71-58-9

Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

This chemical is sensitive to prolonged exposure to air and light. Insoluble in water.

Possible carcinogen.

Flash point data for this chemical are not available; however, MEDROXYPROGESTERONE ACETATE is probably combustible.

Medroxyprogesterone Acetate, also known as Medroxyprogesterone 17-acetate or MPA, is a synthetic progestogen and a steroidal progestin. It is derived from the human hormone progesterone. It prevents fertilization and increases the rate of transport of eggs from the fallopian tubes to the uterus in female ferrets when administered prior to ovulation. Medroxyprogesterone 17-acetate reversibly blocks ovulation in rats when injected on the last day of diestrus. It also has anti-androgenic activity in rats, decreasing plasma testosterone levels via induction of hepatic testosterone reductase activity. Medroxyprogesterone 17-acetate exhibits immunosuppressive effects in vitro and in vivo, inhibiting the production of IFN-γ by CD2/CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) at concentrations ≥10 nM and extending the survival of rabbit skin allografts. Injectable formulations containing medroxyprogesterone 17-acetate have been used as contraceptives.

White or almost white, crystalline powder.

Provera,Upjohn,US,1959

Medroxyprogesterone Acetate is a synthetic progesterone receptor agonist that is used to treat amenorrhea (unusual stopping of menstrual periods) and abnormal uterine bleeding.

ChEBI: Medroxyprogesterone acetate is an acetate ester resulting from the formal condensation of the 17alpha-hydroxy group of medroxyprogesterone with the carboxy group of acetic acid. A widely used progestin in menopausal hormone therapy and in progestogen-only birth control. It has a role as a progestin, an androgen, a female contraceptive drug, a synthetic oral contraceptive, an adjuvant, an inhibitor, an antioxidant and an antineoplastic agent. It is a steroid ester, an acetate ester, a 20-oxo steroid, a 3-oxo-Delta(4) steroid and a corticosteroid. It is functionally related to a medroxyprogesterone.

Amen (Amarin); Curretab (Solvay Pharmaceuticals); Cycrin (ESI); Provera (Pharmacia & Upjohn);Clinovie;Cliovir;Dep0-clinover;Dep0-map;Depcorlutin;Depo-prodasone;Depo-progevera;Depo-promone;Deporone;Dugen;Farlurin;Farlutale;Gesinal;Gestapuran;Gestapuron;G-farlutal;Hysron;Intex;Luteocrin orale;Luteodione;Luteos;Lutoporal;Metigestene;Nadigest;Nogest;Onco-provera;Perlutest;Petogen;Piermap;Povera;Promone-e;Pronone;Proverone;Provest;Sindomens;Sodelut "g";Supprestal;Verafen;Veramix plus v.

Progestin

A depot preparation containing 150 mg medroxyprogesterone acetate was introduced over 20 years ago for use as a long-acting injectable contraceptive. Subsequently, positive results of carcinogenicity studies carried out in beagle bitches led to refusal of registration in the United States. These findings were later considered irrelevant to contraceptive use in women and the drug was approved by the Food and Drug Administration. Menstrual irregularities are the most common adverse effect associated with depot medroxyprogesterone acetate. Risk-benefit judgements differ significantly from country to country, having regard to differing national circumstances. The preparation is, however, widely available and is included in the WHO Model List of Essential Drugs. (Reference: (WHTAC4) The Use of Essential Drugs, 4th Report of the WHO Expert Committee, 796, , 1990)

Medroxyprogesterone acetate is an odorless white to off-white microcrystalline powder. It is a synthetic, acetate derivative of the sex hormone progesterone. (NTP, 1992)

Medroxyprogesterone 17-acetate (MPA) is a synthetic progestin used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis. It is a more potent progestin that the nonacetylated form.

Progestogen:
Cachexia (unlicensed), contraception, epilepsy, male hypersexuality, malignant neoplasms, respiratory disorders, sickle-cell disease, dysfunctional uterine bleeding, endometriosis

In cats, MPA has been used when either castration is ineffective or undesirable to treat sexually dimorphic behavior problems such as roaming, inter-male aggressive behaviors, spraying, mounting, etc. MPA has also been used as a tranquilizing agent to treat syndromes such as feline psychogenic dermatitis and alopecia, but treatment with “true” tranquilizing agents may be preferable.
In humans, parenteral MPA has been used as a long-acting contraceptive in females, to decrease sexually deviant behavior in males, and as an antineoplastic agent for some carcinomas (see Pharmacology section above). Oral MPA is used in human females to treat secondary amenorrhea and to treat abnormal uterine bleeding secondary to hormone imbalances.

Potentially hazardous interactions with other drugs Antibacterials: metabolism of progestogens accelerated by griseofulvin and rifamycins (reduced contraceptive effect). Anticoagulants: progestogens antagonise anticoagulant effect of phenindione and may enhance or reduce effect of coumarins. Antidepressants: contraceptive effect reduced by St John’s Wort - avoid. Antiepileptics: metabolism accelerated by carbamazepine, eslicarbazepine, fosphenytoin, lamotrigine, oxcarbazepine, perampanel, phenytoin, phenobarbital, primidone, rufinamide and topiramate (reduced contraceptive effect); concentration of lamotrigine reduced. Antivirals: contraceptive effect possibly reduced by efavirenz; metabolism accelerated by nevirapine (reduced contraceptive effect). Aprepitant: possible contraceptive failure. Bosentan: possible contraceptive failure. Ciclosporin: progestogens inhibit metabolism of ciclosporin (increased plasma concentration). Cytotoxics: possibly reduced contraceptive effect with crizotinib dabrafenib, olaparib and vemurafenib. Dopaminergics: concentration of selegiline increased - avoid. Fosaprepitant: possible contraceptive failure. Lumacaftor: possible contraceptive failure. Ulipristal: contraceptive effect possibly reduced

Among the first of these substituted 17α-acetoxyprogesterone analogues to be utilized therapeutically was medroxyprogesterone acetate, a 6α-methyl progesterone analogue. This analogue is 25-fold more active than ethisterone. Following oral administration, medroxyprogesterone acetate is completely and rapidly deacetylated by first-pass metabolism to medroxyprogesterone. Medroxyprogesterone is extensively metabolized via pathways similar to those for progesterone, except for 6α-hydroxylation. Most medroxyprogesterone acetate metabolites are excreted in the urine, primarily as glucuronide conjugates. Plasma protein binding for medroxyprogesterone is approximately 86%, primarily to serum albumin, with no binding to SHBG.

1. Chang, M.C. Effects of medroxyprogesterone acetate and of ethinyl oestradiol on the fertilization and transportation of ferret eggs. J. Reprod. Fertil. 13(1), 173-174 (1967). DOI:10.1530/JRF.0.0130173
2. Dickmann, Z. Short-and long-term effects of a single injection of depo-medroxyprogesterone acetate (provera) on the vaginal smear, ovulation and mating in the rat. J. Reprod. Fertil. 32(3), 447-451 (1973). DOI:10.1530/JRF.0.0320447
3. Albin, J., Vittek, J., Gordon, G.G., et al. On the mechanism of the anti-androgenic effect of medroxyprogesterone acetate. Endocrinology 93(2), (1973). DOI:10.1210/ENDO-93-2-417
4. Huijbregts, R.P., Michel, K.G., and Hel, Z. Effect of progestins on immunity: Medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception 90(2), 123-129 (2014). DOI:10.1016/j.contraception.2014.02.006
5. Turcotte, J.G., Haines, R.F., Brody, G.L., et al. Immunosuppression with medroxyprogesterone acetate. Transplantation 6(2), 248-260 (1968). DOI:10.1097/00007890-196803000-00010
6. Hofmeyr, G.J., Singata-Madliki, M., Lawrie, T.A., et al. Effects of the copper intrauterine device versus injectable progestin contraception on pregnancy rates and method discontinuation among women attending termination of pregnancy services in South Africa: A pragmatic randomized controlled trial. Reprod. Health 13, 42 (2016). DOI:10.1186/s12978-016-0153-9
7. Thomas CP, Liu KZ, Vats HS. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate alpha-ENaC and sgk1 expression in renal collecting duct epithelia. Am J Physiol Renal Physiol. 2006 Feb;290(2):F306-12. Epub 2005 Sep 27. DOI:10.1152/AJPRENAL.00062.2005
8. Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, Scheldrup MR, Bowman BL, Bimonte-Nelson HA. Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem. 2010Mar;93(3):444-53. DOI:10.1016/j.nlm.2010.01.002