Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone

Christine Klipping; Ingrid Duijkers; Marie Mawet; Catherine Maillard; Adriana Bastidas; Maud Jost; Jean-Michel Foidart

doi:10.1016/j.contraception.2021.01.001

Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone

Contraception. 2021 Apr;103(4):213-221. doi: 10.1016/j.contraception.2021.01.001. Epub 2021 Jan 9.

Authors

Christine Klipping¹, Ingrid Duijkers¹, Marie Mawet², Catherine Maillard², Adriana Bastidas², Maud Jost³, Jean-Michel Foidart⁴

Affiliations

¹ Dinox BV, Groningen, The Netherlands.
² Estetra SRL, An Affiliate's Company of Mithra Pharmaceuticals, Liège, Belgium.
³ Estetra SRL, An Affiliate's Company of Mithra Pharmaceuticals, Liège, Belgium. Electronic address: mjost@mithra.com.
⁴ Estetra SRL, An Affiliate's Company of Mithra Pharmaceuticals, Liège, Belgium; University of Liège, Liège, Belgium.

PMID: 33428907
DOI: 10.1016/j.contraception.2021.01.001

Abstract

Objectives: To evaluate the effect on endocrine and metabolic parameters of a new combined oral contraceptive (COC) containing estetrol (E4) and drospirenone (DRSP).

Study design: Randomized, open-label, controlled, 3-arm, parallel study. Healthy subjects received either E4 15 mg/DRSP 3 mg (E4/DRSP) (n = 38), or ethinylestradiol (EE) 30 µg/levonorgestrel (LNG) 150 µg (n = 29), or EE 20 µg/DRSP 3 mg (n = 31) for 6 treatment cycles. Median percentage change from baseline to cycle 3 and to cycle 6 were evaluated for endocrine parameters, liver proteins, lipid profile, and carbohydrate metabolism.

Results: At cycle 6, E4/DRSP treatment had less effect on gonadotropins (follicle stimulating hormone [FSH] +30.5%, luteinizing hormone [LH] -7.5%) compared to EE/LNG (FSH -84.0%, LH -92.0%) and EE/DRSP (FSH -64.0%, LH -90.0%). With E4/DRSP increases in total cortisol (+26.0%) and cortisol binding globulin ([CBG] (+40.0%) were less compared to EE/LNG (cortisol +109.0%, CBG +152.0%) and EE/DRSP (cortisol +107.0%, CBG +140.0%). Liver proteins, except CRP, increased, but the effect was less pronounced with E4/DRSP for angiotensinogen (+75.0%) compared to EE/LNG (+170.0%) and EE/DRSP (+206.5%) and for sex hormone binding globulin ([SHBG] +55.0%), compared to EE/LNG (+74.0%) and EE/DRSP (+251.0%). E4/DRSP had minimal impact on lipid parameters; the largest effect was observed for triglycerides (+24.0%), which was less compared to EE/LNG (+28.0%) and EE/DRSP (+65.5%). E4/DRSP had no effect on carbohydrate metabolism.

Conclusions: E4/DRSP treatment has limited effects on endocrine and metabolic parameters. The effects on gonadotropins, cortisol, CBG, angiotensinogen, SHBG and triglycerides were less pronounced compared to EE-containing products.

Implications statement: Combining E4 15 mg with DRSP 3 mg resulted in a COC with a different metabolic profile in comparison to EE-containing products. The clinical relevance of these findings needs to be further assessed, using clinical endpoints to establish the safety profile of this new COC.

Keywords: Combined oral contraception; Drospirenone; Endocrine; Estetrol; Ethinylestradiol; Metabolic.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Androstenes
Contraceptives, Oral, Combined
Estetrol*
Estrogens
Ethinyl Estradiol
Female
Humans
Levonorgestrel
Sex Hormone-Binding Globulin

Substances

Androstenes
Contraceptives, Oral, Combined
Estrogens
Sex Hormone-Binding Globulin
Ethinyl Estradiol
Levonorgestrel
Estetrol
drospirenone