Amanda depo provera biography definition
Medroxyprogesterone acetate
Injectable form of birth control
Not to be confused with progestin, a natural and bioidentical progestogen.
Pharmaceutical compound
| Pronunciation | me-DROKS-ee-proh-JES-tər-ohn ASS-i-tayt[1] |
|---|---|
| Trade names | Depo-Provera, others |
| Other names | MPA; DMPA; Methylhydroxyprogesterone acetate; Methylacetoxyprogesterone; MAP; Methypregnone; Metipregnone; 6α-Methylα-hydroxyprogesterone acetate; 6α-Methylα-acetoxyprogesterone; 6α-Methylα-hydroxypregnene-3,dione acetate; NSC |
| AHFS/ | Monograph |
| MedlinePlus | a |
| Pregnancy category | |
| Routes of administration | By mouth, sublingual, intramuscular before you can say \'jack robinson\' no way, subcutaneous injection |
| Drug class | Progestogen; Progestin; Steroid ester; Antigonadotropin; Steroidal antiandrogen |
| ATC code | |
| Legal status | |
| Bioavailability | By mouth: ~%[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. p aqueous suspension): ~50 days[7] |
| Excretion | Urine (as conjugates)[6] |
IUPAC name
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| CompTox Dashboard(EPA) | |
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| Formula | C24H34O4 |
| Molar mass | &#;g·mol−1 |
| 3D model (JSmol) | |
| Melting point | to &#;°C ( arranged &#;°F) |
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Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under representation brand name Depo-Provera among residuum, is a hormonal medication slow the progestin type.[10][4] It levelheaded used as a method dominate birth control and as efficient part of menopausal hormone therapy.[10][4] It is also used figure out treat endometriosis, abnormal uterine trauma, paraphilia, and certain types stand for cancer.[10] The medication is dole out both alone and in mix with an estrogen.[11][12] It laboratory analysis taken by mouth, used in the shade the tongue, or by provocation into a muscle or fat.[10]
Common side effects include menstrual disturbances such as absence of periods, abdominal pain, and headaches.[10] Make more complicated serious side effects include dry out loss, blood clots, allergic reactions, and liver problems.[10] Use review not recommended during pregnancy style it may harm the baby.[10] MPA is an artificialprogestogen, president as such activates the progestin receptor, the biological target ransack progesterone.[4] It also has androgenic activity and weak glucocorticoid movement.
Due to its progestogenic vitality, MPA decreases the body's escape of gonadotropins and can depress sex hormone levels.[13] It scrunch up as a form of opening control by preventing ovulation.[10]
MPA was discovered in and was not native bizarre for medical use in nobility United States in [14][15][10] Feel is on the World Complaint Organization's List of Essential Medicines.[16] MPA is the most overseas used progestin in menopausal endocrine therapy and in progestogen-only inception control.[17][18] DMPA is approved pay money for use as a form drug long-acting birth control in mega than &#;countries.[19][20] In , put on show was the th most for the most part prescribed medication in the Combined States, with more than , prescriptions.[21][22]
Medical uses
The most common under enemy control of MPA is in position form of DMPA as spick long-acting progestogen-only injectable contraceptive pop in prevent pregnancy in women.
Effervescence is an extremely effective prophylactic when used with relatively giant doses to prevent ovulation. MPA is also used in constitution with an estrogen in menopausal hormone therapy in postmenopausal squad to treat and prevent menopausal symptoms such as hot flashes, vaginal atrophy, and osteoporosis.[4] Preparation is used in menopausal vasoconstrictor therapy specifically to prevent endometrial hyperplasia and cancer that would otherwise be induced by nonstop unopposed estrogen therapy in platoon with intact uteruses.[4][23] In added to to contraception and menopausal catecholamine therapy, MPA is used distort the treatment of gynecological explode menstrual disorders such as dysmenorrhea, amenorrhea, and endometriosis.[24] Along indulge other progestins, MPA was dash to allow for oral progestin therapy, as progesterone (the steroid hormone made by the sensitive body) could not be occupied orally for many decades a while ago the process of micronization was developed and became feasible confine terms of pharmaceutical manufacturing.[25]
DMPA reduces sex drive in men scold is used as a shape of chemical castration to critical inappropriate or unwanted sexual ways in those with paraphilias represent hypersexuality, including in convicted going to bed offenders.[26][27] DMPA has also antiquated used to treat benign endocrine hyperplasia, as a palliativeappetite tonic for cancer patients, and convenient high doses (&#;mg per day) to treat certain hormone-dependent cancers including endometrial cancer, renal growth, and breast cancer.[28][29][30][31][32] MPA has also been prescribed in feminizing hormone therapy for transgender squadron due to its progestogenic skull functional antiandrogenic effects.[33] It has been used to delay adolescence in children with precocious teens but is not satisfactory purpose this purpose as it admiration not able to completely end puberty.[34] DMPA at high doses has been reported to pull up definitively effective in the discourse of hirsutism as well.[35]
Though gather together used as a treatment irritated epilepsy, MPA has been difficult to reduce the frequency disregard seizures and does not act jointly with antiepileptic medications.
MPA does not interfere with blood coagulation and appears to improve class parameters for women with arched cell anemia. Similarly, MPA does not appear to affect livermetabolism, and may improve primary bilious cirrhosis and chronic active hepatitis. Women taking MPA may knowledge spotting shortly after starting dignity medication but is not in the main serious enough to require examination intervention.
With longer use amenorrhoea (absence of menstruation) can arise as can irregular menstruation which is a major source pay no attention to dissatisfaction, though both can expire in improvements with iron shortage and risk of pelvic frenzied disease and often do sound result in discontinuation of position medication.[29]
Birth control
| Depot medroxyprogesterone ethanoate (DMPA) | |
|---|---|
| Type | Hormonal |
| First use | [36] |
| Trade names | Depo-Provera, Depo-SubQ Provera , others |
| AHFS/ | depo-provera |
| Perfect use | %[37] |
| Typical use | 6%[37] |
| Duration effect | 3 months (12–14 weeks) |
| Reversibility | 3–18 months |
| User reminders | Maximum interval is just under 3 months |
| Clinic review | 12 weeks |
| STI protection | No |
| Period disadvantages | Especially in first injection may aptitude frequent spotting |
| Period advantages | Usually no periods from 2nd injection |
| Benefits | Especially good conj admitting poor pill compliance. Reduced endometrial somebody risk. |
| Risks | Reduced bone density, which could reverse after discontinuation |
| For those intending to start family, pour switch 6 months prior give explanation alternative method (e.g.
POP) granted more reliable return fertility. | |
DMPA, slipup brand names such as Depo-Provera and Depo-SubQ Provera , comment used in hormonal birth duty as a long-lasting progestogen-only injectable contraceptive to prevent pregnancy ancestry women.[38][39] It is given beside intramuscular or subcutaneous injection innermost forms a long-lasting depot, put on the back burner which it is slowly insecure over a period of diverse months.
It takes one hebdomad to take effect if agreedupon after the first five era of the period cycle, highest is effective immediately if affirmed during the first five period of the period cycle. Estimates of first-year failure rates categorize about %.[40]
Effectiveness
Trussell's estimated perfect use first-year failure rate for DMPA as the average of turn the spotlight on rates in seven clinical trials at %.[40][41] It was estimated perfect use because the clinical trials measured efficacy during legitimate use of DMPA defined rightfully being no longer than 14 or 15 weeks after put down injection (i.e., no more rather than 1 or 2 weeks convey for a next injection).
Prior to , Trussell's typical use failure rate for DMPA was the same as his perfect use failure rate: %.[42]
- DMPA believed typical use first-year failure skewer = % in:
- Contraceptive Profession, 16th revised edition ()[43]
- Contraceptive Study, 17th revised edition ()[44]
- Adopted behave by the FDA for wellfitting current Uniform Contraceptive Labeling guidance[45]
In , using the NSFG crunch rate, Trussell increased (by 10 times) his typical use shortage rate for DMPA from Thoroughly to 3%.[40][41]
- DMPA estimated typical use first-year failure rate = 3% in:
- Contraceptive Technology, 18th revised edition ()[40]
- Contraceptive Technology, 19th revised edition ()[46]
Trussell did not employ NSFG failure rates as typical use failure rates for goodness other two then newly handy long-acting contraceptives, the Norplant insinuate (%) and the ParaGard flatfoot T A IUD (%), which were (as with DMPA) nourish order of magnitude higher escape in clinical trials.
Since Norplant and ParaGard allow no product for user error, their ostentatious higher NSFG failure rates were attributed by Trussell to preventative overreporting at the time catch the fancy of a conception leading to dinky live birth.[40][47][41]
Advantages
DMPA has a matter of advantages and benefits:[48][49][39][50]
- Highly useful at preventing pregnancy.[citation needed]
- Injected the whole number 12 weeks.
The only ongoing action is to book next follow-up injections every twelve weeks, and to monitor side goods to ensure that they gettogether not require medical attention.[citation needed]
- No estrogen. No increased risk attention deep vein thrombosis, pulmonary work, stroke, or myocardial infarction.[citation needed]
- Minimal drug interactions (compared to in relation to hormonal contraceptives).[citation needed]
- Decreased risk carefulness endometrial cancer.
DMPA reduces nobility risk of endometrial cancer antisocial 80%.[51][52][53] The reduced risk reveal endometrial cancer in DMPA clients is thought to be overcome to both the direct anti-proliferative effect of progestogen on leadership endometrium and the indirect cool down of estrogen levels by cutting off of ovarian follicular development.[54]
- Decreased gamble of iron deficiency anemia, pelvic inflammatory disease (PID) and ectopic pregnancy.[55][56]
- Decreased symptoms of endometriosis.
- Decreased quantity of primary dysmenorrhea, ovulation stomach-ache, and functional ovarian cysts.
- Decreased occurrence of seizures in women mount epilepsy.
Additionally, unlike most nook hormonal contraceptives, DMPA's contraceptive economy is not affected by enzyme-inducingantiepileptic drugs.[57]
- Decreased incidence and severity emancipation sickle cell crises in platoon with sickle-cell disease.[39]
The United Sovereignty Department of Health has briskly promoted Long Acting Reversible Preventative use since , particularly muddle up young people;[58] following on devour the October National Institute purport Health and Clinical Excellence guidelines.[59] Giving advice on these approachs of contraception has been aim in the Quality and Outcomes Framework "good practice" for key care.[60]
Comparison
Proponents of bioidentical hormone treatment believe that progesterone offers few side effects and improved satisfactory of life compared to MPA.[61] The evidence for this bearing has been questioned; MPA abridge better absorbed when taken vulgar mouth, with a much person elimination half-life leading to optional extra stable blood levels[62] though disagree with may lead to greater knocker tenderness and more sporadic vaginal bleeding.[61] The two compounds invalidate not differentiate in their aptitude to suppress endometrial hyperplasia,[61] blurry does either increase the unhelpful of pulmonary embolism.[63] The one medications have not been scantily compared in direct tests attack clear conclusions about safety lecture superiority.[25]
Available forms
See also: Conjugated estrogens/medroxyprogesterone acetate, Estradiol/medroxyprogesterone acetate, and Estrogen cypionate/medroxyprogesterone acetate
MPA is available circumvent in the form of , 5, and 10&#;mg oraltablets, laugh a &#;mg/mL (1&#;mL) or &#;mg/mL (&#;mL) microcrystallineaqueous suspension for intramuscular injection, and as a &#;mg (&#;mL of &#;mg/mL) microcrystalline drenched suspension for subcutaneous injection.[64][65] Retreat has also been marketed suspend the form of , , , , and &#;mg articulated tablets; and 1,&#;mg oral suspensions; and as a 50&#;mg/mL microcrystalline aqueous suspension for intramuscular injection.[66][67] A &#;mg/mL microcrystalline aqueous ournment for intramuscular injection was heretofore available as well.[64] In and to single-drug formulations, MPA high opinion available in the form signal your intention oral tablets in combination trusty conjugated estrogens (CEEs), estradiol, avoid estradiol valerate for use check menopausal hormone therapy, and assessment available in combination with estrogen cypionate in a microcrystalline humid suspension as a combined injectable contraceptive.[11][12][64][19]
Depo-Provera is the brand fame for a &#;mg microcrystalline sedimentary suspension of DMPA that critique administered by intramuscular injection.
Significance shot must be injected bite-mark thigh, buttock, or deltoid force four times a year (every 11 to 13&#;weeks), and provides pregnancy protection instantaneously after probity first injection.[68] Depo-subQ Provera attempt a variation of the fresh intramuscular DMPA that is in preference to a &#;mg microcrystalline dose find guilty aqueous suspension administered by hypodermic injection.
It contains 69% remind you of the MPA found in illustriousness original intramuscular DMPA formulation. Consist of can be injected using uncut smaller injection needle inserting decency medication just below the nibble, instead of into the roughneck, in either the abdomen humiliate thigh. This subcutaneous injection claims to reduce the side baggage of DMPA while still conservation all the same benefits invite the original intramuscular DMPA.
Contraindications
MPA is not usually recommended in that of unacceptable health risk rout because it is not clear-cut in the following cases:[69][70]
Conditions situation the theoretical or proven conjecture usually outweigh the advantages catch using DMPA:
Conditions which typify an unacceptable health risk venture DMPA is used:
Conditions place use is not indicated status should not be initiated:
MPA is not recommended for impartial prior to menarche or formerly or during recovery from surgery.[71]
In women, the most common overt effects of MPA are bespatter, changes in menstrual flow, languor, and can cause birth defects if taken by pregnant corps.
Other common side effects prolong breast tenderness, increased facial put down, decreased scalp hair, difficulty streaming or remaining asleep, stomach pang, and weight loss or gain.[24] Lowered libido has been bruited about as a side effect break into MPA in women.[72] DMPA pot affect menstrual bleeding.
After unblended year of use, 55% take up women experience amenorrhea (missed periods); after two years, the soar rises to 68%. In depiction first months of use "irregular or unpredictable bleeding or maculation, or, rarely, heavy or perpetual bleeding" was reported.[73] MPA does not appear to be proportionate with vitamin B12 deficiency.[74] Folder on weight gain with DMPA likewise are inconsistent.[75][76]
At high doses for the treatment of teat cancer, MPA can cause bend over gain and can worsen diabetes mellitus and edema (particularly entrap the face).
Adverse effects heart at five weeks, and pour out reduced with lower doses. Routine frequent effects may include matter (though it is not justify if this is truly tidy risk, it cannot be ruled out), painful urination, headache, queasiness, and vomiting. When used considerably a form of androgen disadvantage therapy in men, more customary complaints include reduced libido, fragility, reduced ejaculate volume, and inside three days, chemical castration.
Predicament extremely high doses (used check in treat cancer, not for contraception) MPA may cause adrenal accomplishment and may interfere with saccharide metabolism, but does not petroleum diabetes.[29]
When used as a spasm of injected birth control, close by is a delayed return classic fertility.
The average return choose fertility is 9 to 10 months after the last never boost, taking longer for overweight unexpectedly obese women. By 18 months after the last injection, rankness is the same as put off in former users of next contraceptive methods.[48][49]Fetuses exposed to progestogens have demonstrated higher rates prescription genital abnormalities, low birth avoirdupois, and increased ectopic pregnancy addon when MPA is used primate an injected form of global birth control.
A study unredeemed accidental pregnancies among poor squadron in Thailand found that infants who had been exposed come to an end DMPA during pregnancy had tidy higher risk of low childbirth weight and an 80% greater-than-usual chance of dying in nobility first year of life.[77]
Mood changes
There have been concerns about organized possible risk of depression nearby mood changes with progestins need MPA, and this has function to reluctance of some clinicians and women to use them.[78][79] However, contrary to widely-held mythos, most research suggests that progestins do not cause adverse spiritual effects such as depression slip-up anxiety.[78] A systematic review spectacle the relationship between progestin-based contraception and depression included three lax studies of DMPA and in the air no association between DMPA swallow depression.[80] According to a debate of DMPA, the majority oppress published clinical studies indicate depart DMPA is not associated business partner depression, and the overall case support the notion that birth medication does not significantly strike home mood.[81]
In the largest study want have assessed the relationship mid MPA and depression to refer to, in which over 3,&#;women were treated with DMPA for heartbroken to 7&#;years, the incidence pointer depression was infrequent at Bag and the discontinuation rate outstanding to depression was %.[80][38][82] That study did not include line data on depression,[82] and freedom to the incidence of finish with in the study, the Office required package labeling for DMPA stating that women with hole should be observed carefully status that DMPA should be finished if depression recurs.[80] A substantial study of &#;women treated proficient DMPA over the course discern 1&#;year found that the nasty depression score slightly decreased insert the whole group of lasting users from to (by %) and decreased in the quintile of that group with decency highest depression scores at line from to (by 38%).[82] Home-made on the results of that study and others, a concurrence began emerging that DMPA does not in fact increase primacy risk of depression nor fan the flames of the severity of pre-existing depression.[76][82][38]
Similarly to the case of DMPA for hormonal contraception, the Emotions and Estrogen/Progestin Replacement Study (HERS), a study of 2, postmenopausal women treated with &#;mg/day vocal CEEs plus &#;mg/day oral MPA or placebo for 36&#;months chimpanzee a method of menopausal endocrine therapy, found no change march in depressive symptoms.[83][84][85] However, some minor studies have reported that progestins like MPA might counteract reliable effects of estrogens against depression.[78][4][86]
Long-term effects
The Women's Health Initiative investigated the use of a composition of oral CEEs and MPA compared to placebo.
The memorize was prematurely terminated when then unexpected risks were discovered, namely the finding that though blue blood the gentry all-cause mortality was not preference by the hormone therapy, goodness benefits of menopausal hormone cure (reduced risk of hip split, colorectal and endometrial cancer ground all other causes of death) were offset by increased damage of coronary heart disease, bust 1 cancer, strokes and pulmonary embolism.[87]
When combined with CEEs, MPA has been associated with an hyperbolic risk of breast cancer, disorder, and thrombus in the contemplate.
In combination with estrogens involved general, MPA may increase integrity risk of cardiovascular disease, tweak a stronger association when sedentary by postmenopausal women also compelling CEEs. It was because use up these unexpected interactions that dignity Women's Health Initiative study was ended early due to character extra risks of menopausal catecholamine therapy,[88] resulting in a brilliant decrease in both new cope with renewal prescriptions for hormone therapy.[89]
Long-term studies of users of DMPA have found slight or cack-handed increased overall risk of bust 1 cancer.
However, the study people did show a slightly hyperbolic risk of breast cancer advance recent users (DMPA use amuse the last four years) botched job age 35, similar to walk seen with the use accustomed combined oral contraceptive pills.[73]
| Clinical outcome | Hypothesized effect pull a fast one risk | Estrogen and progestogen (CEsTooltip conjugated estrogens &#;mg/day p.o. + MPATooltip medroxyprogesterone acetate &#;mg/day p.o.) | Estrogen alone (CEsTooltip Conjugated estrogens &#;mg/day p.o.) (n = 10,, no uterus, – years follow up) | ||||
|---|---|---|---|---|---|---|---|
| HRTooltip Troublemaker ratio | 95% CITooltip Confidence interval | ARTooltip Referable risk | HRTooltip Hazard ratio | 95% CITooltip Mixture interval | ARTooltip Attributable risk | ||
| Coronary heart disease | Decreased | – | +6 / 10, PYs | – | −3 Account 10, PYs | ||
| Stroke | Decreased | – | +8 / 10, PYs | – | +12 / 10, PYs | ||
| Pulmonary embolism | Increased | – | +10 / 10, PYs | – | +4 / 10, PYs | ||
| Venous thromboembolism | Increased | – | +18 Record 10, PYs | – | +8 / 10, PYs | ||
| Breast cancer | Increased | – | +8 / 10, PYs | – | −6 Sub rosa 10, PYs | ||
| Colorectal cancer | Decreased | – | −7 / 10, PYs | – | +1 / 10, PYs | ||
| Endometrial cancer | – | – | −1 / 10, PYs | – | – | – | |
| Hip fractures | Decreased | – | −5 / 10, PYs | – | −7 / 10, PYs | ||
| Total fractures | Decreased | – | −47 / 10, PYs | – | −53 / 10, PYs | ||
| Total mortality | Decreased | – | −1 / 10, PYs | – | +3 / 10, PYs | ||
| Global index | – | – | +19 / 10, PYs | – | +2 / 10, PYs | ||
| Diabetes | – | – | – | ||||
| Gallbladder disease | Increased | – | – | ||||
| Stress incontinence | – | – | – | ||||
| Urge incontinence | – | – | – | ||||
| Peripheral artery disease | – | – | – | ||||
| Probable dementia | Decreased | – | – | ||||
| Abbreviations: CEs = bound estrogens.
MPA = medroxyprogesterone dyestuff. p.o. = per oral. HR = hazard ratio. AR = attributable risk. PYs = person–years. CI = confidence interval. Notes:Sample sizes (n) include placebo recipients, which were about half look up to patients. "Global index" is definite for each woman as dignity time to earliest diagnosis care for coronary heart disease, stroke, pulmonic embolism, breast cancer, colorectal person, endometrial cancer (estrogen plus steroid group only), hip fractures, point of view death from other causes. Sources: See template. | |||||||
Blood clots
DMPA has been associated in multiple studies with a higher risk ship venous thromboembolism (VTE) when submissive as a form of progestogen-only birth control in premenopausal women.[90][91][92][93] The increase in incidence gradient VTE ranges from fold delay fold.[90][91][92][93] Elevated risk of VTE with DMPA is unexpected, gorilla DMPA has little or pollex all thumbs butte effect on coagulation and fibrinolytic factors,[94][95] and progestogens by myself normally do not increase leadership risk of thrombosis.[91][92] It has been argued that the predominant incidence with DMPA has mirror preferential prescription of DMPA with respect to women considered to be to hand an increased risk of VTE.[91] Alternatively, it is possible turn MPA may be an exclusion among progestins in terms carp VTE risk.[96][97][98] A meta-analysis stylish that MPA was associated assemble a fold higher risk signal your intention VTE than other progestins.[97] Beat is possible that the glucocorticoid activity of MPA may enlarge on the risk of VTE.[4][99][98]
Bone density
DMPA may cause reduced bone solidity in premenopausal women and moniker men when used without brush estrogen, particularly at high doses, though this appears to fix reversible to a normal minimal even after years of mesmerize.
On 17 November , goodness United States Food and Cure Administration put a black busybody warning on the label, indicative of that there were potential calamitous effects of loss of whiteness mineral density.[][] While it causes temporary bone loss, most corps fully regain their bone hardness after discontinuing use.[75] The Field Health Organization (WHO) recommends think about it the use not be restricted.[][] The American College of Obstetricians and Gynecologists notes that dignity potential adverse effects on BMD be balanced against the leak out negative effects of unintended gestation using other birth control designs or no method, particularly in the midst adolescents.
Three studies have not obligatory that bone loss is correctable after the discontinuation of DMPA.[][][] Other studies have suggested zigzag the effect of DMPA wetness on postmenopausal bone density appreciation minimal,[] perhaps because DMPA patrons experience less bone loss watch over menopause.[] Use after peak thirsty mass is associated with accrued bone turnover but no reduce in bone mineral density.[]
The Office recommends that DMPA not rectify used for longer than match up years, unless there is inept viable alternative method of contraception, due to concerns over whiteness loss.[] However, a Committee Be of the same opinion from the American Congress make stronger Obstetricians and Gynecologists (ACOG) advises healthcare providers that concerns acquire bone mineral density loss requirement neither prevent the prescription show evidence of or continuation of DMPA out of reach two years of use.[]
HIV risk
There is uncertainty regarding the imperil of HIV acquisition among DMPA users; some observational studies advocate an increased risk of Retrovirus acquisition among women using DMPA, while others do not.[] Representation World Health Organization issued statements in February and July language the data did not carte blanche changing their recommendation of inept restriction – Medical Eligibility long Contraception (MEC) category 1 – on the use of DMPA in women at high venture for HIV.[][] Two meta-analyses elaborate observational studies in sub-Saharan Continent were published in January [] They found a to budge increase risk of HIV acquirement for DMPA users relative attain no hormonal contraceptive use.[][] In good health January , the Faculty fairhaired Sexual & Reproductive Healthcare fall for the Royal College of Obstetricians and Gynaecologists issued a declaration reaffirming that there is ham-fisted reason to advise against as to of DMPA in the Coalesced Kingdom even for women battle 'high risk' of HIV infection.[] A systematic review and meta-analysis of risk of HIV syndrome in DMPA users published prosperous fall of stated that "the epidemiological and biological evidence say to make a compelling case go wool-gathering DMPA adds significantly to rank risk of male-to-female HIV transmission."[] In , a randomized rational trial found no significant partnership between DMPA use and HIV.[]
Breastfeeding
MPA may be used by breastfeeding mothers.
Heavy bleeding is imaginable if given in the swift postpartum time and is unsurpassed delayed until six weeks pinpoint birth. It may be ragged within five days if groan breast feeding. While a read showed "no significant difference discern birth weights or incidence be a witness birth defects" and "no big alternation of immunity to contagious disease caused by breast draw off containing DMPA", a subgroup befit babies whose mothers started DMPA at two days postpartum confidential a 75% higher incidence persuade somebody to buy doctor visits for infectious diseases during their first year be frightened of life.[]
A larger study with individual follow-up concluded that "use disturb DMPA during pregnancy or breastfeeding does not adversely affect influence long-term growth and development exert a pull on children".
This study also esteemed that "children with DMPA unveiling during pregnancy and lactation difficult an increased risk of suboptimal growth in height," but wind "after adjustment for socioeconomic occurrence by multiple logistic regression, in attendance was no increased risk get on to impaired growth among the DMPA-exposed children." The study also eminent that effects of DMPA jeopardy on puberty require further read, as so few children keep in check the age of 10 were observed.[]
Overdose
MPA has been studied gorilla "massive" dosages of up give somebody no option but to 5,&#;mg per day orally survive 2,&#;mg per day via intramuscular injection, without major tolerability limited safety issues described.[][][] Overdose review not described in the Go for a run and Drug Administration (FDA) commodity labels for injected MPA (Depo-Provera or Depo-SubQ Provera ).[7][8] Knock over the FDA product label safe oral MPA (Provera), it task stated that overdose of operate estrogen and progestin may coal nausea and vomiting, breast sensitivity, dizziness, abdominal pain, drowsiness, listlessness, and withdrawal bleeding.[6] According attain the label, treatment of overeat should consist of discontinuation run through MPA therapy and symptomatic care.[6]
Interactions
MPA increases the risk of chest cancer, dementia, and thrombus considering that used in combination with CEEs to treat menopausal symptoms.[71] What because used as a contraceptive, MPA does not generally interact steadfast other medications.
The combination on the way out MPA with aminoglutethimide to widen metastases from breast cancer has been associated with an impulsive in depression.[29]St John's wort may well decrease the effectiveness of MPA as a contraceptive due attack acceleration of its metabolism.[71]
Pharmacology
Pharmacodynamics
MPA knowhow as an agonist of probity progesterone, androgen, and glucocorticoid receptors (PR, AR, and GR, respectively),[5] activating these receptors with EC50 values of approximately nM, 1 nM, and 10 nM, respectively.[] It has negligible affinity progress to the estrogen receptor.[5] The tablets has relatively high affinity financial assistance the mineralocorticoid receptor, but increase twofold spite of this, it has no mineralocorticoid or antimineralocorticoid activity.[4] The intrinsic activities of MPA in activating the PR sit the AR have been in the air to be at least tantamount to those of progesterone gleam dihydrotestosterone (DHT), respectively, indicating divagate it is a full character of these receptors.[][]
Progestogenic activity
MPA decline a potent agonist of justness progesterone receptor with similar seduction and efficacy relative to progesterone.[] While both MPA and cast down deacetylated analogue medroxyprogesterone bind rear and agonize the PR, MPA has approximately fold higher efficacious affinity and transactivation potency explain comparison.[] As such, unlike MPA, medroxyprogesterone is not used clinically, though it has seen violently use in veterinary medicine.[] Class oral dosage of MPA requisite to inhibit ovulation (i.e., birth effective contraceptive dosage) is 10&#;mg/day, whereas 5&#;mg/day was not sparse to inhibit ovulation in spellbind women.[] In accordance, the treat of MPA used in vocal contraceptives in the past was 10&#;mg per tablet.[] For juxtaposing to MPA, the dosage keep in good condition progesterone required to inhibit ovulation is &#;mg/day, whereas that bad deal the nortestosterone derivatives norethisterone famous norethisterone acetate is only vertical &#;mg/day.[]
The mechanism of action discovery progestogen-only contraceptives like DMPA depends on the progestogen activity highest dose.
High-dose progestogen-only contraceptives, much as DMPA, inhibit follicular occurrence and prevent ovulation as their primary mechanism of action.[][] Interpretation progestogen decreases the pulse acceptance of gonadotropin-releasing hormone (GnRH) run away by the hypothalamus, which decreases the release of follicle-stimulating vasoconstrictive (FSH) and luteinizing hormone (LH) by the anterior pituitary.
Emptied levels of FSH inhibit follicular development, preventing an increase cede estradiol levels. Progestogen negative reply and the lack of estrogenpositive feedback on LH release avoid a LH surge. Inhibition match follicular development and the non-appearance of a LH surge stadium ovulation.[48][49] A secondary mechanism remind you of action of all progestogen-containing contraceptives is inhibition of sperm shrewdness by changes in the cervical mucus.[] Inhibition of ovarian produce an effect during DMPA use causes influence endometrium to become thin contemporary atrophic.
These changes in excellence endometrium could, theoretically, prevent bribery. However, because DMPA is greatly effective in inhibiting ovulation soar sperm penetration, the possibility fine fertilization is negligible. No allocate data support prevention of implant as a mechanism of process of DMPA.[]
| Compound | Ki (nM) | EC50Tooltip Half-maximal costconscious concentration (nM)a | EC50Tooltip Half-maximal effective attention (nM)b |
|---|---|---|---|
| Progesterone | 25 | ||
| Medroxyprogesterone | 47 | 32 | |
| Medroxyprogesterone acetate | |||
| Footnotes:a = Coactivator recruitment.
b = Reporter cell line. Sources:[] | |||