The postmenopausal ovary is not a major androgen-producing gland

There is much reason to believe that androgens are a quality-of-life factor in postmenopausal women, and it presently is thought that the ovaries are a major site of androgen production. This study focused on the steroidogenic potential and gonadotropin responsiveness of postmenopausal ovaries. Ten postmenopausal women 50 to 71 years of age with complete adrenal insufficiency were studied to exclude a contribution by adrenal androgens. Levels of testosterone and androstenedione (Adione) were measured directly in homogenates of ovarian tissue from 17 postmenopausal women at the time of hysterectomy/ salpingo-oophorectomy. Eight other samples were taken from normally cycling women having unilateral oophorectomy for benign disorders. Steroidogenic enzymes and gonadotropin receptors were identified immunocytochemically. Five of the study women had Addison's disease, had five had Cushing's disease treated 20 to 30 years earlier by bilateral adrenalectomy. Three women with adrenal insufficiency who previously underwent ovariectomy for benign conditions also were studied. Fifteen ovariectomized women and 15 postmenopausal women, all with intact adrenal function, made up a control group. Total and free testosterone were undetectable in postmenopausal women with adrenal insufficiency and also in ovariectomized women with this condition (Fig. 1). Total testosterone levels of 16 to 18 ng/dl were found in postmenopausal and ovariectomized women with intact adrenals. Plasma Adione also was undetectable in adrenal-insufficient women. Plasma dehydroepiandrosterone was not detected in adrenal-insufficient women, and only low levels were found in control women with intact adrenals. Neither plasma testosterone nor Adione increased after chorionic gonadotropin injection in postmenopausal adrenal-insufficient women. Dexamethasone markedly lowered levels of testosterone and Adione in postmenopausal women with intact adrenals (Fig. 2). Samples of postmenopausal ovarian tissue had negligible levels of testosterone and Adione. P-450 was invariably absent from the ovaries, and enzymes promoting androgen synthesis were absent or at most present in very low amounts. No gonadotropin receptors could be identified in postmenopausal ovaries. Androgens circulating in postmenopausal women arise not from the ovaries but from the adrenal glands. Furthermore, the climacteric ovary lacks full capacity to synthesize androgens and is not activated by high levels of luteinizing hormone. Because androgen deficiency may impair sexual function and bring about adverse psychological changes, postmenopausal women may well benefit if androgen is added to classic hormone replacement therapy.