Androgens play a vital role in maintaining women’s sexual health and overall well-being as basic science research and clinical trials have begun to delineate the role of androgens in women throughout the reproductive cycle. The pathophysiologic mechanism of androgen receptor expression has been documented in numerous tissue sites including the central nervous system, vagina, pelvic floor, lower urinary and reproductive tracts; as well as in breast tissue, bone, muscle and the cardiovascular system. The impact of advancing age and estrogens on androgen bioavailability, as well as the psychophysiologic role of androgen receptor expression on sexual function demands further research to better define treatment paradigms for improving the quality of life for women across the reproductive life cycle.
A. Introduction
In recent years, increased attention to women’s sexual health has propelled basic science research and clinical trials exploring paradigms for improving quality of life amidst a growing population of menopausal women. As the prevalence of female sexual dysfunction has become manifest, the knowledge of the intricate pathophysiologic role of androgens has fostered a clearer understanding of the biosynthesis pathways and mechanism of action of the androgen receptor and its impact on numerous tissue and cellular sites throughout the body. Understanding androgen physiology and the pathways by which advancing age and medical conditions can alter androgen production will aid in the comprehension of the impact of androgens on female sexual health.
B. Androgen biosynthesis pathways in women
Androgens are important for the development of reproductive function and hormonal homeostasis, and are the precursors for the biosynthesis of estrogens. The physiological role of androgens in women is confounded by the fact that synthesis and metabolism of androgens take place in three compartments: the ovary, adrenal and peripheral tissues which suggest a complex regulation of androgen synthesis by various organs, tissues and enzymes involved in biotransformation. The major androgens in women, listed in descending order of serum concentration, include dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and 5 α-dihydrotestosterone (DHT). Androgen secretion is regulated by stimulation from adrenocorticotropic hormone (ACTH) to the adrenal glands, and by luteinizing hormone (LH) to the ovary, along with other intraglandular autocrine and paracrine mechanisms.1 T and DHT have the most potent biological activity of the androgenic steroids. In women, approximately 25% of androgen biosynthesis occurs in the ovaries, 25% is produced by the adrenal gland, and the remainder is produced in the peripheral tissue. Circulating T functions as a prohormone, converting to DHT or estradiol in target tissues. Furthermore, T can be synthesized in target tissue on demand; consequently resulting in levels of plasma T which may not provide the critical information on the availability of other metabolites. DHEAS, DHEA, and A are the major sources of peripheral androgen production in women.
Androgens have been shown to regulate the development, growth, and maintenance of secondary sex characteristics as well as modulate the physiological function of multiple receptors and tissue sites including the central nervous system, bone, breast, pilosebaceous unit, skeletal muscle, adipose and genital organs and tissues. Androgens not only have direct effects on target sites, but also their effects on these tissues may be mediated by its conversion to estrogens. Hence an imbalance in androgen biosynthesis or metabolism may have ill-effects on female general health, well-being and sexual function.
