19 January, 2015

Blood levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and androgens, such as testosterone, fall with age. Over the last two decades, there have been many clinical trials performed replacing these sex hormones, hoping to improve symptoms such as general well-being, energy, and sex drive. DHEAS is the most abundant steroid in serum; however, no receptor for DHEA has yet been found. It can be interconverted into estrogenic and androgenic metabolites in those tissues that have the appropriate enzyme systems.

Elraiyah and colleagues performed a systematic review and meta-analysis [1] of studies where DHEA was given orally. They identified 23 randomized, controlled trials which enrolled a total of 1188 women. They found that DHEA replacement did not improve sexual desire (or any other measure of sexuality), nor did it have an effect on metabolic markers such as lipids, fasting glucose, weight (or bone mineral density).

Comment

This important meta-analysis confirms the work of others such as Davis [2] that DHEA replacement given to postmenopausal women appears to have no benefit. Despite these reviews, many women around the world are taking DHEA, often compounded and via a number of delivery systems (oral, troche, creams) for dubious reasons.

In contrast to these data, there may be a role for giving low doses of DHEA vaginally [3,4]. The vagina has all the enzyme systems necessary to convert DHEA into estrogens and androgens. Labrie and colleagues have shown that daily DHEA 6.5 mg given vaginally, estrogenizes the vagina and clinically improves menopause-induced vaginal atrophy. Furthermore, using mass spectrometry, they showed that vaginal DHEA did not change serum estrogenic or androgenic metabolites. In other words, vaginal low-dose DHEA improves vaginal atrophy without any systemic effects. Davis points out that, for the average woman, twice weekly vaginal estrogen is probably more convenient [3].

However, vaginal DHEA may prove to be a useful therapy for women who have been treated for breast cancer, where a truly local estrogenic effect in the vagina is desirable. Further studies are needed to examine the impact of breast cancer endocrine therapies such as tamoxifen and aromatase inhibitors on the efficacy of vaginal DHEA.

John Eden
Associate Professor of Reproductive Endocrinology, University of New South Wales; Director, Women's Health and Research Institute of Australia; Head, Barbara Gross Research Unit, Royal Hospital for Women, Sydney, Australia

References

1. Elraiyah T, Sonbol MB, Wang Z, et al. The benefits and harms of systemic DHEA in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab 2014;99:3536-42
http://www.ncbi.nlm.nih.gov/pubmed/25279571 

2. Davis SR, Panjari M, Stanczyk FZ. Clinical review: DHEA replacement for postmenopausal women. J Clin Endocrinol Metab 2011;96:1642-53
http://www.ncbi.nlm.nih.gov/pubmed/21411558 

3. Panjari M, Davis SR. Vaginal DHEA to treat menopause related atrophy: a review of the evidence. Maturitas 2011;70:22-5
http://www.ncbi.nlm.nih.gov/pubmed/21733647 

4. Labrie F, Martel C, Berube R, et al. Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol 2013;138:359-67
http://www.ncbi.nlm.nih.gov/pubmed/23954500