Birth control pills with drospirenone for treating premenstrual syndrome

Premenstrual syndrome (PMS) is a common problem. A severe form is called premenstrual dysphoric disorder (PMDD). Birth control pills with the hormones progestin and estrogen have been studied for treating such symptoms. A birth control pill with the progestin drospirenone may work better than other such pills. A drospirenone pill with low estrogen was approved for treating PMDD, the severe form of PMS, in women who use birth control pills.

We did a computer search for trials that compared a birth control pill containing drospirenone and estrogen to a placebo ('dummy') or another birth control pill in treating premenstrual symptoms. We wrote to researchers to find other trials. We looked at whether the pills reduced symptoms and if side effects were reported. Women recorded their symptoms over time.

We found five trials with 1920 women. Two trials compared a dummy pill to a drospirenone pill with low estrogen. All the women had PMDD, the severe form of PMS, before the trial. After three months, women on the drospirenone pill with low estrogen had less severe premenstrual symptoms than the group taking the dummy pill. Women in the drospirenone group said they could do more and had more social activities and friends. Women on the drospirenone pill had more nausea, bleeding between periods, and breast pain. These side effects are common with birth control pills. Three trials studied a drospirenone pill with more estrogen for treating less severe symptoms. These women did not all have PMDD. One compared the drospirenone pill to a dummy pill but did not have enough data for our review. Two compared the study pill to another birth control pill. The two-year study showed the groups were similar for premenstrual symptoms and side effects. The six-month study did not give enough data on the symptoms.

A drospirenone pill with low estrogen seems to help premenstrual symptoms in women with severe symptoms (PMDD). The drospirenone pill worked a little better than the dummy pill, which also affected symptoms. We do not know if the birth control pill works longer than three cycles, helps women with less severe symptoms, or is better than other birth control pills. Longer and better studies with more women are needed to address these issues. Trials reports should be clearer about how the study was done.

Authors' conclusions: 

Drospirenone 3 mg plus ethinyl estradiol 20 μg may help treat premenstrual symptoms in women with severe symptoms, that is, premenstrual dysphoric disorder. The placebo also had a large effect. We do not know whether the combined oral contraceptive works after three cycles, helps women with less severe symptoms, or is better than other oral contraceptives. Larger and longer trials of higher quality are needed to address these issues. Trials should follow CONSORT guidelines.

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Background: 

Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception.

Objectives: 

To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms.

Search strategy: 

We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials.

Selection criteria: 

We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined.

Data collection and analysis: 

Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated.

Main results: 

We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95% CI -11.16 to -4.67). The drospirenone group had greater mean decreases in impairment of productivity (MD -0.31; 95% CI -0.55 to -0.08), social activities (MD -0.29; 95% CI -0.54 to -0.04), and relationships (MD -0.30; 95% CI -0.54 to -0.06). Side effects more common with the use of the drospirenone COC contraceptive were nausea, intermenstrual bleeding, and breast pain. The respective odds ratios were 3.15 (95% CI 1.90 to 5.22), 4.92 (95% CI 3.03 to 7.96), and 2.67 (95% CI 1.50 to 4.78). Total adverse events related to the study drug were more likely for the drospirenone COC group (OR 2.36; 95% CI 1.62 to 3.44). Three trials studied the effect of drospirenone 3 mg plus ethinyl estradiol 30 μg on less severe symptoms. A placebo-controlled six-month trial had insufficient data for primary outcome analysis. Another six-month study used levonorgestrel 150 µg plus ethinyl estradiol 30 µg for the comparison group but did not provide enough data on premenstrual symptoms. In a two-year trial, the drospirenone COC group had similar premenstrual symptoms to the comparison group given desogestrel 150 µg plus ethinyl estradiol 30 µg (OR 0.87; 95% CI 0.63 to 1.22). The groups were also similar for adverse events related to treatment (OR 1.02; 95% CI 0.78 to 1.33).

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