Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

Abstract

BackgroundThis study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens.Study designIn this Phase III, multicentre, open-label study, women (aged 18–35 years) were randomised to EE/DRSP in the following regimens: flexibleMIB (24–120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexibleMIB regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres.ResultsResults were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexibleMIB, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens.ConclusionsEE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

FSRH Guideline (January 2019, amended October 2023) Combined Hormonal Contraception

“…Metabolic and haemostatic parameters, serum hormone levels and blood pressure were similar in all groups. Numbers of serious adverse events were very low in all groups 50. A smaller trial which randomised 78 women to use extended or standard cyclical regimens of 30 μg EE/DRSP COC found no statistically significant differences in carbohydrate or lipid profiles between the two groups over 6 months of use 51.…”

Continuous use of oral contraceptives: an overview of effects and side‐effects

“…In an RCT (6), 1166 women were randomized to three different regimens: a flexible cycle (tablets for 24–120 days followed by four days of hormone‐free interval when bleeding occurred), a fixed 4/24 cycle or an extended fixed cycle of 4/120 days with active pills. The endometrium was characterized by endometrial biopsy results after one year in 23 women who received the flexible regimen and in 17 who received the fixed extended regimen.…”

Women’s perceptions about reducing the frequency of monthly bleeding: results from a multinational survey

“…In this regard, the efficacy and tolerability of a combined OC in a flexible extended regimen has recently been investigated which, when compared with the conventional 28-day regimen, showed significant reductions in the number of bleeding/spotting days and withdrawal bleeding episodes. 21,22 Previous studies have shown that some women worry about the possibility of menstrual "build-up," creation of an "unnatural" state, and the possibility of pregnancy with "missed" monthly bleeding. [6][7][8]20 These misconceptions were also observed in the present survey, in which most women cited health concerns as the main reason for not reducing bleeding frequency, either occasionally or regularly; a large proportion of women also reported that they felt that monthly bleeding was necessary to cleanse the body.…”