Medroxyprogesterone acetate


Medroxyprogesterone acetate, also known as depot medroxyprogesterone acetate in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of birth control and as a part of menopausal hormone therapy. It is also used to treat endometriosis, abnormal uterine bleeding, paraphilia, and certain types of cancer. The medication is available both alone and in combination with an estrogen. It is taken by mouth, used under the tongue, or by injection into a muscle or fat.
Common side effects include menstrual disturbances such as absence of periods, abdominal pain, and headaches. More serious side effects include bone loss, blood clots, allergic reactions, and liver problems. Use is not recommended during pregnancy as it may harm the baby. MPA is an artificial progestogen, and as such activates the progesterone receptor, the biological target of progesterone. It also has androgenic activity and weak glucocorticoid activity. Due to its progestogenic activity, MPA decreases the body's release of gonadotropins and can suppress sex hormone levels. It works as a form of birth control by preventing ovulation.
MPA was discovered in 1956 and was introduced for medical use in the United States in 1959. It is on the World Health Organization's List of Essential Medicines. MPA is the most widely used progestin in menopausal hormone therapy and in progestogen-only birth control. DMPA is approved for use as a form of long-acting birth control in more than 100 countries. In 2023, it was the 257th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

The most common use of MPA is in the form of DMPA as a long-acting progestogen-only injectable contraceptive to prevent pregnancy in women. It is an extremely effective contraceptive when used with relatively high doses to prevent ovulation. MPA is also used in combination with an estrogen in menopausal hormone therapy in postmenopausal women to treat and prevent menopausal symptoms such as hot flashes, vaginal atrophy, and osteoporosis. It is used in menopausal hormone therapy specifically to prevent endometrial hyperplasia and cancer that would otherwise be induced by prolonged unopposed estrogen therapy in women with intact uteruses. In addition to contraception and menopausal hormone therapy, MPA is used in the treatment of gynecological and menstrual disorders such as dysmenorrhea, amenorrhea, and endometriosis. Along with other progestins, MPA was developed to allow for oral progestogen therapy, as progesterone could not be taken orally for many decades before the process of micronization was developed and became feasible in terms of pharmaceutical manufacturing. MPA has also been prescribed in feminizing hormone therapy for transgender women due to its progestogenic and functional antiandrogenic effects.
DMPA reduces sex drive in men and is used as a form of chemical castration to control inappropriate or unwanted sexual behavior in those with paraphilias or hypersexuality, including in convicted sex offenders. DMPA has also been used to treat benign prostatic hyperplasia, as a palliative appetite stimulant for cancer patients, and at high doses to treat certain hormone-dependent cancers including endometrial cancer, renal cancer, and breast cancer. It has been used to delay puberty in children with precocious puberty but is not satisfactory for this purpose as it is not able to completely suppress puberty. DMPA at high doses has been reported to be definitively effective in the treatment of hirsutism as well.
Though not used as a treatment for epilepsy, MPA has been found to reduce the frequency of seizures and does not interact with antiepileptic medications. MPA does not interfere with blood clotting and appears to improve blood parameters for women with sickle cell anemia. Similarly, MPA does not appear to affect liver metabolism, and may improve primary biliary cirrhosis and chronic active hepatitis. Women taking MPA may experience spotting shortly after starting the medication but is not usually serious enough to require medical intervention. With longer use amenorrhea can occur as can irregular menstruation which is a major source of dissatisfaction, though both can result in improvements with iron deficiency and risk of pelvic inflammatory disease and often do not result in discontinuation of the medication.

Birth control

DMPA, under brand names such as Depo-Provera and Depo-SubQ Provera 104, is used in hormonal birth control as a long-lasting progestogen-only injectable contraceptive to prevent pregnancy in women. It is given by intramuscular or subcutaneous injection and forms a long-lasting depot, from which it is slowly released over a period of several months. It takes one week to take effect if given after the first five days of the period cycle, and is effective immediately if given during the first five days of the period cycle. Estimates of first-year failure rates are about 0.3%.

Effectiveness

Trussell's estimated perfect use first-year failure rate for DMPA as the average of failure rates in seven clinical trials at 0.3%. It was considered perfect use because the clinical trials measured efficacy during actual use of DMPA defined as being no longer than 14 or 15 weeks after an injection.
Prior to 2004, Trussell's typical use failure rate for DMPA was the same as his perfect use failure rate: 0.3%.
  • DMPA estimated typical use first-year failure rate = 0.3% in:
  • * Contraceptive Technology, 16th revised edition
  • * Contraceptive Technology, 17th revised edition
  • ** Adopted in 1998 by the FDA for its current Uniform Contraceptive Labeling guidance
In 2004, using the 1995 NSFG failure rate, Trussell increased his typical use failure rate for DMPA from 0.3% to 3%.
  • DMPA estimated typical use first-year failure rate = 3% in:
  • * Contraceptive Technology, 18th revised edition
  • * Contraceptive Technology, 19th revised edition
Trussell did not use 1995 NSFG failure rates as typical use failure rates for the other two then newly available long-acting contraceptives, the Norplant implant and the ParaGard copper T 380A IUD, which were an order of magnitude higher than in clinical trials. Since Norplant and ParaGard allow no scope for user error, their much higher 1995 NSFG failure rates were attributed by Trussell to contraceptive overreporting at the time of a conception leading to a live birth.

Advantages

DMPA has a number of advantages and benefits:
  • Highly effective at preventing pregnancy.
  • Injected every 12 weeks. The only continuing action is to book subsequent follow-up injections every twelve weeks, and to monitor side effects to ensure that they do not require medical attention.
  • No estrogen. No increased risk of deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction.
  • Minimal drug interactions.
  • Decreased risk of endometrial cancer. DMPA reduces the risk of endometrial cancer by 80%. The reduced risk of endometrial cancer in DMPA users is thought to be due to both the direct anti-proliferative effect of progestogen on the endometrium and the indirect reduction of estrogen levels by suppression of ovarian follicular development.
  • Decreased risk of iron deficiency anemia, pelvic inflammatory disease and ectopic pregnancy.
  • Decreased symptoms of endometriosis.
  • Decreased incidence of primary dysmenorrhea, ovulation pain, and functional ovarian cysts.
  • Decreased incidence of seizures in women with epilepsy. Additionally, unlike most other hormonal contraceptives, DMPA's contraceptive effectiveness is not affected by enzyme-inducing antiepileptic drugs.
  • Decreased incidence and severity of sickle cell crises in women with sickle-cell disease.
The United Kingdom Department of Health has actively promoted use of long-acting reversible contraceptives since 2008, particularly for young people; following on from the October 2005 National Institute for Health and Clinical Excellence guidelines. Giving advice on these methods of contraception has been included in the 2009 Quality and Outcomes Framework "good practice" for primary care.

Comparison

Proponents of bioidentical hormone therapy believe that progesterone offers fewer side effects and improved quality of life compared to MPA. The evidence for this view has been questioned; MPA is better absorbed when taken by mouth, with a much longer elimination half-life leading to more stable blood levels though it may lead to greater breast tenderness and more sporadic vaginal bleeding. The two compounds do not differentiate in their ability to suppress endometrial hyperplasia, nor does either increase the risk of pulmonary embolism. The two medications have not been adequately compared in direct tests to clear conclusions about safety and superiority.

Available forms

MPA is available alone in the form of 2.5, 5, and 10 mg oral tablets, as a 150 mg/mL or 400 mg/mL microcrystalline aqueous suspension for intramuscular injection, and as a 104 mg microcrystalline aqueous suspension for subcutaneous injection. It has also been marketed in the form of 100, 200, 250, 400, and 500 mg oral tablets; 500 and 1,000 mg oral suspensions; and as a 50 mg/mL microcrystalline aqueous suspension for intramuscular injection. A 100 mg/mL microcrystalline aqueous suspension for intramuscular injection was previously available as well. In addition to single-drug formulations, MPA is available in the form of oral tablets in combination with conjugated estrogens, estradiol, and estradiol valerate for use in menopausal hormone therapy, and is available in combination with estradiol cypionate in a microcrystalline aqueous suspension as a combined injectable contraceptive.
Depo-Provera is the brand name for a 150 mg microcrystalline aqueous suspension of DMPA that is administered by intramuscular injection. The shot must be injected into thigh, buttock, or deltoid muscle four times a year, and provides pregnancy protection instantaneously after the first injection. Depo-subQ Provera 104 is a variation of the original intramuscular DMPA that is instead a 104 mg microcrystalline dose in aqueous suspension administered by subcutaneous injection. It contains 69% of the MPA found in the original intramuscular DMPA formulation. It can be injected using a smaller injection needle inserting the medication just below the skin, instead of into the muscle, in either the abdomen or thigh. This subcutaneous injection claims to reduce the side effects of DMPA while still maintaining all the same benefits of the original intramuscular DMPA.