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This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/E808    most recent 00418.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koutkia, P. Articles by Grinspoon, S. Search for Related Content PubMed PubMed Citation Articles by Koutkia, P. Articles by Grinspoon, S.

Increased adrenal androgen secretion with inhibition of 11-hydroxylase in HIV-infected women

¹Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School; and ²Massachusetts General Hospital/Massachusetts Insititute of Technology General Clinical Research Center Core Laboratory, Boston, Massachusetts

Submitted 2 September 2005 ; accepted in final form 14 November 2005

Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg po qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 ± 0.9 yr), weight (91.7 ± 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 ± 54 vs. –0.4 ± 2 ng/dl, P = 0.024), free testosterone (6.5 ± 2.8 vs. 0.1 ± 0.1 pg/ml, P = 0.024), DHEA (5.0 ± 3.2 vs. –0.6 ± 0.5 µg/l, P = 0.024), and 11-deoxycortisol (2,145 ± 820 vs. –14 ± 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 ± 48 vs. 3 ± 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.

human immunodeficiency virus; androgen shunting; stress; metyrapone