DESOGESTREL AND ETHINYL ESTRADIOL
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Desogestrel is a progestin that suppresses gonadotropin release, inhibiting ovulation. Ethinyl estradiol is an estrogen that provides negative feedback on the hypothalamic-pituitary axis, further suppressing ovulation and altering cervical mucus and endometrial lining to reduce sperm penetration and implantation.
| Metabolism | Desogestrel: Converted to active metabolite 3-keto-desogestrel via CYP2C9 and CYP2C19; further metabolized by CYP3A4. Ethinyl estradiol: Metabolized via CYP3A4 and undergoes glucuronidation and sulfation. |
| Excretion | Desogestrel: primarily renal (approximately 60% as metabolites), 30% fecal. Ethinyl estradiol: primarily renal (approximately 40% as glucuronide conjugates), 60% fecal. |
| Half-life | Desogestrel: terminal half-life 23-27 hours (active metabolite etonogestrel); clinically allows once-daily dosing. Ethinyl estradiol: terminal half-life 12-15 hours (range 10-20 hours) with biphasic elimination; supports daily administration. |
| Protein binding | Desogestrel (as etonogestrel): 96-98% bound to sex hormone-binding globulin (SHBG) and albumin. Ethinyl estradiol: 97-98% bound to albumin; induces SHBG synthesis. |
| Volume of Distribution | Desogestrel (etonogestrel): Vd ~2.5 L/kg (large, indicating extensive tissue distribution). Ethinyl estradiol: Vd ~2.0-4.0 L/kg (large, with distribution to breast, liver, and adipose tissues). |
| Bioavailability | Desogestrel: oral bioavailability ~76% (active metabolite etonogestrel). Ethinyl estradiol: oral bioavailability ~40-60% (due to first-pass metabolism; range 38-55%). |
| Onset of Action | Oral: contraceptive effect requires 7 days of continuous dosing to inhibit ovulation; non-contraceptive effects (e.g., cycle control) may begin with first cycle. |
| Duration of Action | Oral: effects last 24 hours with daily dosing; after discontinuation, return of fertility may occur within 1-2 cycles (range 1-3 months). |
One tablet (0.15 mg desogestrel/0.03 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 placebo tablets, then repeat cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m²) due to risk of adverse effects. |
| Liver impairment | Contraindicated in Child-Pugh class A (mild), B (moderate), or C (severe) hepatic impairment due to altered hormone metabolism and potential for adverse hepatic effects. |
| Pediatric use | Approved for post-menarche females (typically age ≥12 years) with adult dosing regimen; weight-based adjustments are not required. |
| Geriatric use | Not indicated for use in postmenopausal women (typically >55 years) due to lack of efficacy and increased risk of thromboembolic events; no specific dosing recommendations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Breastfeeding | Excreted in breast milk in small amounts; estrogen may reduce milk production and composition. M/P ratio not established for desogestrel; ethinyl estradiol M/P ratio approximately 0.04. Generally not recommended; alternative contraception advised. |
| Teratogenic Risk | First trimester: No increase in major malformations in large cohort studies; however, contraindicated due to risk of fetal harm if inadvertently exposed. Second/third trimester: No evidence of teratogenicity but associated with possible increased risk of intrauterine growth restriction (IUGR) if used inadvertently. Overall, use contraindicated during pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Common Effects | osteoporosis prevention |
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Carcinoma of the endometrium or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Hypersensitivity to any component"]
| Precautions | ["Thromboembolic disorders and cardiovascular risks","Cerebrovascular disease","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate and lipid metabolic effects","Ocular lesions","Headache/migraine","Uterine bleeding irregularities","Depression","Carcinoma of breast/cervix","Hereditary angioedema"] |
Loading safety data…
| Fetal Monitoring | Not applicable as contraindicated; if inadvertent exposure, monitor pregnancy (ultrasound for fetal growth, anatomy). No specific maternal monitoring beyond routine prenatal care. |
| Fertility Effects | Reversibly suppresses ovulation; normal fertility returns after discontinuation, typically within 1-3 months. No permanent adverse effects on fertility. |