Continuous oral levonorgestrel/ethinyl estradiol (LNG/EE) as a new treatment for premenstrual dysphoric disorder (PMDD): a randomized, double-blind, placebo-controlled study

Abstract

OBJECTIVE: To investigate the effect of a continuous daily oral contraceptive containing LNG 90 μg/EE 20 μg on PMDD symptoms.DESIGN: A multicenter, randomized double-blind placebo-controlled study of women with DSM-IV PMDD.MATERIALS AND METHODS: Subjects monitored symptoms using the Daily Record of Severity of Problems (DRSP; 21-item 6-point scale). Subjects had to have minimal follicular and moderate-to-severe luteal phase symptoms with functional impairment. Subjects were randomly assigned to receive LNG/EE or placebo daily ×112 days. The 4 co-primary endpoints were changes in DRSP scores from baseline late luteal phase to the same estimated phase of 1st and last on-therapy cycles and to the worst 5 days during 1st and last on-therapy cycles. Secondary analysis included percent responders and remitters. Analysis of covariance with baseline as covariate, treatment and investigator as factors and Fisher's exact test were used for primary and secondary analyses.RESULTS: 367 subjects received ≥1 dose of double-blind treatment (186 LNG/EE;181 placebo). About 30% of each group discontinued. Mean total daily DRSP scores during the late luteal phase and worst 5 days decreased significantly from baseline in both groups at all cycles (p<0.001). Mean change from baseline was significantly greater than placebo in the LNG/EE group for 2 primary endpoints; p=0.051 for the last on-therapy late luteal phase.For worst 5 day analyses, mean decreases were significantly greater with LNG /EE than placebo at cycles 2, 3 and 4 (p< 0.05); on post-hoc analysis excluding days 2-7, the decrease was significantly greater than placebo at cycle 1. Significantly more LNG/EE (52%) than placebo (40%) subjects were responders (≥50% improved) at last on-therapy cycle (p=0.025).The higher percentage of remitters (responders with no PMDD) with LNG /EE than placebo (43% vs 32%) did not reach statistical significance.Table 1Change from baseline in DRSP ScoresLNG/EEPlaceboCyclenAdjusted mean (SE)nAdjusted mean (SE)p vs placeboLate Luteal 1st160-30.5 (1.78)168-22.5 (1.77)<0.001 Last on-therapy161-41.3 (1.73)168-36.8 (1.73)0.051Worst 5 Days 1st160-14.4 (1.59)168-11.5 (1.58)0.167 1st, days 2-7 excluded160-21.4 (1.77)168-16.7 (1.76)0.043 Last on-therapy161-26.8 (1.83)168-20.9 (1.82)0.016 Open table in a new tab CONCLUSIONS: LNG 90 μg/EE 20 μg daily was effective in preventing PMDD during the late luteal phase and reducing symptoms occurring at any time during the cycle. OBJECTIVE: To investigate the effect of a continuous daily oral contraceptive containing LNG 90 μg/EE 20 μg on PMDD symptoms. DESIGN: A multicenter, randomized double-blind placebo-controlled study of women with DSM-IV PMDD. MATERIALS AND METHODS: Subjects monitored symptoms using the Daily Record of Severity of Problems (DRSP; 21-item 6-point scale). Subjects had to have minimal follicular and moderate-to-severe luteal phase symptoms with functional impairment. Subjects were randomly assigned to receive LNG/EE or placebo daily ×112 days. The 4 co-primary endpoints were changes in DRSP scores from baseline late luteal phase to the same estimated phase of 1st and last on-therapy cycles and to the worst 5 days during 1st and last on-therapy cycles. Secondary analysis included percent responders and remitters. Analysis of covariance with baseline as covariate, treatment and investigator as factors and Fisher's exact test were used for primary and secondary analyses. RESULTS: 367 subjects received ≥1 dose of double-blind treatment (186 LNG/EE;181 placebo). About 30% of each group discontinued. Mean total daily DRSP scores during the late luteal phase and worst 5 days decreased significantly from baseline in both groups at all cycles (p<0.001). Mean change from baseline was significantly greater than placebo in the LNG/EE group for 2 primary endpoints; p=0.051 for the last on-therapy late luteal phase. For worst 5 day analyses, mean decreases were significantly greater with LNG /EE than placebo at cycles 2, 3 and 4 (p< 0.05); on post-hoc analysis excluding days 2-7, the decrease was significantly greater than placebo at cycle 1. Significantly more LNG/EE (52%) than placebo (40%) subjects were responders (≥50% improved) at last on-therapy cycle (p=0.025).The higher percentage of remitters (responders with no PMDD) with LNG /EE than placebo (43% vs 32%) did not reach statistical significance. CONCLUSIONS: LNG 90 μg/EE 20 μg daily was effective in preventing PMDD during the late luteal phase and reducing symptoms occurring at any time during the cycle.