKER‡,
RAFFAEL MASSUDA§, ANNA MARTHA VAITSES FONTANARI§,
ANDRÉ OLIVEIRA BORBA§, ANGELO BRADELLI COSTA§,
MAIKO ABEL SCHNEIDER§, ANDRESSA MUELLER§,
BIANCA MACHADO BORBA SOLL§, KARINE SCHWARZ§,
DHIORDAN CARDOSO DA SILVA§ AND
MARIA INÊS RODRIGUES LOBATO§
*Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario,
Canada, †Child, Youth and Family Division, Underserved Populations Research
Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada,
‡Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada and
§Gender Identity Program-PROTIG, Hospital de Clinicas de Porto Alegre,
Rio Grande do Sul, Porto Alegre, Brazil
Summary. Previous research has indicated that biological older brothers
increase the odds of androphilia in males. This ﬁnding has been termed the
fraternal birth order effect. The maternal immune hypothesis suggests that this
effect reﬂects the progressive immunization of some mothers to male-speciﬁc
antigens involved in fetal male brain masculinization. Exposure to these anti-
gens, as a result of carrying earlier-born sons, is hypothesized to produce
maternal immune responses towards later-born sons, thus leading to female-
typical neural development of brain regions underlying sexual orientation.
Because this hypothesis posits mechanisms that have the potential to be
active in any situation where a mother gestates repeated male fetuses, a key
prediction is that the fraternal birth order effect should be observable in
diverse populations. The present study assessed the association between
sexual orientation and birth order in androphilic male-to-female transsexuals
in Brazil, a previously unexamined population. Male-to-female transsexuals
who reported attraction to males were recruited from a specialty gender iden-
tity service in southern Brazil (n=118) and a comparison group of gyne-
philic non-transsexual men (n=143) was recruited at the same hospital.
Logistic regression showed that the transsexual group had signiﬁcantly more
older brothers and other siblings. These effects were independent of one
Corresponding author. Email: email@example.com
another and consistent with previous studies of birth order and male sexual
orientation. The presence of the fraternal birth order effect in the present
sample provides further evidence of the ubiquity of this effect and, therefore,
lends support to the maternal immune hypothesis as an explanation of andro-
philic sexual orientation in some male-to-female transsexuals.
Androphilia refers to sexual attraction and arousal towards adult males whereas gynephilia
refers to sexual attraction and arousal towards adult females. Numerous studies have shown
that older brothers increase the odds of androphilia in later-born males. The observed
increase in odds is typically between 15 and 50% per older brother (e.g. Blanchard &
Bogaert, 1996; Blanchard et al., 1998; Blanchard & Lippa, 2007). This phenomenon has
been termed the fraternal birth order effect. This effect is most easily demonstrated when the
mean number of older brothers is elevated among androphilic, compared with gynephilic,
males and the mean sum of other siblings (i.e. older sisters + younger brothers + younger
sisters) is similar across these groups. If the mean sums of other siblings are not similar, or if
there are other large demographic differences between groups, statistical corrections are
sometimes needed to see the effect (e.g. Blanchard, 2014).
The best-developed explanation of the fraternal birth order effect is the maternal
immune hypothesis (Blanchard & Bogaert, 1996; Bogaert & Skorska, 2011). This
hypothesis argues that antigens from male fetuses’cells enter maternal circulation during
pregnancy, promoting an immune response to these male-speciﬁc antigens. This immune
response would, in turn, produce long-lasting effects on the brain of the male fetus,
preventing its neurons from making a male-typical pattern of connections, resulting in
attraction towards men rather than women. In its general form, the maternal immune
hypothesis does not specify which male-speciﬁc proteins are most likely to be involved.
Based on considerations like tissue distribution and prenatal expression, it has been
conjectured (see Blanchard et al., 2002; Blanchard, 2004) that two likely proteins are
PCDH11Y (Blanco et al., 2000) and NLGN4Y (Jamain et al., 2003). As noted by
Blanchard (2008), the maternal immune hypothesis does not challenge the long-standing
theory that sexual orientation is primarily inﬂuenced via prenatal sex hormone exposure;
rather, it proposes that sexual orientation in the human male brain is inﬂuenced by two
systems: one driven by prenatal sex hormones and a supplementary system driven by
male-speciﬁc proteins under direct genetic control.
Several lines of research support the plausibility of the maternal immune hypothesis.
To begin with, fetal cells and fetal molecular material have been found in maternal
circulation during early pregnancy and postpartum, a phenomenon called microchimerism
(Lo et al.,1996;O’Donoghue et al., 2004; Gammil et al., 2010). Further evidence points
to a speciﬁc T-cell-mediated immune response towards antigens arisen from the
Y-chromosome, called male antigens (HY) (Piper et al., 2007; Khan & Baltimore, 2010;
Lissauer et al., 2012; Dierselhuis et al., 2014) as well as polymorphisms to minor
histocompatibility complexes (Christiansen et al., 2012), which might play a signiﬁcant
role in the maternal immune response to male fetuses. Additional evidence shows higher
prevalence of male fetus miscarriages in women with a supposedly more HY-reactive
528 D. P. VanderLaan et al.
HLA (Hiby et al., 2008; Nielsen et al., 2009), and the number of sons a woman has
throughout life has been associated with age-linked inﬂammation (Marttila et al., 2015),
thus providing further evidence of a male-speciﬁc maternal immune response.
In addition, the fraternal birth order effect does indeed appear to be prenatal in
origin. First, relatively low birth weight provides a marker of prenatal exposure to a
maternal immune response (for review, see VanderLaan et al., 2015) and androphilic
males who have older brothers exhibit lower birth weights (Blanchard & Ellis, 2001;
Blanchard et al., 2002; VanderLaan et al., 2015). Hence, even at the time of birth, there
seems to be a physical marker of sexual orientation (i.e. birth weight) that is related to
the number of older brothers. Second, Bogaert (2006) examined the association between
male sexual orientation and biological siblings (i.e. born from the same mother) and
non-biological siblings (i.e. adoptive, step or paternal half-siblings). Whether and how
long probands were reared with these siblings was also considered. Biological older
brothers signiﬁcantly predicted male sexual orientation regardless of whether or how
long probands were reared with these brothers. In contrast, the remaining sibling
categories, including non-biological older brothers, did not.
By virtue of suggesting that the fraternal birth order effect is prenatal in origin, the
maternal immune hypothesis posits mechanisms that have the potential to operate in any
situation where a mother gestates a male fetus in more than one pregnancy. As such, one
would predict the fraternal birth order effect to be nearly ubiquitous –with the exception
of populations where people do not have older brothers (e.g. China: Xu & Zheng, 2015).
One approach for establishing the ubiquity of this effect has been to examine a variety of
sample types. To date, the fraternal birth order effect has been documented in university
and community convenience samples, national probability samples, clinical samples of
male-to-female transsexuals, clinical samples of men who are primarily attracted to
prepubescent or pubescent children, clinical samples of natal male children and
adolescents who are likely to be androphilic as adults, and archival samples of men
interviewed decades ago (for reviews, see Blanchard, 1997, 2004; Bogaert & Skorska,
2011; VanderLaan et al., 2014; Blanchard & VanderLaan, 2015). In addition, this effect
has been documented in several countries (e.g. Canada: Blanchard & Bogaert, 1996;
Italy: Camperio Ciani et al., 2004; The Netherlands: Schagen et al., 2012; Samoa:
VanderLaan & Vasey, 2011; Spain: Gómez-Gil et al., 2011; Turkey: Bozkurt et al., 2015;
UK: King et al., 2005; USA: Schwartz et al., 2010).
Despite the consistency with which the fraternal birth order effect has been observed,
there has been debate regarding its ubiquity and, by extension, the role of maternal
immune factors in the development of male sexual orientation. Some studies failed to
replicate this effect, raising scepticism about its importance (e.g. Currin et al., 2015;
Frisch & Hviid, 2006; Kashida & Rahman, 2015). Other research reported that
androphilic males show elevations in older brothers and older sisters, raising the
question of whether the male sexual orientation difference in birth order is speciﬁcto
older brothers (e.g. King et al., 2005).
Blanchard and VanderLaan (2015) addressed both of these challenges. First, their re-
analyses of the data presented by Frisch and Hviid (2006) and Kashida and Rahman
(2015), respectively, indicated that the fraternal birth effect was, in fact, evident in these
samples. Further, they noted that failures to replicate (Type II error) are to be expected
in some proportion of studies, as is the case with any true effect. Second, they explained
Birth order and transsexualism in Brazil 529
that number of older brothers tends to be correlated positively with number of older
sisters. Thus, although one would expect to observe older sister effects in some
proportion of samples, older sister effects should not be observed as consistently as older
brother effects. Indeed, Blanchard and VanderLaan (2015) presented a meta-analysis
showing that only the older brother effect was reliably associated with male sexual
orientation across previously published studies.
An additional means of continuing to evaluate the reliability and ubiquity of the fraternal
birth order effect is to examine birth order in relation to male sexual orientation in previously
unexamined populations. The present study did so by comparing numbers of older brothers
and numbers of other siblings in a sample of Brazilian male-to-female transsexuals who are
attracted to men vs a comparison group of non-transsexual gynephilic men.
Participants (N=261) were recruited at the Hospital de Clínicas de Porto Alegre
(HCPA) from 2008 to 2013. All male-to-female transsexual participants (n=118) were
at least 18 years of age and were patients of the Gender Identity Program (PROTIG)
who met the DSM-IV-TR criteria for Gender Identity Disorder (GID; American
Psychiatric Association, 2000). Prior to assessment by PROTIG, all had previously used
hormonal medications without medical guidance, but none had undergone sex-
reassignment surgery. Three individuals assessed by PROTIG were excluded from the
present study because they evidenced psychotic symptoms that limited the ability to
make an accurate diagnosis concerning GID. None had a disorder of sex development.
The comparison group of gynephilic men (n=143) consisted of medication-free
volunteers who had no current, past history, or ﬁrst-degree family history of a major
psychiatric disorder, dementia or mental retardation. The sample was collected from
non-psychiatric medical patients and companions at the outpatient clinics at HCPA,
aged 18 years old or greater.
Male-to-female transsexuals and men completed a questionnaire about their age,
year of birth and numbers of biological older and younger brothers and sisters from the
same biological mother. Information regarding the sexual orientation of transsexual
patients was obtained during semi-structured interviews with a psychiatrist (patients
attended group and/or individual medical appointments on a biweekly basis). On the
basis of this clinical information, all transsexuals were categorized as sexually attracted
towards men. For the comparison group of men, they were asked to self-report their
sexual orientation identity. All men self-reported a heterosexual sexual orientation
identity (i.e. gynephilia, sexual attraction towards women).
This research was approved by the institutional research ethics review board at the
Hospital de Clínicas de Porto Alegre (HCPA).
530 D. P. VanderLaan et al.
Table 1 shows descriptive statistics regarding age, year of birth and numbers of older
brothers and other siblings by group. Male-to-female transsexuals were signiﬁcantly
younger (Levene’s test for equality of variances: F=35.53, p<0.001, two-tailed
independent samples t-test, t(231.71) =−5.48, p<0.001) and had signiﬁcantly later years
of birth (Levene’s test for equality of variances: F=39.18, p<0.001, two-tailed
independent samples t-test, t(227.64) =3.54, p<0.001). The correlation between age and
year of birth was near perfect (two-tailed Pearson’sr=−0.99, p<0.001), indicating that
these variables were redundant with respect to the information they provided. As such, only
age was retained as a control variable when comparing groups on sibship composition.
Table 2 summarizes the results of a logistic regression examining group differences in
sibship composition. Group membership was the criterion variable with the male-to-
female transsexuals coded as 1 and the control men coded as 0. Predictors in the model
included: age, number of older brothers, number of other siblings, the interaction
between age and number of older brothers, and the interaction between age and number
of other siblings. All predictors were ﬁrst centred to reduce multicollinearity and then
entered in the model simultaneously to identify the unique contribution of each variable
to predicting group membership (i.e. male-to-female transsexuals vs men). Male-to-
female transsexuals had signiﬁcantly more older brothers and signiﬁcantly more other
siblings. In addition, there was a signiﬁcant interaction between age and number of other
siblings such that probands in the present sample who were younger and had larger
numbers of other siblings were more likely to be male-to-female transsexuals.
Table 1. Descriptive statistics
Mean SD Mean SD
Age 30.14 8.28 38.02 14.58
Year of birth 1980.02 7.99 1974.98 14.58
Number of older brothers 0.92 1.21 0.74 0.99
Number of other siblings
2.18 1.80 1.98 1.79
Number of older sisters + younger brothers + younger sisters.
Table 2. Logistic regression predicting group membership
Predictor BSE Wald’sχ
(df =1) p-value Odds ratio
Age −0.073 0.014 26.02 <0.001 0.93
Number of older brothers 0.277 0.126 4.86 0.028 1.32
Number of other siblings
0.221 0.091 5.94 0.015 1.25
Age × number of older brothers 0.018 0.013 1.99 0.158 1.02
Age × number of other siblings −0.022 0.009 6.26 0.012 0.98
Group is the criterion variable with men coded as 0 and male-to-female transsexuals coded as 1.
Number of older sisters + younger brothers + younger sisters.
Birth order and transsexualism in Brazil 531
The present study examined the fraternal birth order effect in Brazil, a previously
unexamined population. Consistent with the maternal immune hypothesis and
numerous previous studies conducted in other populations, Brazilian male-to-female
transsexuals who reported sexual attraction towards men had signiﬁcantly greater
numbers of older brothers than a comparison group of gynephilic non-transsexual men.
Importantly, this effect was independent of numbers of other siblings, thus providing
further evidence of the unique contribution of older brothers to the development of
same-sex sexual orientation among males.
In addition to documenting the fraternal birth order effect in the present sample, the
odds ratio associated with this effect is noteworthy. Each additional older brother increased
the odds of being in the male-to-female transsexual group by 32% (see Table 2). This value
falls in the middle of the range of 15–50% reported previously (Blanchard & Bogaert, 1996;
Blanchard et al., 1998; Blanchard & Lippa, 2007) and is remarkably similar to the values of
33% reported for a Canadian sample (Cantor et al., 2002) and 34% reported for a Samoan
sample (VanderLaan & Vasey, 2011). Thus, across diverse populations, the fraternal birth
order effect has been documented and each additional older brother contributes similarly to
the odds of developing an androphilic sexual orientation in natal males. These patterns are
consistent with the maternal immune hypothesis and suggest that the inﬂuence of older
brothers on male sexual orientation development is ubiquitous.
It is less clear, however, whether older brothers, via maternal immune mechanisms,
have a more general inﬂuence on male psychosexual development that includes the
domains of gender behaviour and identity in addition to sexual orientation. Gay men
tend to exhibit elevated cross-gender behaviour and identity during childhood (Bailey &
Zucker, 1995; Rieger et al., 2008) and report some female-typical characteristics during
adulthood (for review, see Lippa, 2005). Also, as was the case with the present study,
many studies documenting the fraternal birth order effect examined samples of natal
males who exhibited marked cross-gender behaviour and identity (for review, see
VanderLaan et al., 2014). As such, some have suggested that fraternal birth order may
not only relate to sexual orientation, but also to female-typical gender expression and
identity, among androphilic natal males (Wampold, 2013; VanderLaan et al., 2015).
To date, data bearing on this issue are limited. Two studies did not ﬁnd associations
between numbers of older brothers and female-typical characteristics among gay men
(Bogaert, 2003; Rahman, 2005; although see VanderLaan et al., 2015, for recent insights
into why these studies may have not found such an effect). In four other studies, there
was no fraternal birth order effect among clinical samples of natal males who exhibited
marked cross-gender behaviour and identity but did not report predominant sexual
attraction towards males (Blanchard & Sheridan, 1992; Blanchard et al., 1996; Green,
2000; VanderLaan et al., 2014). Thus, although further data are needed to address this
issue, it appears that if the fraternal birth order effect and maternal immune hypothesis
apply to variation in natal male gender expression as well as sexual orientation, then
they probably only apply to natal males who exhibit both cross-gender characteristics
and androphilic sexual orientation.
Apart from an older brother effect, two additional effects were observed in the
present study. First, male-to-female transsexuals had greater numbers of siblings other
532 D. P. VanderLaan et al.
than older brothers. It is important to note that this effect was independent of the older
brother effect discussed above. Furthermore, it is not uncommon for other sibling
category effects to be observed in studies of birth order and male sexual orientation,
although they are observed with less regularity than older brother effects (for review, see
Blanchard & VanderLaan, 2015). As such, the presence of the other sibling effect in the
present sample (Table 2) is not inconsistent with research on this topic, the fraternal
birth order effect or the maternal immune hypothesis. Second, there was an interaction
between age and number of other siblings in the prediction of group such that the
transsexual probands were more likely to be younger and to have more other siblings.
Such a ﬁnding has not been reported in the literature previously and there is no a priori
reason to expect such a pattern. Unless this pattern is replicated in future studies, the
most reasonable explanation is that this interaction effect was due to some form of
sampling bias and is, therefore, unlikely to be theoretically meaningful.
DPV was supported by a Canadian Institutes of Health Research Postdoctoral
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