Nomegestrol acetate (NOMAC), sold under the brand names Lutenyl and Zoely among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders.

[15][16] NOMAC was first introduced for medical use, for the treatment of gynecological disorders and in menopausal hormone therapy, in Europe in 1986.

[8][1][17][18] NOMAC is used alone in the treatment of gynecological disorders including menstrual disturbances (e.g., dysmenorrhea, menorrhagia, oligomenorrhea, polymenorrhea, amenorrhea), vaginal bleeding, breast pain, and premenstrual syndrome and in menopausal hormone therapy.

[1] Possible side effects of NOMAC include menstrual irregularities (e.g., abnormal bleeding or spotting), headache, nausea, breast tenderness, and weight gain.

[28][7] Symptoms of NOMAC and estradiol overdose might include nausea, vomiting, and, in young girls, slight vaginal bleeding.

[3] NOMAC is a potent and pure progestogen, acting as a selective, high-affinity full agonist of the progesterone receptor (PR) (Ki = 3 nM, 67–303% of the relative binding affinity of progesterone),[29] and is said to have higher potency and substantially improved selectivity for the PR relative to medroxyprogesterone acetate (the 6-hydrogenated or non-6-7-double bonded analogue of megestrol acetate and the most widely used progestin).

[29][33] Due to its potent antigonadotropic activity, NOMAC has strong functional antiandrogenic and antiestrogenic effects when administered at sufficiently high doses.

[1][5] These activities appear to be PR-dependent, as NOMAC is more potent in producing them in PR-rich cell lines (e.g., T47-D vs. MCF-7) and they can be blocked by the PR antagonist mifepristone (RU-486).

[2][41] Certain progestins have been found to stimulate the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1).

[42] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies.

[1] The medication was first introduced in Europe alone or in combination with estradiol under the respective brand names Lutenyl and Naemis[5] for the treatment of gynecological disorders and menopausal symptoms in 1986, and was subsequently developed and approved in 2011 in Europe as a birth control pill in combination with estradiol under the brand name Zoely.

[8] NOMAC (either alone (e.g., as Lutenyl) or in combination with estradiol (e.g., as Naemis))[5] is available for the treatment of gynecological disorders and menopausal symptoms in Argentina, Belgium, Brazil, Chile, France,[44][45] Georgia, Hong Kong, Indonesia, Italy, Lebanon, Lithuania, Malta, Monaco, the Netherlands, Peru, Poland, Portugal, Romania, Slovakia, Taiwan, Tunisia, Turkey, and Vietnam.

[8][46][47][19] As a component of birth control pills with estradiol (under the brand name Zoely), NOMAC is available in Argentina, Australia, Austria, Belgium, Chile, Colombia, Croatia, Costa Rica, Denmark, the Dominican Republic, El Salvador, Finland, France, Germany, Guatemala, Honduras, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Malaysia, Monaco, the Netherlands, New Zealand, Nicaragua, Norway, Panama, Poland, Portugal, Russia, Spain, Slovakia, Sweden, Switzerland, and the United Kingdom.

[50] Under the tentative brand name Uniplant, NOMAC was under development by Theramex as a 38 mg or 55 mg 4 cm Silastic (silicone-plastic) subcutaneous birth control implant of one-year duration (75 ug/day or 100 μg/day release rate) in Brazil from the 1990s and was extensively studied for this purpose in clinical trials.