in cervical mucus viscosity which inhibits sperm penetration. Hormonal contraceptives also have effects on the endometrium that theoretically could affect implantation, however no scientific evidence indicates that prevention of implantation actually results from their use. Pharmacodynamics Etonogestrel is a progestogen, or an agonist of the progesterone receptor. It is less androgenic than levonorgestrel and norethisterone, and it does not cause a decrease in sex hormone-binding globulin levels. However, it is still associated with acne in up to 13.5% of patients when used as an implant, though this side effect only accounts for 1.3% of premature removals of the implant. In addition to its progestogenic and weak androgenic activity, etonogestrel binds to the glucocorticoid receptor with about 14% of the affinity of dexamethasone (relative to 1% for levonorgestrel) and has very weak glucocorticoid activity. Etonogestrel has no other hormonal activity (e.g., estrogenic, antimineralocorticoid). Some inhibition of 5α-reductase and hepatic cytochrome P450 enzymes has been observed with etonogestrel in vitro, similarly to other 19-nortestosterone progestins. Pharmacokinetics The bioavailability of etonogestrel when given as a subcutaneous implant or as a vaginal ring is 100%. Steady-state levels of etonogestrel are achieved within one week upon insertion as an implant or vaginal ring. The mean volume of distribution of etonogestrel is 201 L. The plasma protein binding of the medication is at least 98%, with 66% bound to albumin and 32% bound to sex hormone-binding globulin. Etonogestrel is metabolized in the liver by CYP3A4. The biological activity of its metabolites is unknown. The elimination half-life of etonogestrel is about 25 to 29 hours. Following removal of an etonogestrel-containing implant, levels of the medication were below the limits of assay detection by one week. The major portion of etonogestrel is eliminated in urine and a minor portion is eliminated in feces. Chemistry Etonogestrel, also known as 11-methylene-17α-ethynyl-18-methyl-19-nortestosterone or as 11-methylene-17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone. It is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins. Etonogestrel is the C3 ketone derivative of desogestrel and the C11 methylene derivative of levonorgestrel and is also known as 3-ketodesogestrel and as 11-methylenelevonorgestrel. History The possibility of the subdermal contraceptive implant began when silicone was discovered in the 1940s and found to be bio-compatible with the human body. In 1964, Folkman and Long published the first study demonstrating that such a