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.

Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals.

BACKGROUND: Anti-Müllerian hormone has become the clinical biomarker-based standard to assess ovarian reserve. As anti-Müllerian hormone testing becomes more common, more individuals are seeking to interpret the values obtained while using contraceptives. To appropriately counsel women, a better understanding of anti-Müllerian hormone levels in women using different contraceptives is needed. OBJECTIVE: To study the association between different forms of contraceptives and anti-Müllerian levels in women of reproductive age. STUDY DESIGN: This is a cross-sectional study including 27,125 US-based women aged 20 to 46 years, accessing reproductive hormone results through Modern Fertility and who provided informed consent to participate in the research. Anti-Müllerian hormone levels were collected through dried blood spot card (95.9%) or venipuncture (4.1%), and previous work has shown high correlation between hormone levels collected by these 2 methods. Multiple linear regressions were run to compare anti-Müllerian hormone levels in women using contraceptives with women not on any contraceptive, controlling for age, age of menarche, body mass index, smoking, sample collection method, cycle day, and self-reported polycystic ovary syndrome diagnosis. We also analyzed whether duration of contraceptive use predicted anti-Müllerian hormone levels in users of the hormonal intrauterine device and combined oral contraceptive pill, given the size of these contraceptive groups. RESULTS: Mean anti-Müllerian hormone levels were statistically significantly lower in women using the combined oral contraceptive pill (23.68% lower; coefficient, 0.76; 95% confidence interval, 0.72-0.81; P<.001), vaginal ring (22.07% lower; coefficient, 0.78; 95% confidence interval, 0.71-0.86; P<.001), hormonal intrauterine device (6.73% lower; coefficient, 0.93; 95% confidence interval, 0.88-0.99; P=.014), implant (23.44% lower; coefficient, 0.77; 95% confidence interval, 0.69-0.85; P<.001), or progestin-only pill (14.80% lower; coefficient, 0.85; 95% confidence interval, 0.76-0.96; P=.007) than women not on any contraceptive when controlling for covariates. Anti-Müllerian hormone levels were not significantly different when comparing women not using any contraceptives to those using the copper intrauterine device (1.57% lower; coefficient, 0.98; 95% confidence interval, 0.92-1.05, P=.600). Associations between contraceptive use and anti-Müllerian hormone levels did not differ based on self-reported polycystic ovary syndrome diagnosis. Duration of hormonal intrauterine device use, but not of combined oral contraceptive pill use, was slightly positively associated with anti-Müllerian hormone levels, although this small magnitude effect is likely not clinically meaningful (coefficient, 1.002; 95% confidence interval, 1.0005-1.003; P=.007). CONCLUSION: Current hormonal contraceptive use is associated with a lower mean anti-Müllerian hormone level than that of women who are not on contraceptives, with variability in the percent difference across contraceptive methods. These data provide guidance for clinicians on how to interpret anti-Müllerian hormone levels assessed while on contraceptives and may facilitate more patients to continue contraceptive use while being evaluated for their ovarian reserve.

Reproductive Health Disparities in the USA: Self-Reported Race/Ethnicity Predicts Age of Menarche and Live Birth Ratios, but Not Infertility.

Self-identified race/ethnicity and socioeconomic status (SES) contribute to disparities in several health domains, although research on their effects on women's reproductive function has largely focused on links between SES and age of menarche. Here, we assessed whether race/ethnicity, SES, and downstream correlates of SES such as food security and health-insurance security are associated with age of menarche, infertility, and live birth ratios (ratios of recognized pregnancies resulting in live births) in the USA. We used cross-sectional data from 1694 women aged 12-18 years for menarche (2007-2016), 974 women aged 23-45 for infertility (2013-2016), and 1714 women aged 23-45 for live birth ratios (2007-2016) from the National Health and Nutrition Examination Survey. We estimated multiple linear and logistic regressions with survey weights to test these associations. When controlling for lifestyle (activity levels, smoking, alcohol consumption) and physiological factors (diabetes, weight status), non-Hispanic (NH) black and Hispanic girls reported a significantly lower age of menarche by about 4.3 (standard error [SE] = 0.08, p < 0.001), and 3.2 months (SE = 0.09, p < 0.001), respectively, relative to NH white girls. NH black women reported live birth ratios 9% (SE = 0.02, p < 0.001) lower than NH white women. Women with unstable health insurance reported live birth ratios 6% (SE = 0.02, p = 0.02) lower than women with stable health insurance. Race/ethnicity, SES, and its downstream correlates were not associated with infertility. One hypothesized explanation for observed disparities in age of menarche and live birth ratios is the embodiment of discrimination faced by NH black women within the USA. Our findings also underscore the importance of health insurance access for favorable reproductive health outcomes. Future work should elucidate the role of embodied discrimination and other downstream correlates of SES in modulating women's reproductive health outcomes to inform strategies to mitigate health disparities.

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.

Parity predicts biological age acceleration in post-menopausal, but not pre-menopausal, women.

Understanding factors contributing to variation in 'biological age' is essential to understanding variation in susceptibility to disease and functional decline. One factor that could accelerate biological aging in women is reproduction. Pregnancy is characterized by extensive, energetically-costly changes across numerous physiological systems. These 'costs of reproduction' may accumulate with each pregnancy, accelerating biological aging. Despite evidence for costs of reproduction using molecular and demographic measures, it is unknown whether parity is linked to commonly-used clinical measures of biological aging. We use data collected between 1999 and 2010 from the National Health and Nutrition Examination Survey (n = 4418) to test whether parity (number of live births) predicted four previously-validated composite measures of biological age and system integrity: Levine Method, homeostatic dysregulation, Klemera-Doubal method biological age, and allostatic load. Parity exhibited a U-shaped relationship with accelerated biological aging when controlling for chronological age, lifestyle, health-related, and demographic factors in post-menopausal, but not pre-menopausal, women, with biological age acceleration being lowest among post-menopausal women reporting between three and four live births. Our findings suggest a link between reproductive function and physiological dysregulation, and allude to possible compensatory mechanisms that buffer the effects of reproductive function on physiological dysregulation during a woman's reproductive lifespan. Future work should continue to investigate links between parity, menopausal status, and biological age using targeted physiological measures and longitudinal studies.

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.

US Women's Perceptions and Acceptance of New Reproductive Health Technologies.

Background: Women have faced persistent problems accessing reproductive health care. New applications of health technologies to reproductive health, specifically online fertility specialist consultations and reproductive hormone self-collection tests (SCTs), present unique opportunities to overcome these issues. This article uses the technology acceptance model to examine factors that influence women's intentions to use these new reproductive health technologies. Materials and Methods: Participants (n = 327 US women) completed an online survey assessing perceptions related to both of these reproductive health technologies, including usefulness, ease of use, risk, trust, subjective norms, and personal responsibility, to learn about fertility. Results: Participants indicated high perceptions of usefulness, ease of use, and trust, as well as low perceptions of risk and subjective norms for both online fertility consultations (OFCs) and reproductive hormone SCTs. Women indicated low perceptions of responsibility to use OFCs, but high perceptions of responsibility to use reproductive hormone SCTs. Structural equation modeling indicated that intentions to use OFCs were predicted by usefulness, subjective norms, and responsibility; intentions to use reproductive hormone SCTs were predicted by usefulness, ease of use, subjective norms, and responsibility. Conclusions: Fertility specialist consultations and reproductive hormone testing can provide women with essential fertility information that facilitates informed reproductive decisions; however, these services have historically been difficult to access. Widespread uptake of new reproductive health technologies could promote positive advances in women's reproductive health outcomes.

No evidence that hormonal contraceptive use or circulating sex steroids predict complex emotion recognition.

Relatively little is known about the effects of endogenous and exogenous steroid hormones on ecologically relevant behavioral and cognitive phenotypes in women, such as emotion recognition, despite the widespread use of steroid hormone-altering hormonal contraceptives (HCs). Though some previous studies have examined the effect of HC use, estradiol, progesterone, and testosterone on emotion recognition in women, they have been limited by cross-sectional designs, small sample sizes (total n < 100), and compromised statistical power to detect significant effects. Using data from two test sessions in a large sample of naturally cycling women (NC; n = 192) and women on HCs (n = 203), we found no group differences in emotion recognition; further, the lack of group differences in emotion recognition was not modulated by item difficulty or emotional valence. Among NC women who provided saliva samples across two sessions that were assayed for estradiol and progesterone concentrations, we found no compelling evidence across models that between-subject differences and within-subject fluctuations in these ovarian hormones predicted emotion recognition accuracy, with the exception that between-subjects estradiol negatively predicted emotion recognition for emotions of neutral valence (p = .042). Among HC women who provided saliva samples across two sessions that were assayed for testosterone, we found no compelling evidence that between-subjects differences and within-subject fluctuations in testosterone predicted emotion recognition accuracy. Overall, our analyses provide little support for the idea that circulating endogenous or exogenous ovarian hormones influence emotion recognition in women.

The neuropsychological phenotype of Chediak-Higashi disease.

BACKGROUND/OBJECTIVES: Chediak-Higashi Disease (CHD) is a rare autosomal disorder, purported to have cognitive and neurological impairments. Prior descriptions of cognitive impairment, however, are solely based on subjective, unstructured observations rather than on formal neuropsychological measures. METHODS: Four pediatric and 14 adult patients with diagnostically confirmed CHD were administered a neuropsychological battery assessing memory, attention, processing speed, psychomotor speed, language fluency, executive function, and general intelligence. Nine of the adult patients received follow-up evaluations to elucidate the longitudinal progression or stability of cognition over time. RESULTS: Pediatric CHD patients performed within the average range. Adult patients, however, performed below average on nearly all measures administered, and endorsed subjective reports of learning difficulties and poor academic performance in childhood. In particular, patients struggled with memory and psychomotor speed tasks, with 75% or more of patients scoring in the bottom 2.3 percentile in these two domains. No significant declines in cognition were observed among the patients who completed follow-up evaluations (M = 39.90, SD = 8.03 months between visits). Exploratory analyses suggested that adult patients who had classic CHD and previously received bone marrow transplants (BMTs; n = 3) exhibited moderately greater cognitive impairment than adult patients who had atypical CHD and had not received BMTs (n = 10). CONCLUSIONS: Adult patients with CHD uniformly exhibit deficits in multiple domains, but in psychomotor speed and memory, in particular. Based on their neuropsychological profile, their ability to hold jobs and succeed in school may require support and special accommodations. The source of cognitive deficits is probably multifactorial including central nervous system involvement in CHD, and, for those transplanted, BMT-related side effects and complications. Absence of cognitive decline at three-year follow-up is encouraging but does not exclude progression at a slower time-scale. Future work should elucidate the possible effects and timing of BMT on cognition, as well as the mechanisms driving neuropsychological impairment in CHD.

Menstrual cycle phase predicts women's hormonal responses to sexual stimuli.

A robust body of research has demonstrated shifts in women's sexual desire and arousal across the menstrual cycle, with heightened desire and arousal coincident with heightened probability of conception (POC), and it is likely that ovarian hormones modulate these shifts. However, studies in which women are exposed to audiovisual sexual stimuli (AVSS) at high POC (mid-follicular) and low POC (luteal) phases have failed to detect significant differences in genital or subjective arousal patterns based on menstrual cycle phase. Here, we tested whether hormonal responsivity to AVSS differs as a function of cycle phase at testing, and whether phase during which participants were first exposed to AVSS influences hormonal responsivity in subsequent test sessions. Twenty-two naturally cycling heterosexual women were exposed to AVSS during the follicular and luteal phases, with phase at first test session counterbalanced across participants. Salivary samples were collected before and after AVSS exposure. Estradiol increased significantly during both follicular and luteal phase sessions, and increases were higher during the follicular phase. Testosterone (T) increased significantly only during the follicular phase session, while progesterone (P) did not change significantly during either cycle phase. Session order and current cycle phase interacted to predict P and T responses, such that P and T increased during the follicular phase in women who were first tested during the luteal phase. These data suggest that menstrual cycle phase influences hormonal responsivity to AVSS, and contribute to a growing body of clinical and empirical literature on the neuroendocrine modulators of women's sexuality.

Concordance Between Self-Report and Performance-Based Measures of Everyday Functioning in HIV-Associated Neurocognitive Disorders.

Self-report is typically used to differentiate between asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) in the assessment of HIV-associated neurocognitive disorders (HAND). Yet, it is unclear whether the lack of self-reported functional impairments in individuals with ANI is indicative of a genuine absence of functional impairment, or of inaccurate self-reports. In the present study, we examined the relationship between previously validated self-report (patient's assessment of own functioning inventory; instrumental activities of daily living inventory) and performance-based (the Texas Functional Living Scale) measures of functional abilities in 112 virologically-controlled HIV-infected, and 40 well-matched, HIV-uninfected participants. Participants with symptomatic cognitive impairment (CI) had significantly lower overall scores and higher rates of impairment on a performance-based measure of everyday functioning as compared to participants with either asymptomatic CI or normal cognitive performance (WNL [within normal limits]; all p < 0.05), while asymptomatic CI and WNL participants had comparable rates of impairment and performance within the average range on the performance-based measure. The concordance between self-report and performance-based measures of everyday functioning in asymptomatic and symptomatic CI provide support for ANI and MND as clinically distinct diagnostic entities, and support the use of self-reports as appropriate measures of everyday functioning in the diagnosis of HAND.