Dehydroepiandrosterone for women in the peri- or postmenopausal phase

Review question
Cochrane authors investigated whether DHEA (dehydroepiandrosterone) supplementation is safe and improves quality of life, menopausal symptoms, and sexual function for women in the peri- or postmenopausal phase.

Background
During menopause a fluctuation and eventually a decrease in estrogen levels occur. These hormonal changes can cause women to experience peri- or postmenopausal symptoms (for example flushes, night sweats, vaginal dryness). DHEA is a so-called precursor hormone which is converted by the body to estrogens and androgens. It is possible that supplementation with DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to decrease menopausal symptoms and improve general wellbeing and sexual function.

The aim of this review was to assess the effectiveness and safety of DHEA in menopausal women, comparing any dose and form of DHEA by any route of administration versus any other treatment, placebo, or no treatment for a minimum treatment duration of seven days.

Search date
The evidence was current to 3 June 2014.

Study characteristics
A total of 28 randomised controlled trials were included, with a total of 1273 menopausal women. Over 95% of the study populations were postmenopausal women. Women's ages ranged from 36 to 80 years. Treatment duration varied from one week to one year. In more than 80% of the trials DHEA was administered orally with the daily doses varying between 10 mg and 1600 mg.

Key results
We found no evidence that DHEA improves quality of life. There was some evidence that it was associated with androgenic side effects (for example acne, unwanted hair growth (hirsutism)). It was uncertain whether DHEA decreased menopausal symptoms, but DHEA may have slightly improved sexual function.

Quality of the evidence
The quality of the evidence was moderate for both quality of life and side effects. We downgraded the quality of evidence based on the lack of data on randomisation, allocation, or blinding; small study sizes overall; and limited data available.

Authors' conclusions: 

There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo.

Read the full abstract...
Background: 

During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of various perimenopausal and postmenopausal symptoms (for example hot flushes, night sweats, vaginal dryness). Dehydroepiandrosterone (DHEA) is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens. It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function (for example libido, dyspareunia, satisfaction). Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety. This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials.

Objectives: 

To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase.

Search strategy: 

The databases that we searched (3 June 2014) with no language restrictions applied were the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the trials registers. Reference lists of retrieved articles were checked.

Selection criteria: 

We included randomised controlled trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment for a minimal treatment duration of seven days in peri- and postmenopausal women.

Data collection and analysis: 

Two authors independently extracted data after assessing eligibility for inclusion and quality of studies. Authors were contacted for additional information.

Main results: 

Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo.

There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison.
There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%).

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