Lack of evidence supporting DHEA for improved overall health for women
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Current evidence does not support dehydroepiandrosterone use to improve women’s menopausal symptoms, sexual health and overall well-being, and long-term use may lead to estrogenic adverse events, according to a review article.
In an article published in The Journal of Clinical Endocrinology and Metabolism, Margaret E. Wierman, MD, and Katja Kiseljak-Vassiliades, DO, both professors of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado Anschutz Medical Campus, said few data have been published on DHEA administration since 2014 and most available data show no association between DHEA and improvements in sexual health, menopausal symptoms and overall well-being.
“Our patients looking for a panacea for all of their symptoms and deluged by targeted media continue to use and abuse prohormones,” the researchers wrote. “For normal women across the life span, there are few data to support the administration of DHEA for sexual, cognitive, mood or overall well-being.”
The researchers conducted a review of studies published on the potential benefits and risks of DHEA therapy from 1985 to 2021. Studies analyzed associations between DHEA therapy and its effects on antiaging, sexual dysfunction, infertility, metabolic bone health, cognition and well-being. Study populations included normal women of all ages as well as those with adrenal insufficiency, hypopituitarism and anorexia.
Inconsistent findings for DHEA use
The review included several studies evaluating DHEA’s effect as an antiaging therapy. Most of the studies showed DHEA did not improve factors such as libido, muscle function and quality of life. Additionally, the researchers wrote there may be long-term risks of using DHEA therapy to increase testosterone and estradiol levels in older women with estrogen-dependent malignancies. Several studies showed DHEA therapy had few effects on menopausal symptoms compared with placebo. A meta-analysis examining 16 trials in perimenopausal women and postmenopausal women showed those who used DHEA had no quality of life improvements, no consistent changes on menopausal symptoms and minor effects on sexual function compared with women who took hormone therapy. Researchers also found few high-quality data examining DHEA therapy’s effect on areas such as cognition.
Study findings varied for DHEA use by women with adrenal insufficiency. In one study, a cohort of mostly premenopausal women with adrenal insufficiency had improved well-being, lower depression, lower anxiety and better sexual interest with DHEA therapy compared with placebo. However, several other studies found no improvements in well-being and sexual function for women receiving daily DHEA therapy.
“These data overall do not support a consistent beneficial effect of DHEA administration to women with adrenal insufficiency,” the researchers wrote.
Similarly, studies analyzing DHEA in women with hypopituitarism reported variable outcomes for quality of life, sexual function and mood. A meta-analysis of 10 studies analyzing DHEA administration in women with primary or secondary adrenal insufficiency found marginal improvements in quality of life and mood, but no changes in anxiety and sexual function. One study found DHEA therapy was associated with psychological and bone turnover marker improvements in women with anorexia, and another small study showed DHEA was associated in a resumption of menses in 50% of women due to a hypothesized increase in estradiol.
The researchers found DHEA therapy was not associated with improvements in several other areas, including sexual function in postmenopausal women, depression and carbohydrate metabolism body composition. Variable effects were found for metabolic bone health, with one study showing the effect DHEA on bone health being less than estrogen therapy or osteoporosis medications. Two meta-analyses examining DHEA’s effect on fertility found conflicting conclusions, and studies with a placebo-controlled arm showed no benefit.
Adverse effect data lacking
The researchers noted most trials did not provide adverse event data for women taking DHEA. Of those providing data, androgenic adverse events were found more often for those taking DHEA compared with placebo, and adverse events were observed among women with adrenal insufficiency, adrenocorticotropic hormone deficiency and anorexia.
“There are conflicting data in the literature concerning the benefit of DHEA administration in women with adrenal insufficiency at any age,” the researchers wrote. “In the premenopausal ages in women with low DHEA sulfate levels, one could argue a trial of DHEA administration for potential benefits on well-being, understanding that the physiologic dose of DHEA in women is somewhere around 25 mg daily and not 50 mg. In the postmenopausal ages, one must consider the additional impact of conversion to testosterone and estradiol to her breast and bone health, cardiac risks and discuss the pros and cons of a short-term trial. Long-term supplementation is not well established.”
Perspective
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Life is complicated and difficult, and we could all use a boost. One of the popular attempts to alleviate symptoms has been administration of hormone precursors, such as dehydroepiandrosterone. Wierman and Kiseljak-Vassiliades provide a scholarly review of the literature on the topic and find little, if any, evidence to support this practice.
Still, DHEA therapy might have some benefits that outweigh risks for certain individuals. The problem is that it is difficult to tease out these details in proper clinical trials, given the large placebo effects and the substantial inter- and intra-individual variability in symptoms.
DHEA therapy has been trialed in older individuals with the age-associated decline of DHEA and in adrenal insufficiency, where DHEA is truly deficient. In the former population, the data supporting DHEA therapy are very weak. Conversely, I am repeatedly astounded how many average-risk women are denied estrogen therapy for incapacitating menopausal symptoms despite the unparalleled efficacy, due to irrational fears and misinterpretation of published data. For adrenal insufficiency, endocrinologists should strive do a better job replacing hydrocortisone and — more importantly — fludrocortisone. Fatigue that does not remit following a hydrocortisone dose is often due to chronic volume depletion. Carefully optimize the fludrocortisone dose before thinking about DHEA.
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