Current Perspectives on the Use of Androgens in Women

Figure 1 Susan R. Davis, M.B.B.S., FRACP, Ph.D.

The therapeutic use of androgens in women remains a highly controversial area of medical practice. The physiological roles of androgens in female sexual function and other aspects of health remain underinvestigated in that, until recent years, research pertaining to testosterone in women has been focused primarily on disorders of androgen excess. This is despite circulating testosterone levels that exceed estradiol levels in healthy young women.

This issue of Seminars in Reproductive Medicine provides the perspectives of key individuals actively involved in clinical research in the field of androgen therapy in women. The articles are all highly relevant to the practicing clinician.

Fundamental to this field is the understanding of androgen physiology and the limitations to the measurement of androgens in women. Drs. Sonia Davison and Robin Bell has provided us with a thorough review of what is known about androgen levels in women at different ages, incorporating her own important research studies addressing differences in androgen levels in women by age. Dr. Frank Stanczyk's critical appraisal of the measurement of androgens provides us with a historical perspective and highlights the current limitations in this aspect of clinical research. Indeed, a recurring theme linking these first two articles with the subsequent ones is the complexity of androgen metabolism and the importance of androgen intracrinology, or, as defined by Fernand Labrie, the formation of active hormones that exert their action in the same cells in which synthesis took place without release into the pericellular compartment.

Although androgens exert effects in multiple tissues, including the brain, bone, muscle, urogenital tract, vasculature, and so forth, the greatest body of research into the use of androgens in women has been with respect to the treatment of diminished female sexual well-being. Drs. Mary-Anne Papalia and Henry Burger pragmatically guide the reader through the clinical evaluation of women presenting with low libido. Dr. Burger has not only made seminal contributions to our understanding of the menopause transition, but has also pioneered the field of androgen use in women. Dr. Papalia has many years of experience in the conduct of clinical trials of testosterone therapy. Together they share with us their insights as practicing clinicians experienced in the administration of testosterone therapy. A key message from this article is that the assessment of women presenting with low libido must include a thorough evaluation of all potential causes, and it is clinically wrong to assume that low libido in women simply relates to low androgen levels. Furthermore, they emphasize that several therapeutic modalities require consideration, including psychological counseling, treatment of underlying medical disorders, review of medications, and sexual therapy and/or counseling.

The last three articles comprehensively address the therapeutic use of dehydroepiandrosterone (DHEA) and testosterone in both premenopausal and postmenopausal women. DHEA is not strictly an androgen; however, it is the most abundant sex steroid in women, which provides a major precursor pool for ovarian and extragonadal androgen production. The unrestricted over-the-counter availability of DHEA in the United States is unique considering the paucity of data to support its use. Drs. Saltzman and Guay have summarized what is known of the physiology of DHEA and the available evidence, from their own and other studies, regarding its therapeutic use as an alternative to testosterone therapy.

The importance of testosterone in premenopausal women and the consequences of testosterone depletion in young women have been blatantly disregarded in the past. However, young women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy, premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal insufficiency, and hypopituitarism may have testosterone deficiency. Drs. Kalantaridou and Calis draw this to our attention and present a firm argument, based on published data including their own research, that this is an area that merits further consideration in both the clinical and research settings.

Finally, the critical issue is not simply the efficacy of androgen therapy but its safety. This aspect of this field probably arouses the greatest debate. Having completed an exhaustive Cochrane Review on the use of testosterone in perimenopausal and postmenopausal women, Dr. Somboonporn concludes that the available data supports benefits in terms of improvement in sexual function with various regimens of testosterone use, and an improved sense of well-being with transdermal testosterone. Furthermore, studies show consistent reductions in both triglycerides and high-density lipoprotein cholesterol with methyl testosterone. She emphasizes that there has been insufficient reporting of other side effects; hence, testosterone therapy should be used with caution. She recommends that “The use of testosterone may be justified in specific clinical circumstances and should be limited to short-term use, as long-term studies are not available”.

I am grateful to each of the contributors to this issue of Seminars in Reproductive Medicine for their comprehensive reviews and their preparedness to tackle such a hot topic. The overall impression clearly is that androgens have important physiological effects in adult women of all ages and that this field merits more research support.