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.

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 10cycles to a 30-mcg ethinyl estradiol (EE)/levonorgestrel (LNG) OC or a 30-mcg EE/drospirenone (DRSP) OC, along with daily use of 50mg dehydroepiandrosterone (DHEA) or placebo during five OC cycles before crossing over from DHEA to placebo or the reverse for another fivecycles. 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<.05). No significant changes were observed for genital response (VPA) and the other two variables of the SSAQ assessed after visual erotic stimulus exposure. Using the SFD, 5 out of 10 variables showed a significant improvement with DHEA. Partner's initiative was rejected less often with OC+DHEA compared to placebo (OC+placebo vs. OC+DHEA: 1.1±1.5 vs. 0.8±1.0; p<.05). Women with free testosterone levels in the upper quartile during DHEA co-administration showed significantly better effects on sexual arousal and desire compared to the three lower quartiles (lower vs. upper quartiles: sexual arousability: 25.0±19.8 vs. 41.2±29.0; sexual desire: 5.6±3.7 vs. 9.6±8.0; desire for sex with partner: 4.9±3.1 vs. 8.6±7.4; number of sex fantasies: 3.0±3.2 vs. 5.5±4.4; all p<.05). 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.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

OBJECTIVE: To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. STUDY DESIGN: A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m2) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. RESULTS: Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. CONCLUSIONS: Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. IMPLICATIONS: A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC.