Diagnostic Approach to Hyperandrogenism in Premenopausal Women

Summary

Hyperandrogenism (HA) is a common condition in premenopausal women. It can affect different tissues and systems, causing variable clinical manifestations such as hirsutism, acne, female-pattern hair loss, reproductive dysfunction, metabolic alterations, and, in more severe and rare cases, virilization. The most common cause is polycystic ovary syndrome (PCOS), which is a diagnosis of exclusion. A thorough evaluation is required in patients with etiologies other than PCOS, particularly in women with rapid progression of symptoms or virilization. This review discusses the physiology of androgens, the most frequent causes of HA, and their diagnostic evaluation in premenopausal women.

Introduction

Hyperandrogenism (HA) is defined as the presence of clinical manifestations due to increased production and/or action of androgens. The clinical or biochemical characteristics of androgen excess are observed in at least 10% of women of reproductive age. Clinical manifestations include hirsutism, female-pattern alopecia, acne, ovulatory dysfunction, infertility, cardiometabolic alterations, and, in severe cases, virilization. Polycystic ovary syndrome (PCOS) is the most frequent cause of HA in premenopausal women. The diagnosis of HA requires a thorough medical history, laboratory tests, and imaging studies. This review aims to provide a practical guide for the diagnostic approach to HA in premenopausal women.

Physiology of Androgens

Androgens play an important role in female health, contributing to bone mineral density, muscle mass, and sexual function. Androgens have direct effects on reproduction through the androgen receptor (AR) and indirect effects through their conversion to estrogens. To understand the causes of HA, it is necessary to have a detailed understanding of androgen physiology in premenopausal women. The ovaries, adrenal glands, and peripheral tissues (e.g., skin, adipose tissue, and liver) play key roles in the production and metabolism of androgens.

The adrenocorticotropic hormone (ACTH) regulates androgen synthesis in the reticular zone of the adrenal cortex. Androgen production in the ovarian follicular unit mainly occurs in the theca cells and is regulated by pituitary secretion of luteinizing hormone (LH). Insulin is a potent regulator of ovarian androgen production and acts directly on the steroidogenesis of the theca cells; it also potentiates the ovarian steroidogenic response to LH. The regulation of androgen synthesis involves trophic hormones as well as paracrine and autocrine mechanisms within the glands.

In women, the main circulating androgens are dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androstenedione, testosterone (T), and dihydrotestosterone (DHT) (in decreasing order of plasma concentrations). DHEA-S and androstenedione have little or no intrinsic androgenic activity and must be converted into T to exhibit androgenic effects, which is why they are considered prohormones.

Liliana Fung

Chief of the Endocrinology and Metabolism Service and Director of the Endocrinology and Metabolic Diseases Postgraduate Program at the University Hospital of Caracas, Central University of Venezuela.

https://www.svemonline.org/wp-content/uploads/2024/12/RVEM.-Vol.-22-No.-3-Ano-2024.pdf