Androgens Throughout the Life of Women

Abstract

Androgens consist of 19 carbon steroids that are synthesized in endocrine tissues from cholesterol as substrate or via conversion from other androgens or precursor steroids in the periphery, including liver, gonads, and adrenals. The commonly studied androgens and androgen metabolites in the human include dehydroepiandrosterone (DHEA) and its metabolite dehydroepiandrosterone sulfate (DHEAS), androstenedi-one (A4), and testosterone and its 5α-reduced metabolite, the potent androgen 5α-dihydrotestosterone (DHT). Circulating levels of androgens are equally low in male and female children prior to adrenarche. During adrenarche, plasma levels of DHEA and DHEAS achieve adult levels at an earlier stage of development than do those of testosterone. Production of androgens in the human female occurs to varying extents as a function of age and physiological status. DHEA and DHEAS are primarily products of the adrenal zona reticularis, whereas A4 and testosterone are synthesized in both the ovary and adrenal; substantial quantities of testosterone arise from peripheral conversion from A4. Modest changes in circulating levels of testosterone occur during the ovarian cycle of women during the reproductive years, with the highest levels seen at mid-cycle; plasma levels of DHEA, DHEAS, and A4 show little change during the ovarian cycle. The suppression that occurs with oral contraceptive use is associated with reductions in plasma levels of androgens, including those produced by the adrenal. Circulating levels of testosterone and A4 increase during pregnancy, probably as a result of human chorionic gonadotropin stimulation of the ovary and increased protein binding. There is also increased production of adrenal androgens in pregnancy through unknown mechanisms, but because of the increased conversion of DHEAS to estrogen in the placenta, plasma levels of this steroid decline during pregnancy. Although the ovary is an important source of androgens in women, there seems to be little impact of menopause on circulating levels of A4 and testosterone. Striking reductions in plasma DHEA and DHEAS occur during aging in women, and these changes appear independent of ovarian status. The best evidence to date is suggestive of a selective deficiency in the Δ5 steroid pathway in the zona reticularis during aging, and this may be because of a loss of cells in this zone. Finally, estrogen treatment of postmenopausal women has not been shown to have consistent effects on the androgenic milieu of women.Key WordsAndrogensadrenarchemenopauseadrenopauseadrenal