1. In a phase III clinical trial, women taking drospirenone-only pills were significantly less likely to have unscheduled bleeding compared to those taking desogestrel pills.
2. This improvement in bleeding profile seen with women taking drospirenone-only pills could improve both quality of life and compliance in those seeking an estrogen-free contraceptive option.
Evidence Rating Level: 2 (Good)
Study Rundown: Compared to combined oral contraceptive pills, progestin-only pills (POPs) have a lower VTE risk, come with fewer metabolic changes, and are a suitable option for women who cannot tolerate or have contraindications to estrogen (ie cardiovascular risk factors, migraines). However, up to 25% of users discontinue POPs due to menstrual disturbances and problematic bleeding. In this randomized controlled trial, 1190 women from primary and secondary gynaecological health care centres across Europe were randomly assigned to either receive a drospirenone-only pill (drospirenone 4mg), the study medication developed to achieve an improved bleeding profile, or the comparator POP for safety, desogestrel 0.075mg (marked as Cerazette® and Cerazet®). Using electronic diaries to capture medication compliance and their bleeding patterns (presence and intensity) for 9 cycles, the primary efficacy endpoint measured was the proportion of women with unscheduled bleeding or spotting in each cycle, cycles 2-4, and cycles 7-9. The proportion of women with unscheduled bleeding/spotting decreased over time in both groups, with this proportion significantly lower in the drospirenone group than in the comparator in every cycle up to cycle 7. The mean number of unscheduled bleeding/spotting days was also significantly lower in the drospirenone group than the desogestrel group during cycles 2-6, with the total number of bleeding/spotting days lower in the drospirenone across all treatment periods. As this is the first head-to-head trial comparing two POPs on bleeding profile, future studies with longer treatment periods, more data in the later menstrual cycles, and more similar dosing regimens between the study and comparator drugs could provide some clarity on these results. Nonetheless, the drospirenone-only pill was associated with significantly lower rates of overall and unscheduled bleeding/spotting in cycles 2-4 and significantly fewer bleeding/spotting days overall, supporting its viability as a POP with a better bleeding profile than those currently on the market.
In-Depth [double-blinded, randomized controlled trial]: This phase III study included women of child-bearing potential, aged 18-45 years old, with systolic blood pressure <140mmHg, diastolic <90mmHg [mean age= 28.9, 99.8% Caucasian, BMI = 22.89], n=858 received the drospirenone-only pill [91.6% with regular menstrual bleeding during last 6 cycles, 73.2% directly switched from another oral contraceptive without break], n=332 received the desogestrel comparator [91.9% with regular menstrual bleeding during last 6 cycles, 78.0% directly switched from another oral contraceptive without break]. Between August 1, 2012 and Januaray 27, 2014, patients were studied from 73 gynaecological health care centres in Austria, Czech Republic, Germany, Hungary, Poland, Romania, Slovakia, and Spain. 27 (3.2%) of the women using drospirenone and 49 (6.6%) of the women using desogestrel experienced abnormal uterine bleeding. The proportion of women with unscheduled bleeding/spotting was significantly lower in cycles 2-6 in the drospirenone group (73.0% vs 88.4%, p<0.0001), having decreased in both group from cycle 2 to cycle 9 (drospirenone: 69.7% to 56.3% vs desogestrel: 74.0% to 45.3%). Scheduled bleeding was any bleeding during hormone-free intervals (days 25-28 +/-1 in drospirenone, no hormone-free days in desogestrel group because given continuously). Thus, unscheduled bleeding/spotting occurs while taking active hormones (days 2-23 in drospirenone group), outside of a scheduled period (up to 8 consecutive days of bleeding). The mean number of unscheduled bleeding/spotting days was also significantly lower in the drospirenone group from cycles 2-9 (21.5 vs 34.7 days, p-0.0003) and excluding amenorrheic women, from cycles 2-6 (18.8 vs 24.6 days, p=0.0365). Limitations include the decrease in available data from patients on bleeding/spotting analyses as treatment progressed in both groups (90.5% and 93.1% for drospirenone and comparator in cycle 1 vs 56.3% and 45.3% in cycle 9). As well, drospirenone was given as 24 active tablets and 4 placebo tablets, while desogestrel was given continuously, as 28 active tablets, which can make defining scheduled bleeding challenging. With an increased proportion of women in both groups who had no bleeding or spotting (30.3% to 43.7% in drospirenone; 26.0% to 54.7% in desogestrel), further research could help determine the efficacy of POPs in improving compliance and bleeding patterns.
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