Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males.

Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes.

The methodological and ethical concerns of genetic studies of same-sex sexual behavior.

Same-sex sexual behavior has long interested genetics researchers in part because, while there is evidence of heritability, the trait as typically defined is associated with fewer offspring. Investigations of this phenomenon began in the 1990s with linkage studies and continue today with the advent of genome-wide association studies. As this body of research grows, so does critical scientific and ethical review of it. Here, we provide a targeted overview of existing genetics studies on same-sex sexual behavior, highlight the ethical and scientific considerations of this nascent field, and provide recommendations developed by the authors to enhance social and ethical responsibility.

A comprehensive genome-wide cross-trait analysis of sexual factors and uterine leiomyoma.

Age at first sexual intercourse (AFS) and lifetime number of sexual partners (NSP) may influence the pathogenesis of uterine leiomyoma (UL) through their associations with hormonal concentrations and uterine infections. Leveraging summary statistics from large-scale genome-wide association studies conducted in European ancestry for each trait (NAFS = 214,547; NNSP = 370,711; NUL = 302,979), we observed a significant negative genomic correlation for UL with AFS (rg = -0.11, P = 7.83×10-4), but not with NSP (rg = 0.01, P = 0.62). Four specific genomic regions were identified as contributing significant local genetic correlations to AFS and UL, including one genomic region further identified for NSP and UL. Partitioning SNP-heritability with cell-type-specific annotations, a close clustering of UL with both AFS and NSP was identified in immune and blood-related components. Cross-trait meta-analysis revealed 15 loci shared between AFS/NSP and UL, including 7 novel SNPs. Univariable two-sample Mendelian randomization (MR) analysis suggested no evidence for a causal association between genetically predicted AFS/NSP and risk of UL, nor vice versa. Multivariable MR adjusting for age at menarche or/and age at natural menopause revealed a significant causal effect of genetically predicted higher AFS on a lower risk of UL. Such effect attenuated to null when age at first birth was further included. Utilizing participant-level data from the UK Biobank, one-sample MR based on genetic risk scores yielded consistent null findings among both pre-menopausal and post-menopausal females. From a genetic perspective, our study demonstrates an intrinsic link underlying sexual factors (AFS and NSP) and UL, highlighting shared biological mechanisms rather than direct causal effects. Future studies are needed to elucidate the specific mechanisms involved in the shared genetic influences and their potential impact on UL development.

Arranged cohabitation among Chinese Muslims.

While modern family-related ideas and behaviors have become more widely accepted in contemporary China, Chinese Muslim minorities continue to hold on to traditional religious practices. Surprisingly, data from our survey conducted in Gansu province in China's northwestern borderlands reveal that Muslims of the Hui and Dongxiang ethnicities reported much higher rates of cohabitation experience than the secular majority Han. Based on follow-up qualitative interviews, we found the answer to lie in the interplay between the highly interventionist Chinese state and the robust cultural resilience of local Islamic communities. While the state maintains a high minimum legal age of marriage, the early marriage norm remains strong in Chinese Muslim communities, where religion constitutes an alternative and often more powerful source of legitimacy-at least in the private sphere of life. Using the 2000 census data, we further show that women in almost all 10 Muslim ethnic groups have higher percentages of underage births and premarital births than Han women, both nationally and in the northwest where most Chinese Muslims live. As the once-outlawed behavior of cohabitation became more socially acceptable during the reform and opening-up era, young Muslim Chinese often found themselves in "arranged cohabitations" as de facto marriages formed at younger-than-legal ages. In doing so, Chinese Muslim communities have reinvented the meaning of cohabitation. Rather than liberal intimate relationship based on individual autonomy, cohabitation has served as a coping strategy by which Islamic patriarchs circumvent the Chinese state's aggressive regulations aimed at "modernizing" the Muslim family.

Contraception ends the genetic maintenance of human same-sex sexual behavior.

Because human same-sex sexual behavior (SSB) is heritable and leads to fewer offspring, it is puzzling why SSB-associated alleles have not been selectively purged. Current evidence supports the antagonistic pleiotropy hypothesis that SSB-associated alleles benefit individuals exclusively performing opposite-sex sexual behavior by increasing their number of sexual partners and consequently their number of offspring. However, by analyzing the UK Biobank, here, we show that having more sexual partners no longer predicts more offspring since the availability of oral contraceptives in the 1960s and that SSB is now genetically negatively correlated with the number of offspring, suggesting a loss of SSB's genetic maintenance in modern societies.

Microglia phagocytosis mediates the volume and function of the rat sexually dimorphic nucleus of the preoptic area.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in mammalian brain and is singular for its presence across a wide range of species from rodents to ungulates to man. This small collection of Nissl-dense neurons is reliably larger in volume in males. Despite its notoriety and intense interrogation, both the mechanism establishing the sex difference and the functional role of the SDN have remained elusive. Convergent evidence from rodent studies led to the conclusion that testicular androgens aromatized to estrogens are neuroprotective in males and that higher apoptosis (naturally occurring cell death) in females determines their smaller SDN. In several species, including humans, a smaller SDN correlates with a preference for mating with males. We report here that this volume difference is dependent upon a participatory role of phagocytic microglia which engulf more neurons in the female SDN and assure their destruction. Selectively blocking microglia phagocytosis temporarily spared neurons from apoptotic death and increased SDN volume in females without hormone treatment. Increasing the number of neurons in the SDN in neonatal females resulted in loss of preference for male odors in adulthood, an effect paralleled by dampened excitation of SDN neurons as evidenced by reduced immediate early gene (IEG) expression when exposed to male urine. Thus, the mechanism establishing a sex difference in SDN volume includes an essential role for microglia, and SDN function as a regulator of sexual partner preference is confirmed.

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

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.

Initial impressions of compatibility and mate value predict later dating and romantic interest.

Romantic first impressions seem to linger, but why? Few studies have investigated how romantic desire during initial interactions predicts later relational outcomes (e.g., later romantic interest, contact attempts) using a design that can tease apart different possible mechanisms (e.g., mate value, selectivity, compatibility). Across three speed-dating studies (n = 559) with longitudinal follow-ups (including college and community samples, and a sample of men who date men), we investigated whether different components of initial romantic impressions predicted later romantic outcomes and relationship initiation. Using the social relations model, we partitioned initial desire at speed dating (determined from 6,600+ total dates) into partner effects (a date's consensual desirability, e.g., mate value), actor effects (a participant's general desirousness, e.g., selectivity), and relationship effects (a participant's unique liking for a date over and beyond partner and actor effects, e.g., compatibility) to predict later evaluations (romantic interest, physical attraction, and desire to know better) and behaviors (direct messaging and going on dates). Meta-analyses across the three studies showed that, across 6,100+ follow-up reports, partner and relationship effects were especially strong predictors of relationship initiation variables. Consistent with evolutionary models of human pair bonding, these findings suggest that both consensually desirable traits and unique impressions of compatibility have lingering effects on relationship development, even from the moment that two potential partners meet.

More comprehensive sex education reduced teen births: Quasi-experimental evidence.

Women in the United States are much more likely to become mothers as teens than those in other rich countries. Teen births are particularly likely to be reported as unintended, leading to debate over whether better information on sex and contraception might lead to reductions in teen births. We contribute to this debate by providing causal evidence at the population level. Our causal identification strategy exploits county-level variation in the timing and receipt of federal funding for more comprehensive sex education and data on age-specific teen birth rates at the county level constructed from birth certificate natality data covering all births in the United States. Our results show that federal funding for more comprehensive sex education reduced county-level teen birth rates by more than 3%. Our findings thus complement the mixed evidence to date from randomized control trials on teen pregnancies and births by providing population-level causal evidence that federal funding for more comprehensive sex education led to reductions in teen births.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOSVMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.

The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study.

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioral adaptations. METHODS: We developed a transmission model and accounted for possible behavioral adaptations: fewer casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioral adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioral adaptations in the model, we found a decline of 16%-18% in numbers of casual partners in June and 13%-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioral adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.

Sexual Exposures Associated With Mpox Infection: California, November 2022 to June 2023.

BACKGROUND: Exposures associated with mpox infection remain imperfectly understood. METHODS: We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox case patients and test-negative controls. RESULTS: Thirteen of 54 case patients (24.1%) and 5 of 117 controls (4.3%) reported sexual exposure to individuals they identified as potential mpox case patients ("index contacts"; odds ratio [OR], 7.7 [95% confidence interval (CI), 2.5-19.3] relative to individuals who did not report exposure to potential mpox case patients). Among these participants, 10 of 13 case patients (76.9%) and 2 of 5 controls (40.0%) reported that their index contacts were not experiencing symptoms visible to participants during sex (OR, 14.9 [95% CI, 3.6-101.8]). Only 3 of 54 case patients (5.6%) reported exposure to symptomatic index contacts. Case patients reported more anal/vaginal sex partners than did controls (adjusted OR, 2.2 [95% CI, 1.0-4.8] for 2-3 partners and 3.8 [1.7-8.8] for ≥4 partners). Male case patients with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR, 9.3 [95% CI, 1.6-54.8]). Case patients with anorectal lesions more commonly reported receptive anal sex than those without anorectal lesions (adjusted OR, 14.4 [95% CI, 1.0-207.3]). CONCLUSIONS: Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to more sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants' assessment of symptoms in partners may be imperfect, these findings suggest that individuals without visibly prominent mpox symptoms transmit infection.

Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth.

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.

Characteristics of the Sexual Networks of Men Who Have Sex With Men in Montréal, Toronto, and Vancouver: Insights from Canada's 2022 Mpox Outbreak.

BACKGROUND: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). We investigated differences in GBM's sexual partner distributions across Canada's 3 largest cities and over time, and how they shaped transmission. METHODS: The Engage Cohort Study (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n = 2449). We compared reported sexual partner distributions across cities and periods: before COVID-19 (2017-2019), pandemic (2020-2021), and after lifting of restrictions (2021-2023). We used Bayesian regression and poststratification to model partner distributions. We estimated mpox's basic reproduction number (R0) using a risk-stratified compartmental model. RESULTS: Pre-COVID-19 pandemic distributions were comparable: fitted average partners (past 6 months) were 10.4 (95% credible interval: 9.4-11.5) in Montréal, 13.1 (11.3-15.1) in Toronto, and 10.7 (9.5-12.1) in Vancouver. Sexual activity decreased during the pandemic and increased after lifting of restrictions, but remained below prepandemic levels. Based on reported cases, we estimated R0 of 2.4 to 2.7 and similar cumulative incidences (0.7%-0.9%) across cities. CONCLUSIONS: Similar sexual partner distributions may explain comparable R0 and cumulative incidence across cities. With potential for further recovery in sexual activity, mpox vaccination and surveillance strategies should be maintained.

Prevalence of Sexually Transmitted Infections Among Transgender Women With and Without HIV in the Eastern and Southern United States.

BACKGROUND: Data on the epidemiology of sexually transmitted infections (STIs) among transgender women (TGW) with and without human immunodeficiency virus (HIV) are limited. METHODS: We analyzed baseline data collected from a cohort of adult TGW across 6 eastern and southern US cities between March 2018 and August 2020 (n = 1018). Participants completed oral HIV screening, provided self-collected rectal and urogenital specimens for chlamydia and gonorrhea testing, and provided sera specimens for syphilis testing. We assessed associations with ≥1 prevalent bacterial STI using modified Poisson regression. RESULTS: Bacterial STI prevalence was high and differed by HIV status: 32% among TGW with HIV and 11% among those without HIV (demographic-adjusted prevalence ratio = 1.91; 95% confidence interval = 1.39-2.62). Among TGW without HIV, bacterial STI prevalence differed by geographic region, race and ethnicity, and gender identity, and was positively associated with reporting >1 sexual partner, hazardous alcohol use, homelessness, having safety concerns regarding transit to health care, and no prior receipt of gender-affirming health services. Among TGW with HIV, older age was inversely associated with bacterial STI. CONCLUSIONS: TGW had a high prevalence of bacterial STIs. The prevalence and correlates of bacterial STI differed by HIV status, highlighting the unique needs and risks of TGW with and without HIV. Tailored interventions may reduce sexual health-related inequities.

"Do We Stay or Do We Go?" The Impact of Anti-LGBTQ+ Legislation on the HIV Workforce in the South.

The human immunodeficiency virus (HIV) workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti- lesbian, gay, bisexual, transgender and queer (LGBTQ+) legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient's lives, including those needing gender-affirming care. The recent legislative targets against transgender patients, which involves many people with HIV, will clearly add to the burden on individual HIV care providers and therefore the HIV workforce. Recruitment and retention efforts in states impacted by these laws will become increasingly difficult without advocacy for the patients we serve. The HIV workforce must work together with LGBTQ+ populations to address these recent laws and promote the well-being of all our patients and colleagues.

Role of Direct Sexual Contact in Human Transmission of Monkeypox Virus, Italy.

The 2022 global mpox outbreak was driven by human-to-human transmission, but modes of transmission by sexual relationship versus sexual contact remain unclear. We evaluated sexual transmission of mpox by using monkeypox virus (MPXV) G2R-mRNA as a marker of ongoing viral replication through in vitro experiments. We analyzed clinical samples of 15 MPXV-positive patients in Italy from different biological regions by using the setup method. The presence of MPXV DNA, MPXV G2R-mRNA, or both in all analyzed lesion swab samples, independent of viral load, confirmed a higher infectivity risk from skin lesions. Positivity for MPXV G2R-mRNA in nasopharyngeal swabs was associated with high MPXV load, whereas positive results for MPXV G2R-mRNA were obtained only in the 2 semen samples with the lowest MPXV loads. Our results suggest that close or skin-to-skin contact during sexual intercourse is the main route of sexual transmission and that semen is a minor driver of infection, regardless of MPXV load.

Mpox Epidemiology and Risk Factors, Nigeria, 2022.

To investigate epidemiology of and risk factors for laboratory-confirmed mpox during the 2022 outbreak in Nigeria, we enrolled 265 persons with suspected mpox. A total of 163 (61.5%) were confirmed to have mpox; 137 (84.0%) were adults, 112 (68.7%) male, 143 (87.7%) urban/semi-urban dwellers, 12 (7.4%) self-reported gay men, and 3 (1.8%) female sex workers. Significant risk factors for adults were sexual and nonsexual contact with persons who had mpox, as well as risky sexual behavior. For children, risk factors were close contact with an mpox-positive person and prior animal exposure. Odds of being mpox positive were higher for adults with HIV and lower for those co-infected with varicella zoster virus (VZV). No children were HIV-seropositive; odds of being mpox positive were higher for children with VZV infection. Our findings indicate mpox affects primarily adults in Nigeria, partially driven by sexual activity; childhood cases were driven by close contact, animal exposure, and VZV co-infection.