The effect of dehydroepiandrosterone (DHEA) supplementation on estradiol levels in women: A dose-response and meta-analysis of randomized clinical trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 34246664 · doi:10.1016/j.steroids.2021.108889
What was done
Researchers conducted a systematic review and dose-response meta-analysis of randomized controlled trials across PubMed/Medline, Embase, Web of Science, and Scopus through May 10, 2021, without time or language restrictions. They evaluated the effect of oral DHEA supplementation versus control on circulating estradiol concentrations in women using a random-effects model with the generic inverse of variance method. The meta-analysis included 21 trial arms comprising 1,223 participants (610 intervention, 613 control).
What was found
DHEA supplementation significantly increased circulating estradiol levels overall compared to controls (weighted mean difference [WMD]: 7.02 pg/mL, 95% CI: 5.43 to 8.62, P = 0.000). Stratified analyses showed: - Age ≥60 years: WMD 8.56 pg/mL (95% CI: 6.97 to 10.16, I² = 94%) - Duration ≥26 weeks: WMD 7.30 pg/mL (95% CI: 6.28 to 8.32, I² = 61%) - Dosage of 50 mg/day: WMD 7.75 pg/mL (95% CI reported in abstract as 9.12 to 9.39, I² = 94%) - Postmenopausal women: WMD 7.61 pg/mL (95% CI: 5.97 to 9.24, I² = 93%)
Why it matters
This review demonstrates that exogenous DHEA elevates circulating estradiol in women, confirming functional peripheral aromatization, especially in postmenopausal women with low baseline estrogens.
Limits
Statistical heterogeneity was extremely high across most subgroup analyses (I² up to 94%). The abstract contains an apparent typo in the reported 95% CI for the 50 mg/day subgroup. Clinical outcomes, safety, adverse effects, and quality assessment/risk of bias of included studies were not detailed in the abstract.
Cited by
- supports Studies investigating DHEA supplementation typically use doses between 25 and 50 milligrams.