ArticlePDF Available

BIRTH ORDER AND ANDROPHILIC MALE-TO-FEMALE TRANSSEXUALISM IN BRAZIL

November 2016
Journal of Biosocial Science 49(4):1-10

DOI:10.1017/S0021932016000584

Authors:

Doug P. Vanderlaan

University of Toronto

Ray Blanchard

University of Toronto

Kenneth J. Zucker

University of Toronto

Raffael Massuda

Federal University of Paraná

Show all 13 authorsHide

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 antigens, 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 identity service in southern Brazil ( n= 118) and a comparison group of gynephilic 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 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 androphilic sexual orientation in some male-to-female transsexuals.

. Descriptive statistics

…

. Logistic regression predicting group membership

…

Figures - uploaded by Kenneth J. Zucker

Content may be subject to copyright.

Content uploaded by Kenneth J. Zucker

Content may be subject to copyright.

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

MALE-TO-FEMALE TRANSSEXUALISM

IN BRAZIL

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: doug.vanderlaan@utoronto.ca

527

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

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.

Introduction

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.

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

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

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

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.

Methods

Participants

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.

Measures

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).

Ethics statement

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.

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

Results

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

Male-to-female transsexuals

(n=118)

Gynephilic men

(n=143)

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

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

Discussion

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.

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

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.

Acknowledgments

DPV was supported by a Canadian Institutes of Health Research Postdoctoral

Fellowship and by the University of Toronto Mississauga.

References

American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders,

4th edition. American Psychiatric Association, Washington, DC.

Bailey, J. M. & Zucker, K. J. (1995) Childhood sex-typed behavior and sexual orientation: a

conceptual analysis and quantitative review. Developmental Psychology 31,43–55.

Blanchard, R. (1997) Birth order and sibling sex ratio in homosexual versus heterosexual males

and females. Annual Review of Sex Research 8,27–67.

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. (2008) Review and theory of handedness, birth order, and homosexuality in men.

Laterality: Asymmetries of Body, Brain and Cognition 13,51–70.

Blanchard, R. (2014) Detecting and correcting for family size differences in the study of sexual

orientation and fraternal birth order. Archives of Sexual Behavior 43, 845–852.

Blanchard, R. & Bogaert, A. F. (1996) Biodemographic comparisons of homosexual and hetero-

sexual men in the Kinsey interview data. Archives of Sexual Behavior 25, 551–579.

Blanchard, R. & Ellis, L. (2001) Birth weight, sexual orientation and the sex of preceding siblings.

Journal of Biosocial Science 33, 451–467.

Blanchard, R. & Lippa, R. A. (2007) Birth order, sibling sex ratio, handedness, and sexual

orientation of male and female participants in a BBC Internet research project. Archives of

Sexual Behavior 36, 163–176.

Blanchard, R. & Sheridan, P. M. (1992) Sibship size, sibling sex ratio, birth order, and parental age

in homosexual and nonhomosexual gender dysphorics. Journal of Nervous and Mental Disease

180,40–47.

Blanchard, R. & VanderLaan, D. P. (2015) Commentary on Kishida and Rahman (2015),

including a meta-analysis of relevant studies on fraternal birth order and sexual orientation in

men. Archives of Sexual Behavior 44, 1503–1509.

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.

Birth order and transsexualism in Brazil 533

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

Blanchard, R., Zucker, K. J., Cohen-Kettenis, P. T., Gooren, L. J. & 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.

Blanchard, R., Zucker, K. J., Siegelman, M., Dickey, R. & Klassen, P. (1998) The relation of birth

order to sexual orientation in men and women. Journal of Biosocial Science 30, 511–519.

Blanco, P., Sargent, C. A., Boucher, C. A., Mitchell, M. & Affara, N. A. (2000) Conservation of

PCDHX in mammals; expression of human X/Y genes predominantly in brain. Mammalian

Genome 11, 906–914.

Bogaert, A. F. (2003) Interaction of older brothers and sex-typing in the prediction of sexual

orientation in men. Archives of Sexual Behavior 32, 129–134.

Bogaert, A. F. (2006) Biological versus nonbiological older brothers and men’s sexual orientation.

Proceedings of the National Academy of Sciences of the USA 103, 10771–10774.

Bogaert, A. F. & Skorska, M. (2011) Sexual orientation, fraternal birth order, and the maternal

immune hypothesis: a review. Frontiers in Neuroendocrinology 32, 247–254.

Bozkurt, A., Bozkurt, O. H. & Sonmez, I. (2015) Birth order and sibling sex ratio in a population

with high fertility: are Turkish male-to-female transsexuals different? Archives of Sexual

Behavior 44, 1331–1337.

Camperio Ciani, A., Corna, F. & Capiluppi, C. (2004) Evidence for maternally inherited factors

favoring male homosexuality and promoting female fecundity. Proceedings of the Royal Society

of London, Series B: Biological Sciences 271, 2217–2221.

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 31,63–71.

Christiansen, O. B., Kolte, A. M., Dahl, M., Larsen, E. C., Steffensen, R., Nielsen, H. S. & Hviid, T. V.

(2012) Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene

and carriage of HLA class II alleles restricting HY immunity predispose to unexplained

secondary recurrent miscarriage and low birth weight in children born to these patients. Human

Immunology 73, 699–705.

Currin, J. M., Gibson, L. & Hubach, R. D. (2015) Multidimensional assessment of sexual

orientation and the fraternal birth order effect. Psychology of Sexual Orientation and Gender

Diversity 2, 113–122.

Dierselhuis, M. P., Jankowska-Gan, E., Blokland, E., Pool, J., Burlingham, W. J., van Halteren, A. G. S.

& Goulmy, E. (2014) HY immune tolerance is common in women without male offspring. PLoS

One 9, e91274.

Frisch, M. & Hviid, A. (2006) Childhood family correlates of heterosexual and homosexual

marriages: a national cohort study of two million Danes. Archives of Sexual Behavior 35,

533–547.

Gammil, H. S., Guthrie, K. A., Ayedelotte, T. M., Adams Waldorf, K. M. & Nelson, J. L. (2010)

Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host? Blood

116, 2706–2712.

Gómez-Gil, E., Esteva, I., Carrasco, R., Cruz Almaraz, M., Pasaro, E., Salamero, M. & Guillamon, A.

(2011) Birth order and ratio of brothers to sisters in Spanish transsexuals. Archives of Sexual

Behavior 40, 505–510.

Green, R. (2000) Birth order and ratio of brothers to sisters in transsexuals. Psychological Medicine

30, 789–795.

Hiby, S. E., Regan, L., Lo, W., Farrell, L., Carrington, M. & Moffett, A. (2008) Association

of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotyoes with

recurrent miscarriages. Human Reproduction 23, 972–976.

Jamain, S., Quach, H., Betancur, C., Rastam, M., Colineaux, C., Gillberg, I. C. et al.(2003)

Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated

with autism. Nature Genetics 34,27–29.

534 D. P. VanderLaan et al.

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

Khan, D. A. & Baltimore, D. (2010) Pregnancy induces a fetal antigen-speciﬁc maternal T

regulatory response that contributes to tolerance. Proceedings of the National Academy of

Sciences of the USA 107, 9299–9304.

King, M. D., Green, J., Osborn, D. P. J., Arkell, J., Hetherton, J. & Pereira, E. (2005) Family size

in white gay and heterosexual men. Archives of Sexual Behavior 34, 117–122.

Kishida, M. & Rahman, Q. (2015) Fraternal birth order and extreme right-handedness as predictors of

sexual orientation and gender nonconformity in men. Archives of Sexual Behavior 44, 1493–1501.

Lippa, R. A. (2005) Sexual orientation and personality. Annual Review of Sex Research 16,119–153.

Lissauer, D., Piper, K., Goodyear, O., Kilby, M. D. & Moss, P. A. H. (2012) Fetal-speciﬁc CD8+

cytotoxic T cell response develop during normal human pregnancy and exhibit broad functional

capacity. Journal of Immunology 189, 1072–1080.

Lo, Y. M., Lo, E. S., Watson, N., Noakes, L., Sargent, I. L., Thilaganathan, B. & Wainscoat, J. S.

(1996) Two-way cell trafﬁc between mother and fetus: biologic and clinical implications. Blood

88, 4390–4395.

Marttila, S., Nevalainen, T., Kananen, L., Jylhävä, J., Jylhä, M., Hervonen, A., Ilonen, J. &

Hurme, M. (2015) Number of sons contributes to ageing-associated inﬂammation. Scientiﬁc

Reports 5, 8631.

Nielsen, H. S., Steffensen, R., Varming, K., Van Hakteren, A. G. S., Spierings, E., Ryder, L. P.

et al.(2009) Association between HY-restricting HLA class II alleles with pregnancy outcome in

patients with recurrent miscarriage subsequent to a ﬁrstborn boy. Human Molecular Genetics 18,

1684–1691.

O’Donoghue, K., Chan, J., de la Fuente, J., Kenna, N., Sandison, A., Anderson, J. R. et al.(2004)

Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell

trafﬁcking in pregnancy. Lancet 364, 179–182.

Piper, K. P., McLarnon, A., Arrazi, J., Horlock, C., Ainsworth, J., Killby, M. D. et al.(2007)

Functional HY-speciﬁc CD8 + T cells are found in a high proportion of women following

pregnancy with a male fetus. Biology of Reproduction 76,96–101.

Rahman, Q. (2005) The association between the fraternal birth order effect in male homosexuality

and other markers of human sexual orientation. Biology Letters 1, 393–395.

Rieger, G., Linsenmeier, J. A., Gygax, L. & Bailey, J. M. (2008) Sexual orientation and gender

nonconformity: evidence from home videos. Developmental Psychology 44,46–58.

Schagen, S. E. E., Delemarre-van de Waal, H. A., Blanchard, R. & Cohen-Kettenis, P. T. (2012)

Sibling sex ratio and birth order in early-onset gender dysphoric adolescents. Archives of Sexual

Behavior 41, 541–549.

Schwartz, G., Kim, R. M., Kolundzija, A. B., Rieger, G. & Sanders, A. R. (2010) Biodemographic

and physical correlates of sexual orientation in men. Archives of Sexual Behavior 39,93–109.

VanderLaan, D. P., Blanchard, R., Wood, H., Garzon, L. & Zucker, K. J. (2015) Birth weight

and two possible types of maternal effects on male sexual orientation: a clinical study of children

and adolescents referred to a Gender Identity Service. Developmental Psychobiology 57,25–34.

VanderLaan, D. P., Blanchard, R., Wood, H. & Zucker, K. J. (2014) Birth order and sibling sex

ratio of children and adolescents referred to a Gender Identity Service. PLoS One 9, e90257.

VanderLaan, D. P. & Vasey, P. L. (2011) Male sexual orientation in Independent Samoa: evidence

for fraternal birth order and maternal fecundity effects. Archives of Sexual Behavior 40,495–503.

Wampold, C. H. (2013) Redesigning fraternal birth order studies from top to bottom [Letter to the

Editor]. Archives of Sexual Behavior 42, 1387–1389.

Xu, Y. & Zheng, Y. (2015) Fraternal birth order, handedness, and sexual orientation in a Chinese

population. Journal of Sex Research. doi: 10.1080/00224499.2015.1104530.

Birth order and transsexualism in Brazil 535

https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0021932016000584

Downloaded from https:/www.cambridge.org/core. University of Toronto, on 01 Jun 2017 at 14:36:18, subject to the Cambridge Core terms of use, available at

Are Sibship Characteristics Predictive of Same Sex Marriage? An Examination of Fraternal Birth Order and Female Fecundity Effects in Population-level Administrative Data from the Netherlands

Article

Full-text available

Jan 2022

Despite historical increases in the number of individuals engaging in same-sex relations and entering same-sex unions, the causes of sexual orientation remain an open question. Two biological processes that have received some degree of empirical validation are the fraternal birth-order effect (FBOE) and the female-fecundity effect (FFE). Respectively, these processes posit that having a greater number of older brothers and being part of larger sibships independently increase the odds of male homosexuality. Nevertheless, previous studies have relied on suboptimal data and methods, including underpowered and selected samples, and models that fail to fully disentangle the two processes. In addition, they have rarely analyzed samples of women. We address these limitations using high-quality, population-level linked register data from the Netherlands (n = 9,073,496). Applying a novel multivariable approach, we jointly examine the FBOE and FFE by comparing the sibship characteristics of men (n = 26,542) and women (n = 33,534) who entered a same-sex union against those who did not (n = 4,607,785 men and 4,405,635 women). Our analyses yield robust evidence of an FBOE on both male and female homosexuality, but no support for the FFE. Additionally, we find that individuals’ birth order affects the probability of entering a same-sex union, regardless of the sex of older siblings.

Testing Fraternal Birth Order Effects and Antagonistic Effects for Homosexual Men: Power Comparison of Various Methods

Article

Full-text available

Mar 2024
ARCH SEX BEHAV

Research on the biological determinants of male homosexual preference has long realized that the older brother effect (FBOE, i.e., a higher fraternal birth rank of homosexuals) and the antagonist effect (AE, i.e., more fertile women have a higher chance of having a homosexual son) can both generate family data where homosexual men have more siblings and more older siblings than heterosexual men. Various statistical approaches were proposed in the recent literature to evaluate whether the action of FBOE or AE could be discriminated from empirical data, by controlling for the other effect. Here, we used simulated data to formally compare all the approaches that we could find in the relevant literature for their ability to reject the null hypothesis in the presence of a specified alternative hypothesis (tests based on regression, Bayesian modeling, or contingency tables). When testing for the FBOE, the relative performance of the different tests was different depending on the specific function generating the older brother effect. Even if no tests were found to always perform better than the others, some tests performed systematically poorly, and some tests displayed a systematic high rate of type-I error. For testing the AE, the relative performance of the tests was generally not changed across all parameter values assayed, providing a clear ranking of the various proposed approaches. Pros and cons for each candidate test are discussed, taking into consideration power and the rate of type-I error but also practicability, the possibility to control for confounding variables, and to consider alternative hypotheses.

Carving the Biodevelopment of Same-Sex Sexual Orientation at Its Joints

Article

Full-text available

Aug 2022
ARCH SEX BEHAV

Sexual orientation is a core aspect of human experience and understanding its development is fundamental to psychology as a scientific discipline. Biological perspectives have played an important role in uncovering the processes that contribute to sexual orientation development. Research in this field has relied on a variety of populations, including community, clinical, and cross-cultural samples, and has commonly focused on female gynephilia (i.e., female sexual attraction to adult females) and male androphilia (i.e., male sexual attraction to adult males). Genetic, hormonal, and immunological processes all appear to influence sexual orientation. Consistent with biological perspectives, there are sexual orientation differences in brain development and evidence indicates that similar biological influences apply across cultures. An outstanding question in the field is whether the hypothesized biological influences are all part of the same process or represent different developmental pathways leading to same-sex sexual orientation. Some studies indicate that same-sex sexually oriented people can be divided into subgroups who likely experienced different biological influences. Consideration of gender expression in addition to sexual orientation might help delineate such subgroups. Thus, future research on the possible existence of such subgroups could prove to be valuable for uncovering the biological development of sexual orientation. Recommendations for such future research are discussed.

Male androphilia, fraternal birth order, and female fecundity in Samoa: A 10-y retrospective

Article

Dec 2023
P NATL ACAD SCI USA

Two separate but related literatures have examined familial correlates of male androphilia (i.e., sexual attraction and arousal to masculine adult males). The fraternal birth order effect (FBOE) is a widely established finding that each biological older brother a male has increased the probability of androphilia 20–35% above baseline rates. Other family demographic variables, such as reproduction by mothers, maternal aunts, and grandmothers, have been used to test evolutionary hypotheses that sexually antagonistic genes lead to androphilia among males, lowering or eliminating reproduction, which is offset by greater reproductive output among their female relatives. These proposed female fecundity effects (FFEs), and the FBOE, have historically been treated as separate yet complementary ways to understand the development and evolution of male androphilia. However, this approach ignores a vital confound within the data. The high overall reproductive output indicative of an FFE results in similar statistical patterns as the FBOE, wherein women with high reproductive output subsequently produce later-born androphilic sons. Thus, examination of the FBOE requires analytic approaches capable of controlling for the FFE, and vice-versa. Here, we present data simultaneously examining the FBOE and FFE for male androphilia in a large dataset collected in Samoa across 10 y of fieldwork, which only shows evidence of the FBOE.

Hyperandrogenism-related metabolic changes in drug-naïve transmen compared to cisgender women: a case-controlled study

Article

Aug 2023

Introduction: The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded unselected populations. Our reason for performing this study is to evaluate trans men's hormone profile and metabolic status to compare with cisgender women in a more selected population. This is the first case-controlled study to compare anthropometric, metabolic, and endocrinological parameters of drug-naïve trans men with those of cisgender women. Material and methods: We designed this study as a single-centre observational cohort study. We included 70 drug naïve trans men, and the control group comprised 34 healthy cisgender women. We measured and compared hormone profiles and metabolic parameters in the 2 groups. Results: Of the 70 trans men individuals, 16 (22.85%) met the Rotterdam criteria and were diagnosed with polycystic ovary syndrome (PCOS); 4 individuals in the control group met the criteria (11.7%). Although we matched body mass index in the groups, total testosterone, free androgen index, androstenedione, 17 hydroxyprogesterone, muscle strength, triglyceride, and homeostatic model assessment of insulin resistance levels were significantly higher in the trans men than in the cisgender women (p < 0.05). Even after were excluded PCOS patients, hyperandrogenaemia was apparent in the trans men. Conclusion: Our study showed that trans men have clearly higher androgen levels, which may have been the reason for metabolic changes compared to cisgender women. However, the main reason for hyperandrogenism in drug-naïve trans men is still not known, and more comprehensive studies are needed.

Prevalence of Gender Dysphoria in Southern Brazil: A Retrospective Study

Article

Full-text available

Nov 2021
ARCH SEX BEHAV

To ensure that public health services provide comprehensive and inclusive health care to the general population, it is important for countries to estimate how many of their citizens experience gender dysphoria and wish to receive specialized hormone treatment or gender-affirming surgery. The aim of this study was to estimate the prevalence of individuals with gender dysphoria seeking transgender health care in a public teaching hospital in southern Brazil. In this retrospective follow-up study, we analyzed the medical records and sociodemographic data of individuals aged > 15 years living in Rio Grande do Sul, Brazil, that enrolled in a specialized program to receive hormone therapy and gender-affirming surgery between 2000 and 2018. This study is the first to attempt estimating the prevalence of gender dysphoria in Rio Grande do Sul; it describes novel data on the clinical profile of individuals with gender dysphoria treated in a public hospital specialized in providing transgender health care. Prevalence estimates were calculated based on statewide annual population data in the study period. Of 934 identified individuals, 776 (601 trans women and 175 trans men) were included in this study. The overall prevalence of individuals with gender dysphoria was 9.3 per 100,000 individuals (95% CI: 8.6 to 9.8). Meanwhile, there were 15 trans women per 100,000 people (95% CI: 14 to 16) and 4.1 trans men per 100,000 people (95% CI: 3.5 to 4.8). There was a progressive increase in the number of people seeking hormone therapy and gender-affirming surgery during the study period. Future research is needed to determine the size of the trans population in other regions of Brazil and to expand the knowledge regarding gender dysphoria to allow for the development of effective public policies for people with gender dysphoria.

Effect of birth order on stereoacuity in Chinese preschool children: a cross-sectional study

Article

Full-text available

Oct 2020

Objective This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60–72 months. Design Cross-sectional. Participants 1342 children with complete data on the questionnaire, stereoacuity and refraction were included. Results The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis. Conclusion Later-borns had poorer stereoacuity than first-borns.

The fraternal birth-order effect as a statistical artefact: convergent evidence from probability calculus, simulated data, and multiverse meta-analysis

Article

Aug 2023

The fraternal-birth order effect (FBOE) is a research claim which states that each older brother increases the odds of homosexual orientation in men via an immunoreactivity process known as the maternal immune hypothesis. Importantly, older sisters supposedly either do not affect these odds, or affect them to a lesser extent. Consequently, the fraternal birth-order effect predicts that the association between the number of older brothers and homosexual orientation in men is greater in magnitude than any association between the number of older sisters and homosexual orientation. This difference in magnitude represents the main theoretical estimand of the FBOE. In addition, no comparable effects should be observable among homosexual vs heterosexual women. Here, we triangulate the empirical foundations of the FBOE from three distinct, informative perspectives, complementing each other: first, drawing on basic probability calculus, we deduce mathematically that the body of statistical evidence used to make inferences about the main theoretical estimand of the FBOE rests on incorrect statistical reasoning. In particular, we show that throughout the literature researchers ascribe to the false assumptions that effects of family size should be adjusted for and that this could be achieved through the use of ratio variables. Second, using a data-simulation approach, we demonstrate that by using currently recommended statistical practices, researchers are bound to frequently draw incorrect conclusions. And third, we re-examine the empirical evidence of the fraternal birth-order effect in men and women by using a novel specification-curve and multiverse approach to meta-analysis (64 male and 17 female samples, N = 2,778,998). When analyzed correctly, the specific association between the number of older brothers and homosexual orientation is small, heterogenous in magnitude, and apparently not specific to men. In addition, existing research evidence seems to be exaggerated by small-study effects.

Carving the Biodevelopment of Same-Sex Sexual Orientation at Its Joints

Chapter

Aug 2022

Sexual orientation is a core aspect of human experience and understanding its development is fundamental to psychology as a scientific discipline. Biological perspectives have played an important role in helping to uncover the processes that contribute to sexual orientation development. Research in this field has relied on a variety of populations, including community, clinical, and cross-cultural samples, and has commonly focused on female gynephilia (i.e., female sexual attraction to adult females) and male androphilia (i.e., male sexual attraction to adult males). Genetic, hormonal, and immunological processes all appear to influence sexual orientation. Consistent with biological perspectives, there are sexual orientation differences in brain development and evidence indicates that similar biological influences apply across cultures. An outstanding question in the field is whether the hypothesized biological influences are all part of the same process or represent different developmental pathways leading to same-sex sexual orientation. Some studies indicate that same-sex sexually oriented people can be divided into subgroups who likely experienced different biological influences. Consideration of gender expression in addition to sexual orientation might help delineate such subgroups. Thus, future research on the possible existence of such subgroups could prove to be valuable for uncovering the biological development of sexual orientation. Recommendations for such future research are discussed.KeywordsSexual orientationDevelopmentGeneticsSex hormonesMaternal immune hypothesisGender expression

New Data on Birth Order in Homosexual Men and Women and a Reply to Vilsmeier et al. (2021a, 2021b)

Article

Full-text available

Jun 2022
ARCH SEX BEHAV

The fraternal birth order effect (FBOE) is the repeated finding that older brothers increase the odds of homosexuality in later-born males. It has been our working assumption, based on the majority of previous studies, that a similar FBOE does not occur in females. In an elaborate quantitative review posted last year to a preprint server, Vilsmeier et al. (2021a) concluded that there is no valid evidence for an FBOE in men or women. Ablaza et al. (2022) subsequently published a study of population-level data from the Netherlands with conclusions completely opposite to those of Vilsmeier et al., namely, that there is robust evidence of an FBOE in both men and women. The present research was initially undertaken to refute the assertion of Vilsmeier et al. that there is no proof of an FBOE in men and to investigate how they obtained such a discrepant conclusion. We found evidence that the discrepancy may relate to Vilsmeier et al.’s use of the large and demonstrably unreliable sample published by Frisch and Hviid (2006). After the publication by Ablaza et al., we expanded our article to address their finding of an FBOE in women. We argue that our preferred explanation of the FBOE in men—that it reflects the progressive immunization of some mothers to Y-linked antigen by each succeeding male fetus and the concomitantly increasing effects of anti-male antibody on sexual differentiation in the brain in each succeeding male fetus—could plausibly be extended to female homosexuality.

Fraternal Birth Order, Handedness, and Sexual Orientation in a Chinese Population

Article

Full-text available

Dec 2015

We examined the relationship between handedness, fraternal birth order, and sexual orientation in a Chinese population, and analyzed the influence of the components assessing sexual orientation and criteria classifying individuals as homosexual on this relationship. A large sample of heterosexual, bisexual, and homosexual men and women participated in a web-based survey. Our results showed that homosexual women are more likely to be non-right-handed than heterosexual women, regardless of how sexual orientation was defined, whereas bisexual women are more likely to be non-right-handed than heterosexual women when sexual orientation was assessed via sexual attraction and sexual identity. Bisexual men are more likely to be non-right-handed than heterosexual men when sexual orientation was assessed via sexual attraction. We found neither a fraternal birth-order effect nor an interaction between sibling sex ratio, handedness, and sexual orientation. The small number of siblings may be the reason why we could not replicate the fraternal birth-order effect in this Chinese population, which highlights the importance of cultural differences in the understanding of handedness, fraternal birth order, and sexual orientation.

Multidimensional Assessment of Sexual Orientation and the Fraternal Birth Order Effect

Article

Full-text available

Jun 2015

Previous research demonstrates that for every older male sibling a male child has, the odds are increased by 33% over the naturally occurring odds that he will be nonheterosexual. This concept is known as the Fraternal Birth Order Effect (FBOE). Although this finding has been duplicated in multiple studies, researchers have not used other dimensions of sexual orientation when measuring the presence of the FBOE. The present study measures the FBOE in a racially diverse sample of right-handed men using a multidimensional assessment of sexual orientation that measures self-identified sexual orientation, sexual behaviors, sexual attractions, and sexual fantasies. The current study did not find the presence of the FBOE using Slater’s Index, Berglin’s Index, or Blanchard’s Proportion in right-handed men regardless of being grouped by self-identified sexual orientation, sexual behaviors, sexual attractions, or sexual fantasies. Reasons for not observing a FBOE in the current data set are discussed and implications for future research are proposed.

Commentary on Kishida and Rahman (2015), Including a Meta-analysis of Relevant Studies on Fraternal Birth Order and Sexual Orientation in Men

Article

Full-text available

May 2015
ARCH SEX BEHAV

Number of sons contributes to ageing-associated inflammation

Article

Full-text available

Feb 2015

The rate of inflammation increases in elderly individuals, a phenomenon called inflammaging, and is associated with degenerative diseases. However, the causes of inflammaging and the origin of the associated inflammatory mediators have remained enigmatic. We show herein that there is a positive correlation between the number of sons born and C-reactive protein concentrations in 90-year-old women. This association is influenced by HLA genetics known to regulate the immune response against HY antigens.

Fraternal Birth Order and Extreme Right-Handedness as Predictors of Sexual Orientation and Gender Nonconformity in Men

Article

Full-text available

Feb 2015
ARCH SEX BEHAV

The present study explored whether there were relationships between number of older brothers, handedness, recalled childhood gender nonconformity (CGN), and sexual orientation in men. We used data from previous British studies conducted in our laboratory (N = 1,011 heterosexual men and 921 gay men). These men had completed measures of demographic variables, number and sex of siblings, CGN, and the Edinburgh Handedness Inventory. The results did not replicate the fraternal birth order effect. However, gay men had fewer "other siblings" than heterosexual men (even after controlling for the stopping-rule and family size). In a sub-sample (425 gay men and 478 heterosexual men) with data available on both sibling sex composition and handedness scores, gay men were found to show a significantly greater likelihood of extreme right-handedness and non-right-handedness compared to heterosexual men. There were no significant effects of sibling sex composition in this sub-sample. In a further sub-sample (N = 487) with data available on sibling sex composition, handedness, and CGN, we found that men with feminine scores on CGN were more extremely right-handed and had fewer other-siblings compared to masculine scoring men. Mediation analysis revealed that handedness was associated with sexual orientation directly and also indirectly through the mediating factor of CGN. We were unable to replicate the fraternal birth order effect in our archived dataset but there was evidence for a relationship among handedness, sexual orientation, and CGN. These data help narrow down the number of possible neurodevelopmental pathways leading to variations in male sexual orientation.

Birth Weight and Two Possible Types of Maternal Effects on Male Sexual Orientation: A Clinical Study of Children and Adolescents Referred to a Gender Identity Service

Article

Full-text available

Jan 2015
DEV PSYCHOBIOL

This study tested predictions regarding two hypothesized maternal immune responses influencing sexual orientation: one affecting homosexual males with high fraternal birth order and another affecting firstborn homosexual individuals whose mothers experience repeated miscarriage after the birth of the first child. Low birth weight was treated as a marker of possible exposure to a maternal immune response during gestation. Birth weight was examined relative to sibship characteristics in a clinical sample of youth (N = 1,722) classified as heterosexual or homosexual based on self-reported or probable sexual orientation. No female sexual orientation differences in birth weight were found. Homosexual, compared to heterosexual, males showed lower birth weight if they had one or more older brothers-and especially two or more older brothers-or if they were an only-child. These findings support the existence of two maternal immune responses influencing male sexual orientation and possibly also cross-gender behavior and identity. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.

Birth Order and Sibling Sex Ratio of Children and Adolescents Referred to a Gender Identity Service

Article

Full-text available

Mar 2014
PLOS ONE

In adult male samples, homosexuality is associated with a preponderance of older brothers (i.e., the fraternal birth order effect). In several studies comparing gender dysphoric youth, who are likely to be homosexual in adulthood, to clinical or non-clinical control groups, the findings have been consistent with the fraternal birth order effect in males; however, less is known about unique sibship characteristics of gender dysphoric females. The current study investigated birth order and sibling sex ratio in a large sample of children and adolescents referred to the same Gender Identity Service (N = 768). Probands were classified as heterosexual males, homosexual males, or homosexual females based on clinical diagnostic information. Groups differed significantly in age and sibship size, and homosexual females were significantly more likely to be only children. Subsequent analyses controlled for age and for sibship size. Compared to heterosexual males, homosexual males had a significant preponderance of older brothers and homosexual females had a significant preponderance of older sisters. Similarly, the older sibling sex ratio of homosexual males showed a significant excess of brothers whereas that of homosexual females showed a significant excess of sisters. Like previous studies of gender dysphoric youth and adults, these findings were consistent with the fraternal birth order effect. In addition, the greater frequency of only children and elevated numbers of older sisters among the homosexual female group adds to a small literature on sibship characteristics of potential relevance to the development of gender identity and sexual orientation in females.

Two-way cell traffic between mother and fetus: biologic and clinical implications

Article

Dec 1996

The bilateral trafficking of nucleated cells between the fetus and the mother was studied using polymerase chain reaction (PCR)-based systems sensitive enough to detect 1 target cell in 100,000 background cells. Sixty-six mother-baby pairs were recruited; maternal and cord blood samples were collected at delivery for DNA extraction. Cell trafficking was studied in informative cases using PCR-genotyping of polymorphic regions in the beta-globin cluster, the glutathione S-transferase M1 locus and the angiotensin converting enzyme gene. In addition, Y-PCR was also used in conjunction with these systems for the detection of fetal cells in maternal circulation. Fetal cells were detected in maternal peripheral blood in 26 of 51 cases whereas maternal cells were detected in 16 of 38 fetal umbilical cord blood samples. The proportion of umbilical samples with detectable maternal sequences was much higher than previously reported. In the 28 cases informative for both mother and baby, there was no obvious correlation between the cell traffic from mother to baby as compared to that from baby to mother. These findings may have implications for the use of cord blood for bone marrow transplantation, the vertical transmission of infectious agents, and the physiology of the feto-maternal relationship.

Birth Order and Sibling Sex Ratio in a Population with High Fertility: Are Turkish Male to Female Transsexuals Different?

Article

Oct 2014
ARCH SEX BEHAV

Western studies have consistently found that androphilic (sexually attracted to men) male-to-female transsexuals have a later birth order and a relative excess of brothers compared with appropriate control participants. However, non-Western studies on birth order and sibling sex ratio in androphilic males (transsexual or non-transsexual) are rare. The objective of the study was to test the hypothesis that androphilic male-to-female transsexuals have a late birth order and a relative excess of brothers in a non-Western culture with a higher fertility rate. The participants were 60 androphilic male-to-female transsexuals and 61 male heterosexual controls. The transsexual participants had significantly more older brothers than the control participants, but the groups did not differ in their numbers of older sisters, younger brothers, or younger sisters. The foregoing pattern is usually referred to as the "fraternal birth order effect." Slater's and Berglin's Indexes both showed that the mean birth order of the control participants was very close to that expected from a random sample drawn from a demographically stable population whereas the mean birth order of the transsexual participants was later. A measure of sibship composition, brothers/all siblings, showed that the transsexual group had a higher proportion of male siblings compared with the control group. In conclusion, the present study found that Turkish androphilic male-to-female transsexuals show the same high fraternal birth order that has been found in comparable androphilic samples in Western Europe, North America, and the South Pacific, which suggests a common underlying biological causal mechanism.

Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients

Article

Jan 2007

Homozygous carriage of a 14 base pair (bp) insertion in exon 8 of the HLA-G gene may be associated with low levels of soluble HLA-G and recurrent miscarriage (RM). We investigated the G14bp insertion(ins)/deletion(del) polymorphism in 339 women with unexplained RM and 125 control women. In all patients and patients with secondary RM after a firstborn boy, 19.2% and 23.9%, respectively, were G14bp ins/ins compared with 11.2% of controls (p<0.05 and p<0.01). Among secondary RM patients with a firstborn boy, G14bp del/del and no carriage of an HLA class II (HYrHLA) allele restricting immunity against male-specific minor HY antigens was found less often than in controls (p<0.05) whereas G14bp ins/ins and carriage of HYrHLA predisposed (p<0.08) to this clinical entity. The mean birth weight of firstborn boys born to G14bp ins positive secondary RM patients was significantly lower than expected (p<0.001) but only in carriers of HYrHLA alleles (p<0.01). In conclusion, homozygosity for G14bp ins predisposes to RM. The combination of G14 ins homozygosity and carriage of HYrHLA predisposes to secondary RM in women with a firstborn boy and negatively affects birth weight in these boys