Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV-infected women.
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 11beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg p.o. 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 microg/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 11beta-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.
Koutkia
Polyxeni
P
Program in Nutritional Metabolism and Neuroendocrine Unit, Mass General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA.
Berry
Jacqueline
J
Eaton
Kristina
K
Breu
Jeff
J
Grinspoon
Steven
S
D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003366:Cosyntropin / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000097:blood; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008797:Metyrapone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D000728:Androgens; D004791:Enzyme Inhibitors; D003366:Cosyntropin; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D013252:Steroid 11-beta-Hydroxylase; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone