Combined oral contraceptive with estetrol plus drospirenone: from pharmacokinetics to clinical applications

ABSTRACT

Introduction

Drospirenone/estetrol (DRSP/E4) is a combined oral contraceptive (COC) recently approved in several countries. It is composed of 15 mg of E4, a natural estrogen produced by human fetal liver throughout pregnancy, and 3 mg of DRSP, the first synthetic progestin used in oral contraception derived from 17-α-spirolactone. E4 and DRSP synergistically prevent pregnancy by inhibiting ovulation. E4 differs from 17-β-estradiol or ethinylestradiol because it represents a native estrogen with selective action in tissues (NEST), therefore it displays both agonist and antagonist estrogenic effects in different tissues.

Areas Covered

In this paper, we reviewed the scientific literature published in English prior to April 2023 and gathered information on the pharmacodynamics and pharmacokinetics of DRSP, E4 and their combination for contraception. We also proposed possible clinical applications based on the characteristics of the components of this COC.

Expert Opinion

E4/DRSP-based COC has shown high tolerability, safety and satisfaction and may represent a viable choice in young girls in need of oral contraception and pill users who suffer from high cholesterol, breast tenderness or water retention. Moreover, this new COC shows higher scheduled bleeding rate compared to other pills containing natural estrogens. All the data are reassuring, permitting long-term use.

KEYWORDS:

• Estetrol
• drospirenone
• oral contraceptive
• pharmacokinetic
• pharmacodynamic
• clinical application

Declaration of interests

G Grandi received honoraria for sponsored lectures and participation in advisory boards from Bayer AG, Italfarmaco, Theramex, Organon, Gedeon Richter, and Exeltis, not related to this manuscript.

The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer: Grants/Research: Mylan Pharmaceuticals Inc, Sumitomo Pharma America, Inc., Organon & Co, Sagami Rubber Industries, Co Ltd, Sebela Pharmaceuticals

Honoraria/Speakers Bureau: Agile Therapeutics, Bayer, Mayne Pharma, Merck, Organon & Co

Consultant/Advisory Board: Agile Therapeutics, Bayer, Mayne Pharma, Sumitomo Pharma America. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.