Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled crossover trial
PubMed 27393080 · doi:10.1016/j.contraception.2016.06.022
What was done
A randomized, double-blind, placebo-controlled, two-way crossover study in 81 healthy women (ages 20–35, BMI 18–35 kg/m²) evaluated whether oral DHEA coadministration prevents contraceptive-induced androgen suppression. Participants discontinued oral contraceptives for at least one menstrual cycle, then received five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG) or drospirenone (EE/DRSP) together with either DHEA (50 mg/day orally) or placebo, followed by a crossover to the alternate co-treatment arm for an additional five cycles. Androgens, SHBG, estradiol, and estrone were measured, and free testosterone was calculated.
What was found
Both oral contraceptives reduced all measured androgens compared to baseline. Total testosterone decreased by 54.5% with EE/LNG and 11.3% with EE/DRSP (p < .05), while free testosterone decreased by 66.8% and 75.6%, respectively (p < .05). Adding 50 mg/day DHEA significantly increased all androgens compared with placebo, fully restoring free testosterone to baseline in both contraceptive groups. DHEA restored total testosterone to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG levels were significantly higher with EE/DRSP than EE/LNG (p < .0001) and were not affected by DHEA.
Why it matters
Combined oral contraceptives strongly suppress circulating free and total testosterone, which may contribute to androgen-deficiency side effects such as reduced libido. This study establishes that 50 mg/day DHEA can normalize free testosterone levels in women taking oral contraceptives without altering SHBG concentrations.
Limits
The abstract reports only surrogate endocrine biomarkers and does not provide clinical or patient-reported outcomes such as sexual function, mood, or metabolic impact. The trial was limited to 81 healthy young women and followed them for only five cycles per treatment arm, leaving long-term safety and efficacy unaddressed.
Cited by
- supports Oral DHEA supplementation can fully attenuate the testosterone suppression induced by combined oral contraceptives in women.