Medroxyprogesterone Acetate

Medroxyprogesterone is a synthetic progestin, a type of hormone that has similar effects to the female hormone progesterone. It is often used in hormonal therapy and contraception. Medroxyprogesterone is commonly used as medroxyprogesterone acetate (MPA), which can be taken orally or injected.

In women, medroxyprogesterone is frequently used as part of hormonal replacement therapy (HRT) during menopause to alleviate symptoms such as hot flashes and prevent endometrial hyperplasia. It’s also used as a contraceptive in birth control pills, often in combination with estrogen.

Additionally, medroxyprogesterone has been used to treat certain gynecological and breast cancers.

It’s important to note that any hormonal medication should be used under the guidance and prescription of a healthcare professional, as it can have various effects on the body and may interact with other medications or conditions.

Pharmacokinetics

Medroxyprogesterone is absorbed from the gastrointestinal tract. In the blood, it is highly protein-bound, principally to albumin. It is metabolized in the liver and excreted as glucuronide conjugates in the urine and feces. It has a half-life of about 16 to 30 hours after oral doses; the half-life may be as long as 50 days after intramuscular injection. Medroxyprogesterone is reported to be distributed into breast milk.

Uses and Administration

Medroxyprogesterone acetate is a progestogen structurally related to progesterone, with actions and uses similar to the progestogens in general. It is given orally or, for prolonged action, as an aqueous suspension by intramuscular or subcutaneous injection, depending on the product. It treats menorrhagia and secondary amenorrhoea in oral doses of 2.5 to 10 mg daily for 5 to 10 days starting on the assumed or calculated 16th to 21st day of the menstrual cycle. However, treatment may begin on any day in secondary amenorrhoea.

In treating mild to moderate endometriosis, usual oral doses are 10 mg three times daily for 90 consecutive days, 50 mg weekly, or 100 mg every two weeks by intramuscular injection for at least six months. An alternative formulation for treating pain associated with endometriosis is given in a dose of 104 mg in 0.65 mL subcutaneous injection every 12 to 14 weeks.

Medroxyprogesterone acetate is also given by injection as a contraceptive. As a progestogen-only contraceptive, an intramuscular dose of 150 mg is given every 12 or 13 weeks. A combined contraceptive injection containing medroxyprogesterone acetate 25 mg with estradiol cipionate 5 mg is given monthly as an intramuscular injection. An alternative formulation used as a progestogen-only contraceptive is given as a dose of medroxyprogesterone acetate 104 mg in 0.65 mL by subcutaneous injection every 12 to 14 weeks. When used as the progestogen component of menopausal HRT, medroxyprogesterone acetate is given orally in a variety of regimens, including 1.5, 2.5, or 5 mg daily continuously, 5 or 10 mg daily for 12 to 14 days of a 28-day cycle, and 20 mg daily for 14 days of a 91-day cycle.

Medroxyprogesterone acetate may also be used in the palliative treatment of some hormone-dependent malignant neoplasms. In breast carcinoma, oral doses of 0.4 to 1.5 g daily may be given, although doses up to 2 g daily have been used in the past. Intramuscular medroxyprogesterone acetate has been given in initial doses of 500 mg daily for four weeks, then in maintenance doses twice weekly. In endometrial (below) and renal carcinoma, oral doses have ranged from 200 to 600 mg daily. Initial doses of 0.6 to 1.2 g weekly have been given by intramuscular injection, reducing to a maintenance schedule of as little as 450 mg monthly. In prostatic carcinoma, oral doses have been 100 to 600 mg daily. 500 ьп injections have also been given intramuscularly, initially twice weekly for three months, then once weekly for maintenance.

Cachexia

Medroxyprogesterone may improve appetite and food intake and prevent body weight loss in cachexia associated with severe chronic disorders, although information is limited.

Contraception

Medroxyprogesterone acetate has an established use as a parenteral progestogen-only contraceptive. It has also been developed as the progestogenic component of a combined injectable contraceptive and investigated as a component of hormonal contraceptives for men. References.

Epilepsy

Early findings suggested that medroxyprogesterone acetate might be valuable in managing catamenial epilepsy. A later review suggested hormonal manipulation with drugs such as medroxyprogesterone should be reserved for highly selected groups under close supervision.

Male Hypersexuality

The anti-androgenic action of medroxyprogesterone has been used to suppress libido in controlling men with deviant or disinhibited sexual behavior. Most have received intramuscular medroxyprogesterone acetate doses of about 300 mg weekly but ranged from 100 mg each month to 500 mg each week in one report of 5 cases and up to 750 mg each week in another case. Oral treatment with 30 mg daily was also successful in 1 case.

Malignant neoplasms

Breast

Progestogens are second or third-choice drugs in advanced breast cancer hormonal therapy. Some references to using medroxyprogesterone acetate in advanced breast cancer are cited below. Comparative studies have shown that patients respond equally well to medroxyprogesterone, mepitiostane, aminoglutethimide, or oophorectomy.

Endometrium

Progestogens are used to treat advanced endometrial carcinoma, but there are doubts about their value in the earlier stages of the disease. Medroxyprogesterone acetate was effective in a rare case of low-grade endometrial stromal sarcoma. It has also been used in a few patients as adjuvant therapy after surgery and for treating metastatic disease.

Respiratory Disorders

Reviews of the use of medroxyprogesterone acetate in obstructive sleep apnoea have concluded that it has a limited role.

Progesterone and, more commonly, medroxyprogesterone acetate is used to treat pulmonary lymphangioleiomyomatosis, a rare disease affecting only women. Anecdotal evidence suggests some patients improve or stabilize on treatment, possibly those with chylous effusions or ascites. However, some groups have observed a more rapid decline in lung function with progestogen therapy. Medroxyprogesterone acetate was reported to be effective in treating congenital central hypoventilation syndrome in 2 children. It has also been used in adults with central hypoventilation resulting from brainstem stroke and other causes. Medroxyprogesterone has also been investigated for its effects on respiration in chronic obstructive pulmonary disease, sometimes with acetazolamide.

Sickle-Cell Disease

The frequency of painful crises has been reduced in women with homozygous sickle-cell disease, given intramuscular depot medroxyprogesterone acetate, and it is now considered a suitable contraceptive for this group.

Adverse Effects and Precautions

Medroxyprogesterone acetate may have glucocorticoid effects when given long-term at high doses.

Breastfeeding

Medroxyprogesterone is reported to be distributed into breast milk when given as a depot progestogen-only contraceptive. No adverse effects have been seen in breastfed infants. The American Academy of Pediatrics considers that it is, therefore, compatible with breastfeeding. Progestogen-only parenteral contraceptives should not be used until six weeks after birth if the woman is breastfeeding.

Carcinogenicity

The risk of various cancers associated with using depot medroxyprogesterone acetate as a contraceptive has been evaluated by WHO. Overall, there was no increase in the risk of breast cancer, although there is some evidence that current or recent use may be associated with a slight increase in risk. There was no significant increased risk of cervical cancer and a protective effect against endometrial cancer. In contrast to combined oral contraceptives, there was no evidence of a protective effect against ovarian cancer.

Effects on Bone Density

Medroxyprogesterone acetate as a parenteral progestogen-only contraceptive has been associated with reductions in bone density. This effect has also been reported after oral doses for menstrual disorders and is thought to be due to medroxyprogesterone-induced estrogen deficiency.

Effects on the Skin

Acute local skin necrosis has been reported after the intramuscular injection of medroxyprogesterone acetate as a depot contraceptive. A case of pigmented purpura on the lower legs, occurring about four months after starting medroxyprogesterone acetate injections, has been described.

Glucocorticoid Effects

There have been reports of Cushing’s syndrome induced by medroxyprogesterone acetate in patients receiving long-term therapy with high doses for treating malignant neoplasms or paraphilia. Cushingoid symptoms regressed when treatment was stopped. Medroxyprogesterone possesses glucocorticoid activity, and there is a risk of adrenal insufficiency during stress or after sudden withdrawal of treatment. Some consider that patients should be monitored for glucose intolerance and adrenal insufficiency during treatment.

Porphyria

Medroxyprogesterone is associated with acute porphyria attacks and is considered unsafe in patients with porphyric. However, for a reference to the use of medroxyprogesterone acetate with buserelin acetate in preventing premenstrual exacerbations of porphyria in 2 women.

Interactions

As for progestogens in general. Aminoglutethimide markedly reduces plasma concentrations of medroxyprogesterone, so an increase in medroxyprogesterone dosage is likely required.

Medroxyprogesterone can interact with various medications and conditions, so informing your healthcare provider about all your medications and medical history is crucial. Some interactions and precautions include the following.

Drug Interactions

• Anticonvulsants: Medications like phenytoin, carbamazepine, and phenobarbital may reduce the effectiveness of medroxyprogesterone.
• Rifampin: An antibiotic used to treat tuberculosis, which can also decrease the effectiveness of medroxyprogesterone.
• St. John’s Wort: An herbal supplement known to induce certain enzymes that may reduce the effectiveness of medroxyprogesterone.

Medical Conditions

• Liver Disease: Medroxyprogesterone is metabolized by the liver, so individuals with liver problems may require special monitoring.
• Blood Clotting Disorders: There may be an increased risk of blood clot formation, especially in individuals with a history of thromboembolic disorders.
• Diabetes: Medroxyprogesterone can affect glucose tolerance and may require adjustments in diabetic medications.

Other Considerations

• Breast Cancer: Women with a history of breast cancer should use medroxyprogesterone cautiously, and its use should be discussed with an oncologist.
• Cardiovascular Disease: There may be an increased risk of cardiovascular events in specific populations, and its use should be carefully considered in individuals with a history of heart disease.

Always follow your healthcare provider’s instructions and inform them about all medications, supplements, and health conditions you have. This helps ensure the safe and effective use of medroxyprogesterone or any other medication prescribed to you.

Drug Approvals

(British Approved Name Modified, rINNM)

Synonyms: Medroksiprogesteroniasetaatti; Medroksiprogesterono acetatas; Medroxiprogesterona, acetato de; Medroxiprogesteronacetat; Medroxiprogeszteron-acetát; Medroxyprogesteron-acetát; Medroxyprogesteroni Acetas; Methylacetoxyprogesterone; Metipregnone; NSC-26386

BAN: Medroxyprogesterone Acetate [BANM]

INN: Medroxyprogesterone Acetate [rINNM (en)]

INN: Acetato de medroxiprogesterona [rINNM (es)]

INN: Médroxyprogestérone, Acétate de [rINNM (fr)]

INN: Medroxyprogesteroni Acetas [rINNM (la)]

INN: Медроксипрогестерона Ацетат [rINNM (ru)]

Chemical name: 6α-Methyl-3,20-dioxopregn-4-en-17α-yl acetate; 17α-Hydroxy-6α-methylpregn-4-ene-3,20-dione acetate

Molecular formula: C24H34O4 =386.5

CAS: 520-85-4 (medroxyprogesterone); 71-58-9 (medroxyprogesterone acetate)

ATC code: G03AC06; G03DA02; L02AB02

Pharmacopoeias. In China, Europe, International, and the US.

European Pharmacopoeia, 6th ed. (Medroxyprogesterone Acetate). A white or almost white crystalline powder. It is almost insoluble in water, sparingly soluble in alcohol, soluble in acetone, and freely soluble in dichloromethane. Protect from light.

The United States Pharmacopeia 31, 2008 (Medroxyprogesterone Acetate). A white to off-white, odorless, crystalline powder. Insoluble in water, sparingly soluble in alcohol and methyl alcohol, soluble in acetone and dioxane, freely soluble in chloroform, and slightly soluble in ether. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.

Preparations

British Pharmacopoeia 2008: Medroxyprogesterone Injection; Medroxyprogesterone Tablets

The United States Pharmacopeia 31, 2008: Medroxyprogesterone Acetate Injectable; Suspension Medroxyprogesterone Acetate Tablets

Single-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed

Argentina: Cycrin¤; Depo-Provera¤; Farlutale; Livomedrox; Map An; Medrosterona; Veraplex;
Australia: Depo-Provera; Depo-Ralovera; Farlutal¤; Medroxyhexal; Provera; Ralovera;
Austria: Depo-Provera¤; Depocon; Farlutal; Prodafem; Provera;
Belgium: Depo-Provera; Farlutal; Provera;
Brazil: Acemedrox; Acetoflux; Contracep; Cycrin; Depo-Provera; Farlutal; Medroxitest; Progesan; Provera; Tricilon;
Canada: Alti-MPA¤; Apo-Medroxy; Depo-Provera; Gen-Medroxy; Novo-Medrone; Proclim¤; Provera; ratio-MPA;
Chile: Depo-Prodasone; Farlutal; Farlutes; Prodasone; Provera; Sicrit¤;
Czech Republic: Depo-Provera; Provera;
Denmark: Depo-Provera; Perlutex; Provera;
Finland: Cykrina¤; Depo-Provera; Farlutal; Gestapuran; Lutopolar; Mepastat; Provera;
France: Depo-Prodasone; Depo-Provera; Farlutal; Gestoral¤; Prodasone¤;
Germany: Clinofem; Clinovir; Depo-Clinovir; Farlutal; G-Farlutal¤; GestaPolar¤; MPA Gyn; MPA-beta; MPA-Noury¤; MPA;
Greece: Depo-Provera; Farlutal; Gestoral; Progevera; Provera;
Hong Kong: Depo-Provera; Farlutal; Provera;
Hungary: Depo-Provera; Provera;
India: Depo-Provera; Meprate;
Ireland: Depo-Provera; Provera;
Israel: Aragest; Depo-Provera; Provera;
Italy: Depo-Provera; Farlutal; Lutoral¤; Provera;
Malaysia: Depo-Provera; Farlutal¤; Petogen¤; Provera; Veraplex;
Mexico: Ciclotal; Cycrin¤; Depo-Provera; Farlutal; Megestrin; Megestron; Progezzard¤; Protarin¤; Provera;
Netherlands: Depo-Provera; Farlutal; Provera;
Norway: Depo-Provera; Farlutal; Perlutex; Provera;
New Zealand: Depo-Provera; Farlutal¤; Provera;
Portugal: Depo-Provera; Provera;
Russia: Ciclotal (Циклотал); Depo-Provera (Депо-провера); Veraplex (Вераплекс);
South Africa: Depo-Provera; Farlutal¤; Petogen; Provera;
Singapore: Depo-Provera; Farlutal; Provera;
Spain: Depo-Progevera; Farlutal; Progevera 250; Progevera;
Sweden: Cykrina¤; Depo-Provera; Farlutal; Gestapuran; Provera;
Switzerland: Depo-Provera; Farlutal; Prodafem; Provera¤;
Thailand: Contracep; Depo-Gestin; Depo-Progesno; Depo-Progesta; Depo-Provera; Farlutal; Manodepo; Medeton; Provera;
United Kingdom: Adgyn Medro¤; Climanor; Depo-Provera; Farlutal; Provera;
United States: Amen¤; Curretab¤; Cycrin¤; Depo-Provera; Depo-subQ Provera; Provera;
Venezuela: Depo-Provera; Farlutal; Provera

Multi-ingredient Preparations

Argentina: Dilena; Farludiol Ciclo; Farludiol; Periofem Ciclico¤; Periofem Continuo¤; Premelle Ciclico; Premelle Continuo;
Australia: Divina¤; Estrapak¤; Menoprem¤; Premia Continuous; Premia Low; Premia; Provelle¤;
Austria: Cyclo-Premarin-MPA¤; Cyclo-Premella¤; Femipak; Filena; Perennia; Premarin MPA¤; Premella¤; Sequennia; Tri-Filena¤;
Belgium: Diviplus¤; Diviva¤; Premelle Cycle; Premelle; Trivina¤;
Brazil: Cyclofemina; Dilena; Menosedan Ciclo; Menosedan Fase; Menosedan MPA; Premarin MPA¤; Premelle Ciclo; Premelle; Prempro Bifasico; Prempro Monofasico; Repogen Ciclo; Repogen Conti; Selecta;
Canada: Premplus;
Chile: Climatrol Continuo; Climatrol HT Continuo; Climatrol HT; Conpremin Pak Plus; Conpremin Pak; Cyclofem; Enadiol CC; Enadiol MP; Estranova 30 Simple; Estranova CC; Farlupost; Farlutal Estrogeno; Kilios; Novafac 30; Novafac CC; Novafac; Novafem; Prempak; Primaquin MP Continuo; Primaquin MP; Profemina CC; Profemina MP;
Czech Republic: Cyclo-Premella; Divina; Diviseq; Indivina; Premella;
Denmark: Divina Plus; Divina; Indivina; Klimalet; Klimaxil¤; Trevina;
Finland: Divina; Divitren; Indivina;
France: Divina; Diviseq; Duova; Precyclan;
Germany: Climopax Cyclo; Climopax; CycloPolar¤; Estrafemol; Gianda; Indivina; Osmil; Procyclo; Sisare 28; Sisare; Vitrena;
Greece: Divina; Estopause; Premelle Cycle; Premelle;
Hong Kong: Dilena; Premelle Cycle; Premelle;
Hungary: Cyclo-Premella; Divina; Divitren; Premella;
Ireland: Diviseq¤; Femplan-MA¤; Indivina; Premique Cycle; Premique; Tridestra¤;
Israel: Meno-MPA¤; Premaril MP; Premaril Plus MP;
Italy: Filena; Premelle Combinato; Premelle S¤; Premelle Sequenziale;
Malaysia: Plentiva Cycle 5; Plentiva; Premelle; Mexico: Cyclofemina; Dilena; Premelle;
Netherlands: Divina¤; Premelle Cycle; Premelle; PremelleLite;
Norway: Diviseq¤; Indivina;
New Zealand: Menoprem; Premia Continuous; Premia; Provette Continuous¤; Provette Sequential¤;
Portugal: Dilena; Medrivas Antibiotico; Medrivas¤; Premelle Cycle; Premelle;
Russia: Divina (Дивина); Diviseq (Дивисек); Divitren (Дивитрен); Indivina (Индивина);
South Africa: Divina; Premelle; Trivina;
Singapore: Premelle Cycle; Premelle;
Spain: Medricol¤; Medrivas Antib; Medrivas; Perifem; Premelle Ciclico; Premelle;
Sweden: Divina Plus; Divina; Indivina; Premelle Sekvens; Premelle; Trivina;
Switzerland: Cyclo-Premella ST; Cyclo-Premella¤; Diviseq; Indivina; OestroTabs Plus Cyclic¤; Premella; Premia; Triaval;
Thailand: Indivina; Premelle Cycle; Premelle;
United Kingdom: Improvera¤; Indivina; Premique Cycle; Premique; Tridestra;
United States: Lunelle¤; Premphase; Prempro;
Venezuela: Climatrol HT Ciclico; Climatrol HT Continuo; Premelle Ciclico; Premelle Continuo; Premelle Plus Continuo