Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime

Abstract

Background A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. Methods Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. Results No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. Conclusions The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. Trial registration EudraCT registration numbers: 2010–021787-15 & 2011–002396-42. Clincaltrials.gov: NCT02269241.

Oral Progestins in Hormonal Contraception: Importance and Future Perspectives of a New Progestin Only-Pill Containing 4 mg Drospirenone

“…The clinical programme demonstrated the favourable thromboembolic safety profile of 4 mg DRSP, also for women with VTE risk factors. Cigarette smoking in women > 35 years of age was the most common risk factor in the European studies (10.1% and 12%, respectively) 37 , 38 , 41 . In the US study 39 , 41 , this incidence was 5.1%.…”

“…Over the period of the entire clinical development programme (> 20 000 cycles), no reports of VTEs in women taking 4 mg DRSP were reported 41 . The documented risk factors included a family history of thromboembolic events, evidence of a predisposition to vascular or metabolic disease, smoking if over 35 years of age, not smoking and over 40 years of age, and a body mass index (BMI) of ≥ 30 kg/m 2 .…”

“…These observations are consistent with the fact that 4 mg DRSP was neutral with regard to the haemostaseological parameters examined in the above-mentioned long-term study. Future epidemiological studies will be needed to corroborate the clinical data on cardiovascular safety 41 .…”

“…The first study demonstrated a median decrease of 8 mmHg (SBP) and 5 mmHg (DBP) in participants with a baseline SBP of ≥ 130 mHg and a baseline DBP of ≥ 85 mmHg (n = 137) 36 , 37 . In participants with a baseline SBP of < 130 mmHg and a baseline DBP of < 85 mmHg (n = 548), the absolute median change was 0 mmHg for both SBP and DBP 41 .…”

An Update on Contraception in Polycystic Ovary Syndrome

“…Progestin-only pills, or mini-pills, containing low daily doses of progestins (e.g., levonorgestrel 30 μg, norethindrone 35 μg, desogestrel 75 μg) need to be used continuously [ 113 ], except for the drospirenone-only pill, which is taken daily for 24 days followed by 4 days of placebo [ 114 ]. In continuous use, higher rates of breakthrough bleeding than that of COCs were reported [ 115 ].…”