Abstract
Dehydroepiandrosterone (DHEA) is commonly used by HIV-infected men, but its endocrine
effects in this population are not well defined. We conducted an 8-week randomized,
placebo-controlled trial to determine the effects of escalating doses (100-400 mg/d)
of DHEA on the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes,
and on a number of metabolic parameters in 69 HIV-positive men (31 in DHEA-treated
group, 38 in placebo group). High-dose (250 μg) corticotropin and luteinizing hormone–releasing hormone stimulation tests were
carried out in all subjects. Fifty-four subjects (26 in the DHEA-treated group and
28 in the placebo group) also underwent optional corticotropin-releasing hormone test,
and 67 subjects (31 in DHEA-treated group and 36 in placebo group) underwent optional
low-dose (1 μg) corticotropin stimulation test. All tests were performed at baseline and at the
end of week 8. Repeated-measures analysis of variance was used to analyze the data.
We observed significant increases in circulating levels of DHEA, DHEA-sulfate, free
testosterone, dihydrotestosterone, androstenedione, and estrone, and a decline in
the serum concentration of sex hormone–binding globulin in the DHEA-treated group
but not in the placebo group (P < .001). There were no differences between the groups in other endocrine or metabolic
parameters or in the results of the stimulation tests. In conclusion, oral DHEA therapy
in HIV-positive men significantly increases circulating levels of DHEA and DHEA-sulfate,
free testosterone, dihydrotestosterone, androstenedione, and estrone and suppresses
circulating concentration of sex hormone–binding globulin. Long-term studies are needed
to assess the clinical significance of these hormonal changes in subjects with HIV
infection receiving oral DHEA therapy.
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References
- DHEA and peripheral androgen and estrogen formation: intracrinology.Ann N Y Acad Sci. 1995; 774: 16-28
- Age changes and sex differences in serum dehydroepiandrosterone sulfate concentration throughout adulthood.J Clin Endocrinol Metab. 1984; 59: 551-555
- Decreased serum dehydroepiandrosterone is associated with an increased progression of HIV infection in men with CD4 cell counts 200-499.J Infect Dis. 1991; 164: 864-868
- Endogenous levels of DHEA sulfate; but not other sex hormones; are associated with depressed mood in older women: The Rancho Bernardo Study.J Am Geriatr Soc. 1999; 47: 685-691
- Induction of peroxisomal beta-oxidation enzymes by dehydroepiandrosterone and its sulfate in primary cultures of rat hepatocytes.Biochem Biophys Acta. 1992; 1137: 231-235
- Dehydroepiandrosterone sulfate and beta-cell function.Diabetes. 2000; 49: 2012-2020
- Dehydroepiandrosterone sulfate enhances natural killer cell toxicity in humans via locally generated immunoreactive insulin-like growth factor I.J Clin Endocrinol Metab. 1999; 84: 3260-3267
- Dehydroepiandrosterone increases endothelial cell proliferation in vitro and improves endothelial function in vivo by mechanisms independent of androgen and estrogen receptors.J Clin Endocrinol Metab. 2004; 89: 4708-4715
- Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men.J Gerontol Am Biol Sci Med. 1997; 52: M1-M7
- Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice fed dehydroepiandrosterone.J Clin Invest. 1985; 75: 2091-2093
- Dehydroepiandrosterone enhances influenza immunization in aged mice.Ann N Y Acad Sci. 1995; 774: 297-299
- Mechanism of cancer preventive action of DHEA. Role of glucose-6-phosphate dehydrogenase.Ann N Y Acad Sci. 1995; 774: 180-186
- Prevention of obesity in Avy/a mice by dehydroepiandrosterone.Lipids. 1977; 12: 409-413
- Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind; placebo-controlled; randomized clinical trial.Arthritis Rheum. 1995; 38: 1826-1831
- Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized; double-blind; placebo-controlled trial.Arthritis Rheum. 2002; 46: 2924-2927
- DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.Psychoneuroendocrinology. 2000; 25: 53-68
- Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women.Am J Obstet Gynecol. 1993; 169: 1536-1539
- Effect of DHEA on abdominal fat and insulin action in elderly women and men.JAMA. 2004; 292: 2243-2248
- Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men.J Clin Endocrinol Metab. 2003; 88: 3190-3195
- Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men.J Clin Endocrinol Metab. 1988; 66: 57-61
- The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women.J Clin Endocrinol Metab. 1990; 71: 696-704
- Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of 2 week dehydroepiandrosterone treatment.J Clin Endocrinol Metab. 1998; p3: 1756-1761
- The effect of six month treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.Clin Endocrinol (Oxf). 1998; 49: 421-432
- Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.J Clin Endocrinol Metab. 1994; 78: 1360-1367
- Evidence for changes in adrenal and testicular steroids during HIV infection.Psychoneuroendorinology. 1997; 22: S11-S18
- Blood cortisol and dehydroepiandrosterone sulphate (DHEAS) levels and CD4 T cell counts in HIV infection.Clin Exp Rheumatol. 1997; 15: 87-90
- Dehydroepiandrosterone sulfate (DHEAS) and testosterone: relation to HIV disease illness stage and progression over one year.J Acquir Immune Defic Syndr. 1999; 22: 146-154
- DHEA effects on mild depression in HIV/AIDS: a placebo-controlled trial.Am J Psych. 2006; 163: 59-66
- A novel serum protein similar to C1q, produced exclusively in adipocytes.J Biol Chem. 1995; 270: 26746-26749
- Diagnostic and statistical manual of mental disorders—fourth edition (DSM-IV).American Psychiatric Association, Washington (DC)1994
- Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-419
- Novel insulin sensitivity index derived from oral glucose tolerance test.J Clin Endocrinol Metab. 2003; 88: 1019-1023
- DHEA: a coming of age.Ann N Y Acad Sci. 1995; 774: ix-xi
- Does DHEA exert direct effects on androgen and estrogen receptors, and does it promote or prevent prostate cancer?.Endocrinology. 2005; 146: 4565-4567
- Healing HIV: how to rebuild your immune system. HealthFirst Press, Mill Valley (Calif)1999: 170-180
- Double-blind treatment of major depression with dehydroepiandrosterone.Am J Psychol. 1999; 156: 646-649
- DHEA and HIV illness.AIDS Read. 1997; 17: 29-38
- Dehydroepiandrosterone (DHEA) the multifunctional steroid: effects on the CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of action?.Ann N Y Acad Sci. 1994; 719: 564-575
- Endocrine disorders in men infected with HIV.Am J Med. 1988; 84: 611-616
- 24 hr urinary free cortisol in patients with acquired immune deficiency syndrome.Metabolism. 1998; 47: 690-694
- Endocrinological and metabolic manifestations of AIDS.Mt Sinai J Med. 1990; 57: 236-241
- Testicular dysfunction in human immunodeficiency virus infected men.Metabolism. 1995; 44: 946-953
- Laboratory reference values. Case records of the Massachusetts General Hospital.N Engl J Med. 2004; 351: 1548-1563
- Relationship between sex steroid hormone levels and CD4 lymphocytes in HIV infected men.Exp Clin Endocrinol Diabetes. 1996; 104: 30-136
- Evaluation of serum and urinary estrogen levels in male patients with HIV-infection.Eur J Med Res. 1998; 3: 533-537
- Adrenocortical function in acquired immunodeficiency syndrome.J Clin Endocrinol Metab. 1987; 65: 482-487
- The adrenal gland in AIDS.Endocr Pathol. 1993; 4: 4-14
- Vagot: cortisol resistance in acquired immunodeficiency syndrome.J Clin Endocrinol Metab. 1992; 74: 608-613
- Dehydroepiandrosterone replacement administration: pharmacokinetics and pharmacodynamic studies in healthy elderly subjects.J Clin Endocrinol Metab. 2000; 85: 3208-3217
- Dehydroepiandrosterone supplementation in healthy men with age-related decline of dehydroepiandrosterone secretion.J Clin Endocrinol Metab. 2001; 86: 4686-4692
- Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.J Clin Endocrinol Metab. 1999; 84: 2170-2176
- Dehydroepiandrosterone replacement in women with adrenal insufficiency.N Engl J Med. 1999; 341: 1013-1020
- Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial.J Clin Endocrinol Metab. 2000; 85: 4650-4656
- Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial.J Clin Endocrinol Metab. 2003; 88: 1112-1118
- Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects on body composition, serum leptin, bone turnover, and exercise capacity.J Clin Endocrinol Metab. 2001; 86: 1968-1972
- Dehydroepiandrosterone reduces plasma plasminogen activator inhibitor type 1 and tissue plasminogen activator antigen in men.Am J Med Sci. 1996; 311: 205-210
- Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men.J Clin Endocrinol Metab. 2002; 87: 1544-1549
- Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge study to a sociobiomedical issue.Proc Natl Acad Sci U S A. 2000; 97: 4279-4284
- Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo controlled trial.J Clin Endocrinol Metab. 2002; 87: 2046-2052
- Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women.J Clin Endocrinol Metab. 1997; 82: 3498-3505
- The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.J Clin Endocrinol Metab. 1999; 84: 3896-3902
- Cardiovascular risk and body-fat abnormalities in HIV-infected adults.N Engl J Med. 2005; 352: 48-62
- Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial.J Clin Endocrinol Metab. 2002; 87: 4935-4941
- Comparison of 1 μg and 250 μg ACTH stimulation tests for the evaluation of adrenal function in patients with AIDS.Metabolism. 2003; 52: 647-651
- Insulin-related ovarian regulatory system in health and disease.Endocr Rev. 1999; 20: 535-582
- Inhibition of sex hormone-binding globulin production in the human hepatoma (HepG2) cell line by insulin and prolactin.J Clin Endocrinol Metab. 1988; 67: 460-464
- Relationship of insulin secretory pulses to sex hormone-binding globulin in normal men.J Clin Endocrinol Metab. 1993; 76: 279-282
Article info
Publication history
Accepted:
February 10,
2006
Received:
August 15,
2005
Identification
Copyright
© 2006 Published by Elsevier Inc.
