Review question
We wanted to find out whether birth control pills containing drospirenone and oestrogen were effective in improving premenstrual syndrome (PMS) symptoms in women with PMS, compared to either a placebo ('dummy') pill or another birth control pill. We also wanted to find out what side effects the women might experience.
Background
PMS is a common problem. A severe form is called premenstrual dysphoric disorder (PMDD). Symptoms could include behaviour changes, and physical signs and symptoms that impact daily life. Birth control pills with the hormones progestin and oestrogen to treat these symptoms have been studied. A birth control pill with drospirenone combined with low-dose oestrogen was approved in the USA for treating PMDD.
Study characteristics
We found five trials with 858 women. All the trials compared a dummy pill to a drospirenone with low oestrogen pill. A majority of the women had PMDD, the severe form of PMS, before the trial. The evidence is current to June 2022.
Key results
After three months, women on the drospirenone with low oestrogen pill had less severe premenstrual symptoms than the group taking the dummy pill. Women on the drospirenone with low oestrogen pill said they could do more, and had more social activities and friends. However, women on the drospirenone with low oestrogen pill were more likely to pull out of the trials due to side effects. They reported more side effects overall; specifically, nausea, bleeding between periods, and breast pain, which are all common side effects with birth control pills. We do not know if the drospirenone with low oestrogen pill works longer than three cycles, helps women with less severe symptoms, or is better than other birth control pills.
The beneficial effects from the drospirenone with low oestrogen pill on premenstrual symptoms were small to moderate, although there was significant benefit from the dummy pill too. The evidence suggests that if the chance of pulling out of the trials due to side effects while on the dummy pill is assumed to be 3%, the chance while on the drospirenone with low oestrogen pill would be between 6% and 16%. It also suggests that if the risk of having side effects from the dummy pill is assumed to be 28%, the risk from the drospirenone with low oestrogen pill would be between 40% and 54%.
Quality of the evidence
The evidence was of very low to moderate quality. The main limitations of the evidence were poor reporting of trial methods, and lack of precision and consistency in the findings.
COCs containing drospirenone and EE may improve premenstrual symptoms that result in functional impairments in women with PMDD. The placebo also had a significant effect. COCs containing drospirenone and EE may lead to more adverse effects compared to placebo. We do not know whether it works after three cycles, helps women with less severe symptoms, or is better than other combined oral contraceptives that contain a different progestogen.
Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC), which provide both progestin and oestrogen, have been examined for their ability to relieve premenstrual symptoms. A combined oral contraceptive containing drospirenone and a low oestrogen dose has been approved for treating PMDD in women who choose combined oral contraceptives for contraception.
To evaluate the effectiveness and safety of COCs containing drospirenone in women with PMS.
We searched the Cochrane Gynaecology and Fertility Group trial register, CENTRAL (now containing output from two trials registers and CINAHL), MEDLINE, Embase, PsycINFO, LILACS, Google Scholar, and Epistemonikos on 29 June 2022. We checked included studies' reference lists and contacted study authors and experts in the field to identify additional studies.
We included randomised controlled trials (RCT) that compared COCs containing drospirenone with placebo or with another COC for treatment of women with PMS.
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were effects on premenstrual symptoms that were prospectively recorded, and withdrawal due to adverse events. Secondary outcomes included effects on mood, adverse events, and response rate to study medications.
We included five RCTs (858 women analysed, most diagnosed with PMDD). The evidence was very low to moderate quality; the main limitations were serious risk of bias due to poor reporting of study methods, and serious inconsistency and imprecision.
COCs containing drospirenone and ethinylestradiol (EE) versus placebo
COCs containing drospirenone and EE may improve overall premenstrual symptoms (standardised mean difference (SMD) ‐0.41, 95% confidence interval (CI) ‐0.59 to ‐0.24; 2 RCTs, N = 514; I2 = 64%; low-quality evidence); and functional impairment due to premenstrual symptoms in terms of productivity (mean difference (MD) ‐0.31, 95% CI ‐0.55 to ‐0.08; 2 RCTs, N = 432; I2 = 47%; low-quality evidence), social activities (MD ‐0.29, 95% CI ‐0.54 to ‐0.04; 2 RCTs, N = 432; I2 = 53%; low-quality evidence), and relationships (MD ‐0.30, 95% CI ‐0.54 to ‐0.06; 2 RCTs, N = 432; I2 = 45%; low-quality evidence). The effects from COCs containing drospirenone may be small to moderate.
COCs containing drospirenone and EE may increase withdrawal from trials due to adverse effects (odds ratio (OR) 3.41, 95% CI 2.01 to 5.78; 4 RCT, N = 776; I2 = 0%; low-quality evidence). This suggests that if you assume the risk of withdrawal due to adverse effects from placebo is 3%, the risk from drospirenone plus EE will be between 6% and 16%.
We are uncertain of the effect of drospirenone plus EE on premenstrual mood symptoms, when measured by validated tools that were not developed to assess premenstrual symptoms.
COCs containing drospirenone may lead to more adverse effects in total (OR 2.31, 95% CI 1.71 to 3.11; 3 RCT, N = 739; I2 = 0%; low-quality evidence). This suggests that if you assume the risk of having adverse effects from placebo is 28%, the risk from drospirenone plus EE will be between 40% and 54%. It probably leads to more breast pain, and may lead to more nausea, intermenstrual bleeding, and menstrual disorder. Its effect on nervousness, headache, asthenia, and pain is uncertain. There was no report of any rare but serious adverse effects, such as venous thromboembolism in any of the included studies.
COCs containing drospirenone may improve response rate (OR 1.65, 95% CI 1.13 to 2.40; 1 RCT, N = 449; I2 not applicable; low-quality evidence). This suggests that if you assume the response rate from placebo is 36%, the risk from drospirenone plus EE will be between 39% and 58%.
We did not identify any studies that compared COCs containing drospirenone with other COCs.