Division of Endocrinology, Diabetes and Metabolism University of Pennsylvania Philadelphia, Pennsylvania 19104-6149
Address correspondence and requests for reprints to: Dr. Peter J. Snyder, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6149.
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Introduction |
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Sources of androgens in women |
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Dehydroepiandrosterone and dehydroepiandrosterone sulfate seem to be secreted almost exclusively by the adrenal glands in both premenopausal and postmenopausal women, as demonstrated by hormonal suppression studies. Administration of dexamethasone causes an 8090% reduction in the serum concentrations of these steroids in pre- and postmenopausal women (3), but estrogen administration does not.
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Conditions in which androgens might be subnormal in women |
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As for pituitary disease, one would predict that panhypopituitarism, by causing decreased secretion of both ovarian and adrenal androgens, would result in severe androgen deficiency. The study by Miller et al. (1) confirms this prediction. They measured the serum concentrations of testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate in 55 women who had pituitary disease and in 92 control women. Whether the women who had pituitary disease were of premenopausal or postmenopausal age, or if they were taking exogenous estrogen or not, they had serum concentrations of all of these androgens that were far below those of comparable women who did not have pituitary disease. If any women have deleterious consequences of androgen deficiency, therefore, women with hypopituitarism are the most likely. The question, then, is what deleterious effects might result from androgen deficiency?
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Possible roles for androgens in women |
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Several studies have addressed the role of androgens in increasing libido using different conditions of androgen deficiency and different androgen preparations. In one study, 71 women who had surgical oophorectomy but presumably intact adrenal function, who were being treated with conjugated equine estrogens, and who had impaired sexual function, were treated for 12 weeks each with two doses of testosterone by a transdermal patch or with a placebo patch in a double-blind fashion (4). The higher dose of testosterone, which resulted in an increase in the serum free testosterone concentration from just below the lower limit of normal to just within the upper end of normal, resulted in an increase in sexual function greater than that of placebo treatment, but the lower dose of testosterone, which resulted in an increase in the serum testosterone to mid-normal, did not increase sexual function more than placebo. In another study, 34 postmenopausal women were randomized to receive implants of estradiol alone or estradiol plus testosterone for 2 yr (5). Treatment with testosterone as well as estradiol increased the serum testosterone concentration to high in the normal range and increased several parameters of sexual function more than placebo did. In a third study, 24 women who had primary or secondary adrenal insufficiency were treated with dehydroepiandrosterone and placebo in random order for 4 months each (6). Dehydroepiandrosterone treatment increased the serum testosterone concentration from subnormal to the lower part of the normal range and increased several parameters of sexual function compared with placebo.
Several studies have also addressed the role of androgens on bone. In one study, 28 postmenopausal women who had not taken estrogen for at least 6 months were randomized to receive either conjugated equine estrogens or esterified estrogens plus 2.5 mg methyltestosterone a day for 9 weeks (7). Both treatment groups experienced a decrease in markers of bone breakdown, but only the group treated with methyltestosterone plus estrogen experienced an increase in markers of bone formation. In another study, 65 women who had undergone oophorectomy were randomized in a double-blind fashion to receive esterified estrogens alone or esterified estrogens plus 2.5 mg methyltestosterone for 2 yr (8). Bone mineral density was evaluated in only 48 of the 65 women and was not significantly different between the two groups after 2 yr of treatment. In a third study, 34 postmenopausal women were randomized to receive implants of estradiol alone or estradiol plus testosterone for 2 yr (5). A greater increase in bone mineral density in both the spine and trochanter occurred in the group treated with estradiol plus testosterone than in the group treated with estrogen alone.
Studies, to date, in short, offer tantalizing evidence that androgens may play an important role in women, but they are not fully convincing because most have been performed in women who are only partially deficient in androgens, and most have been performed with doses of androgens that are probably at least somewhat excessive. The value of the study by Miller et al. (1) is that it demonstrates that panhypopituitarism is the best condition in which to test the possibility that physiologic amounts of androgens affect libido, energy, muscle mass and strength, and bone mineral density in women.
Received January 9, 2001.
Accepted January 9, 2001.
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References |
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