Marie Foegh

Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder

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 &mgr;g. 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 &mgr;g improves symptoms associated with premenstrual dysphoric disorder. Level of Evidence: I

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.

Low-dose levonorgestrel and ethinyl estradiol patch and pill: a randomized controlled trial.

OBJECTIVE: To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding. METHODS: Women (17–40 years; body mass index 16–60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy. RESULTS: Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1–6) were 4.45 (2.34–6.57) for Patch and 4.02 (0.50–7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98–4.67) for Patch and 3.80 (0.08–7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference). CONCLUSIONS: Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479. LEVEL OF EVIDENCE: I