Maintaining physiologic testosterone levels during combined oral contraceptives by adding dehydroepiandrosterone: II. Effects on sexual function. A phase II randomized, double-blind, placebo-controlled study

Abstract Objective The objective was to evaluate the effect of combined oral contraceptives (OCs) on sexual function, either alone or together with dehydroepiandrosterone (DHEA). Study design An exploratory randomized, double-blind, placebo-controlled, comparative, crossover study was conducted in 81 OC users. Subjects discontinued their OC for one cycle before being randomized for 10 cycles to a 30-mcg ethinyl estradiol (EE)/levonorgestrel (LNG) OC or a 30-mcg EE/drospirenone (DRSP) OC, along with daily use of 50 mg dehydroepiandrosterone (DHEA) or placebo during five OC cycles before crossing over from DHEA to placebo or the reverse for another five cycles. First, the effect on sexual function of five OC cycles + placebo was compared to baseline. Then, the effect of five OC cycles + DHEA was compared to the OC + placebo. Results regarding endocrine changes have been published separately. Primary efficacy outcomes of the current study were genital response (measured by vaginal pulse amplitude [VPA]) and sexual feelings (measured by the subjective self-assessment questionnaire [SSAQ]) to self-induced erotic fantasy and visual sexual stimuli in a laboratory setting and measures of desire and arousability using a sexual function diary (SFD). Secondary efficacy outcomes were the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale Revised. Results Eighty-one women were enrolled, and 74 women completed the study. Five cycles of OC + placebo resulted in a significant decline compared to baseline of four out of six SFD self-ratings of sexual desire and arousability with both OCs. The LNG OC also resulted in significant declines in the FSFI scores (baseline vs. LNG OC + placebo: total score, 28.7±3.7 vs. 25.6±7.4; arousal, 5.0±0.7 vs. 4.5±1.4; lubrication, 5.2±0.9 vs. 4.6±1.7; pain, 4.9±0.9 vs. 4.5±1.4), but no changes were observed using the DRSP OC. In the laboratory setting, five cycles of OC + DHEA showed no significant differences with placebo except for a significant increase in genital sensations (SSAQ) during erotic fantasy (OC + placebo vs. OC + DHEA: 3.3±1.4 vs. 3.6±1.5; p Conclusions In this exploratory study, OC use was associated with decreases in some measures of sexual functioning, whereas others remained unchanged. Maintaining or restoring physiological testosterone concentrations by the co-administration of DHEA to the OC may prevent these effects on sexuality, particularly in women with relatively high but physiologic levels of free testosterone during DHEA co-administration. Implications The results of this exploratory study warrant further testing of the hypothesis that restoration and/or preservation of physiologic testosterone levels during OC use by co-administration of DHEA has favorable effects on those aspects of sexual function compromised by OCs.