Nomegestrol acetate

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.{{Cite web |url=http://www.teva.com.ar/productos/Documents/SmPC/LUTENYL%2003-15.pdf |title= Lutenyl Nomegestrol acetato 5 mg |access-date=2018-01-09 |archive-date=2018-01-09 |archive-url=https://web.archive.org/web/20180109181400/http://www.teva.com.ar/productos/Documents/SmPC/LUTENYL%2003-15.pdf |url-status=dead }} It is used in combination with estradiol as a birth control pill and in menopausal hormone therapy. NOMAC-only tablets are also used as a form of progestogen-only birth control, although they are not specifically licensed as such.{{cite journal | vauthors = Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, Fredenrich A, Gompel A, Lamiche-Lorenzini F, Moreau C, Plu-Bureau G, Vambergue A, Vergès B, Kerlan V | display-authors = 6 | title = Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology | journal = Annales d'Endocrinologie | volume = 73 | issue = 5 | pages = 469–487 | date = November 2012 | pmid = 23078975 | doi = 10.1016/j.ando.2012.09.001 }}

NOMAC is available both alone and in combination with estrogens.{{cite web | title = Zoely Assessment Report | publisher = Europeans Medicines Agency | date = 22 March 2011 | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001213/WC500115833.pdf | access-date = 9 January 2018 | archive-date = 4 April 2018 | archive-url = https://web.archive.org/web/20180404043347/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001213/WC500115833.pdf | url-status = dead }} The following formulations are available:

• NOMAC 3.75 mg and 5 mg oral tablets (Lutenyl) – indicated for menopausal hormone therapy and gynecological disorders
• NOMAC 3.75 mg and estradiol 1.5 mg oral tablets (Naemis) – indicated for menopausal hormone therapy
• NOMAC 2.5 mg and estradiol 1.5 mg oral tablets (Zoely) – indicated for birth control

The availability of these formulations differs by country.

Because NOMAC is metabolized by the liver, hepatic impairment can result in an accumulation of the medication.{{cite journal | vauthors = Bińkowska M, Woroń J | title = Progestogens in menopausal hormone therapy | journal = Przeglad Menopauzalny = Menopause Review | volume = 14 | issue = 2 | pages = 134–143 | date = June 2015 | pmid = 26327902 | pmc = 4498031 | doi = 10.5114/pm.2015.52154 }}

The side effects of NOMAC are similar to those of other progestogens. It is well tolerated and often produces no side effects. Possible side effects of NOMAC include menstrual irregularities (e.g., abnormal bleeding or spotting), headache, nausea, breast tenderness, and weight gain.{{cite journal | vauthors = Rowlands S | title = Newer progestogens | journal = The Journal of Family Planning and Reproductive Health Care | volume = 29 | issue = 1 | pages = 13–16 | date = January 2003 | pmid = 12626173 | doi = 10.1783/147118903101197188 | doi-access = free }}{{cite journal| vauthors = Lyseng-Williamson KA, Yang LP, Plosker GL |title=Nomegestrol acetate/estradiol: a guide to its use in oral contraception|journal=Drugs & Therapy Perspectives|volume=29|issue=1|year=2012|pages=1–6|issn=1172-0360|doi=10.1007/s40267-012-0005-9|s2cid=71591520}} However, body weight is generally unchanged. Rarely, meningiomas have been reported in association with NOMAC.{{cite journal | vauthors = Passeri T, Champagne PO, Bernat AL, Hanakita S, Salle H, Mandonnet E, Froelich S | title = Spontaneous regression of meningiomas after interruption of nomegestrol acetate: a series of three patients | journal = Acta Neurochirurgica | volume = 161 | issue = 4 | pages = 761–765 | date = April 2019 | pmid = 30783806 | doi = 10.1007/s00701-019-03848-x | s2cid = 67750259 }}{{cite journal | vauthors = Champagne PO, Passeri T, Froelich S | title = Combined hormonal influence of cyproterone acetate and nomegestrol acetate on meningioma: a case report | journal = Acta Neurochirurgica | volume = 161 | issue = 3 | pages = 589–592 | date = March 2019 | pmid = 30666456 | doi = 10.1007/s00701-018-03782-4 | s2cid = 58573065 }}{{cite journal | vauthors = Amelot A, van Effenterre R, Kalamarides M, Cornu P, Boch AL | title = Natural history of cavernous sinus meningiomas | journal = Journal of Neurosurgery | volume = 130 | issue = 2 | pages = 435–442 | date = March 2018 | pmid = 29600913 | doi = 10.3171/2017.7.JNS17662 | doi-access = free }}{{Cite web|url=https://www.ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Luteran-acetate-de-chlormadinone-et-Lutenyl-acetate-de-nomegestrol-et-leurs-generiques-des-cas-de-meningiome-rapportes-Point-d-information|title = Actualité - Luteran (Acétate de chlormadinone) et Lutényl (Acétate de nomégestrol) et leurs génériques : Des cas de méningiome rapportés - ANSM}}

There have been no reports of serious adverse effects due to overdose of NOMAC. NOMAC has been administered alone at a dosage of up to 40 times the recommended dosage, and the combination of NOMAC and estradiol has been administered in multiple doses of up to 5 times the recommended dosage to women in clinical trials, and no safety concerns or harmful effects were observed in either case.{{Cite web |url=http://mri.cts-mrp.eu/download/BE_H_0137_001_FinalSPC.pdf |title= NOGEST, 5 mg tablets |access-date=2018-09-01 |archive-date=2018-09-01 |archive-url=https://web.archive.org/web/20180901215807/http://mri.cts-mrp.eu/download/BE_H_0137_001_FinalSPC.pdf |url-status=dead }} Symptoms of NOMAC and estradiol overdose might include nausea, vomiting, and, in young girls, slight vaginal bleeding. There is no antidote for NOMAC overdose and treatment of overdose should be based on symptoms.

The metabolism of NOMAC is dependent on CYP3A4, so inhibitors and inducers of this enzyme such as ketoconazole and rifampicin, respectively, as well as some anticonvulsants, may pose a clinically significant drug interaction with NOMAC. (For a list of CYP3A4 inhibitors and inducers, see here.)

NOMAC has progestogenic activity, antigonadotropic effects, antiandrogenic activity, and no other important hormonal activity.

NOMAC is a potent and pure progestogen, acting as a selective, high-affinity full agonist of the progesterone receptor (PR) (K_i = 3 nM, 67–303% of the relative binding affinity of progesterone),{{cite journal | vauthors = Mueck AO, Sitruk-Ware R | title = Nomegestrol acetate, a novel progestogen for oral contraception | journal = Steroids | volume = 76 | issue = 6 | pages = 531–539 | date = May 2011 | pmid = 21335021 | doi = 10.1016/j.steroids.2011.02.002 | s2cid = 27419175 }} 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).{{cite book| vauthors = Goldstein I, Meston CM, Davis S, Traish A |title=Women's Sexual Function and Dysfunction: Study, Diagnosis and Treatment|url=https://books.google.com/books?id=3J7TnwpbZQwC&pg=PA554|date=17 November 2005|publisher=CRC Press|isbn=978-1-84214-263-9|pages=554–}}{{cite journal | vauthors = Hapgood JP, Africander D, Louw R, Ray RM, Rohwer JM | title = Potency of progestogens used in hormonal therapy: toward understanding differential actions | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 142 | pages = 39–47 | date = July 2014 | pmid = 23954501 | doi = 10.1016/j.jsbmb.2013.08.001 | s2cid = 12142015 }} In accordance, NOMAC is a potent antigonadotropin and exhibits no androgenic, estrogenic,{{cite book| vauthors = Pasqualini JR |title=Breast Cancer: Prognosis, Treatment, and Prevention|url=https://books.google.com/books?id=l4XLBQAAQBAJ&pg=PA224|date=17 July 2002|publisher=CRC Press|isbn=978-0-203-90924-9|pages=224–}} glucocorticoid, or antimineralocorticoid activity, but does possess some antiandrogenic activity.{{cite journal | vauthors = Sitruk-Ware R | title = Progestogens in hormonal replacement therapy: new molecules, risks, and benefits | journal = Menopause | volume = 9 | issue = 1 | pages = 6–15 | year = 2002 | pmid = 11791081 | doi = 10.1097/00042192-200201000-00003 | s2cid = 12136231 }} Due to its potent antigonadotropic activity, NOMAC has strong functional antiandrogenic and antiestrogenic effects when administered at sufficiently high doses.

Like many other progestogens,{{cite journal | vauthors = Pasqualini JR | title = Progestins and breast cancer | journal = Gynecological Endocrinology | volume = 23 | issue = sup1 | pages = 32–41 | date = October 2007 | pmid = 17943537 | doi = 10.1080/09513590701585003 | s2cid = 46634314 }}{{cite journal | vauthors = Pasqualini JR | title = Breast cancer and steroid metabolizing enzymes: the role of progestogens | journal = Maturitas | volume = 65 | issue = Suppl 1 | pages = S17–S21 | date = December 2009 | pmid = 19962254 | doi = 10.1016/j.maturitas.2009.11.006 }} NOMAC has been assessed and found in vitro to inhibit the conversion of estrone sulfate to estrone (via inhibition of steroid sulfatase) and estrone to estradiol (via inhibition of {{abbrlink|17β-HSD|17β-hydroxysteroid dehydrogenase}}) at high concentrations (0.5–50 μM) and to stimulate the conversion of estrone into estrone sulfate (via activation of estrogen sulfotransferase activity) at low concentrations (0.05–0.5 μM), whilst not affecting aromatase activity at any tested concentration (up to 10 μM). 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). Although the clinical implications of these actions are unclear and they have yet to be confirmed in vivo or assessed in clinical studies, it has been suggested that NOMAC and certain other progestins may be useful in the treatment of {{abbrlink|ER|estrogen receptor}}-positive breast cancer by decreasing levels of estrogens in breast tissue. In accordance with this notion, in vitro, NOMAC does not have proliferative effects on breast tissue, does not stimulate breast cell proliferation via {{abbrlink|PGRMC1|progesterone receptor membrane component 1}} (similarly to progesterone), and reduces the breast proliferative effects of estradiol when added to it in medium.{{cite journal | vauthors = Del Pup L, Berretta M, Di Francia R, Cavaliere C, Di Napoli M, Facchini G, Fiorica F, Mileto M, Schindler AE | display-authors = 6 | title = Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk | journal = Anti-Cancer Drugs | volume = 25 | issue = 7 | pages = 745–750 | date = August 2014 | pmid = 24346139 | doi = 10.1097/CAD.0000000000000050 | s2cid = 33806950 }}

The ovulation-inhibiting dosage of NOMAC is 1.5 to 5 mg/day.{{cite journal | vauthors = Kuhl H | title = Pharmacology of Progestogens | journal = J Reproduktionsmed Endokrinol | year = 2011 | volume = 8 | issue = 1 | pages = 157–177 | url = http://www.kup.at/kup/pdf/10168.pdf}} Due to its high antigonadotropic activity and its long elimination half-life, the contraceptive effectiveness of NOMAC is maintained even when a dose is missed; clinical studies found no increased incidence of pregnancy with one missed pill of Zoely or even with two missed pills during days 8 to 17 of the menstrual cycle.{{cite journal | vauthors = Ruan X, Seeger H, Mueck AO | title = The pharmacology of nomegestrol acetate | journal = Maturitas | volume = 71 | issue = 4 | pages = 345–353 | date = April 2012 | pmid = 22364709 | doi = 10.1016/j.maturitas.2012.01.007 }}

NOMAC acts as an antagonist of the androgen receptor (AR), with approximately 12 to 31% of the relative binding affinity of testosterone for the AR and 42% of the affinity of metribolone for the AR.{{cite book| vauthors = Genazzani AR |title=Hormone Replacement Therapy and Cardiovascular Disease: The Current Status of Research and Practice|url=https://books.google.com/books?id=9vRBX0JqXiAC&pg=PA94|date=15 May 2001|publisher=CRC Press|isbn=978-1-84214-038-3|pages=94–}} Estimates of the antiandrogenic potency of NOMAC are mixed, ranging from 5 to 20%, 20 to 30%, and 90% of that of cyproterone acetate depending on the source.{{cite journal | vauthors = Wiegratz I, Kuhl H | title = Metabolic and clinical effects of progestogens | journal = The European Journal of Contraception & Reproductive Health Care | volume = 11 | issue = 3 | pages = 153–161 | date = September 2006 | pmid = 17056444 | doi = 10.1080/13625180600772741 | s2cid = 27088428 }}{{cite journal | vauthors = Sitruk-Ware R, Husmann F, Thijssen JH, Skouby SO, Fruzzetti F, Hanker J, Huber J, Druckmann R | display-authors = 6 | title = Role of progestins with partial antiandrogenic effects | journal = Climacteric | volume = 7 | issue = 3 | pages = 238–254 | date = September 2004 | pmid = 15669548 | doi = 10.1080/13697130400001307 | s2cid = 23112620 }}{{cite journal | vauthors = Kuhl H | title = Comparative pharmacology of newer progestogens | journal = Drugs | volume = 51 | issue = 2 | pages = 188–215 | date = February 1996 | pmid = 8808163 | doi = 10.2165/00003495-199651020-00002 | s2cid = 1019532 }} The antiandrogenic activity of NOMAC may be useful in helping to alleviate acne, seborrhea, and other androgen-dependent symptoms in women.

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).{{cite journal | vauthors = Neubauer H, Ma Q, Zhou J, Yu Q, Ruan X, Seeger H, Fehm T, Mueck AO | display-authors = 6 | title = Possible role of PGRMC1 in breast cancer development | journal = Climacteric | volume = 16 | issue = 5 | pages = 509–513 | date = October 2013 | pmid = 23758160 | doi = 10.3109/13697137.2013.800038 | s2cid = 29808177 }} Progesterone and NOMAC, in contrast, act neutrally in this assay. It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies.{{cite journal | vauthors = Trabert B, Sherman ME, Kannan N, Stanczyk FZ | title = Progesterone and Breast Cancer | journal = Endocrine Reviews | volume = 41 | issue = 2 | pages = 320–344 | date = April 2020 | pmid = 31512725 | pmc = 7156851 | doi = 10.1210/endrev/bnz001 | doi-access = free }}

NOMAC is well-absorbed, with an oral bioavailability of 63%. It is 97.5 to 98% protein-bound, to albumin, and does not bind to sex hormone-binding globulin or corticosteroid-binding globulin. The medication is metabolized hepatically via hydroxylation by the enzymes CYP3A3, CYP3A4, and CYP2A6. It has six main metabolites, all of which have no or minimal progestogenic activity. The elimination half-life of NOMAC is approximately 50 hours, with a range of 30 to 80 hours. Steady-state concentrations of NOMAC are achieved after five days of repeated administration. As Zoely (2.5 mg/day NOMAC), the average circulating concentrations of NOMAC are 4.5 ng/mL at steady-state, with minimum and maximum concentrations of 3.1 ng/mL and 12.3 ng/mL, respectively. The medication is eliminated via urine and feces.

{{See also|List of progestogens|Progestogen ester|List of progestogen esters|Steroidal antiandrogen|List of steroidal antiandrogens}}

NOMAC, also known as 17α-acetoxy-6-methyl-δ⁶-19-norprogesterone or as 17α-acetoxy-6-methyl-19-norpregna-4,6-diene-3,20-dione, is a synthetic norpregnane steroid and a derivative of progesterone belonging to the 19-norprogesterone and 17α-hydroxyprogesterone groups. NOMAC is the C17α acetate ester of nomegestrol and the 19-demethylated (or 19-nor) analogue of megestrol acetate, and can also be referred to as 19-normegestrol acetate.

Nomegestrol was patented in 1975, and NOMAC, under the developmental code name TX-066, was first described in the literature in 1983.{{cite journal | vauthors = Paris J, Thévenot R, Bonnet P, Granero M | title = The pharmacological profile of TX 066 (17 alpha-acetoxy-6-methyl-19-nor-4,6-pregna-diene-3,20-dione), a new oral progestative | journal = Arzneimittel-Forschung | volume = 33 | issue = 5 | pages = 710–715 | year = 1983 | pmid = 6683550 }} It was developed by Theramex Laboratories, a pharmaceutical company in Monaco (a satellite country of France). The medication was first introduced in Europe alone or in combination with estradiol under the respective brand names Lutenyl and Naemis 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. As Zoely, NOMAC has been studied in over 4,000 women as a method of birth control.

Nomegestrol acetate is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}.{{cite book| vauthors = Elks J |title= The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PR2|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|page=883}}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA747|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=747–}} It is also known by its former developmental code name TX-066.

NOMAC is marketed in combination with estradiol as a birth control pill primarily under the brand name Zoely, in combination with estradiol for use in menopausal hormone therapy primarily under the brand name Naemis, and as a standalone medication for use in menopausal hormone therapy and the treatment of gynecological disorders primarily under the brand name Lutenyl. NOMAC is also marketed alone or in combination with estradiol under a variety of other less common brand names throughout the world.

File:Nomegestrol acetate availability.png

NOMAC (either alone (e.g., as Lutenyl) or in combination with estradiol (e.g., as Naemis)) is available for the treatment of gynecological disorders and menopausal symptoms in Argentina, Belgium, Brazil, Chile, France,{{cite journal | vauthors = Löwy I, Weisz G | title = French hormones: progestins and therapeutic variation in France | journal = Social Science & Medicine | volume = 60 | issue = 11 | pages = 2609–2622 | date = June 2005 | pmid = 15814185 | doi = 10.1016/j.socscimed.2004.10.021 | author1-link = Ilana Löwy }}{{cite journal | vauthors = Foidart JM, Béliard A, Hedon B, Ochsenbein E, Bernard AM, Bergeron C, Thomas JL | title = Impact of percutaneous oestradiol gels in postmenopausal hormone replacement therapy on clinical symptoms and endometrium | journal = British Journal of Obstetrics and Gynaecology | volume = 104 | issue = 3 | pages = 305–310 | date = March 1997 | pmid = 9091006 | doi = 10.1111/j.1471-0528.1997.tb11458.x | s2cid = 28718791 }} Georgia, Hong Kong, Indonesia, Italy, Lebanon, Lithuania, Malta, Monaco, the Netherlands, Peru, Poland, Portugal, Romania, Slovakia, Taiwan, Tunisia, Turkey, and Vietnam.http://www.micromedexsolutions.com/micromedex2/{{Dead link|date=April 2020 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |page=2119 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1}} 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. It was expected that Zoely would become available in the United States in 2010,{{cite book| vauthors = Lentz GM, Lobo RA, Gershenson DM, Katz VL |title=Comprehensive Gynecology|url=https://books.google.com/books?id=X5KT_w6Nye8C&pg=PA223|date=21 February 2012|publisher=Elsevier Health Sciences|isbn=978-0-323-09131-2|pages=223–}} but the {{abbrlink|FDA|Food and Drug Administration}} rejected the {{abbrlink|NDA|New Drug Application}} for Zoely in 2011{{Cite web|url=http://www.medpagetoday.com/publichealthpolicy/fdageneral/29571|title=FDA Turns Down Merck Birth Control Pill, Glaucoma Drug|date=10 November 2011}} and NOMAC ultimately has not been introduced in any form in this country.{{cite web | title = Drugs@FDA: FDA Approved Drug Products | publisher = United States Food and Drug Administration | access-date = 9 December 2016 | url = http://www.accessdata.fda.gov/scripts/cder/daf/}}

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.{{cite journal | vauthors = Brache V, Faundes A, Alvarez F, Cochon L | title = Nonmenstrual adverse events during use of implantable contraceptives for women: data from clinical trials | journal = Contraception | volume = 65 | issue = 1 | pages = 63–74 | date = January 2002 | pmid = 11861056 | doi = 10.1016/S0010-7824(01)00289-X }}{{cite journal | vauthors = Erkkola R, Landgren BM | title = Role of progestins in contraception | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 84 | issue = 3 | pages = 207–216 | date = March 2005 | pmid = 15715527 | doi = 10.1111/j.0001-6349.2005.00759.x | s2cid = 6887415 | doi-access = free }}{{cite book| vauthors = Shoupe D |title=Contraception|url=https://books.google.com/books?id=ksjJcx1CeKcC&pg=PA62|date=10 February 2011|publisher=John Wiley & Sons|isbn=978-1-4443-4263-5|pages=62–}}{{cite journal | vauthors = Royer PA, Jones KP | title = Progestins for contraception: modern delivery systems and novel formulations | journal = Clinical Obstetrics and Gynecology | volume = 57 | issue = 4 | pages = 644–658 | date = December 2014 | pmid = 25314087 | doi = 10.1097/GRF.0000000000000072 }} The clinical studies included 19,900 women-months of use and demonstrated a one-year failure rate of 0.94%. Uniplant was regarded as showing high effectiveness, and was well tolerated. In spite of this however, "[f]urther plans to make it available have been deferred by decision of the company holding the progestin patent",{{cite journal | vauthors = Croxatto HB | title = Progestin implants | journal = Steroids | volume = 65 | issue = 10–11 | pages = 681–685 | year = 2000 | pmid = 11108876 | doi = 10.1016/S0039-128X(00)00124-0 | s2cid = 42296395 }} and, although it continued to be investigated as late as 2006,{{cite journal | vauthors = Barbosa IC, Maia H, Coutinho E, Lopes R, Lopes AC, Noronha C, Botto A | title = Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year | journal = Contraception | volume = 74 | issue = 6 | pages = 492–497 | date = December 2006 | pmid = 17157108 | doi = 10.1016/j.contraception.2006.07.013 | url = http://www.repositorio.ufba.br/ri/handle/ri/6314 | archive-date = 2020-10-28 | access-date = 2023-05-30 | archive-url = https://web.archive.org/web/20201028141436/https://repositorio.ufba.br/ri/handle/ri/6314 | url-status = dead }} the implant ultimately never became commercially available.{{cite journal | vauthors = Croxatt HB | title = Progestin implants for female contraception | journal = Contraception | volume = 65 | issue = 1 | pages = 15–19 | date = January 2002 | pmid = 11861051 | doi = 10.1016/S0010-7824(01)00293-1 }}{{cite journal | vauthors = McDonald-Mosley R, Burke AE | title = Contraceptive implants | journal = Seminars in Reproductive Medicine | volume = 28 | issue = 2 | pages = 110–117 | date = March 2010 | pmid = 20352560 | doi = 10.1055/s-0030-1248135 | s2cid = 38781450 }}

Oral NOMAC was under development for the treatment of breast cancer and for use as a progestogen-only pill for birth control but did not complete development for these indications.{{Cite web|url=https://adisinsight.springer.com/drugs/800010246|title=Nomegestrol oral | work = AdisInsight | publisher = Springer Nature Switzerland AG }} An estradiol and NOMAC vaginal ring was under development for use in birth control and to treat dysmenorrhea but did not complete development and was not marketed.{{Cite web|url=https://adisinsight.springer.com/drugs/800036861|title=Estradiol/Nomegestrol intravaginal ring | work = AdisInsight | publisher = Springer Nature Switzerland AG }} A continuous oral formulation of estradiol and NOMAC was under development for the treatment of menopausal symptoms and the treatment or prevention of postmenopausal osteoporosis but did not complete development.{{Cite web |url=https://adisinsight.springer.com/drugs/800010259 |title=Estradiol/Nomegestrol continuous | work = AdisInsight | publisher = Springer Nature Switzerland AG }}

{{Reflist}}

{{refbegin}}

• {{cite journal | vauthors = Lello S | title = Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy | journal = Drugs | volume = 70 | issue = 5 | pages = 541–559 | date = March 2010 | pmid = 20329803 | doi = 10.2165/11532130-000000000-00000 | s2cid = 24780717 }}
• {{cite journal | vauthors = Mueck AO, Sitruk-Ware R | title = Nomegestrol acetate, a novel progestogen for oral contraception | journal = Steroids | volume = 76 | issue = 6 | pages = 531–539 | date = May 2011 | pmid = 21335021 | doi = 10.1016/j.steroids.2011.02.002 | s2cid = 27419175 }}
• {{cite journal | vauthors = Ruan X, Seeger H, Mueck AO | title = The pharmacology of nomegestrol acetate | journal = Maturitas | volume = 71 | issue = 4 | pages = 345–353 | date = April 2012 | pmid = 22364709 | doi = 10.1016/j.maturitas.2012.01.007 }}
• {{cite journal | vauthors = van Diepen HA | title = Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative | journal = Reproductive Biology and Endocrinology | volume = 10 | issue = 1 | pages = 85 | date = October 2012 | pmid = 23043680 | pmc = 3571880 | doi = 10.1186/1477-7827-10-85 | doi-access = free }}
• {{cite journal | vauthors = Yang LP, Plosker GL | title = Nomegestrol acetate/estradiol: in oral contraception | journal = Drugs | volume = 72 | issue = 14 | pages = 1917–1928 | date = October 2012 | pmid = 22950535 | doi = 10.2165/11208180-000000000-00000 | s2cid = 44335732 }}
• {{cite journal | vauthors = Burke A | title = Nomegestrol acetate-17b-estradiol for oral contraception | journal = Patient Preference and Adherence | volume = 7 | pages = 607–619 | year = 2013 | pmid = 23836965 | pmc = 3702550 | doi = 10.2147/PPA.S39371 | doi-access = free }}

{{refend}}

{{Progestogens and antiprogestogens}}

{{Androgens and antiandrogens}}

{{Progesterone receptor modulators}}

{{Androgen receptor modulators}}

Category:Acetate esters

Category:Antigonadotropins

Category:Diketones

Category:Drugs developed by Merck & Co.

Category:Hormonal contraception

Category:Implants (medicine)

Category:Norpregnanes

Category:Progestogen esters

Category:Progestogens

Category:Steroidal antiandrogens