DHEA is well-tolerated, but may cause side effects by increasing estrogen or testosterone levels. For example, in a study of postmenopausal women, 3 of 38 women in the DHEA group experienced acne, and 2 of 38 experienced facial hair growth.^[15] In another study, the researchers noted an increase in voice lowering, another common effect of testosterone supplementation in women, among the DHEA group as compared to the placebo group.^[16]

Supplementation with testosterone itself may adversely affect cardiovascular risk factors.^[17] However, trials examining cardiovascular-risk-related outcomes (blood pressure^[14] and liver enzymes^[18]) have found no change after DHEA supplementation.

There are commonly occurring associations between sex hormones and the risk of certain types of cancer. For example, supplemental estrogen may increase the risk of some breast and gynecological cancers, and supplemental testosterone and its metabolite, dihydrotestosterone (DHT), may increase the risk of prostate cancer. For instance, one meta-analysis reported a 23% increased risk of breast cancer in participants who had used hormone replacement therapy (HRT).^[19] Another meta-analysis examined exercise, HRT, and breast cancer risk. This study found that women who exercised the most reduced their risk of breast cancer—with the exception of women who also used HRT, who saw no exercise-related reduction in their breast cancer risk.^[20] Furthermore, an increased risk of breast cancer recurrence was associated with HRT in hormone-receptor-positive breast cancer survivors.^[21]

With regard to DHEA and gynecological cancers, the evidence is less clear. One study reported that in participants with endometrial cancer, increased DHEA and DHEA-S levels were noted in participants who survived longer, compared to participants with shorter survival duration.^[22] Larger, stronger studies note that the evidence linking estrogen-containing HRT with endometrial cancer is so weak that it does not suggest significant harm, though the researchers noted a lack of high-quality evidence in certain areas.^[23]^[24]^[25]^[26]

One meta-analysis reported no association between the risk of prostate cancer and DHEA-S levels, and also found no association with other androgens such as testosterone and DHT,^[27] which have sometimes, but not consistently, been found to be associated with prostate cancer risk.^[28] Furthermore, while this meta-analysis did find a relationship between sex hormone binding globulin (SHBG) and prostate cancer risk, DHEA does not tend to affect SHBG levels.^[29]^[10]

Based on the possible increased risks of breast cancer, anyone supplementing with DHEA should discuss their plans with their doctor, with whom the benefits and risks of DHEA supplementation, and the resultant possible changes in sex hormones, can be appropriately evaluated for their individual situation.

How does DHEA work?