A | B | C | D | E | F | G | H | CH | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9
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| Clinical data | |
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| Pronunciation | /mɛˌdrɒksiproʊˈdʒɛstəroʊn ˈæsɪteɪt/ me-DROKS-ee-proh-JES-tər-ohn ASS-i-tayt[1] |
| Trade names | Depo-Provera, others |
| Other names | MPA; DMPA; Methylhydroxy |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a604039 |
| Pregnancy category |
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| Routes of administration | By mouth, sublingual, intramuscular injection, subcutaneous injection |
| Drug class | Progestogen; Progestin; Progestogen ester; Antigonadotropin; Steroidal antiandrogen |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | By mouth: ~100%[4][5] |
| Protein binding | 88% (to albumin)[5] |
| Metabolism | Liver (hydroxylation (CYP3A4), reduction, conjugation)[6][4][9] |
| Elimination half-life | By mouth: 12–33 hours[6][4] IM (aq. susp.): ~50 days[7] SC (aq. susp.): ~40 days[8] |
| Excretion | Urine (as conjugates)[6] |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.000.689 |
| Chemical and physical data | |
| Formula | C24H34O4 |
| Molar mass | 386.532 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 207 to 209 °C (405 to 408 °F) |
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| (verify) | |
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type.[10][4] It is used as a method of birth control and as a part of menopausal hormone therapy.[10][4] It is also used to treat endometriosis, abnormal uterine bleeding, paraphilia, and certain types of cancer.[10] The medication is available both alone and in combination with an estrogen.[11][12] It is taken by mouth, used under the tongue, or by injection into a muscle or fat.[10]
Common side effects include menstrual disturbances such as absence of periods, abdominal pain, and headaches.[10] More serious side effects include bone loss, blood clots, allergic reactions, and liver problems.[10] Use is not recommended during pregnancy as it may harm the baby.[10] MPA is an artificial progestogen, and as such activates the progesterone receptor, the biological target of progesterone.[4] 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.[13] It works as a form of birth control by preventing ovulation.[10]
MPA was discovered in 1956 and was introduced for medical use in the United States in 1959.[14][15][10] It is on the World Health Organization's List of Essential Medicines.[16] MPA is the most widely used progestin in menopausal hormone therapy and in progestogen-only birth control.[17][18] DMPA is approved for use as a form of long-acting birth control in more than 100 countries.[19][20] In 2021, it was the 238th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[21][22]
Medical usesedit
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.[4] 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.[4][23] 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.[24] Along with other progestins, MPA was developed to allow for oral progestogen therapy, as progesterone (the progestogen hormone made by the human body) could not be taken orally for many decades before the process of micronization was developed and became feasible in terms of pharmaceutical manufacturing.[25]
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.[26][27] DMPA has also been used to treat benign prostatic hyperplasia, as a palliative appetite stimulant for cancer patients, and at high doses (800 mg per day) to treat certain hormone-dependent cancers including endometrial cancer, renal cancer, and breast cancer.[28][29][30][31][32] MPA has also been prescribed in feminizing hormone therapy for transgender women due to its progestogenic and functional antiandrogenic effects.[33] 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.[34] DMPA at high doses has been reported to be definitively effective in the treatment of hirsutism as well.[35]
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 (absence of menstruation) 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.[29]
Birth controledit
| Depot medroxyprogesterone acetate (DMPA) | |
|---|---|
 | |
| Background | |
| Type | Hormonal |
| First use | 1969[36] |
| Trade names | Depo-Provera, Depo-SubQ Provera 104, others |
| AHFS/Drugs.com | depo-provera |
| Failure rates (first year) | |
| Perfect use | 0.2%[37] |
| Typical use | 6%[37] |
| Usage | |
| Duration effect | 3 months (12–14 weeks) |
| Reversibility | 3–18 months |
| User reminders | Maximum interval is just under 3 months |
| Clinic review | 12 weeks |
| Advantages and disadvantages | |
| STI protection | No |
| Period disadvantages | Especially in first injection may be frequent spotting |
| Period advantages | Usually no periods from 2nd injection |
| Benefits | Especially good if poor pill compliance. Reduced endometrial cancer risk. |
| Risks | Reduced bone density, which may reverse after discontinuation |
| Medical notes | |
| For those intending to start family, suggest switch 6 months prior to alternative method (e.g. POP) allowing more reliable return fertility. | |
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.[38][39] 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%.[40]
Effectivenessedit
Trussell's estimated perfect use first-year failure rate for DMPA as the average of failure rates in seven clinical trials at 0.3%.[40][41] 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 (i.e., no more than 1 or 2 weeks late for a next injection).
Prior to 2004, Trussell's typical use failure rate for DMPA was the same as his perfect use failure rate: 0.3%.[42]
- DMPA estimated typical use first-year failure rate = 0.3% in:
In 2004, using the 1995 NSFG failure rate, Trussell increased (by 10 times) his typical use failure rate for DMPA from 0.3% to 3%.[40][41]
- DMPA estimated typical use first-year failure rate = 3% in:
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 (2.3%) and the ParaGard copper T 380A IUD (3.7%), which were (as with DMPA) 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.[40][47][41]
Advantagesedit
DMPA has a number of advantages and benefits:[48][49][39][50]
- Highly effective at preventing pregnancy.[citation needed]
- 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.[citation needed]
- No estrogen. No increased risk of deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction.[citation needed]
- Minimal drug interactions (compared to other hormonal contraceptives).[citation needed]
- Decreased risk of endometrial cancer. DMPA reduces the risk of endometrial cancer by 80%.[51][52][53] 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.[54]
- Decreased risk of iron deficiency anemia, pelvic inflammatory disease (PID) and ectopic pregnancy.[55][56]
- 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.[57]
- Decreased incidence and severity of sickle cell crises in women with sickle-cell disease.[39]
The United Kingdom Department of Health has actively promoted Long Acting Reversible Contraceptive use since 2008, particularly for young people;[58] following on from the October 2005 National Institute for Health and Clinical Excellence guidelines.[59] Giving advice on these methods of contraception has been included in the 2009 Quality and Outcomes Framework "good practice" for primary care.[60]
Comparisonedit
Proponents of bioidentical hormone therapy believe that progesterone offers fewer side effects and improved quality of life compared to MPA.[61] 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[62] though it may lead to greater breast tenderness and more sporadic vaginal bleeding.[61] The two compounds do not differentiate in their ability to suppress endometrial hyperplasia,[61] nor does either increase the risk of pulmonary embolism.[63] The two medications have not been adequately compared in direct tests to clear conclusions about safety and superiority.[25]
Available formsedit
MPA is available alone in the form of 2.5, 5, and 10 mg oral tablets, as a 150 mg/mL (1 mL) or 400 mg/mL (2.5 mL) microcrystalline aqueous suspension for intramuscular injection, and as a 104 mg (0.65 mL of 160 mg/mL) microcrystalline aqueous suspension for subcutaneous injection.[64][65] 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.[66][67] A 100 mg/mL microcrystalline aqueous suspension for intramuscular injection was previously available as well.[64] In addition to single-drug formulations, MPA is available in the form of oral tablets in combination with conjugated estrogens (CEEs), 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.[11][12][64][19]
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 (every 11 to 13 weeks), and provides pregnancy protection instantaneously after the first injection.[68] 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.
Contraindicationsedit
MPA is not usually recommended because of unacceptable health risk or because it is not indicated in the following cases:[69][70]
Conditions where the theoretical or proven risks usually outweigh the advantages of using DMPA:
- Multiple risk factors for arterial cardiovascular disease
- Current deep vein thrombosis or pulmonary embolus
- Migraine headache with aura while using DMPA
- Before evaluation of unexplained vaginal bleeding suspected of being a serious condition
- A history of breast cancer and no evidence of current disease for five years
- Active liver disease: (acute viral hepatitis, severe decompensated cirrhosis, benign or malignant liver tumours)
- Conditions of concern for estrogen deficiency and reduced HDL levels theoretically increasing cardiovascular risk:
- Hypertension with vascular disease
- Current and history of ischemic heart disease
- History of stroke
- Diabetes for over 20 years or with nephropathy/retinopathy/neuropathy or vascular disease
Conditions which represent an unacceptable health risk if DMPA is used:
- Current or recent breast cancer (a hormonally sensitive tumour)
Conditions where use is not indicated and should not be initiated:
MPA is not recommended for use prior to menarche or before or during recovery from surgery.[71]
Side effectsedit
In women, the most common adverse effects of MPA are acne, changes in menstrual flow, drowsiness, and can cause birth defects if taken by pregnant women. Other common side effects include breast tenderness, increased facial hair, decreased scalp hair, difficulty falling or remaining asleep, stomach pain, and weight loss or gain.[24] Lowered libido has been reported as a side effect of MPA in women.[72] DMPA can affect menstrual bleeding. After a year of use, 55% of women experience amenorrhea (missed periods); after two years, the rate rises to 68%. In the first months of use "irregular or unpredictable bleeding or spotting, or, rarely, heavy or continuous bleeding" was reported.[73] MPA does not appear to be associated with vitamin B12 deficiency.[74] Data on weight gain with DMPA likewise are inconsistent.[75][76]
At high doses for the treatment of breast cancer, MPA can cause weight gain and can worsen diabetes mellitus and edema (particularly of the face). Adverse effects peak at five weeks, and are reduced with lower doses. Less frequent effects may include thrombosis (though it is not clear if this is truly a risk, it cannot be ruled out), painful urination, headache, nausea, and vomiting. When used as a form of androgen deprivation therapy in men, more frequent complaints include reduced libido, impotence, reduced ejaculate volume, and within three days, chemical castration. At extremely high doses (used to treat cancer, not for contraception) MPA may cause adrenal suppression and may interfere with carbohydrate metabolism, but does not cause diabetes.[29]
When used as a form of injected birth control, there is a delayed return of fertility. The average return to fertility is 9 to 10 months after the last injection, taking longer for overweight or obese women. By 18 months after the last injection, fertility is the same as that in former users of other contraceptive methods.[48][49] Fetuses exposed to progestogens have demonstrated higher rates of genital abnormalities, low birth weight, and increased ectopic pregnancy particularly when MPA is used as an injected form of long-term birth control. A study of accidental pregnancies among poor women in Thailand found that infants who had been exposed to DMPA during pregnancy had a higher risk of low birth weight and an 80% greater-than-usual chance of dying in the first year of life.[77]
Mood changesedit
There have been concerns about a possible risk of depression and mood changes with progestins like MPA, and this has led to reluctance of some clinicians and women to use them.[78][79] However, contrary to widely-held beliefs, most research suggests that progestins do not cause adverse psychological effects such as depression or anxiety.[78] A 2018 systematic review of the relationship between progestin-based contraception and depression included three large studies of DMPA and reported no association between DMPA and depression.[80] According to a 2003 review of DMPA, the majority of published clinical studies indicate that DMPA is not associated with depression, and the overall data support the notion that the medication does not significantly affect mood.[81]
In the largest study to have assessed the relationship between MPA and depression to date, in which over 3,900 women were treated with DMPA for up to 7 years, the incidence of depression was infrequent at 1.5% and the discontinuation rate due to depression was 0.5%.[80][38][82] This study did not include baseline data on depression,[82] and due to the incidence of depression in the study, the FDA required package labeling for DMPA stating that women with depression should be observed carefully and that DMPA should be discontinued if depression recurs.[80] A subsequent study of 495 women treated with DMPA over the course of 1 year found that the mean depression score slightly decreased in the whole group of continuing users from 7.4 to 6.7 (by 9.5%) and decreased in the quintile of that group with the highest depression scores at baseline from 15.4 to 9.5 (by 38%).[82] Based on the results of this study and others, a consensus began emerging that DMPA does not in fact increase the risk of depression nor worsen the severity of pre-existing depression.[76][82][38]
Similarly to the case of DMPA for hormonal contraception, the Heart and Estrogen/Progestin Replacement Study (HERS), a study of 2,763 postmenopausal women treated with 0.625 mg/day oral CEEs plus 2.5 mg/day oral MPA or placebo for 36 months as a method of menopausal hormone therapy, found no change in depressive symptoms.[83][84][85] However, some small studies have reported that progestins like MPA might counteract beneficial effects of estrogens against depression.[78][4][86]
Long-term effectsedit
The Women's Health Initiative investigated the use of a combination of oral CEEs and MPA compared to placebo. The study was prematurely terminated when previously unexpected risks were discovered, specifically the finding that though the all-cause mortality was not affected by the hormone therapy, the benefits of menopausal hormone therapy (reduced risk of hip fracture, colorectal and endometrial cancer and all other causes of death) were offset by increased risk of coronary heart disease, breast cancer, strokes and pulmonary embolism.[87]
When combined with CEEs, MPA has been associated with an increased risk of breast cancer, dementia, and thrombus in the eye. In combination with estrogens in general, MPA may increase the risk of cardiovascular disease, with a stronger association when used by postmenopausal women also taking CEEs. It was because of these unexpected interactions that the Women's Health Initiative study was ended early due to the extra risks of menopausal hormone therapy,[88] resulting in a dramatic decrease in both new and renewal prescriptions for hormone therapy.[89]
Long-term studies of users of DMPA have found slight or no increased overall risk of breast cancer. However, the study population did show a slightly increased risk of breast cancer in recent users (DMPA use in the last four years) under age 35, similar to that seen with the use of combined oral contraceptive pills.[73]
| Clinical outcome | Hypothesized effect on risk |
Estrogen and progestogen (CEs 0.625 mg/day p.o. + MPA 2.5 mg/day p.o.) (n = 16,608, with uterus, 5.2–5.6 years follow up) |
Estrogen alone (CEs 0.625 mg/day p.o.) (n = 10,739, no uterus, 6.8–7.1 years follow up) | ||||
|---|---|---|---|---|---|---|---|
| HR | 95% CI | AR | HR | 95% CI | AR | ||
| Coronary heart disease | Decreased | 1.24 | 1.00–1.54 | +6 / 10,000 PYs | 0.95 | 0.79–1.15 | −3 / 10,000 PYs |
| Stroke | Decreased | 1.31 | 1.02–1.68 | +8 / 10,000 PYs | 1.37 | 1.09–1.73 | +12 / 10,000 PYs |
| Pulmonary embolism | Increased | 2.13 | 1.45–3.11 | +10 / 10,000 PYs | 1.37 | 0.90–2.07 | +4 / 10,000 PYs |
| Venous thromboembolism | Increased | 2.06 | 1.57–2.70 | +18 / 10,000 PYs | 1.32 | 0.99–1.75 | +8 / 10,000 PYs |
| Breast cancer | Increased | 1.24 | 1.02–1.50 | +8 / 10,000 PYs | 0.80 | 0.62–1.04 | −6 / 10,000 PYs |
| Colorectal cancer | Decreased | 0.56 | 0.38–0.81 | −7 / 10,000 PYs | 1.08 | 0.75–1.55 | +1 / 10,000 PYs |
| Endometrial cancer | – | 0.81 | 0.48–1.36 | −1 / 10,000 PYs | – | – | – |
| Hip fractures | Decreased | 0.67 | 0.47–0.96 | −5 / 10,000 PYs | 0.65 | 0.45–0.94 | −7 / 10,000 PYs |
| Total fractures | Decreased | 0.76 | 0.69–0.83 | −47 / 10,000 PYs | 0.71 | 0.64–0.80 | −53 / 10,000 PYs |
| Total mortality | Decreased | 0.98 | 0.82–1.18 | −1 / 10,000 PYs | 1.04 | 0.91–1.12 | +3 / 10,000 PYs |
| Global index | – | 1.15 | 1.03–1.28 | +19 / 10,000 PYs | 1.01 | 1.09–1.12 | +2 / 10,000 PYs |
| Diabetes | – | 0.79 | 0.67–0.93 | 0.88 | 0.77–1.01 | ||
| Gallbladder disease | Increased | 1.59 | 1.28–1.97 | 1.67 | 1.35–2.06 | ||
| Stress incontinence | – | 1.87 | 1.61–2.18 | 2.15 | 1.77–2.82 | ||
| Urge incontinence | – | 1.15 | 0.99–1.34 | Zdroj:https://en.wikipedia.org?pojem=Medroxyprogesterone_acetate||||