Impact of Oral DHEA Supplementation on Androgen Levels in Women Using Combined Oral Contraceptives: A Randomized Study

Background: Combined oral contraceptives (COCs) reduce androgen levels, particularly Testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and increasing Sex Hormone-Binding Globulin (SHBG). This can lead to testosterone deficiency, which is associated with negative effects on well-being, mood, energy, cognitive function, sexual functioning, muscle mass, and bone density. Objective: To evaluate the effects of adding oral Dehydroepiandrosterone (DHEA) to Combined Oral Contraceptives (COCs) on the hormonal profile in Caucasian women. Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted with 35 healthy Caucasian women aged 21-35 years (BMI: 18.5-25 kg/m²) who used a COC containing 30μg ethinyl estradiol (EE) and 150μg Levonorgestrel (LNG). Participants discontinued COC use for three menstrual cycles before being randomized to receive either COCs with 50 mg/day DHEA (n=18) or placebo (n=17) for six cycles. Hormonal levels were measured at baseline and after 1, 3, and 6 months of treatment. Results: COC use significantly reduced Total Testosterone (by 56.2%), Free Testosterone (by 65.7%), Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate, and Androstenedione levels while increasing SHBG concentration (P<0.001). Adding DHEA to COCs restored both Free and Total Testosterone levels to baseline (P<0.001). Discussion: The addition of DHEA to COCs was effective in maintaining physiological androgen levels, potentially counteracting the adverse effects of COCs on female sexual function and overall well-being. Conclusion: Adding 50 mg/day DHEA to EE/LNG-containing COCs maintains physiological levels of Free and Total Testosterone in Caucasian women, potentially mitigating the adverse effects of COCs on female sexual function. Further comprehensive clinical trials are warranted to evaluate these clinical effects.