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Mechanisms of Androgen Deficiency in Human Immunodeficiency Virus-Infected Women with the Wasting Syndrome

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School (S.G., C.C., T.S., J.R., S.W.), Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: sgrinspoon{at}partners.org

Abstract

Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, iv) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 ± 2 vs. 25 ± 2 ng/dl (0.6 ± 0.1 vs. 0.9 ± 0.1 nmol/liter); P = 0.02], free T [1.5 ± 0.1 vs. 2.4 ± 0.2 pg/ml (5.3 ± 0.5 vs. 8.3 ± 0.6 pmol/liter); P = 0.001], androstenedione [119 ± 6 vs. 162 ± 14 ng/dl (4.16 ± 0.20 vs. 5.66 ± 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 ± 0.17 vs. 1.55 ± 0.19 µg/ml (2.6 ± 0.5 vs. 4.2 ± 0.5 µmol/liter); P = 0.047] levels compared with the control subjects. T [8 ± 2 vs. 6 ± 2 ng/dl (0.3 ± 0.1 vs. 0.2 ± 0.1 nmol/liter); P = 0.48], free T [0.5 ± 0.2 vs. 0.4 ± 0.1 pg/ml (1.7 ± 0.7 vs. 1.5 ± 0.5 pmol/liter); P = 0.85], 17hydroxyprogesterone [0.5 ± 0.2 vs. 0.7 ± 0.2 µg/liter (1.6 ± 0.6 vs. 2.0 ± 0.6 nmol/liter); P = 0.63], and androstenedione [-1 ± 12 vs. 8 ± 11 ng/dl (-0.03 ± 0.42 vs. 0.28 ± 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 ± 11 vs. 107 ± 10; P = 0.02) and 90 (63 ± 8 vs. 102 ± 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 ± 9 vs. 36 ± 5 µg/24 h (99 ± 26 vs. 100 ± 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contrast, our data suggest intact ovarian androgen responsivity to hCG stimulation. Further studies of the mechanism of adrenal steroid shunting and the efficacy of androgen replacement in human immunodeficiency virus-infected women are necessary.

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