DHEA Replacement in Women with Adrenal Insufficiency
DHEA Replacement in Women with Adrenal Insufficiency
November 1999; Volume 2: 131
Arlt W, et al. Dehydroepiandrosterone re-placement in women with adrenal insufficiency. N Engl J Med 1999;341:1013-1020.
The physiologic role of dehydroepiandrosterone (DHEA) in hu-mans is still unclear. Adrenal insufficiency leads to a deficiency of DHEA; we therefore investigated the effects of DHEA replacement in patients with adrenal insufficiency.
In a double-blind study, 24 women (mean age 42 +/-9 years) with adrenal insufficiency of a mean 9 +/-2 years duration received in random order 50 mg of DHEA orally each morning for four months and placebo daily for four months, with a one month washout period. All women continued to take standard medication, including estrogen-progestin replacement therapy, if appropriate. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin. We evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment; after one and four months of DHEA treatment, and placebo treatment; and one month after the end of the second treatment period.
Treatment with DHEA raised the initially low serum concentrations of DHEA, DHEA Sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high density lipoprotein cholesterol decreased significantly.
DHEA significantly reduced serum total cholesterol and HDL concentrations. DHEA significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from baseline was -0.18 +/-0.29 after four months of DHEA therapy, as compared with 0.03 +/-0.29 after four months of placebo (P = 0.02). As compared with placebo, DHEA significantly increased the frequency of sexual thoughts (P = 0.0006), sexual interest (P = 0.002), and satisfaction with both mental and physical aspects of sexuality (P = 0.0009 and P = 0.02, respectively). Five of the 24 women reported greasy skin, acne, and increased growth of body hair.
We conclude that DHEA improves well-being and sexuality in women with adrenal insufficiency.
Comment
This well-designed, carefully performed, double-blind study by German investigators raises the bar for evidence-based research in alternative medicine. As O’Mathúna reported last month, the FDA categorized DHEA as an unapproved drug in 1985, making it available only by prescription. The 1994 Dietary Supplement Health and Education Act reclassified it as a dietary supplement. Since then, its popularity has exploded. Unfortunately, DHEA supplementation cannot be recommended as an evidence-based therapeutic option for relief of menopausal symptoms. (See Alternative Medicine Alert, October 1999, pp. 113-116.)
But DHEA did wonders for constitutional signs of adrenal insufficiency. And its supplementation is pharmacologic replacement: The adrenal cortex does normally secrete DHEA and DHEA Sulfate. Supplemental corticosteroids are lifesaving in this disease; supplemental DHEA appears to be quality-of-life-saving.
DHEA did not raise estrogen concentrations, did lower HDL levels, and vastly improved the sex lives of these women. As an androgen precursor, could DHEA do so for men too?
DHEA has been evaluated in a double-blind, randomized trial with 40 men (mean age, 56 years), healthy except for erectile dysfunction. The men used 50 mg DHEA daily. Drop-out was high (three taking DHEA; seven on placebo), but those taking DHEA scored higher on all five domains of the International Index of Erectile Function (Reiter WJ, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: A prospective, double-blind, randomized, placebo-controlled study. Urology 1999;53:590-595).
Whether DHEA should be considered for patients consigned to prolonged high-dose glucocorticoid therapy and patients with postmenopausal osteoporosis awaits similar trials. Healthy men and women will soon order the stuff by the truckload, like Viagra, only cheaper.
Limitations to this study include its short duration and its exclusion of men. It is logical but not demonstrated that the risk of breast (and prostate) cancer increases with DHEA supplementation.
Recommendation
Small doses of DHEA should be part of a therapeutic regimen in primary and secondary adrenal insufficiency. Patients should be closely monitored and screened for androgen-related problems, including cancers.
November 1999; Volume 2: 131
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