What is the mechanism of action of combined oral contraceptives?

Mechanism of Action of Combined Oral Contraceptives

Combined oral contraceptives prevent pregnancy primarily by suppressing ovulation through inhibition of gonadotropin-releasing hormone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), while also thickening cervical mucus to impede sperm entry and thinning the endometrium to reduce implantation likelihood. 1, 2

Primary Mechanism: Ovulation Suppression

• The progestin component is the primary driver of ovulation inhibition, suppressing the mid-cycle LH surge that triggers ovulation 3, 4
• The estrogen component (typically ethinyl estradiol) acts synergistically with progestin to enhance ovulation suppression and provides cycle control 4, 5
• Complete ovulation blockage occurs with standard-dose formulations, though lower-dose pills may permit some follicular activity while still maintaining contraceptive efficacy through other mechanisms 4

Secondary Contraceptive Mechanisms

• Cervical mucus thickening: The progestin increases cervical mucus viscosity, creating a physical barrier that prevents sperm from entering the uterus 2, 5
• Endometrial changes: COCs decidualize the endometrial lining and suppress mitotic activity, making the endometrium less receptive to implantation 2, 3
• These secondary mechanisms provide backup contraceptive protection even when breakthrough ovulation occurs with lower-dose formulations 4

Hormonal Effects and Pharmacology

• Progestin potency varies significantly: Different progestins demonstrate more than 20-fold variation in ovulation-inhibiting activity, with newer-generation progestins (desogestrel, norgestimate, drospirenone) requiring lower doses than first-generation compounds 4
• COCs increase sex hormone-binding globulin (SHBG) production, which binds and reduces free testosterone levels—this contributes to the anti-androgenic benefits seen with acne treatment 1, 6
• The estrogen component (ethinyl estradiol 10-50 μg) is rapidly absorbed with approximately 93-100% bioavailability and is 98% protein-bound 2

Anti-Androgenic Properties (Relevant for Acne Treatment)

• COCs decrease ovarian androgen production through gonadotropin suppression 1
• They increase SHBG, which binds and inactivates free testosterone 1, 6
• They reduce 5α-reductase activity and block androgen receptors 1
• Fourth-generation progestins like drospirenone have additional anti-androgenic and anti-mineralocorticoid properties 1, 7

Clinical Implications

• Seven consecutive days of pill-taking is necessary to reliably suppress ovulation, which is why backup contraception is required for the first 7 days when starting COCs 7
• Lower-dose formulations (20 μg ethinyl estradiol) show more follicular activity when pills are missed compared to 30 μg formulations, emphasizing the importance of adherence 7
• The contraceptive effect is completely reversible upon discontinuation, with no negative impact on long-term fertility 7

Common Pitfall to Avoid

• Do not assume that the estrogen component is the primary contraceptive mechanism—the progestin drives ovulation suppression, while estrogen primarily provides cycle control and synergistic enhancement of contraceptive efficacy 4, 5