Levonorgestrel Oral Contraceptives Research Articles

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

ObjectiveThe objective was to evaluate the effect of combined oral contraceptives (OCs) on sexual function, either alone or together with dehydroepiandrosterone (DHEA). Study designAn 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. ResultsEighty-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). ConclusionsIn 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. ImplicationsThe 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.

Postmarketing study of ORTHO EVRA ® and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of ethinyl estradiol in relation to nonfatal venous thromboembolism

Background Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA ® patch is higher compared to users of oral contraceptives (OCs). Study Design We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results The ORs (95% CI) for VTE in users of the patch compared to levonorgestrel-containing OCs were 2.0 (0.9–4.1) and 1.3 (0.8–2.1) in the PharMetrics and MarketScan databases, respectively. ORs (95% CI) restricted to women aged 39 years or younger were 1.4 (0.6–3.0) and 1.2 (0.7–2.0), respectively. Conclusion These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older.