The vagina as source and target of androgens: implications for treatment of GSM/VVA, including DHEA.

The vagina is traditionally thought of as a passive organ in the female reproductive system, serving primarily as a passageway for menstrual blood, sexual intercourse and childbirth. However, recent research has shed light on the vagina's role as an endocrine organ that plays a crucial role in female hormonal balance and overall health. Particularly, growing evidence shows that the human vagina can be considered both as source and target of androgens, in view of the novel concept of 'intracrinology'. Besides the well-known role of estrogens, androgens are also crucial for the development and maintenance of healthy genitourinary tissues in women. As androgen levels decline with age, and estrogen levels fall during the menopausal transition, the tissues in the vagina, together with those in the urinary tract, become thinner, drier and less elastic, leading to a variety of uncomfortable and sometimes painful symptoms, clustered in the genitourinary syndrome of menopause (GSM). Given the lack of testosterone-based or androstenedione-based products approved by regulatory agencies to treat GSM, the possibility of using intravaginal prasterone, which works by providing a local source of dehydroepiandrosterone (DHEA) to the vaginal tissues, appears to be a targeted treatment. Further studies are needed to better assess its safety and efficacy.

Can analysis of serum androgens aid in the diagnosis of polycystic ovary syndrome (PCOS) in adolescents?

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a female metabolic disorder that is characterized by ovulatory dysfunction, elevated serum androgen concentrations, and polycystic ovarian morphology (PCOM). However, diagnosis of PCOS in adolescents is challenging. AREAS COVERED: The mechanisms of PCOS pathophysiology are discussed that include: i) dysregulation of the levels of steroidal enzymes ii) abnormalities in the secretion of gonadotropin releasing hormone, luteinizing hormone, and follicle stimulating hormone , and iii) abnormalities in ovarian Thecal and Granulosa cell function. Current clinical diagnosis protocols for PCOS in women are covered. The challenges in diagnosis of PCOS particularly in adolescents are highlightedWe highlighted an important unmet need for an accurate serum test for the early diagnosis of adolescent girls with PCOS. EXPERT OPINION: Steroid metabolite profiling that captures hyperandrogenism has shown some early promise to serve as a biomarker for early diagnosis of PCOS in women, something that would be especially useful in adolescents.

Exogenous Testosterone Does Not Influence 11-Oxygenated C19 Steroid Concentrations in Healthy Postmenopausal Women.

CONTEXT: 11ß-Hydroxyandrostenedione (11OHA4), 11ß-hydroxytestosterone (11OHT), and their respective peripheral derivatives, 11-ketoandrostenedione (11KA4) and 11-ketotesosterone (11KT), have been implicated in androgen-related physiopathology. Little is known of these steroids in postmenopausal women or whether exogenous testosterone therapy influences their levels. OBJECTIVE: The impact of exogenous testosterone on serum levels of 11-oxygenated steroids was determined in healthy postmenopausal women. PARTICIPANTS AND METHODS: Levels of 19-carbon (C19) steroids were measured by liquid chromatography-tandem mass spectrometry in serum obtained at baseline and at 12 and 26 weeks from 73 healthy postmenopausal women, aged 55 to 65 years, who participated in a randomized, double-blind, placebo-controlled clinical trial assessing the effects of transdermal testosterone on cognitive performance. RESULTS: Of the 11-oxygenated androgens, 11OHA4 was the most abundant (median, 6.46 nmol/L; range, 1.51 to 23.82 nmol/L), with concentrations several fold greater than its precursor androstenedione (median, 1.38 nmol/L; range, 0.52 to 2.92 nmol/L). Baseline median (range) testosterone and 11KT levels were similar [0.56 (0.23 to 1.48) nmol/L; 0.85 (0.25 to 2.86) nmol/L, respectively). 11OHT was closely correlated with 11KT (Spearman rank correlation coefficient, 0.79; P < 0.001) and 11OHA4 correlated with 11KA4 (Spearman rank correlation coefficient, 0.73; P < 0.001). Testosterone therapy resulted in an increase in serum testosterone level, whereas all 11-oxygenated androgens remained unchanged throughout the 26 weeks of treatment. CONCLUSION: After menopause, the adrenal production of 11-oxygenated derivatives of androstenedione and testosterone contributes importantly to the total circulating androgen pool. Exogenous testosterone does not influence the circulating levels 11-oxygenated C19 steroids.