Low Perinatal Androgens Predict Recalled Childhood Gender Nonconformity in Men.

The contributions of gonadal hormones to the development of human behavioral sex differences are subjects of intense scientific and social interest. Isolated gonadotropin-releasing-hormone deficiency (IGD) is a rare endocrine disorder that can reveal a possible role of early gonadal hormones. IGD is characterized by low or absent gonadal hormone production after the first trimester of gestation, but external genitalia and hence gender of rearing are concordant with chromosomal and gonadal sex. We investigated recalled childhood gender nonconformity in men (n = 65) and women (n = 32) with IGD and typically developing men (n = 463) and women (n = 1,207). Men with IGD showed elevated childhood gender nonconformity, particularly if they also reported undescended testes at birth, a marker of low perinatal androgens. Women with IGD did not differ from typically developing women. These results indicate that early androgen exposure after the first trimester contributes to male-typical gender-role behaviors in childhood.

Evidence that perinatal ovarian hormones promote women's sexual attraction to men.

Ovarian estrogens may influence the development of the human brain and behavior, but there are few opportunities to test this possibility. Isolated GnRH deficiency (IGD) is a rare endocrine disorder that could provide evidence for the role of estrogens in organizing sexually differentiated phenotypes: Unlike typical development, development in individuals with IGD is characterized by low or absent gonadal hormone production after the first trimester of gestation. Because external genitalia develop in the first trimester, external appearance is nevertheless concordant with gonadal sex in people with IGD. We therefore investigated the effects of gonadal hormones on sexual orientation by comparing participants with IGD (n = 97) to controls (n = 1670). Women with IGD reported lower male-attraction compared with typically developing women. In contrast, no consistent sexuality differences between IGD and typically developing men were evident. Ovarian hormones after the first trimester appear to influence female-typical dimensions of sexual orientation.

Relationships between ovarian hormone concentrations and mental rotations performance in naturally-cycling women.

Circulating gonadal hormones have been linked to variation in the structure and function of the adult human brain, raising the question of how cognition is affected by sex hormones in adulthood. The impacts of progestogens and estrogens are of special interest due to the widespread use of hormone supplementation. Multiple studies have analyzed relationships between ovarian hormones and mental rotation performance, one of the largest known cognitive sex differences; however, results are conflicting. These discrepancies are likely due in part to modest sample sizes and reliance on self-report measures to assess menstrual cycle phase. The present study aimed to clarify the impact of progestogens and estrogens on visuospatial cognition by relating mental rotation task performance to salivary hormone concentrations. Across two studies totaling 528 naturally-cycling premenopausal women, an internal meta-analysis suggested a small, positive effect of within-subjects changes in progesterone on MRT performance (estimate = 0.44, p = 0.014), though this result should be interpreted with caution given multiple statistical analyses. Between-subjects differences and within-subject changes in estradiol did not significantly predict MRT. These results shed light on the potential cognitive effects of endogenous and exogenous hormone action, and the proximate mechanisms modulating spatial cognition.

Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.

Timing of peripubertal steroid exposure predicts visuospatial cognition in men: Evidence from three samples.

Experiments in male rodents demonstrate that sensitivity to the organizational effects of steroid hormones decreases across the pubertal window, with earlier androgen exposure leading to greater masculinization of the brain and behavior. Similarly, some research suggests the timing of peripubertal exposure to sex steroids influences aspects of human psychology, including visuospatial cognition. However, prior studies have been limited by small samples and/or imprecise measures of pubertal timing. We conducted 4 studies to clarify whether the timing of peripubertal hormone exposure predicts performance on male-typed tests of spatial cognition in adulthood. In Studies 1 (n = 1095) and 2 (n = 173), we investigated associations between recalled pubertal age and spatial cognition in typically developing men, controlling for current testosterone levels in Study 2. In Study 3 (n = 51), we examined the relationship between spatial performance and the age at which peripubertal hormone replacement therapy was initiated in a sample of men with Isolated GnRH Deficiency. Across Studies 1-3, effect size estimates for the relationship between spatial performance and pubertal timing ranged from. -0.04 and -0.27, and spatial performance was unrelated to salivary testosterone in Study 2. In Study 4, we conducted two meta-analyses of Studies 1-3 and four previously published studies. The first meta-analysis was conducted on correlations between spatial performance and measures of the absolute age of pubertal timing, and the second replaced those correlations with correlations between spatial performance and measures of relative pubertal timing where available. Point estimates for correlations between pubertal timing and spatial cognition were -0.15 and -0.12 (both p < 0.001) in the first and second meta-analyses, respectively. These associations were robust to the exclusion of any individual study. Our results suggest that, for some aspects of neural development, sensitivity to gonadal hormones declines across puberty, with earlier pubertal hormone exposure predicting greater sex-typicality in psychological phenotypes in adulthood. These results shed light on the processes of behavioral and brain organization and have implications for the treatment of IGD and other conditions wherein pubertal timing is pharmacologically manipulated.