Mechanism of Action of Nexplanon (Etonogestrel)
Nexplanon exerts its contraceptive effect primarily by suppressing ovulation, with secondary mechanisms including thickening of cervical mucus to impede sperm entry and thinning of the endometrium to reduce implantation likelihood. 1, 2
Primary Mechanism: Ovulation Suppression
- The etonogestrel implant works predominantly through suppression of gonadotropins (FSH and LH), which prevents the ovarian follicle from releasing an egg 1, 2
- This represents the main contraceptive action that accounts for the exceptional effectiveness of the device 2
Secondary Mechanisms
- Cervical mucus alterations: Etonogestrel increases the viscosity and reduces the quality of cervical mucus, creating a physical barrier that makes sperm penetration into the uterus significantly more difficult 1
- Endometrial changes: The progestin causes endometrial thinning and alterations that reduce the likelihood of successful implantation should fertilization occur 1
Pharmacokinetic Profile Supporting Mechanism
- The implant releases etonogestrel continuously at an average rate of 30-100 mcg/day, maintaining stable serum levels throughout its 3-year duration 3
- Etonogestrel achieves approximately 100% bioavailability after subdermal insertion, with mean serum concentrations ranging from 1374-1578 pg/mL during the first three weeks and remaining therapeutically effective throughout the approved duration 1
- The sustained release maintains consistent suppression of ovulation without the need for daily compliance, contributing to its failure rate of less than 0.05% over 3 years 4
Clinical Implications
- When inserted within the first 5 days of menstrual bleeding, ovulation suppression occurs immediately and no backup contraception is required 4
- If inserted 6 or more days after menstrual bleeding starts, backup contraception is needed for 7 days while therapeutic progestin levels establish full ovulatory suppression 4
- Hepatic enzyme-inducing medications (efavirenz, nevirapine, most protease inhibitors) can increase etonogestrel metabolism and potentially reduce contraceptive effectiveness, though standard oral antibiotics do not affect efficacy 4