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Oral contraceptives (OCs) are hormone-containing medications taken to prevent pregnancy and for management of various gynecologic conditions. They are among the most widely used medicines globally, and have undergone major changes in formulation, pharmacokinetics, and safety since their introduction.
Types of Oral Contraceptives
| Type | Active Ingredients | Examples | Clinical Features |
|---|---|---|---|
| Combined Oral Contraceptives (COCs) | Estrogen (usually ethinylestradiol) + progestin (various generations) | EE+levonorgestrel, EE+drospirenone | Most common; cycle control, wide indications, more side effects |
| Progestin-only Pills (POPs/Mini Pills) | Progestin only (norethindrone, drospirenone) | Norethindrone, desogestrel | Used if estrogen contraindicated; menstrual changes common |
Generations of Progestins in COCs
| Generation | Common Progestins | Key Features |
|---|---|---|
| 1st | Norethindrone, norethynodrel | Androgenic, older compounds |
| 2nd | Levonorgestrel, norgestrel | Low estrogen dose, more androgenic |
| 3rd | Desogestrel, norgestimate, gestodene | Less androgenic, slightly higher VTE risk |
| 4th | Drospirenone, dienogest | Anti-mineralocorticoid, antiandrogenic; higher VTE risk |
Mechanism of Action
- COCs: Suppress ovulation (primary), inhibit development of endometrium (secondary), thicken cervical mucus (secondary). These result from negative feedback of estrogen and progestin on FSH and LH pituitary secretion, prevention of follicle maturation, and mid-cycle LH surge.
- POPs: Thicken cervical mucus (primary), alter endometrial environment and suppress ovulation (in up to ~60–70% of cycles for traditional POPs; more reliably in newer POPs).
Pharmacokinetics
- Estrogens (ethinylestradiol, estradiol): Well absorbed, significant first-pass hepatic metabolism. Ethinylestradiol is more resistant to breakdown, improving bioavailability (45%). Peak plasma in 1–2 hours, high protein binding (sex hormone binding globulin, albumin), hepatic metabolism (CYP3A4/2C9). t1/2: 12–36 hours.
- Progestins: Variable PK per compound. Metabolized by CYP3A4 and others; some have active metabolites (norgestimate → norelgestromin, desogestrel → etonogestrel). t1/2: 8–36 hours.
- Steady state: Most OCs reach steady-state within 7 days. Ethinylestradiol rapidly clears; some progestins accumulate more over time. Both undergo enterohepatic circulation, which can be impaired by broad-spectrum antibiotics.
Clinical Indications
- Contraception
- Menstrual cycle regulation
- Treatment of dysmenorrhea, endometriosis, PCOS, acne, hirsutism
- Menstrual migraine management
- Prevention/treatment of anemia due to heavy menstrual bleeding
- Lower risk for ovarian, endometrial, and colorectal cancers with long-term use
Adverse Effects
| Effect | Frequency/Type | Management/Notes |
|---|---|---|
| Breakthrough bleeding | Common early (esp. low-dose), resolves | Raise estrogen, alternate progestin |
| Nausea/vomiting | Mild, transient | Take at night |
| Breast tenderness | Common, dose-dependent | Lower estrogen dose |
| Mood changes | Mild-moderate, variable | Switch progestin |
| Decreased libido | Reports vary | No clear solution |
| Weight gain | Rare with modern pills | Lifestyle |
| Headache | Switch pill, check for migraine | Avoid if migraine with aura |
| Hypertension | Up to 4–5% of users; higher in pre-existing cases | Monitor BP |
| VTE (venous thromboembolism) | RR 1.5–6 (higher risk with EE >35mcg, 3rd/4th gen progestins, obesity, smoking, family risk) | Lowest risk pills preferable, avoid with major risk factors |
| Stroke/MI | Absolute risk low (<1/100,000 patient-years in <35y), much higher with age, smokers, migraine + aura | Contraindicated if significant risk factors present |
| Acne | Some progestins worsen, some improve | Consider antiandrogenic pill |
Absolute Contraindications
- History or risk of VTE, major thrombophilia (Factor V Leiden, SLE/APLS)
- Major arterial event history (MI, stroke)
- Migraine with aura
- Uncontrolled hypertension
- Known/suspected hormone-sensitive cancer
- Severe liver disease, active hepatitis
Drug Interactions
- Enzyme inducers (CYP3A4): rifampin, phenytoin, carbamazepine, phenobarbital lower efficacy
- Protease inhibitors: may lower or increase OCP levels, depending on PI
- Broad-spectrum antibiotics: controversial, only relevant if enterohepatic circulation is interrupted (very rare clinically, except rifampin*)
- OCs can alter metabolism of other drugs (warfarin, benzodiazepines, corticosteroids)
Formulations and Regimens
| Type/Name | Estrogen Dose | Progestin Type | Cycle Pattern |
|---|---|---|---|
| Monophasic | Fixed EE + fixed progestin for 21 days | Any | 21 active + 7 inactive |
| Biphasic | Fixed EE, increasing progestin | Any | 2 dose phases |
| Triphasic | Increasing EE, progestin, or both | Any | 3 dose phases |
| Extended cycle | EE + progestin 84 days, 7 days inactive | Any | Fewer withdrawal bleeds |
| POP | No estrogen | Specific | Daily, no hormone-free interval |
Clinical Pearls
- Modern OCs use <35 mcg EE, lowering estrogen-related risks.
- 3rd/4th generation progestins (e.g., desogestrel, drospirenone) have reduced androgenic side effects but slightly higher VTE risk.
- Continuous/extended cycle pills beneficial for dysmenorrhea, endometriosis, menstrual suppression.
- Long-term use lowers risk of ovarian and endometrial cancer; no protective effect for breast cancer.
- In obesity or certain drug interactions, less reliable—consider alternate methods.
- POPs best for breastfeeding, estrogen contraindications; less forgiving of missed doses.
References
- Back DJ, Orme ML. Pharmacokinetic drug interactions with oral contraceptives. Clin Pharmacokinet. 1990;18(6):472–495.
- Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. New York: McGraw-Hill; 2017.
- Oral Contraceptive Pills—StatPearls [Internet]. 2024 Feb 28.
- Wikipedia. Combined Oral Contraceptive Pill.
- Choosing a combined oral contraceptive pill. Aust Prescr. 2015;38(1):6–11.
- Contraception—StatPearls. 2023 Jul 23.
- Osmosis. Oral Contraceptives. Jan 2025.
- Xin X, Yuan C, et al. Pharmacokinetics of Oral Combination Contraceptive Drugs Containing Ethinyl Estradiol and Levonorgestrel in Healthy Female Chinese Volunteers. Thieme. 2016.
How to cite this page
Mentor, Pharmacology. Oral Contraceptives: OCPs. Pharmacology Mentor. Available from: https://pharmacologymentor.com/oral-contraceptives-ocps/. Accessed on October 20, 2025 at 09:47.
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