Elsevier

Contraception

Volume 103, Issue 6, June 2021, Pages 386-393
Contraception

Effects of an oral contraceptive containing estetrol and drospirenone on ovarian function

https://doi.org/10.1016/j.contraception.2021.03.003Get rights and content
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Abstract

Objective

To evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function.

Study design

Single-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of ovulation after treatment cessation, and safety throughout the study.

Results

None of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated.

Conclusions

E4 15 mg/DRSP 3 mg results in adequate ovulation inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP.

Implications statement

Treatment with E4 15 mg/DRSP 3 mg showed complete ovulation inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP.

Keywords

Estetrol
Drospirenone
Ethinylestradiol
Ovarian function
Hoogland score
Combined oral contraception

Cited by (0)

Funding: The study was funded by Estetra SRL, an affiliate's company of Mithra Pharmaceuticals, Liège, Belgium.

Conflict of Interest: ID and CK are directors of Dinox BV, a CRO that received funding for the study via PRA Health Sciences. VK, MJ and AB are employees of Estetra SRL, an affiliate's company of Mithra Pharmaceuticals. JMF is a member of the board at Mithra Pharmaceuticals and received financial support for the supervision of this study.