Pharmacodynamics of combined estrogen-progestin oral contraceptives 3. Inhibition of ovulation

ABSTRACT

Introduction: Following a historical overview, the ovulation-inhibiting effect of various orally administered estrogen-progestin combinations (combined oral contraceptives [COCs]) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens.

Areas covered: Inhibition of ovulation with progestins alone; estrogens alone; various progestins in combination with ethinyl estradiol; various progestins in combination with natural estrogens (estradiol, estradiol valerate, and estetrol).

Expert commentary: The original idea to achieve ovulation blockage through the administration of steroid hormones involved the use a progestogen (both progesterone and its synthetic homologous). The ability of a progestin to inhibit ovulation depends on the type of compound and on its dosage and a difference of more than 20-fold in activity exists between compounds utilized today in COCs.

Initially, the estrogenic component was present only because it contaminated the first progestin utilized. It was soon found that an estrogen is necessary for proper cycle control. It was also found that the estrogen acts synergistically in inhibiting ovulation. For almost half a century, most COCs contained ethinyl estradiol. Today, also natural estrogens are being employed.

Inhibition of ovulation was complete with all early high dose preparations. Decreasing dosage allowed some ovarian activity to occur, occasionally leading to a mature follicle. Even in this situation, defective corpus luteum formation assured contraceptive protection.

KEYWORDS:

• Androgens
• combined oral contraceptives
• drospirenone
• estradiol
• estradiol valerate
• estrogens
• ethinyl estradiol
• hemostasis
• nomegestrol acetate
• progestins

Declaration of interest

The 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

A reviewer on this paper has disclosed their company Pantarhei Oncology is developing E4 for the treatment of breast and prostate cancer. They have developed E4 until and including phase 2 for contraception until 2013 and sold the project to Actavis (Warson) that year. Thereafter they have had no influence on the further development of E4 for contraception and since then they have no financial interest in E4 for contraception.

Additional information

Funding

This paper was not funded.