Etonogestrel

Chemical compound

Side effects of etonogestrel include menstrual irregularities, breast tenderness, mood changes, acne, headaches, vaginitis, and others. It became available in the United States in 2006. A closely related and more widely known and used progestin, desogestrel, is a prodrug of etonogestrel in the body. The failure rate of the implants is 0.05% for both perfect use and typical use because the method requires no user action after placement. Studies of one type, which include over 2,467 women years of exposure, found no pregnancies. Other studies have found some failures with this method, some attributed to failures of the method itself and others to improper placement, drug interactions, or conception prior to method insertion. In comparison, tubal sterilization has a failure rate of 0.5% and IUDs have a failure rate of 0.2–0.8%.

Irregular bleeding and spotting: Many women will experience some type of irregular, unpredictable, prolonged, frequent, or infrequent bleeding. In some cases, a serious complication occurs when the provider fails to insert, and the rod is left in the inserter. An Australian study reported 84 pregnancies as a result of such failure. Correct subdermal insertion over the triceps muscle reduces the risk of these events. Possible weight gain: Some women may experience slight weight gain when using the implant. Pregnancy: it is recommended that implants be removed if a pregnancy does occur. However, there is no evidence to suggest that the implant has a negative effect on pregnancy or a developing fetus.

Efavirenz, an inducer of the liver enzyme CYP3A4, appears to decrease etonogestrel levels and increase rates of undesired pregnancy among implant users. Similar effects are expected for other CYP3A4 inducers, but it is not known whether these are clinically relevant. The opposite is true of CYP3A4 inhibitors such as ketoconazole, itraconazole and clarithromycin: they might increase etonogestrel concentrations in the body. It is similar to a matchstick in size. The rod contains 68 mg of etonogestrel (sometimes called 3 keto destrogestrel), a type of progestin. Serum levels maintain relatively stable through 36 months, which implies that the method may be effective for longer than three years. Although not formally approved by the manufacturer for more than three years, studies have shown it remains a highly effective contraceptive for five years. Before insertion, the arm is washed with a cleaning solution and a local anesthetic is applied to the upper arm around the insertion area. The average time for insertion is 0.5 to 1 minute. Implants can be removed at any time if pregnancy is desired. The rod must also be removed by an experienced clinician. At removal, a local anesthetic is again used around the implant area at the distal end. Fertility levels will return to what they were before implant insertion.

The mechanism of action of progestin only contraceptives depends on the progestin activity and dose. Intermediate dose progestin only contraceptives like Nexplanon or Implanon allow some follicular development but inhibit ovulation in almost all cycles as the primary mechanism of action. Ovulation was not observed in studies of Implanon in the first two years of use and only rarely in the third year with no pregnancies. A secondary mechanism of action is the progestogenic increase 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.

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 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. In 1964, Folkman and Long published the first study demonstrating that such a rod could be used to deliver drugs. In 1966 Dziuk and Cook published a study that looked at release rates and suggested that the rods could be well suited for contraception. After a study that used implants with progestogens for contraception, the Population Council developed and patented Norplant and Jadelle. Norplant has six rods and is considered a first generation implant. Jadelle (Norplant II), a two rod implant, and other single rod implants that followed, were developed because of complications resulting from Norplant's six rod system. The Jadelle system contains two silicone rods mixed with levonorgestrel. In 1990 De Nijs patented a co axial extrusion technique of ethylene vinylacetate copolymers and 3 keto desogestrel (etonogestrel) for the preparation of long acting contraceptive devices, such as Implanon, Nexplanon and Nuvaring. The single rods were less visible under the skin and used etonogestrel as opposed to levonorgestrel in the hopes that it would reduce side effects. Norplant was used internationally beginning in 1983 and was marketed in the United States and the United Kingdom in 1993. There were many complications associated with Norplant removal in the United States and it was taken off the market in 2002. Although Jadelle was approved by the FDA, it has never been marketed in the United States, but it is widely used in Africa and Asia. was marketed in the United Kingdom shortly thereafter, and approved for use in the United States in 2006. It is also known by its developmental code name ORG 3236. Etonogestrel has been studied for use as a potential male contraceptive.