The efficacy, safety, and tolerability of an estrogen-free oral contraceptive drospirenone 4 mg (24/4-day regimen) in obese users

Mitchell D Creinin; Alicyoy Angulo; Enrico Colli; David F Archer

doi:10.1016/j.contraception.2023.110136

The efficacy, safety, and tolerability of an estrogen-free oral contraceptive drospirenone 4 mg (24/4-day regimen) in obese users

Contraception. 2023 Dec:128:110136. doi: 10.1016/j.contraception.2023.110136. Epub 2023 Aug 5.

Authors

Mitchell D Creinin¹, Alicyoy Angulo², Enrico Colli³, David F Archer⁴

Affiliations

¹ Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, CA, United States.
² Exeltis, Madrid, Spain.
³ Exeltis, Madrid, Spain. Electronic address: Enrico.Colli@exeltis.com.
⁴ Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, United States.

PMID: 37544572
DOI: 10.1016/j.contraception.2023.110136

Abstract

Objectives: This study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight.

Study design: We analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index <30 kg/m²) and obese (body mass index ≥30 kg/m²) users. We used data from the US trial to calculate the Pearl Index (pregnancies per 100 woman-years) in nonbreastfeeding participants aged ≤35 years at enrollment for confirmed pregnancies. We assessed safety outcomes from all trials based on reported treatment-emergent adverse events. We evaluated pharmacokinetics by bodyweight in the US trial.

Results: The three trials combined comprised 2152 nonobese and 425 obese participants, including 590 nonobese and 325 obese participants in the US trial. Eight nonobese and four obese participants had confirmed pregnancies in the US trial, resulting in Pearl Indices of 3.0 (95% CI: 1.3-5.8) and 2.9 (95% CI: 0.8-7.3), respectively. Two-hundred forty-four (11.3%) nonobese and 39 (9.2%) obese participants discontinued due to a treatment-emergent adverse event. The pharmacokinetic analysis included 814 participants with a median weight of 73 (interquartile range 61-89) kg and median plasma drospirenone exposure (AUC_0-24ss) of 661.3 (interquartile range 522-828) ng∙h/mL. Changing bodyweight from the median to the fifth percentile (51 kg) or 95th percentile (118 kg) changed drospirenone exposure (AUC_0-24,ss) by 22.2% and -23.6%, respectively.

Conclusions: Drospirenone 4 mg demonstrated similar contraceptive efficacy for both nonobese and obese users despite a difference in exposure based on bodyweight.

Implications: Our limited comparison between obese and nonobese users of drospirenone-only oral contraception demonstrated no evidence that efficacy or discontinuation for adverse events differs between groups. Serum drospirenone levels vary by bodyweight and may correlate with bleeding outcomes.

Keywords: Bleeding profile; Drospirenone; Obesity; Oral contraceptive; Pearl Index; Progestin-only pill; Safety.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Contraception / methods
Contraceptives, Oral, Combined / adverse effects
Contraceptives, Oral, Hormonal*
Estrogens*
Female
Humans
Obesity / drug therapy
Pregnancy

Substances

Contraceptives, Oral, Combined
Contraceptives, Oral, Hormonal
drospirenone
Estrogens