The utility of androgen replacement therapy in women with androgen deficiency is currently under study. Androgen replacement in these women results in improved bone density, higher quality of life, and enhanced libido. Testosterone has 20 times the androgen potency of dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEAS). In premenopausal women, most circulating testosterone results from androstenedione produced by the ovaries, with the remainder coming from the adrenal gland. In postmenopausal women, the ovaries contribute less to circulating androstenedione levels. Most production of DHEAS occurs in the adrenal glands. Miller reviews the changes in androgen levels that occur in women as they age.
Although DHEA and androstenedione levels decrease, circulating testosterone is less clearly affected. Hypoandrogenemia, with a drop in DHEA, androstenedione and testosterone, clearly occurs in patients with hypopituitarism and secondary hypogonadism and/or hypoadrenalism. Medications that can reduce androgen levels include estrogen, gonadotropin-releasing hormone agonists, and glucocorticoids.
Currently, there are no guidelines for androgen replacement in women, but making the diagnosis of hypoandrogenemia is sometimes important. Measurement of total testosterone is not useful because of variable levels of binding with serum hormone-binding globulin. The free testosterone level and serum hormone-binding globulin level are better indicators of true hypogonadism, but making the diagnosis of hypoandrogenemia is difficult because of laboratory limitations.
Hypoandrogenemia results in decreased bone density, increased lean body mass, diminished libido, and decreased quality of life. Androgen supplementation appears to increase bone density, enhance libido, increase sexual satisfaction, raise the over-all sense of well-being, and have unclear effects on body fat. Although oral androgens can increase low-density lipoproteins (LDL) and decrease high-density lipoproteins (HDL), other androgen preparations do not have the same adverse cardiovascular effect. Preliminary studies of oral therapy with DHEA similarly demonstrate a decrease in HDL.
Androgen replacement therapy is difficult at present because safe and effective androgen preparations that can reliably raise androgen levels to a normal range in women are unavailable. Oral methyltestosterone, combined with esterified estradiol, is available as Estratest. DHEA is not regulated by the U.S. Food and Drug Administration and is available over-the-counter. Preparations are poorly standardized. Side effects of iatrogenic hyperandrogenemia, other than lipid changes, include facial hair growth, acne, and hair loss. These can occur even with elevations of testosterone to just slightly above normal. Oral androgen preparations can cause liver abnormalities, including tumors and cholestatic jaundice. Transdermal patches, once they are standardized to achieve physiologic circulating androgen levels in women, will be helpful. Clear contraindications to androgen therapy include pregnancy, lactation, signs of hyperandrogenemia, and presence of androgen-dependent tumors.
Miller concludes that further study is needed to determine the clinical significance of androgen deficiency in women. Specifically in postmenopausal women, physiologic low-dose androgen replacement therapy may result in improved bone density, enhanced libido, and increased satisfaction with life. Androgen preparations that avoid liver metabolism and produce physiologic serum androgen levels will enhance treatment of androgen deficiency in women. Until such preparations are available, routine screening of women for androgen deficiency cannot be recommended.