A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials

Background: Dehydroepiandrosterone (DHEA) has been aggressively sold as a dietary supplement to boost testosterone levels although the impact of DHEA supplementation on testosterone levels has not been fully established. Therefore, we performed a systematic review and meta-analysis of RCTs to investigate the effect of oral DHEA supplementation on testosterone levels. Methods: A systematic literature search was performed in Scopus, Embase, Web of Science, and PubMed databases up to February 2020 for RCTs that investigated the effect of DHEA supplementation on testosterone levels. The estimated effect of the data was calculated using the weighted mean difference (WMD). Subgroup analysis was performed to identify the source of heterogeneity among studies. Results: Overall results from 42 publications (comprising 55 arms) demonstrated that testosterone level was significantly increased after DHEA administration (WMD: 28.02 ng/dl, 95% CI: 21.44-34.60, p = 0.00). Subgroup analyses revealed that DHEA increased testosterone level in all subgroups, but the magnitude of increment was higher in females compared to men (WMD: 30.98 ng/dl vs. 21.36 ng/dl); DHEA dosage of 12 weeks compared to 12 weeks (WMD: 44.64 ng/dl vs. 19 ng/dl); healthy participants compared to postmenopausal women, pregnant women, non-healthy participants and androgen-deficient patients (WMD: 52.17 ng/dl vs. 25.04 ng/dl, 16.44 ng/dl and 16.47 ng/dl); and participants below 60 years old compared to above 60 years old (WMD: 31.42 ng/dl vs. 23.93 ng/dl). Conclusion: DHEA supplementation is effective for increasing testosterone levels, although the magnitude varies among different subgroups. More study needed on pregnant women and miscarriage.