Prenatal oestrogen-testosterone balance as a risk factor of migraine in adults

Background Migraine is a common neurological disease with extremely debilitating, but fully reversible symptoms. Women suffer from migraine more often than men. It was assumed that fluctuation of oestrogen level during menstrual cycle is one of many factors responsible for more frequent migraine attacks. The second-to-fourth digit ratio (2D:4D) is considered as an indicator of prenatal sex steroids. Balance of prenatal androgens (testosterone) and oestrogen has been studied in numerous diseases that are affected by hormones. However, the relationship between migraine and the sex steroids balance in prenatal development is still unexplained. The aim of this paper is to provide an evidence of relationship between prenatal oestrogen and testosterone exposure following 2D:4D digit ratio, and migraine prevalence in adults. Methods We examined a group of 151 adults (33 males, 118 females) with migraine and a control group of 111 adults (45 males, 66 females). 2D:4D digit ratio of both hands was measured using sliding Vernier calliper. Results Significant differences were found in the right hand. Female migraineurs had lower value of 2D:4D ratio than the control group and the right 2D:4D was lower than left 2D:4D (Δ2D:4D), suggesting prenatal testosterone dominance. The opposite relationship was observed in males. Male migraineurs had higher value of 2D:4D ratio and Δ2D:4D was greater than the control group, suggesting prenatal oestrogen dominance. Conclusions Our results suggest that depending on sex, different proportion of prenatal sex steroids might be a risk factor of migraine in adults. Women with migraine were presumably exposed in prenatal life to higher testosterone levels relative to oestrogen, while men with migraine were probably exposed in prenatal life to higher levels of oestrogen relative to testosterone.

Sexual Orientation, Sexual Arousal, and Finger Length Ratios in Women

In general, women show physiological sexual arousal to both sexes. However, compared with heterosexual women, homosexual women are more aroused to their preferred sex, a pattern typically found in men. We hypothesized that homosexual women’s male-typical arousal is due to their sex-atypical masculinization during prenatal development. We measured the sexual responses of 199 women (including 67 homosexual women) via their genital arousal and pupil dilation to female and male sexual stimuli. Our main marker of masculinization was the ratio of the index to ring finger, which we expected to be lower (a masculine pattern) in homosexual women due to increased levels of prenatal androgens. We further measured observer- and self-ratings of psychological masculinity–femininity as possible proxies of prenatal androgenization. Homosexual women responded more strongly to female stimuli than male stimuli and therefore had more male-typical sexual responses than heterosexual women. However, they did not have more male-typical digit ratios, even though this difference became stronger if analyses were restricted to white participants. Still, variation in women's digit ratios did not account for the link between their sexual orientation and their male-typical sexual responses. Furthermore, homosexual women reported and displayed more masculinity than heterosexual women, but their masculinity was not associated with their male-typical sexual arousal. Thus, women’s sexual and behavioral traits, and potential anatomical traits, are possibly masculinized at different stages of gestation.

A study of second to fourth digit ratio in relation to verbal and numerical intelligence among medical students

Introduction and Aim: Prenatal androgens are believed to be one of the probable etiological factors influencing intellectual development of an individual. In-utero testosterone exposure has been thought to affect the digit ratio which is the ratio of lengths of index finger and ring finger (2D:4D). In the present work we intended to study the correlation of 2D:4D with numerical and verbal intelligence believed to be variable among genders. The aim of our study was to find the association of 2D:4D with Verbal Intelligence and Numerical Intelligence in a sample of medical students. Materials and Methods: This study was conducted in a sample of medical students. 44 female and 44 male students participated in the study. 2D:4D measurements were made using standard procedure after which the participants completed a questionnaire containing 20 questions each to test numerical and verbal intelligence. Results: In this study, Males were found to have a lower 2D:4D when compared to females. Individuals with lower 2D:4D in their right-hand were seen to have lower verbal intelligence and higher numerical intelligence thus suggesting that males are born with better numerical intelligence and females with greater verbal intelligence. Conclusion: Digit ratio can be considered as a valuable indicator of individual differences in terms of intelligence, although the exact role of testosterone on brain to cause variation in these cognitive domains is yet to be clearly understood.

Evidence and Implications From a Natural Experiment of Prenatal Androgen Effects on Gendered Behavior

Sex and gender are key to people’s lives, and are the focus of scientific and popular interest and controversy. Sex-related psychological characteristics reflect more than socialization; they are influenced by sex hormones present during sensitive periods of development, particularly androgens that are present prenatally. Studies of females with congenital adrenal hyperplasia (CAH) show how prenatal androgens affect behavior across the life span; these hormones have large effects on interest and engagement in gendered activities, moderate effects on spatial abilities, and relatively small (or no) effects on gender identity, gender cognitions, and gendered peer involvement. In addition to showing the complexity of androgens’ effects on gendered behavior, studies of females with CAH provide an opportunity to test theories of gender development, gain insight into how nature and nurture work together, and examine mechanisms of development. The implications of this work have often been misunderstood, so we consider what it means—and does not mean—for biology to influence gender-related behavior.

Differences in digit ratios between gay men who prefer receptive versus insertive sex roles indicate a role for prenatal androgen

Among non-human mammals, exposure to androgens during critical periods of development leads to gynephilia (attraction to females), whereas the absence or low levels of prenatal androgens leads to androphilia (attraction to males). However, in humans, retrospective markers of prenatal androgens have only been associated with gynephilia among women, but not with androphilia among men. Here, we asked whether an indirect indication of prenatal androgen exposure, 2D:4D, differs between subsets of gay men delineated by anal sex role (ASR). ASR was used as a proxy for subgroups because ASR groups tend to differ in other measures affected by brain sexual differentiation, such as gender conformity. First, we replicated the finding that gay men with a receptive ASR preference (bottoms) report greater gender nonconformity (GNC) compared to gay men with an insertive ASR preference (tops). We then found that Tops have a lower (male-typical) average right-hand digit ratio than Bottoms, and that among all gay men the right-hand 2D:4D correlated with GNC, indicating that a higher (female-typical) 2D:4D is associated with increased GNC. Differences were found between non-exclusive and exclusive same-sex attraction and GNC, and ASR group differences on digit ratios do not reach significance when all non-heterosexual men are included in the analyses, suggesting greater heterogeneity in the development of non-exclusive same-sex sexual orientations. Overall, results support a role for prenatal androgens, as approximated by digit ratios, in influencing the sexual orientation and GNC of a subset of gay men.

Neuroendocrine Influences on Human Sexuality

While prenatal sex hormones guide the development of sex-typical reproductive structures, they also act on the developing brain, resulting in sex differences in brain and behavior in animal models. Stemming from this literature is the prominent hypothesis that prenatal neuroendocrine factors underlie sex differences in human sexual orientation, to explain why most males have a preference for female sexual partners (gynephilia), whereas most females display a preference for male sexual partners (androphilia). Convergent evidence from experiments of nature and indirect markers of prenatal hormones strongly support a role for prenatal androgens in same-same sexual orientations in women, although this finding is specific to a subset of lesbians who are also gender nonconforming (“butch”). More gender-conforming lesbians (“femmes”) do not show evidence of increased prenatal androgens. The literature has been more mixed for male sexual orientation: some report evidence of low prenatal androgen exposure, while others report evidence of high androgen levels and many other studies find no support for a role of prenatal androgen exposure in the development of androphilia in males. Recent evidence suggests there may be subgroups of gay men who owe their sexual orientation to distinct biodevelopmental mechanisms, which could account for these mixed findings. Although this research is young, it is similar to findings from lesbian populations, because gay men who are more gender nonconforming, and report a preference for receptive anal sex, differ on markers of prenatal development from gay men who are more gender conforming and report a preference for insertive anal sex. This chapter concludes with future research avenues including assessing whether multiple biodevelopmental pathways underlie sexual orientation and whether neuroendocrine factors and other biological mechanisms (e.g., immunology, genetics) interact to promote a same-sex sexual orientation.