Modern combined oral contraceptives contain 20 to 35 micrograms of ethinyl estradiol in the majority of prescribed preparations. The 20 microgram dose provides adequate contraceptive efficacy with the lowest venous thromboembolism risk within the ethinyl estradiol-containing class. The 35 microgram dose produces greater sex hormone-binding globulin induction and therefore a greater reduction in free androgen levels, making it preferable when treating androgen-excess conditions such as polycystic ovary syndrome and acne. Ultra-low-dose preparations (10 to 15 micrograms) provide minimal cycle control and are rarely first-line choices.

All ethinyl estradiol-containing combined oral contraceptives increase venous thromboembolism risk approximately three to four times above the non-pregnant, non-pill baseline. Within this class, the progestin component determines the relative risk ranking.

Second-generation progestins — levonorgestrel and norgestrel — carry the lowest venous thromboembolism risk of any ethinyl estradiol-containing combination and have the longest safety record. They are the reference standard for venous thromboembolism risk comparisons. Third-generation progestins — desogestrel, gestodene, and norgestimate — have lower androgenic activity and a more favorable lipid profile than levonorgestrel, but epidemiological data consistently show approximately 1.5 to 2 times higher venous thromboembolism risk than levonorgestrel-containing pills. Drospirenone-containing pills carry a similar or slightly higher venous thromboembolism risk compared to levonorgestrel formulations.

The absolute excess venous thromboembolism risk from any modern low-dose combined oral contraceptive is small — approximately 5 to 10 additional events per 10,000 woman-years — and substantially lower than the venous thromboembolism risk of pregnancy itself. The relative risk difference between progestin generations is most clinically relevant in women who already have venous thromboembolism risk factors, where the additive risk of a higher-risk progestin generation matters more.

The combination of estradiol valerate and dienogest (Natazia/Qlaira) is the only combined oral contraceptive using natural estradiol rather than ethinyl estradiol. Estradiol valerate is rapidly converted after absorption to 17-beta-estradiol, producing lower hepatic estrogenic stimulation than ethinyl estradiol. Dienogest provides anti-androgenic progestational activity. This formulation is an option for women who desire a combined oral contraceptive with a more physiological estrogen component, though cycle control is somewhat less predictable than with standard ethinyl estradiol preparations.

Levonorgestrel 1.5 mg (Plan B and generics) works by inhibiting or delaying ovulation when taken before the luteinizing hormone surge. It has no consistent effect after ovulation has already occurred — its mechanism is entirely pre-ovulatory. Efficacy is highest within 24 hours of unprotected intercourse and falls substantially by 48 to 72 hours, defining a practical 72-hour window.

Body weight substantially reduces efficacy. At body mass index above approximately 26 kg/m², levonorgestrel concentrations are lower and ovulation suppression becomes less reliable. At body mass index above 35 kg/m², efficacy is substantially impaired and an alternative should be offered. Ulipristal acetate or the copper intrauterine device are preferred in women above this weight threshold.

Ulipristal acetate 30 mg is a selective progesterone receptor modulator that can inhibit follicular rupture even after the luteinizing hormone surge has begun — a capability levonorgestrel lacks. This extends its effective window to 120 hours (5 days) after unprotected intercourse. Within the 72-hour window shared with levonorgestrel, ulipristal acetate is more effective, particularly as time elapses and the luteinizing hormone surge has already started. It shows less weight-dependent attenuation than levonorgestrel and is the preferred pharmacological emergency contraceptive in women with body mass index above 26 kg/m².

A critical pharmacological interaction exists between ulipristal acetate and progestins. Because ulipristal acetate partially antagonizes the progesterone receptor, co-administration with progestin-containing methods reduces its efficacy. Women currently using a combined oral contraceptive, progestin-only pill, implant, depot medroxyprogesterone acetate, or levonorgestrel intrauterine device who need emergency contraception should not rely on ulipristal acetate — the copper intrauterine device is the appropriate choice. Additionally, ulipristal acetate use should be followed by a 5-day delay before starting any progestin-containing contraceptive method.

The copper intrauterine device is the most effective emergency contraception available, with a failure rate below 0.1% when inserted within 5 days of unprotected intercourse. Its mechanism — cytotoxic effects of copper ions on sperm — is entirely independent of ovulation timing and entirely independent of body weight or concurrent hormonal methods. It provides ongoing highly effective contraception for up to 10 years. It is the preferred emergency contraception option for women with body mass index above 35 kg/m², women currently using a progestin-containing method, and women who require the most reliable ongoing contraception.

The World Health Organization Medical Eligibility Criteria for Contraceptive Use grades contraceptive safety in the presence of medical conditions using four categories: Category 1 means no restriction; Category 2 means advantages generally outweigh risks; Category 3 means risks generally outweigh advantages (use only when other options are unavailable); Category 4 is an absolute contraindication representing an unacceptable health risk.

The following conditions are absolute contraindications (Category 4) for combined hormonal contraceptives — the combined oral contraceptive, contraceptive patch, and vaginal ring. These contraindications arise predominantly from the ethinyl estradiol component and its effects on coagulation, blood pressure, hepatic function, and stroke risk.

For most conditions that are Category 3 or 4 for combined hormonal methods, progestin-only methods (progestin-only pills, implant, depot medroxyprogesterone acetate, levonorgestrel intrauterine device) are Category 1 or 2. This includes prior venous thromboembolism, thrombophilia, migraine with aura, hypertension, age over 35 with smoking, breastfeeding in the first 6 weeks postpartum, and most liver conditions. The one major exception is current breast cancer, which is Category 4 for all hormonal methods.