|Trade names||Circlet, Implanon, Nexplanon, Nuvaring|
|Other names||ORG-3236; SCH-900702 (with EE); 3-Ketodesogestrel; 3-Oxodesogestrel; 11-Methylenelevonorgestrel; 11-Methylene-17α-ethynyl-18-methyl-19-nortestosterone; 11-Methylene-17α-ethynyl-18-methylestr-4-en-17β-ol-3-one|
|AHFS/Drugs.com||Multum Consumer Information|
|Subcutaneous implant, vaginal ring|
|Drug class||Progestogen; Progestin|
Vaginal ring: 100%
|Protein binding||≥98% (66% to albumin, 32% to SHBG)|
|Elimination half-life||21–38 hours|
|Excretion||Urine (major), feces (minor)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||324.464 g·mol−1|
|3D model (JSmol)|
Etonogestrel is a progestin medication which is used as a means of birth control for women. It is available alone as an implant placed under the skin of the upper arm under the brand names Nexplanon and Implanon and in combination with ethinylestradiol, an estrogen, as a vaginal ring under the brand names NuvaRing and Circlet. Etonogestrel is effective as a means of birth control within 8 hours of insertion.
Side effects of etonogestrel include menstrual irregularities, headaches, vaginitis, breast tenderness, mood changes, abdominal pain, pharyngitis, acne, and others. Etonogestrel is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has very weak androgenic and glucocorticoid activity and no other important hormonal activity.
Etonogestrel was patented in 1972 and introduced for medical use in 1998. It became available in the United States in 2006. Etonogestrel is sometimes referred to as a "third-generation" progestin. It is marketed throughout the world. A closely related and more widely known and used progestin, desogestrel, is a prodrug of etonogestrel in the body.
Etonogestrel is used in hormonal contraception, most notably the etonogestrel contraceptive implant (brand names Nexplanon, Implanon) and the contraceptive vaginal ring (brand names NuvaRing, Circlet).
The most common side effects of etonogestrel when used as an implant, experienced by greater than or equal to 10% of women, include menstrual irregularities (with menstrual bleeding patterns including hypomenorrhea (33.6%), amenorrhea (22.2%), menorrhagia (17.7%), and polymenorrhea (6.7%)), headache (24.9%), vaginitis (14.5%), weight gain (13.7%), acne (13.5%), breast pain (12.8%), abdominal pain (10.9%), and pharyngitis (10.5%). Less common side effects of etonogestrel when used as an implant, experienced by 5 to 10% of women, include leukorrhea (9.6%), implant site reactions (8.6%), influenza-like symptoms (7.6%), dizziness (7.2%), dysmenorrhea (7.2%), back pain (6.8%), emotional lability (6.5%), nausea (6.4%), pain (5.6%), nervousness (5.6%), depression (5.5%), hypersensitivity (5.4%), and insertion site pain (5.2%). Implant site reactions included erythema (3.3%), hematoma (3.0%), bruising (2.0%), pain (1.0%), and swelling (0.7%). Reasons for discontinuation of etonogestrel implant treatment included menstrual irregularities (11.1%), emotional lability (2.3–6.1%), weight gain (2.3%), headache (1.6%), acne (1.3%), and depression (1.0–2.4%).
Other potential side effects of etonogestrel may include ectopic pregnancy, thrombosis and other vascular events, ovarian cysts, breast cancer, cervical cancer, cervical intraepithelial neoplasia, liver adenomas, elevated blood pressure, gallbladder disease, mild insulin resistance, small changes in glucose levels, hyperlipidemia, fluid retention, and visual changes or changes in lens tolerance in those with contact lenses. Many additional possible side effects of etonogestrel have been reported in postmarketing surveillance.
Etonogestrel is the active metabolite of the inactive prodrug desogestrel, one of two third-generation progestins found in some epidemiological studies of combined birth control pills to be associated with a higher risk of venous thrombosis than combined birth control pills containing certain second-generation progestins. Because hormones are released continuously from etonogestrel-containing vaginal rings, peak and total estrogen and progestin doses are significantly lower than with combined birth control pills, although it is not known whether this lowers the risk of blood clots.
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.
|Sources: Values are percentages (%). Reference ligands (100%) were prome-gestone for the PR, metribolone for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: |
|Steroid||Class||TR (↑)a||GR (%)b|
|Footnotes: a = Thrombin receptor (TR) upregulation (↑) in vascular smooth muscle cells (VSMCs). b = RBA (%) for the glucocorticoid receptor (GR). Strength: – = No effect. + = Pronounced effect. ++ = Strong effect. Sources: See template.|
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.
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.
Desogestrel (3-deketoetonogestrel), a prodrug of etonogestrel, was introduced for medical use in 1981. Etonogestrel itself was first introduced, as Implanon in Indonesia, in 1998, and was subsequently marketed in the United Kingdom shortly thereafter and in the United States in 2006.
Etonogestrel is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, Australia, New Zealand, South Africa, Latin America, South, East, and Southeast Asia, and elsewhere in the world.
The elimination half-life for 3-keto-desogestrel is approximately 38 ± 20 hours at steady state.
In 1981, desogestrel was marketed as a new low dose oral contraceptive under the trade names Marvelon® and Desogen®.32