The KiSS-1 gene codes for a family of neuropeptides called kisspeptins which bind to the G-protein-coupled receptor GPR54. To assess the possible effects of kisspeptins on gonadotropin secretion, we injected kisspeptin-52 into the lateral cerebral ventricles of adult male rats and found that kisspeptin-52 increased the serum levels of luteinizing hormone (p < 0.05). To determine whether the kisspeptin-52-induced stimulation of luteinizing hormone secretion was mediated by gonadotropin-releasing hormone (GnRH), we pretreated adult male rats with a GnRH antagonist (acyline), then challenged the animals with intracerebroventricularly administered kisspeptin-52. The GnRH antagonist blocked the kisspeptin-52-induced increase in luteinizing hormone. To examine whether kisspeptins stimulate transcriptional activity in GnRH neurons, we administered kisspeptin-52 intracerebroventricularly and found by immunocytochemistry that 86% of the GnRH neurons coexpressed Fos 2 h after the kisspeptin-52 challenge, whereas fewer than 1% of the GnRH neurons expressed Fos following injection of the vehicle alone (p < 0.001). To assess whether kisspeptins can directly act on GnRH neurons, we used double-label in situ hybridization and found that 77% of the GnRH neurons coexpress GPR54 mRNA. Finally, to determine whether KiSS-1 gene expression is regulated by gonadal hormones, we measured KiSS-1 mRNA levels by single-label in situ hybridization in intact and castrated males and found significantly higher levels in the arcuate nucleus of castrates. These results demonstrate that GnRH neurons are direct targets for regulation by kisspeptins and that KiSS-1 mRNA is regulated by gonadal hormones, suggesting that KiSS-1 neurons play an important role in the feedback regulation of gonadotropin secretion.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for t...

Introduction Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.” Aim We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL. Methods We conducted standardized interviews with 71 otherwise healthy men aged 21–46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride. Main Outcome Measures The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use. Results Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale (P &lt;0.0001 for both). The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels. Conclusion Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.

Clinicians and potential users of finasteride should be aware of the potential risk of depressive symptoms and suicidal thoughts. The preliminary findings of this study warrant further research with controlled studies.

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Introduction Finasteride has been associated with sexual side effects that may persist despite discontinuation of the medication. In a clinical series, 20% of subjects with male pattern hair loss reported persistent sexual dysfunction for ≥6 years, suggesting the possibility that the dysfunction may be permanent. These subjects also reported a wide range of symptoms including changes in cognition, ejaculate quality, and genital sensation. Other medications have been associated with irreversible neurological effects, such as phenothiazines with tardive dyskinesias. Aim To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time. Methods Subjects (N = 54) with persistent sexual side effects associated with finasteride were reassessed after 9–16 months (mean 14 months). All subjects were otherwise healthy young men without any baseline sexual dysfunction, medical conditions, psychiatric conditions, or use of oral prescription medications prior to taking finasteride for male pattern hair loss. Main Outcome Measure Scores from the Arizona Sexual Experience Scale (ASEX). Results The participation rate was 81%. At reassessment persistent sexual side effects continued to be present in 96% of subjects. According to the ASEX scores, 89% of subjects met the definition of sexual dysfunction. Neither the length of finasteride use nor the duration of the sexual side effects correlated to changes in scores of sexual dysfunction. Conclusion In most men who developed persistent sexual side effects (≥3 months) despite the discontinuation of finasteride, the sexual dysfunction continued for many months or years. Although several rat studies have shown detrimental changes to erectile function caused by 5 alpha reductase inhibitors, the persistent nature of these changes is an area of active research. Prescribers of finasteride and men contemplating its use should be made aware of the potential adverse medication effects.

The American Psychological Association defines gender identity as, "A person's deeply-felt, inherent sense of being a boy, a man, or a male; a girl, a woman, or a female; or an alternative gender (e.g., genderqueer, gender nonconforming, gender neutral) that may or may not correspond to a person's sex assigned at birth or to a person's primary or secondary sex characteristics" (American Psychological Association, Am Psychol 70(9):832-864, 2015). Here we review the evidence that gender identity and related socially defined gender constructs are influenced in part by innate factors including genes. Based on the data reviewed, we hypothesize that gender identity is a multifactorial complex trait with a heritable polygenic component. We argue that increasing the awareness of the biological diversity underlying gender identity development is relevant to all domains of social, medical, and neuroscience research and foundational for reducing health disparities and promoting human-rights protections for gender minorities.

This review examines the relationship between exogenous sex steroids and cardiovascular events and surrogate markers in trans (transgender) people. Data from trans populations is compared to data from postmenopausal women and hypogonadal men when appropriate. In an age-adjusted comparison with cisgender people, trans people appear to have an increased risk for myocardial infarction and death due to cardiovascular disease. It is uncertain whether hormone therapy in trans people affects their risk of stroke. In studies that followed trans people on hormone therapy, the rates of myocardial infarction and stroke were consistently higher in trans women than trans men. There is strong evidence that estrogen therapy for trans women increases their risk for venous thromboembolism over 5 fold. Extrapolating from studies of hormone therapy in postmenopausal women, transdermal estrogen likely carries a lower risk for venous thromboembolism than oral estrogen. Regarding red blood cells, testosterone therapy increases hemoglobin in trans men, and lowering testosterone in trans women has the opposite effect. Regarding blood pressure, the effects of hormone therapy on systolic blood pressure in trans women are inconsistent, with most studies showing an increase. In trans men, testosterone therapy consistently increases systolic blood pressure and may increase diastolic blood pressure. For lipids, hormone therapy may increase triglycerides in both trans women and men. In trans men, testosterone therapy also may increase LDL-cholesterol and decrease HDL-cholesterol.