Mass General Hospital

Harvard Medical School

Oral Contraceptives for the Treatment of Premenstrual Mood Symptoms

Oral contraceptives are commonly prescribed for the treatment of premenstrual symptoms and premenstrual dysphoric disorder (PMDD); however, the evidence supporting the use of oral contraceptives in this setting is limited. While most studies have shown that oral contraceptives are not effective for the treatment of premenstrual symptoms, there is preliminary evidence that a new oral contraceptive pill, Yaz, which contains low-dose estrogen and a novel progestin called drospirenone, may alleviate the symptoms of PMDD.

In a multicenter, double-blind, placebo-controlled study, participants (n=450) were randomized to receive treatment with Yaz, an oral contraceptive formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mcg, or placebo for three cycles after a washout period of two treatment-free cycles. Hormones were administered for 24 days, followed by 4 days of inactive pills.

Scores on the total Daily Record of Severity of Problems decreased by -37.49 in the active treatment group and by -29.99 in the placebo group (adjusted mean difference -7.5; p < 0.001). Response, defined as a 50% reduction in the severity of daily symptoms, occurred in 48% of the treatment group and in 36% of the placebo group.

In comparing the current study to previous studies assessing the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in women with PMDD, the authors noted that the overall effect size observed in the Yaz study was similar to that found for SSRIs. In both the Yaz and the SSRI studies, placebo response rates tended to be high. In addition, the authors noted that physical symptoms responded well to Yaz. In contrast, these symptoms were less likely to respond to SSRIs or required higher doses for response.

The authors speculated that the efficacy of Yaz may be related to the addition of the novel progestin, drospirenone. Drospirenone is distinct from the progestins used in other oral contraceptives and is chemically related to spironolactone, a diuretic that is sometimes used to treat fluid retention in women with premenstrual symptoms.

Ruta Nonacs, MD PhD

Yonkers KA, Brown C, Pearlstein TB, et al. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 2005; 106: 492-501.

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