Objective: To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder.
Methods: This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 μg. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4).
Results: Scores on the total Daily Record of Severity of Problems decreased by –37.49 in the drospirenone/ethinyl estradiol group and by –29.99 in the placebo group (adjusted mean difference –7.5, 95% confidence interval [CI] –11.2 to –3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by –19.2 and –15.3 in active-treatment and placebo groups, respectively (adjusted mean difference –3.9, 95% CI –5.84 to –2.01; P = .003); physical symptom scores were reduced by –10.7 and –8.6 in active-treatment and placebo groups, respectively (adjusted mean difference –2.1, 95% CI –3.3 to –0.95; P < .001); and behavioral symptom scores were reduced by –7.7 and –6.2 in active-treatment and placebo groups, respectively (adjusted mean difference –1.5, 95% CI –2.251 to –0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients.
Conclusion: A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 μg improves symptoms associated with premenstrual dysphoric disorder.
Level of Evidence: I