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词条 Megestrol acetate
释义

  1. Medical uses

     Available forms 

  2. Contraindications

  3. Side effects

  4. Overdose

  5. Interactions

  6. Pharmacology

     Pharmacodynamics  Progestogenic activity  Antigonadotropic and anticorticotropic effects  Androgenic and antiandrogenic activity  Glucocorticoid activity  Appetite stimulation  Miscellaneous  Pharmacokinetics 

  7. Chemistry

     Synthesis 

  8. History

  9. Society and culture

     Generic names  Brand names  Availability  Generation 

  10. Research

  11. Veterinary use

  12. See also

  13. References

  14. Further reading

{{Drugbox
| IUPAC_name = [(8R,9S,10R,13S,14S,17R)-17-acetyl-6,10,13-trimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
| image = Megestrol acetate.svg
| width = 235px
| image2 = Megestrol acetate molecule ball.png
| width2 = 225px
| tradename = Megace, others
| pregnancy_US = X
| pregnancy_category =
| legal_status = Rx-only
| routes_of_administration = By mouth (tablets, suspension)
| class = Progestin; Progestogen; Progestogen ester; Antigonadotropin; Steroidal antiandrogen
| bioavailability = 1%[1]
| protein_bound = Majority to albumin (no affinity for {{abbrlink|SHBG|sex hormone-binding globulin}} or {{abbrlink|CBG|corticosteroid-binding globulin}})[1][1]
| metabolism = Liver (hydroxylation, reduction, conjugation)[2]
| elimination_half-life = Mean: 34 hours[5]
Range: 13–105 hours[5]
| excretion = Urine: 57–78%[2]
Feces: 8–30%[2]
| CAS_number = 595-33-5
| ATC_prefix = G03
| ATC_suffix = AC05
| PubChem = 11683
| DrugBank = DB00351
| ChemSpiderID = 11192
| UNII = TJ2M0FR8ES
| synonyms = MGA; BDH-1298; NSC-71423; SC-10363; 17α-Acetoxy-6-dehydro-6-methylprogesterone; 17α-Acetoxy-6-methylpregna-4,6-diene-3,20-dione
| C=24 | H=32 | O=4
| molecular_weight = 384.516 g/mol
| SMILES = CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=CC(=O)CC4)C
| StdInChI = 1S/C24H32O4/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26/h12-13,18-20H,6-11H2,1-5H3/t18-,19+,20+,22-,23+,24+/m1/s1
| StdInChIKey = RQZAXGRLVPAYTJ-GQFGMJRRSA-N
}}Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia.[3][4][5][6] It is also used to treat breast cancer and endometrial cancer, and has been used in birth control.[4][5][15][16] MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations.[17] It is usually taken by mouth.[3]Side effects of MGA include increased appetite, weight gain, vaginal bleeding, nausea, edema, low sex hormone levels, sexual dysfunction, osteoporosis, cardiovascular complications, glucocorticoid effects, and others.[5] MGA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[3] It has weak partial androgenic activity, weak glucocorticoid activity, and no other important hormonal activity.[3] Due to its progestogenic activity, MGA has antigonadotropic effects.[5] The mechanism of action of the appetite stimulant effects of MGA is unknown.[23][24][25]

MGA was discovered in 1959 and was introduced for medical use, specifically in birth control pills, in 1963.[15][16][28] It may be considered a "first-generation" progestin.[7] The medication was withdrawn in some countries in 1970 due to concerns about mammary toxicity observed in dogs, but this turned out not to apply to humans.[30][31][32][33][34] MGA was approved for the treatment of endometrial cancer in 1971 and wasting syndromes in 1993.[5][36] It is marketed widely throughout the world.[37][38] It is available as a generic medication.[8]

{{TOC limit|3}}

Medical uses

MGA is used mainly as an appetite stimulant to promote weight gain in a variety of situations.[9][10][11] When given at very high dosages, it can substantially increase appetite in most individuals, even those with advanced cancer, and is often used to boost appetite and induce weight gain in patients with cancer or HIV/AIDS-associated cachexia.[9] In addition to its effects on appetite, MGA appears to have antiemetic effects.[12][13] MGA is also used as an antineoplastic agent in the treatment of breast cancer and endometrial cancer.[9][14] It is significantly inferior to aromatase inhibitors in both clinical effectiveness and tolerability as a second-line therapy for breast cancer after tamoxifen failure.[15] MGA was formerly used in combined oral contraceptives in combination with ethinylestradiol or mestranol,[15][16][51] and has been used in a combined injectable contraceptive in combination with estradiol as well.[52]

Although it has not been approved for these uses, MGA has been studied and/or used off-label for a variety of indications including menopausal hormone therapy[16][17][18] and the treatment of hot flashes,[19][20][21][22] gynecological/menstrual disorders,[23][24] endometriosis,[25] endometrial hyperplasia,[26] ovarian cancer,[27][28][29][30] prostate cancer,[31][69][32][33][34][73][35] benign prostatic hyperplasia,[36][37] male breast cancer,[38] and precocious puberty.[2][5][39]

Appetite stimulation is achieved with MGA with oral dosages of 400 to 800 mg/day.[81] The optimal dosage with maximum effect for appetite stimulation has been determined to be 800 mg/day.[40] The recommended oral dosage of MGA for breast cancer is 40 mg four times per day (160 mg/day total), while the medication is used at an oral dosage of 40 to 320 mg/day in divided doses for endometrial cancer.[81][4] It has been used at far lower dosages (e.g., 1–5 mg/day oral, 25 mg/month {{abbrlink|i.m.|intramuscular injection}}) in combination with an estrogen for contraceptive purposes.[15][16][51][52]

Available forms

{{See also|Estradiol/megestrol acetate}}

MGA is available as 5 mg, 20 mg, and 40 mg oral tablets and in oral suspensions of 40 mg/mL, 125 mg/mL, 625 mg/5 mL, and 820 mg/20 mL.[41][42] It was used at doses of 1 mg, 2 mg, 4 mg, and 5 mg in combined oral contraceptives.[15][16][51][52] MGA is formulated at a dose of 25 mg in combination with a dose of 3.75 mg estradiol in a microcrystalline aqueous suspension for use as a once-monthly combined injectable contraceptive in women.[43]

Contraindications

Contraindications of MGA include hypersensitivity to MGA or any component of its formulation, known or suspected pregnancy, and breastfeeding.[6] MGA is a teratogen in animals and may have the potential to cause fetal harm, such as decreased fetal weight and feminization of male fetuses.[6]

Side effects

The most common side effect of MGA is weight gain, with an incidence of 15 to 70% at the high dosages used to treat breast cancer.[2][4] Other side effects include vaginal bleeding (7–8%), nausea (7%), and edema (5%), as well as others such as dizziness and shortness of breath.[2][4][44] MGA can cause hypogonadism and associated symptoms like diminished secondary sexual characteristics, sexual dysfunction, osteoporosis, and reversible infertility in men and premenopausal women.[45][46][47] Combining MGA with an androgen/anabolic steroid like oxandrolone, nandrolone decanoate, or testosterone in men can alleviate MGA-associated symptoms of hypoandrogenism as well as further increase appetite and weight gain.[46][48][49][50] Less common but more serious side effects of MGA include cardiovascular/thromboembolic complications such as thrombophlebitis.[4] It may also cause glucocorticoid side effects such as Cushing syndrome-like symptoms, steroid diabetes, and adrenal insufficiency at high dosages.[111][51][52] Case reports of deep vein thrombosis, pulmonary embolism, jaundice, intrahepatic cholestasis, and meningiomas in association with high-dosage MGA have been published.[53][54][55][56]

Overdose

MGA has been studied at very high dosages of as much as 1,600 mg/day with no serious adverse effects observed.[6][57] No clear increase in rate or severity of side effects have been observed up to 1,600 mg/day MGA except for weight gain, mild increases in blood pressure, and some fluid retention.[57] In post-marketing experience, limited reports of overdose have been received.[6] Signs and symptoms described in these reports have included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain.[6] There is no specific antidote for overdose of MGA.[6] Treatment should be supportive and based on symptoms.[6] MGA has not been assessed for dialyzability.[6] However, due to its low solubility, it is thought that dialysis would not be useful for treating MGA overdose.[6]

Interactions

Interactions of MGA include significantly decreased exposure to indinavir, which may necessitate an increased dosage of the medication.[6] When MGA is co-administered with zidovudine and rifabutin, there is no significant change in exposure to these medications and no dosage adjustment is necessary.[6]

Pharmacology

Pharmacodynamics

MGA has progestogenic activity, antigonadotropic effects, weak partial androgenic activity, and weak glucocorticoid activity.[3][1][131]

Relative affinities (%) of megestrol acetate
Compound PR|Progesterone receptorAR|Androgen receptorER|Estrogen receptorGR|Glucocorticoid receptorMR|Mineralocorticoid receptorSHBG|Sex hormone-binding globulinCBG|Corticosteroid binding globulin
Megestrol acetate 65 5 0 30 0 0 0
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the {{abbrlink|PR|progesterone receptor}}, metribolone for the {{abbrlink|AR|androgen receptor}}, estradiol for the {{abbrlink|ER|estrogen receptor}}, dexamethasone for the {{abbrlink|GR|glucocorticoid receptor}}, aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}, dihydrotestosterone for {{abbrlink|SHBG|sex hormone-binding globulin}}, and cortisol for {{abbrlink|CBG|Corticosteroid-binding globulin}}. Sources: [3][1][131]
{{Relative affinities of antiandrogens at steroid-hormone receptors}}

Progestogenic activity

MGA is a progestogen, or an agonist of the progesterone receptor (PR).[3][58][59] It has about 65% of the affinity of promegestone and 130% of the affinity of progesterone for the PR.[58][59] Like other progestogens, MGA has functional antiestrogenic effects in certain tissues such as the endometrium and has antigonadotropic effects.[3][9][142] The total endometrial transformation dose of MGA is 50 mg per cycle.[142]

{{Parenteral potencies and durations of progestogens}}

Antigonadotropic and anticorticotropic effects

MGA has antigonadotropic effects in humans at sufficient doses, capable of profoundly suppressing circulating androgen and estrogen concentrations.[9][33][60][61][62][63] The antigonadotropic effects of MGA are the result of activation of the PR, which suppresses the secretion of the gonadotropins – peptide hormones responsible for signaling the body to produce not only progesterone but also the androgens and the estrogens – from the pituitary gland as a form of negative feedback inhibition, and hence downregulates the hypothalamic–pituitary–gonadal axis (HPG axis), resulting in decreased levels of the sex hormones and interference with fertility.[64] As such, MGA has functional antiandrogenic and antiestrogenic effects as well as contraceptive effects via its antigonadotropic effects.[5]

The precise ovulation-inhibiting dosage of MGA appears to be unknown.[142][65] However, doses of 1 to 5 mg MGA were previously used in combined birth control pills in combination with the estrogen ethinylestradiol or mestranol.[15][16][51] MGA is an effective contraceptive by itself at dosages of 0.35 to 0.5 mg/day, but is not effective at a dosage of 0.25 mg/day.[5] MGA alone does not inhibit ovulation at a dosage of 0.5 mg/day, nor does it fully inhibit ovulation at a dosage of 0.7 mg/day.[5][66] The combination of 2 to 3 mg/day MGA and 100 μg/day mestranol appears to consistently inhibit ovulation.[67]

Suppression of testosterone levels by MGA is responsible for its effectiveness in the treatment of conditions like prostate cancer and benign prostatic hyperplasia.[5][68] In one study, 120 to 160 mg/day MGA suppressed testosterone levels in men by 72%.[62] However, a recovery or "escape" of testosterone levels, gradually returning to near-normal values, has been observed in most men after 2 to 6 months of MGA therapy, and this has limited the usefulness of the medication.[9][69][70][71] The combination of a lower dosage of MGA (40–80 mg/day) and a low oral dosage of an estrogen such as estradiol (0.5–1.5 mg/day), diethylstilbestrol (0.1–0.2 mg/day) or ethinylestradiol (50 µg/day) is able to suppress testosterone levels into the castrate range in men, maintain this suppression long-term, and achieve equivalent effectiveness to high-dosage estrogen monotherapy in the treatment of prostate cancer with comparatively greatly reduced toxicity and side effects.[9][5][69][33][34][72][73][74][75][5] In spite of these results however, this combination has been very rarely used to treat prostate cancer in the United States.[69]

The antigonadotropic as well as anticorticotropic effects of MGA may be involved in its effectiveness in the treatment of postmenopausal breast cancer via substantially decreasing gonadal and adrenal production of sex steroids and by extension circulating levels of estrogens, by about 80%.[76][77][78]

Androgenic and antiandrogenic activity

MGA is a weak partial agonist of the androgen receptor (AR).[79][80][81] It has been reported to bind to this receptor with 5% of the affinity of the anabolic steroid metribolone.[3][1][58] Despite its weak intrinsic activity at the AR, at clinical doses in humans, MGA appears to behave, for all intents and purposes, purely as an antiandrogen.[82] This is based on the fact that no virilizing side effects have been observed with the use of MGA in patients of either sex at dosages up to as high as 1,600 mg per day, the highest that has been assessed.[82] Furthermore, MGA produces detectable androgenic effects in animals only at a dose that is the equivalent of approximately 200 times that typically used for the treatment of prostate cancer in men.[83] However, the medication does have moderate androgenic effects on serum lipids in humans, causing a significant reduction of {{abbr|HDL|high-density lipoprotein}} and {{abbr|LDL|low-density lipoprotein}} cholesterol levels and no change in triglyceride levels at a dosage of only 5 mg/day.[3] The weak but significant androgenic activity of MGA may serve to limit its clinical effectiveness in the treatment of prostate cancer.[80][81][84][85]

{{Affinities of selected ligands at the androgen receptor}}

Glucocorticoid activity

MGA is an agonist of the glucocorticoid receptor (GR), the biological target of glucocorticoids like cortisol.[3][1][58] It has been found to possess 30% of the affinity of the corticosteroid dexamethasone for this receptor.[3][1][58] MGA shows the lowest ratio of PR affinity to GR affinity of a broad selection of marketed progestins, suggesting that it may have among the highest relative glucocorticoid effect of the progestins used in medicine.[3] MGA produces observable glucocorticoid effects, with one study finding that, in the dose range tested, it possessed about 50% of the eosinopenic and hyperglycemic activity (markers of glucocorticoid activity) of an equal amount of medroxyprogesterone acetate and about 25% that of hydrocortisone.[86] Accordingly, manifestations of its glucocorticoid activity, including symptoms of Cushing's syndrome, steroid diabetes, and adrenal insufficiency, have been reported with the use of MGA in the literature, albeit sporadically.[87]

Appetite stimulation

MGA is frequently used as an appetite stimulant to promote weight gain.[9][10][11] The direct mechanism of appetite enhancement is unclear, but it is known that MGA induces a variety of downstream changes to cause the effect, including stimulation of the release of neuropeptide Y in the hypothalamus, neurosteroid-like modulation of calcium channels in the ventromedial hypothalamus,[88] and inhibition of the secretion of proinflammatory cytokines including interleukin 1α, interleukin 1β, interleukin 6, and tumor necrosis factor α, all of which have been implicated in facilitation of appetite.[89][90][91] Increased levels of insulin-like growth factor 1 (IGF-1) may also be involved, specifically in its anabolic effects.[212]

Miscellaneous

Unlike the case of the AR, MGA has no significant affinity for the ER.[3][1][58] As such, it does not possess the capacity to directly activate the ER.[3][1][58] Furthermore, unlike antiandrogens such as spironolactone and bicalutamide but similarly to cyproterone acetate, there is relatively little risk of indirectly mediated estrogenic side effects (e.g., gynecomastia) with MGA.[92] This is because MGA strongly suppresses both androgen and estrogen levels at the same time.[9][33][60][61][62][63] Similarly to the case of the ER, MGA has negligible affinity for the mineralocorticoid receptor (MR), and hence does not possess mineralocorticoid or antimineralocorticoid activity.[3][1][58]

MGA has been found to dose-dependently increase total and free IGF-1 levels up to a dosage of 120 mg/day.[93] Total IGF-1 levels were described as "profoundly" increased, gradually increasing, significantly by 3 days of treatment, up to a maximum of 2.66-fold by 5 to 6 months of treatment.[93] Free (readily dissociable) concentrations of IGF-1 were increased to a smaller extent, by 1.23–2.15-fold, and were described as increasing "moderately".[93] It was suggested that the increase in IGF-1 levels with high-dosage MGA therapy may explain the anabolic effects of MGA in patients with cachexia.[93]

Pharmacokinetics

The oral bioavailability of MGA is approximately 100%.[3] After a single low oral dose of 4 mg MGA, peak serum concentrations of MGA were about 7 ng/dL (18 nmol/L) and occurred after 3 hours.[3] Following a single high oral dose of 160 mg micronized MGA in men, peak circulating levels of MGA were 125 ng/mL (325 nmol/L) and occurred after 6.3 hours.[94] This study found that micronized MGA at this dose showed considerably improved absorption relative to its conventional tablet form.[94] In terms of plasma protein binding, MGA is bound mostly to albumin and is not bound to sex hormone-binding globulin or to corticosteroid-binding globulin.[3][1] The medication is metabolized in the liver mainly by hydroxylation of the C21, C2α, and C6 positions, as well as by reduction and conjugation.[3][2] Its elimination half-life is 34 hours on average, with a range of 13 to 105 hours.[4] MGA is excreted 57 to 78% in urine and 8 to 30% in feces.[2]

At high doses, MGA has profoundly greater bioavailability and potency than medroxyprogesterone acetate, regardless of whether the route of administration of the latter is oral or parenteral.[2][244][95] Following oral administration of 80 to 160 mg MGA or 500 to 1,000 mg medroxyprogesterone acetate, circulating levels of MGA were 2- to 10-fold higher than those of medroxyprogesterone acetate.[95][244][2] Similar findings have been found for oral MGA relative to medroxyprogesterone acetate administered via intramuscular injection.[2] MGA also reaches steady-state levels more quickly than medroxyprogesterone acetate.[95] The improved potency of MGA compared to medroxyprogesterone acetate may be due to increased resistance to metabolism of MGA afforded by its C6(7) double bond (medroxyprogesterone acetate being identical to MGA in structure except lacking this feature).[2][96][97]

The pharmacokinetics of MGA have been reviewed.[3][142][98]

Chemistry

{{See also|List of progestogens|Progestogen ester|List of progestogen esters|Steroidal antiandrogen|List of steroidal antiandrogens}}

MGA, also known as 17α-acetoxy-6-dehydro-6-methylprogesterone or as 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione, is a synthetic pregnane steroid and a derivative of progesterone.[99][100] It is specifically a derivative of 17α-hydroxyprogesterone with a methyl group at the C6 position, a double bond between the C6 and C7 positions, and an acetate ester at the C17α position.[99][100] MGA is the C17α acetate ester of megestrol, which, in contrast to MGA, was never marketed.[99][100] Analogues of MGA include other 17α-hydroxyprogesterone derivatives such as acetomepregenol, anagestone acetate, chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and nomegestrol acetate.[99][100] MGA differs from medroxyprogesterone acetate only by its C6(7) double bond.[101] Close analogues of MGA that were never marketed include cymegesolate (megestrol acetate 3β-cypionate) and megestrol caproate.[102][103][104]

Synthesis

Chemical syntheses of MGA have been published.[105][106]

History

MGA was synthesized at Syntex in 1959.[107] It was derived from medroxyprogesterone acetate, which had been synthesized at Syntex in 1957.[107][108] MGA was the third synthetic derivative of progesterone to be developed for use as a medication, following hydroxyprogesterone caproate in 1954 and medroxyprogesterone acetate in 1957.[107] The medication was introduced for medical use in combination with ethinylestradiol (EE) as an oral contraceptive in 1963 by British Drug Houses in the United Kingdom under the brand name Volidan (4 mg MGA and 50 μg EE tablets),[109][110] and this was followed by Serial 28 (1 mg MGA and 100 μg EE tablets) and Volidan 21 (4 mg MGA and 50 μg EE tablets) in 1964 and Nuvacon (2 mg MGA and 100 μg EE tablets) in 1967, all by British Drug Houses also in the United Kingdom.[111] It was also marketed under the brand name Delpregnin (5 mg MGA and 100 μg mestranol tablets) by 1965, among others.[112][113][114][115]

In the early 1970s, MGA was found to be associated with mammary tumors in beagle dogs, and along with several other progestogens, was withdrawn as an oral contraceptive from several markets including the United Kingdom, Canada, and Germany.[116][117][118] It was also under investigation for use as a contraceptive in the United States, but development was discontinued in 1972 following the mammary toxicity findings in dogs, and MGA was never marketed as an oral contraceptive in the United States.[118][119][287] Subsequent research, such as monkey studies, revealed that there is no similar risk in humans.[120][2] Following its withdrawal from the market, MGA was eventually reintroduced for the treatment of hormone-sensitive cancers.[121] In addition, MGA was marketed for veterinary use in dogs in 1969 in the United Kingdom and in 1974 in the United States.[122][123][124]

Progesterone was first found to be effective in the treatment of endometrial hyperplasia in 1951,[2] and progestins were first found to be effective in the treatment of endometrial cancer in 1959.[125] MGA was reported to be effective in the treatment of endometrial hyperplasia in the mid-1960s.[2] It first started to be studied as a treatment for endometrial cancer in 1967, with findings published in 1973.[2][126][127] MGA was reportedly introduced for the treatment of endometrial cancer in the United States in 1971.[5] Progesterone was studied in the treatment of breast cancer in 1951 and 1952, but with relatively modest results.[301][128][129] MGA was first studied in the treatment of breast cancer in 1967, and was one of the first progestins to be evaluated for the treatment of this disease.[2][130][14] A second study was conducted in 1974.[2][131] A "breakthrough" and surge of interest in progestins for breast cancer occurred in 1978 when a study using a massive dosage of medroxyprogesterone acetate to treat breast cancer was published.[132][133] A third study of MGA for breast cancer was published in 1980, and this was followed by additional studies in the 1980s and beyond.[2][134][135] MGA was approved for the treatment of breast cancer in the United States by at least 1983.[2]

Progestogens, including progesterone and ethisterone, were studied in the treatment prostate cancer in 1949.[136][2] MGA was first studied in the treatment of prostate cancer in 1970.[2][137] Additional studies were conducted in 1975 and 1978, followed by others thereafter.[2][138][139][5] However, results of MGA therapy for prostate cancer have been "disappointing",[140] and the medication has not been approved for the treatment of prostate cancer in the United States or elsewhere.[69]

Clinical studies of very high dosages of MGA for breast cancer conducted in the 1980s observed markedly increased appetite and weight gain in treated patients despite them having advanced cancer.[141][326] This led to potential interest in MGA as an appetite stimulant,[141] and in 1986, a paper was published proposing the study and potential use of MGA in cachexia.[142][143][144] MGA was subsequently studied for this indication[145] and, following completion of phase III clinical trials, was approved as an oral suspension for the treatment of anorexia–cachexia syndrome due to cancer and other chronic conditions such as HIV/AIDS in the United States in 1993.[146][147]

Society and culture

Generic names

Megestrol acetate is the generic name of the drug and its {{abbrlink|INNM|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, and {{abbrlink|BANM|British Approved Name}}, while megestrol is the {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}} and mégestrol the {{abbrlink|DCF|Dénomination Commune Française}} of megestrol, the free alcohol form of MGA.[99][100][148][149] The medication is also known by its developmental code names BDH-1298, NSC-71423, and SC-10363.[99][100][149][148]

Brand names

MGA is marketed under a variety of brand names throughout the world but is most commonly sold under the brand name Megace.[99][100][149] It is also available under the brand name Megace ES in the United States and under the brand name Megace OS in Canada.[149] For use in veterinary medicine, MGA is sold as Ovaban in the United States and as Ovarid in the United Kingdom.[149]

Availability

{{See also|List of progestogens available in the United States}}

MGA is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, Australia, New Zealand, Latin America, Asia, and a few African countries.[100][149] It does not appear to be marketed in Germany, Russia, South Africa, Japan, India, or Mexico, among other countries.[149]

Generation

Progestins in birth control pills are sometimes grouped by generation.[150][151] While the 19-nortestosterone progestins are consistently grouped into generations, the pregnane progestins that are or have been used in birth control pills are typically omitted from such classifications or are grouped simply as "miscellaneous" or "pregnanes".[150][151] In any case, based on its date of introduction in such formulations of 1963, MGA could be considered a "first-generation" progestin.[7]

Research

MGA has been studied in men in combination with testosterone as a male hormonal contraceptive to suppress spermatogenesis.[5][152]

Veterinary use

MGA has been used in veterinary medicine under the brand name Ovaban in the treatment of medical conditions in cats and dogs.[100][153] Due to its ability to suppress testosterone levels, MGA can control sexually dimorphic traits in males.[154][155] As a result, MGA has been used to reduce dominance, inter-male aggression, mounting, urine spraying, and roaming in male dogs and cats.[154][155]

See also

  • Estradiol/megestrol acetate

References

1. ^1 2 3 4 5 6 7 8 9 {{cite journal |vauthors=Schindler AE, Campagnoli C, Druckmann R, etal | title = Classification and pharmacology of progestins | journal = Maturitas | volume = 46 Suppl 1 | issue = | pages = S7–S16 |date=December 2003 | pmid = 14670641 | doi = 10.1016/j.maturitas.2003.09.014| url = http://linkinghub.elsevier.com/retrieve/pii/S037851220300330X}}
2. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 {{cite journal | vauthors = Canetta R, Florentine S, Hunter H, Lenaz L | title = Megestrol acetate | journal = Cancer Treat. Rev. | volume = 10 | issue = 3 | pages = 141–57 | date = September 1983 | pmid = 6352021 | doi = | url = }}
3. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 {{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 Suppl 1 | issue = | pages = 3–63 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}}
4. ^1 2 3 4 5 6 7 8 {{cite book|author1=Richard R. Barakat|author2=Maurie Markman|author3=Marcus Randall|title=Principles and Practice of Gynecologic Oncology|url=https://books.google.com/books?id=hsMne5mAXSIC&pg=PA447|year=2009|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-7845-9|pages=447–}}
5. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 {{cite journal | vauthors = Schacter L, Rozencweig M, Canetta R, Kelley S, Nicaise C, Smaldone L | title = Megestrol acetate: clinical experience | journal = Cancer Treat. Rev. | volume = 16 | issue = 1 | pages = 49–63 | date = March 1989 | pmid = 2471590 | doi = 10.1016/0305-7372(89)90004-2 | url = }}
6. ^1 2 3 4 5 6 7 8 9 10 11 https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021778s018lbl.pdf
7. ^1 {{cite book|author=John David Gordon|title=Obstetrics, Gynecology & Infertility: Handbook for Clinicians|url=https://books.google.com/books?id=2JLC6yiA7fcC&pg=PA228|year=2007|publisher=Scrub Hill Press, Inc.|isbn=978-0-9645467-7-6|pages=228–}}
8. ^https://www.drugs.com/availability/generic-megace.html
9. ^1 2 3 4 5 6 7 8 {{cite book | author = Kenneth L. Becker | title = Principles and Practice of Endocrinology and Metabolism | url = https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1195 | accessdate = 27 May 2012 | date = 24 April 2001 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-1750-2 | pages = 1195–1196}}
10. ^1 {{cite journal | vauthors = Taylor JK, Pendleton N | title = Progesterone therapy for the treatment of non-cancer cachexia: a systematic review | journal = BMJ Support Palliat Care | volume = 6 | issue = 3 | pages = 276–86 | date = September 2016 | pmid = 27098973 | doi = 10.1136/bmjspcare-2015-001041 | url = }}
11. ^1 {{cite journal | vauthors = Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S | title = Megestrol acetate for treatment of anorexia-cachexia syndrome | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD004310 | date = March 2013 | pmid = 23543530 | doi = 10.1002/14651858.CD004310.pub3 | url = }}
12. ^{{cite journal | vauthors = Loprinzi C, Jatoi A | title = Antiemetic properties of megestrol acetate | journal = J Palliat Med | volume = 9 | issue = 2 | pages = 239–40 | date = April 2006 | pmid = 16629544 | doi = 10.1089/jpm.2006.9.239 | url = }}
13. ^{{cite journal | vauthors = Zang J, Hou M, Gou HF, Qiu M, Wang J, Zhou XJ, Luo de Y, Yang Y, Jiang M, Cao D, Bi F, Xu F, Shen Y, Yi C | title = Antiemetic activity of megestrol acetate in patients receiving chemotherapy | journal = Support Care Cancer | volume = 19 | issue = 5 | pages = 667–73 | date = May 2011 | pmid = 20419494 | doi = 10.1007/s00520-010-0886-x | url = }}
14. ^1 {{cite journal | author = Sedlacek SM | title = An overview of megestrol acetate for the treatment of advanced breast cancer | journal = Seminars in Oncology | volume = 15 | issue = 2 Suppl 1 | pages = 3–13 | date = April 1988 | pmid = 3285483 | doi = | url = }}
15. ^{{cite book|author1=Charles Swanton|author2=Stephen R. D. Johnston|title=Handbook of Metastatic Breast Cancer, Second Edition|url=https://books.google.com/books?id=eYTOBQAAQBAJ&pg=PA18|date=14 November 2011|publisher=CRC Press|isbn=978-1-84184-812-9|pages=18–}}
16. ^{{cite journal | vauthors = Kauppila A, Kivinen S, Leinonen P, Tuimala R, Vihko R, Ylöstalo P | title = Comparison of megestrol acetate and clomiphene citrate as supplemental medication in postmenopausal oestrogen replacement therapy | journal = Arch. Gynecol. | volume = 234 | issue = 1 | pages = 49–58 | date = 1983 | pmid = 6660928 | doi = | url = }}
17. ^{{cite journal | vauthors = Erlik Y, Meldrum DR, Lagasse LD, Judd HL | title = Effect of megestrol acetate on flushing and bone metabolism in post-menopausal women | journal = Maturitas | volume = 3 | issue = 2 | pages = 167–72 | date = August 1981 | pmid = 7289887 | doi = | url = }}
18. ^{{cite journal | vauthors = Farish E, Barnes JF, O'Donoghue F, Fletcher CD, Ekevall K, Hart DM | title = The role of megestrol acetate as an alternative to conventional hormone replacement therapy | journal = Climacteric | volume = 3 | issue = 2 | pages = 125–34 | date = June 2000 | pmid = 11910653 | doi = | url = }}
19. ^{{cite journal | vauthors = Loprinzi CL, Michalak JC, Quella SK, O'Fallon JR, Hatfield AK, Nelimark RA, Dose AM, Fischer T, Johnson C, Klatt NE | title = Megestrol acetate for the prevention of hot flashes | journal = N. Engl. J. Med. | volume = 331 | issue = 6 | pages = 347–52 | date = August 1994 | pmid = 8028614 | doi = 10.1056/NEJM199408113310602 | url = }}
20. ^{{cite journal | vauthors = Guise TA, Oefelein MG, Eastham JA, Cookson MS, Higano CS, Smith MR | title = Estrogenic side effects of androgen deprivation therapy | journal = Rev Urol | volume = 9 | issue = 4 | pages = 163–80 | year = 2007 | pmid = 18231613 | pmc = 2213888 | doi = | url = }}
21. ^{{cite journal | vauthors = Frisk J | title = Managing hot flushes in men after prostate cancer--a systematic review | journal = Maturitas | volume = 65 | issue = 1 | pages = 15–22 | year = 2010 | pmid = 19962840 | doi = 10.1016/j.maturitas.2009.10.017 | url = }}
22. ^{{cite journal | vauthors = Bertelli G, Venturini M, Del Mastro L, Bergaglio M, Sismondi P, Biglia N, Venturini S, Porcile G, Pronzato P, Costantini M, Rosso R | title = Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study | journal = Ann. Oncol. | volume = 13 | issue = 6 | pages = 883–8 | date = June 2002 | pmid = 12123333 | doi = | url = }}
23. ^{{cite journal | vauthors = Ostergaard E | title = The oral progestational and anti-ovulatory properties of megestrol acetate and its therapeutic use in gynaecological disorders | journal = J Obstet Gynaecol Br Emp | volume = 72 | issue = 1 | pages = 45–48 | date = February 1965 | pmid = 12332461 | doi = | url = }}
24. ^{{cite journal | vauthors = Palti Z | title = Clinical results of treatment with megestrol acetate in menstrual disorders and contraception | journal = Indian Pract | volume = 19 | issue = 8 | pages = 597–600 | date = August 1966 | pmid = 5916119 | doi = | url = }}
25. ^{{cite journal | vauthors = Schlaff WD, Dugoff L, Damewood MD, Rock JA | title = Megestrol acetate for treatment of endometriosis | journal = Obstet Gynecol | volume = 75 | issue = 4 | pages = 646–8 | date = April 1990 | pmid = 2314784 | doi = | url = }}
26. ^{{cite journal | vauthors = Gal D, Edman CD, Vellios F, Forney JP | title = Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia | journal = Am. J. Obstet. Gynecol. | volume = 146 | issue = 3 | pages = 316–22 | date = June 1983 | pmid = 6859142 | doi = | url = }}
27. ^{{cite journal | vauthors = Geisler HE | title = Megestrol acetate for the palliation of advanced ovarian carcinoma | journal = Obstet Gynecol | volume = 61 | issue = 1 | pages = 95–8 | date = January 1983 | pmid = 6185891 | doi = | url = }}
28. ^{{cite journal | vauthors = Geisler HE | title = The use of high-dose megestrol acetate in the treatment of ovarian adenocarcinoma | journal = Semin. Oncol. | volume = 12 | issue = 1 Suppl 1 | pages = 20–2 | date = March 1985 | pmid = 3975647 | doi = | url = }}
29. ^{{cite journal | vauthors = Sikic BI, Scudder SA, Ballon SC, Soriero OM, Christman JE, Suey L, Ehsan MN, Brandt AE, Evans TL | title = High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group | journal = Semin. Oncol. | volume = 13 | issue = 4 Suppl 4 | pages = 26–32 | date = December 1986 | pmid = 3099393 | doi = | url = }}
30. ^{{cite journal | vauthors = Veenhof CH, van der Burg ME, Nooy M, Aalders JG, Pecorelli S, Oliveira CF, Rotmensz N, Vermorken JB | title = Phase II study of high-dose megestrol acetate in patients with advanced ovarian carcinoma | journal = Eur. J. Cancer | volume = 30A | issue = 5 | pages = 697–8 | date = 1994 | pmid = 8080689 | doi = | url = }}
31. ^{{cite journal | vauthors = Frick J, Marberger H, Swoboda HP | title = [Hormone therapy of prostatic neoplasms] | language = German | journal = Urologe | volume = 10 | issue = 3 | pages = 117–9 | date = May 1971 | pmid = 4104209 | doi = | url = }}
32. ^{{cite journal | vauthors = Block M, Bonomi P, Anderson K, Wolter J, Showel J, Pessis D, Slayton R | title = Treatment of stage D prostatic carcinoma with megestrol acetate | journal = J Surg Oncol | volume = 17 | issue = 4 | pages = 367–71 | date = 1981 | pmid = 7265976 | doi = | url = }}
33. ^1 2 3 {{cite journal | vauthors = Geller J, Albert J, Yen SS, Geller S, Loza D | title = Medical castration of males with megestrol acetate and small doses of diethylstilbestrol | journal = J. Clin. Endocrinol. Metab. | volume = 52 | issue = 3 | pages = 576–80 | date = March 1981 | pmid = 6161942 | doi = 10.1210/jcem-52-3-576 | url = }}
34. ^1 {{cite journal | vauthors = Geller J, Albert J, Yen SS, Geller S, Loza D | title = Medical castration with megestrol acetate and minidose of diethylstilbestrol | journal = Urology | volume = 17 | issue = 4 Suppl | pages = 27–33 | date = April 1981 | pmid = 6782738 | doi = | url = }}
35. ^{{cite journal | vauthors = Bonomi P, Pessis D, Bunting N, Block M, Anderson K, Wolter J, Rossof A, Slayton R, Harris J | title = Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer | journal = Semin. Oncol. | volume = 12 | issue = 1 Suppl 1 | pages = 36–9 | date = March 1985 | pmid = 3975650 | doi = | url = }}
36. ^{{cite journal | vauthors = Lebech PE, Nordentoft EL | title = A study of endocrine function in the treatment of benign prostatic hypertrophy with megestrol acetate | journal = Acta Obstet Gynecol Scand | volume = 46 | issue = | pages = Suppl 9:25–38 | date = 1967 | pmid = 4169449 | doi = | url = }}
37. ^{{cite journal | vauthors = Donkervoort T, Zinner NR, Sterling AM, Donker PJ, Van Ness J, Ritter RC | title = Megestrol acetate in treatment of benign prostatic hypertrophy | journal = Urology | volume = 6 | issue = 5 | pages = 580–7 | date = November 1975 | pmid = 52933 | doi = | url = }}
38. ^{{cite journal | vauthors = Mitsuyasu R, Bonomi P, Anderson K, Fischer W | title = Response to megestrol in male breast carcinoma | journal = Arch. Intern. Med. | volume = 141 | issue = 6 | pages = 809–10 | date = May 1981 | pmid = 6263202 | doi = | url = }}
39. ^{{cite journal | vauthors = Cai DP, Ji ZY, Shi YM | title = [Clinical study on treatment of female idiopathic precocious puberty with combined therapy of Chinese medicine and megestrol acetate] | language = Chinese | journal = Zhongguo Zhong Xi Yi Jie He Za Zhi | volume = 21 | issue = 10 | pages = 732–5 | date = October 2001 | pmid = 12575602 | doi = | url = }}
40. ^{{cite journal | vauthors = Loprinzi CL, Bernath AM, Schaid DJ, Malliard JA, Athmann LM, Michalak JC, Tschetter LK, Hatfield AK, Morton RF | title = Phase III evaluation of 4 doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia | journal = Oncology | volume = 51 Suppl 1 | issue = | pages = 2–7 | date = October 1994 | pmid = 7970505 | doi = 10.1159/000227407 | url = }}
41. ^1 2 {{cite book|author1=Shamim Tejani|author2=Cynthia Sanoski|title=Davis's Pocket Clinical Drug Reference|url=https://books.google.com/books?id=1WH2AAAAQBAJ&pg=PA167|date=16 March 2009|publisher=F.A. Davis|isbn=978-0-8036-2305-7|pages=167–}}
42. ^{{cite book|author=Mari J. Wirfs, PhD, MN, APRN, ANP-BC, FNP-BC, CNE|title=The APRN’s Complete Guide to Prescribing Pediatric Drug Therapy 2|url=https://books.google.com/books?id=98ypDgAAQBAJ&pg=PA18|date=26 July 2017|publisher=Springer Publishing Company|isbn=978-0-8261-6669-2|pages=18–}}
43. ^1 2 3 {{cite journal | vauthors = Newton JR, D'arcangues C, Hall PE | title = A review of "once-a-month" combined injectable contraceptives | journal = J Obstet Gynaecol (Lahore) | volume = 4 Suppl 1 | issue = | pages = S1–34 | date = 1994 | pmid = 12290848 | doi = | url = }}
44. ^{{cite journal | vauthors = Willemse PH, van der Ploeg E, Sleijfer DT, Tjabbes T, van Veelen H | title = A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer | journal = Eur. J. Cancer | volume = 26 | issue = 3 | pages = 337–43 | date = March 1990 | pmid = 2141491 | doi = | url = }}
45. ^{{cite book|author1=Stephen J. Winters|author2=Ilpo T. Huhtaniemi|title=Male Hypogonadism: Basic, Clinical and Therapeutic Principles|url=https://books.google.com/books?id=UFi-DgAAQBAJ&pg=PA407|date=25 April 2017|publisher=Humana Press|isbn=978-3-319-53298-1|pages=407–}}
46. ^1 {{cite journal | vauthors = Gullett NP, Hebbar G, Ziegler TR | title = Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting | journal = Am. J. Clin. Nutr. | volume = 91 | issue = 4 | pages = 1143S–1147S | year = 2010 | pmid = 20164318 | pmc = 2844687 | doi = 10.3945/ajcn.2010.28608E | url = }}
47. ^{{cite journal | vauthors = Wermers RA, Hurley DL, Kearns AE | title = Osteoporosis associated with megestrol acetate | journal = Mayo Clin. Proc. | volume = 79 | issue = 12 | pages = 1557–61 | date = December 2004 | pmid = 15595341 | doi = 10.4065/79.12.1557 | url = }}
48. ^{{cite journal | vauthors = Cuerda C, Zugasti A, Bretón I, Camblor M, Miralles P, García P | title = Treatment with nandrolone decanoate and megestrol acetate in HIV-infected men | journal = Nutr Clin Pract | volume = 20 | issue = 1 | pages = 93–7 | date = February 2005 | pmid = 16207650 | doi = 10.1177/011542650502000193 | url = }}
49. ^{{cite journal | vauthors = Mulligan K, Zackin R, Von Roenn JH, Chesney MA, Egorin MJ, Sattler FR, Benson CA, Liu T, Umbleja T, Shriver S, Auchus RJ, Schambelan M | title = Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial | journal = J. Clin. Endocrinol. Metab. | volume = 92 | issue = 2 | pages = 563–70 | date = February 2007 | pmid = 17090640 | doi = 10.1210/jc.2006-0954 | url = }}
50. ^{{cite journal | vauthors = Casaburi R, Nakata J, Bistrong L, Torres E, Rambod M, Porszasz J | title = Effect of Megestrol Acetate and Testosterone on Body Composition and Hormonal Responses in COPD Cachexia | journal = Chronic Obstr Pulm Dis | volume = 3 | issue = 1 | pages = 389–397 | date = November 2015 | pmid = 28848861 | pmc = 5559120 | doi = 10.15326/jcopdf.3.1.2015.0128 | url = }}
51. ^{{cite journal |vauthors=Chidakel AR, Zweig SB, Schlosser JR, Homel P, Schappert JW, Fleckman AM | title = High prevalence of adrenal suppression during acute illness in hospitalized patients receiving megestrol acetate | journal = Journal of Endocrinological Investigation | volume = 29 | issue = 2 | pages = 136–40 | date = February 2006 | pmid = 16610239 | doi = 10.1007/bf03344086 | url = http://www.jendocrinolinvest.it/jei/en/abstract.cfm?articolo_id=1175 }}
52. ^{{cite journal |vauthors=Bulchandani D, Nachnani J, Amin A, May J | title = Megestrol acetate-associated adrenal insufficiency | journal = The American Journal of Geriatric Pharmacotherapy | volume = 6 | issue = 3 | pages = 167–72 | date = August 2008 | pmid = 18775392 | doi = 10.1016/j.amjopharm.2008.08.004 | url = http://linkinghub.elsevier.com/retrieve/pii/S1543-5946(08)00043-3 }}
53. ^{{cite journal | vauthors = Marshall LL | title = Megestrol acetate therapy in geriatric patients: case reviews and associated deep vein thrombosis | journal = Consult Pharm | volume = 18 | issue = 9 | pages = 764–73 | date = September 2003 | pmid = 16563066 | doi = | url = }}
54. ^{{cite journal | vauthors = Foitl DR, Hyman G, Lefkowitch JH | title = Jaundice and intrahepatic cholestasis following high-dose megestrol acetate for breast cancer | journal = Cancer | volume = 63 | issue = 3 | pages = 438–9 | date = February 1989 | pmid = 2912522 | doi = | url = }}
55. ^{{cite journal | vauthors = Gruber T, Dare AO, Balos LL, Lele S, Fenstermaker RA | title = Multiple meningiomas arising during long-term therapy with the progesterone agonist megestrol acetate. Case report | journal = J. Neurosurg. | volume = 100 | issue = 2 | pages = 328–31 | date = February 2004 | pmid = 15086241 | doi = 10.3171/jns.2004.100.2.0328 | url = }}
56. ^{{cite journal | vauthors = Gruber TJ, Fabiano AJ, Deeb G, Lele SB, Fenstermaker RA | title = Intracranial meningiomas in patients with uterine sarcoma treated with long-term megestrol acetate therapy | journal = World Neurosurg | volume = 76 | issue = 5 | pages = 477.e16–20 | date = November 2011 | pmid = 22152580 | doi = 10.1016/j.wneu.2011.03.035 | url = }}
57. ^1 {{cite journal | vauthors = Schacter LP, Rozencweig M, Canetta R, Kelley S, Nicaise C, Smaldone L | title = Overview of hormonal therapy in advanced breast cancer | journal = Semin. Oncol. | volume = 17 | issue = 6 Suppl 9 | pages = 38–46 | date = December 1990 | pmid = 2148026 | doi = | url = http://www.seminoncol.org/article/0093-7754(90)90007-P/abstract | quote = Doses [of megestrol acetate] of as high as 1,600 mg/d, given in divided doses three or four times daily, have been given with no clear increase in side effects except for weight gain, mild increases in blood pressure (BP), and some fluid retention.45}}
58. ^1 2 3 4 5 6 7 8 9 {{cite journal|last1=Schindler|first1=Adolf E.|title=Pharmacology of Progestogens|year=2015|pages=33–40|doi=10.1007/978-3-319-14385-9_2}}
59. ^1 {{cite journal | vauthors = Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH | title = Classification and pharmacology of progestins | journal = Maturitas | volume = 61 | issue = 1-2 | pages = 171–80 | date = 2008 | pmid = 19434889 | doi = | url = }}
60. ^1 {{cite journal | author = Venner PM | title = Therapeutic options in treatment of advanced carcinoma of the prostate | journal = Seminars in Oncology | volume = 17 | issue = 6 Suppl 9 | pages = 73–7 | date = December 1990 | pmid = 2259929 | doi = | url = }}
61. ^1 {{cite journal |vauthors=Lundgren S, Lønning PE, Utaaker E, Aakvaag A, Kvinnsland S | title = Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--I. General findings | journal = Journal of Steroid Biochemistry | volume = 36 | issue = 1-2 | pages = 99–104 | date = June 1990 | pmid = 2362454 | doi = 10.1016/0022-4731(90)90118-c | url = }}
62. ^1 2 {{cite journal |vauthors=Geller J, Albert J, Geller S | title = Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue | journal = The Prostate | volume = 3 | issue = 1 | pages = 11–5 | year = 1982 | pmid = 6176985 | doi = 10.1002/pros.2990030103 | url = }}
63. ^1 {{cite journal | author = Blumenschein GR | title = The role of progestins in the treatment of breast cancer | journal = Seminars in Oncology | volume = 10 | issue = 4 Suppl 4 | pages = 7–10 | date = December 1983 | pmid = 6230722 | doi = | url = }}
64. ^{{cite journal |vauthors=Alexieva-Figusch J, Blankenstein MA, de Jong FH, Lamberts SW | title = Endocrine effects of the combination of megestrol acetate and tamoxifen in the treatment of metastatic breast cancer | journal = European Journal of Cancer & Clinical Oncology | volume = 20 | issue = 9 | pages = 135–40 | date = September 1984 | pmid = 6434315 | doi = | url = }}
65. ^{{cite journal | vauthors = Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B | title = Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide | journal = Contraception | volume = 84 | issue = 6 | pages = 549–57 | date = December 2011 | pmid = 22078182 | doi = 10.1016/j.contraception.2011.04.009 | url = }}
66. ^{{cite journal|last1=Vessey|first1=M.P.|last2=Mears|first2=Eleanor|last3=Andolšek|first3=Lidija|last4=Ogrinc-Oven|first4=Majda|title=RANDOMISED DOUBLE-BLIND TRIAL OF FOUR ORAL PROGESTAGEN-ONLY CONTRACEPTIVES|journal=The Lancet|volume=299|issue=7757|year=1972|pages=915–922|issn=01406736|doi=10.1016/S0140-6736(72)91492-4}}
67. ^{{cite book|author=Gregory Pincus|title=The Control of Fertility|url=https://books.google.com/books?id=ehQlBQAAQBAJ&pg=PA222|date=3 September 2013|publisher=Elsevier|isbn=978-1-4832-7088-3|pages=222–}}
68. ^{{cite book|author=Louis Denis|title=The Medical Management of Prostate Cancer|url=https://books.google.com/books?id=T78hBQAAQBAJ&pg=PT45|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73238-6|pages=45–}}
69. ^1 2 3 {{cite book|author1=James P. Karr|author2=Hidetoshi Yamanaka|title=Prostate Cancer and Bone Metastasis|url=https://books.google.com/books?id=rgnrBwAAQBAJ&pg=PA309|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4615-3398-6|pages=309–}}
70. ^{{cite book|author1=Kenneth A. Foon|author2=Hyman B. Muss|title=Biological and Hormonal Therapies of Cancer|url=https://books.google.com/books?id=So3IAwAAQBAJ&pg=PA73|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4615-6189-7|pages=73–}}
71. ^{{cite journal | vauthors = Smith JA | title = New methods of endocrine management of prostatic cancer | journal = J. Urol. | volume = 137 | issue = 1 | pages = 1–10 | date = January 1987 | pmid = 3540320 | doi = | url = }}
72. ^{{cite journal | vauthors = Venner PM, Klotz PG, Klotz LH, Stewart DJ, Davis IR, Orovan WL, Ramsey EW | title = Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate | journal = Semin. Oncol. | volume = 15 | issue = 2 Suppl 1 | pages = 62–7 | date = April 1988 | pmid = 3285485 | doi = | url = }}
73. ^{{cite journal | vauthors = Johnson DE, Babaian RJ, Swanson DA, von Eschenbach AC, Wishnow KI, Tenney D | title = Medical castration using megestrol acetate and minidose estrogen | journal = Urology | volume = 31 | issue = 5 | pages = 371–4 | date = May 1988 | pmid = 3284149 | doi = | url = }}
74. ^{{cite journal | vauthors = Geller J | title = Megestrol acetate and minidose estrogen in prostatic carcinoma | journal = Urology | volume = 32 | issue = 3 | pages = 281–3 | date = September 1988 | pmid = 3413920 | doi = | url = }}
75. ^{{cite journal | vauthors = Geller J | title = Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma | journal = Urol. Clin. North Am. | volume = 18 | issue = 1 | pages = 83–91 | date = February 1991 | pmid = 1825145 | doi = | url = }}
76. ^{{cite journal | vauthors = Lundgren S, Helle SI, Lonning PE | title = Profound suppression of plasma estrogens by megestrol acetate in postmenopausal breast cancer patients | journal = Clin. Cancer Res. | volume = 2 | issue = 9 | pages = 1515–21 | date = September 1996 | pmid = 9816328 | doi = | url = }}
77. ^{{cite journal | vauthors = Pommier RF, Woltering EA, Fletcher WS | title = Changes in serum sex steroid levels during megestrol acetate therapy | journal = Surg Oncol | volume = 3 | issue = 6 | pages = 351–9 | date = December 1994 | pmid = 7773452 | doi = | url = }}
78. ^{{cite journal | vauthors = Lønning PE | title = Additive endocrine therapy for advanced breast cancer - back to the future | journal = Acta Oncol | volume = 48 | issue = 8 | pages = 1092–101 | date = 2009 | pmid = 19863216 | doi = 10.3109/02841860903117816 | url = }}
79. ^{{cite journal |vauthors=Eil C, Edelson SK | title = The use of human skin fibroblasts to obtain potency estimates of drug binding to androgen receptors | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 59 | issue = 1 | pages = 51–5 | date = July 1984 | pmid = 6725525 | doi = 10.1210/jcem-59-1-51}}
80. ^1 {{cite journal |vauthors=Luthy IA, Begin DJ, Labrie F | title = Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 5 | pages = 845–52 | date = November 1988 | pmid = 2462135 | doi = 10.1016/0022-4731(88)90295-6 | url = }}
81. ^1 {{cite journal |vauthors=Poyet P, Labrie F | title = Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate | journal = Molecular and Cellular Endocrinology | volume = 42 | issue = 3 | pages = 283–8 | date = October 1985 | pmid = 3930312 | doi = 10.1016/0303-7207(85)90059-0 | url = }}
82. ^1 {{cite journal | author = Farrar DJ | title = Megestrol acetate: promises and pitfalls | journal = AIDS Patient Care and STDs | volume = 13 | issue = 3 | pages = 149–52 | date = March 1999 | pmid = 10375262 | doi = 10.1089/apc.1999.13.149 | url = }}
83. ^{{cite journal |vauthors=Tisell LE, Salander H | title = Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats | journal = Acta Endocrinologica | volume = 78 | issue = 2 | pages = 316–24 | date = February 1975 | pmid = 1172901 | doi = 10.1530/acta.0.0780316 | url = }}
84. ^{{cite book|author1=Timothy L. Ratliff|author2=William J. Catalona|title=Genitourinary Cancer: Basic and Clinical Aspects|url=https://books.google.com/books?id=QUp-BgAAQBAJ&pg=PA171|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4613-2033-3|pages=171–}}
85. ^{{cite journal | vauthors = Labrie C, Cusan L, Plante M, Lapointe S, Labrie F | title = Analysis of the androgenic activity of synthetic "progestins" currently used for the treatment of prostate cancer | journal = J. Steroid Biochem. | volume = 28 | issue = 4 | pages = 379–84 | date = October 1987 | pmid = 2444770 | doi = | url = }}
86. ^{{cite journal |vauthors=Briggs MH, Briggs M | title = Glucocorticoid properties of progestogens | journal = Steroids | volume = 22 | issue = 4 | pages = 555–9 | date = October 1973 | pmid = 4747450 | doi = 10.1016/0039-128x(73)90011-1 | url = }}
87. ^1 {{cite journal |vauthors=Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M | title = Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature | journal = Archives of Internal Medicine | volume = 157 | issue = 15 | pages = 1651–6 | year = 1997 | pmid = 9250225 | doi = 10.1001/archinte.157.15.1651 | url = http://archinte.jamanetwork.com/article.aspx?volume=157&page=1651 }}
88. ^{{cite book|author1=Martine El-Etr|author2=Michaël Schumacher|author3=Etienne-Emile Baulieu|chapter=Effects of Progesterone and Related Steroids in the Brain|editor1=Régine Sitruk-Ware|editor2=Daniel R. Mishell|title=Progestins and Antiprogestins in Clinical Practice|url=https://books.google.com/books?id=vGJJHsJASekC|date=10 November 1999|publisher=Taylor & Francis|isbn=978-0-8247-8291-7|pages=15–58|quote=Specific actions of neurosteroids on ion transport across the neuronal plasma membrane have been described (see Fig. 2[10). In hippocampal CA1 neurons, Ffrench Mullen et al. (76) observed an inhibition by PREG, PREGS, and 3α,5β-TH PROG (but not PROG) of both the N- and L-type calcium channel currents, mediated by a pertussis toxin-sensitive G protein mechanism, associated with the activation of protein kinase C. PROG still has no effect on calcium channels of hypothalamic neurons from the ventromedial nucleus; however, the synthetic progestin megestrol acetate inhibits some high-threshold Ca2+ channel currents: not the N-type nor the P-type Ca2+ channel currents, but the residual current. Appetite enhancement induced by megestrol acetate might be partly due to the inhibition of these Ca2+ channel currents, and the attenuation of the firing of ventromedial nucleus neurons, involved in satiety mechanisms (77). }}
89. ^1 {{cite book | author1 = Ann M. Berger | author2 = John L. Shuster | author3 = Jamie H. Von Roenn | title = Principles And Practice of Palliative Care And Supportive Oncology | url = https://books.google.com/books?id=LngD6RFXY_AC&pg=PA128 | accessdate = 27 May 2012 | date = 6 October 2006 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-9595-1 | page = 128}}
90. ^1 {{cite book | author = Achim Jörres | title = Management of Acute Kidney Problems | url = https://books.google.com/books?id=pS3ff7txLl4C&pg=PA210 | accessdate = 27 May 2012 | date = 19 February 2010 | publisher = Springer | isbn = 978-3-540-69413-7 | page = 210}}
91. ^1 {{cite book | author = David S. Ettinger | title = Supportive Care in Cancer Therapy | url = https://books.google.com/books?id=Erhb8XfG3qIC&pg=PA61 | accessdate = 27 May 2012 | date = 11 November 2008 | publisher = Springer | isbn = 978-1-58829-941-3 | page = 61}}
92. ^{{cite book | author = Kenneth A. Foon | title = Biological and Hormonal Therapies of Cancer | url = https://books.google.com/books?id=8KnTy0eCQ9AC&pg=PA73 | accessdate = 2 June 2012 | year = 1998 | publisher = Springer | isbn = 978-0-7923-9997-1 | page = 73}}
93. ^1 2 3 4 {{cite journal | vauthors = Helle SI, Lundgren S, Geisler S, Ekse D, Holly JM, Lønning PE | title = Effects of treatment with megestrol acetate on the insulin-like growth factor system: time and dose dependency | journal = Eur. J. Cancer | volume = 35 | issue = 7 | pages = 1070–5 | date = July 1999 | pmid = 10533450 | doi = | url = }}
94. ^1 {{cite journal | vauthors = Stanczyk FZ | title = Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception | journal = Rev Endocr Metab Disord | volume = 3 | issue = 3 | pages = 211–24 | date = September 2002 | pmid = 12215716 | doi = | url = }}
95. ^1 2 {{cite journal | vauthors = Gadducci A, Genazzani AR | title = Endocrine therapy for gynecological cancer | journal = Gynecol. Endocrinol. | volume = 13 | issue = 6 | pages = 441–56 | date = December 1999 | pmid = 10685337 | doi = | url = }}
96. ^{{cite book|author=Gerald Litwack|title=Biochemical Actions of Hormones|url=https://books.google.com/books?id=tX9GwWPsMbQC&pg=PA330|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-15344-7|pages=330–}}
97. ^{{cite book|author1=David A. Williams|author2=William O. Foye|author3=Thomas L. Lemke|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=qLJ6Bs1Qml4C&pg=PA699|year=2002|publisher=Lippincott Williams & Wilkins|isbn=978-0-683-30737-5|pages=699–}}
98. ^{{cite book|title=Die Gestagene|url=https://books.google.com/books?id=t8GpBgAAQBAJ&pg=PA281|date=27 November 2013|publisher=Springer-Verlag|isbn=978-3-642-99941-3|page=281}}
99. ^1 2 3 4 5 6 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA657|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=657–}}
100. ^1 2 3 4 5 6 7 8 9 {{cite book | title = Index Nominum 2000: International Drug Directory | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA641 | accessdate = 2 June 2012 | year = 2000 | publisher = Taylor & Francis US | isbn = 978-3-88763-075-1 | page = 641}}
101. ^{{cite book|author=Aman U. Buzdar|title=Endocrine Therapies in Breast Cancer|url=https://books.google.com/books?id=4aAH2Ik-9KcC&pg=PT75|date=8 November 2007|publisher=OUP Oxford|isbn=978-0-19-921814-1|pages=75–}}
102. ^{{cite journal | vauthors = Yang YQ, Li SX, Gu XG | title = [Effect of progestin no. 1 (cymegesolate) on menstrual cycles and plasma levels of progesterone in rhesus monkeys] | language = Chinese | journal = Sheng Li Xue Bao | volume = 37 | issue = 4 | pages = 368–73 | date = August 1985 | pmid = 3837333 | doi = | url = }}
103. ^{{cite journal | vauthors = Wu JZ, Yun XJ, Wu MZ, Shen HY, Wang AL | title = [Clinical study of a long-acting progestogen contraceptive 3-cyclopentyl propionate of megestrol acetate (progestin no. 1)] | language = Chinese | journal = Shengzhi Yu Biyun | volume = 3 | issue = 2 | pages = 36–8 | date = February 1983 | pmid = 12339176 | doi = | url = }}
104. ^{{cite journal | vauthors = Pirzada OL | title = Effect of megestrol caproate on the reproductive function of laboratory animals | journal = Bull. Exp. Biol. Med. | volume = 133 | issue = 6 | pages = 574–6 | date = June 2002 | pmid = 12447469 | doi = | url = }}
105. ^{{cite journal|last1=Ringold|first1=H. J.|last2=Ruelas|first2=J. Perez|last3=Batres|first3=E.|last4=Djerassi|first4=Carl|title=Steroids. CXVIII.16-Methyl Derivatives of 17α-Hydroxyprogesterone and of Reichstein's Substance "S"|journal=Journal of the American Chemical Society|volume=81|issue=14|year=1959|pages=3712–3716|issn=0002-7863|doi=10.1021/ja01523a055}}
106. ^{{cite journal | vauthors = Cooley G, Kellie AE | title = Synthesis of [1,2-3H2]medroxyprogesterone acetate (17-alpha-acetoxy-6-alpha-methyl[1,2-3H2]pregn-4-ene-3,20-dione) and [1,2-3H2]megestrol acetate (17-alpha-acetoxy-6-methyl[1,2-3H2]pregna-4,6-diene-3,20-dione) | journal = Biochem. J. | volume = 93 | issue = 1 | pages = 8C–9C | date = October 1964 | pmid = 5320316 | doi = | url = }}
107. ^1 2 3 4 5 6 {{cite journal | vauthors = Kuhl H | title = Pharmacology of progestogens | journal = Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology | volume = 8 | issue = Special Issue 1 | pages = 157–176 | year = 2011 | pmid = | doi = | url = http://www.kup.at/kup/pdf/10168.pdf}}
108. ^1 {{cite book|title=Benign Prostatic Hypertrophy|url=https://books.google.com/books?id=Z5K-BwAAQBAJ&pg=PA277|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5476-8|pages=277–}}
109. ^1 2 3 4 5 6 {{cite book|author=Lara Marks|title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA78|year=2010|publisher=Yale University Press|isbn=978-0-300-16791-7|pages=77–78}}
110. ^1 2 3 4 5 6 {{cite journal | vauthors = MEARS E | title = A new type of oral contraceptive | journal = Br Med J | volume = 1 | issue = 5341 | pages = 1318–20 | year = 1963 | pmid = 13934321 | pmc = 2123904 | doi = 10.1136/bmj.1.5341.1318| url = }}
111. ^1 2 3 4 {{cite book|author=Lara Marks|title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=GgvLA3bqwnoC&pg=PA78|year=2001|publisher=Yale University Press|isbn=978-0-300-08943-1|pages=78–}}
112. ^{{cite book|author=David P. Rose|title=Oral Contraceptives: Psychological and Physiological Effects|url=https://books.google.com/books?id=lhL3R4WTPEEC&pg=PA12|year=1973|publisher=Ardent Media|isbn=978-0-8422-7101-1|pages=12–}}
113. ^{{cite book|author=Statens seruminstitut (Denmark)|title=Communications: Extraits|url=https://books.google.com/books?id=xyLQAAAAMAAJ|year=1966|quote=Each Delpregnin tablet contains 5 mg megestrol acetate + 0.1 mg mestranol.}}
114. ^{{cite book|title=Unlisted Drugs|url=https://books.google.com/books?id=wxNtAAAAMAAJ|year=1965|publisher=Pharmaceutical Section, Special Libraries Association.}}
115. ^1 2 {{cite book|author1=Harry W. Rudel|author2=Fred A. Kincl|author3=Milan R. Henzl|title=Birth Control; Contraception and Abortion|url=https://books.google.com/books?id=B6hsAAAAMAAJ|year=1973|publisher=Macmillan}}
116. ^1 {{cite book|title=Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments|url=https://books.google.com/books?id=leVCukUgNlsC&pg=PA137|year=1983|publisher=United Nations Publications|isbn=978-92-1-130230-1|pages=137–}}
117. ^1 {{cite journal | vauthors = Nelson LW, Weikel JH, Reno FE | title = Mammary nodules in dogs during four years' treatment with megestrol acetate or chlormadinone acetate | journal = J. Natl. Cancer Inst. | volume = 51 | issue = 4 | pages = 1303–11 | date = October 1973 | pmid = 4126857 | doi = | url = }}
118. ^1 2 {{cite book|title=FDA Consumer|url=https://books.google.com/books?id=pLG-19fghW8C|date=February 1976|publisher=U.S. Department of Health, Education, and Welfare, Public Health Service, Food and Drug Administration|quote=Several foreign countries, including Germany, Canada, and Great Britain, have banned the sale of birth control pills containing megestrol acetate after a study done at FDA's request indicated it caused breast cancer in dogs. Megestrol acetate has never been marketed in the United States as an oral contraceptive. FDA routinely requires long-term animal studies before any drug can be marketed for human use. Following animal studies with megestrol acetate, FDA in the late sixties and early seventies allowed limited studies of the drug in women. In 1972, after noticing a significant number of test dogs developing breast nodules (none of them malignant), FDA ordered that megestrol acetate be discontinued in human oral contraceptive studies.}}
119. ^1 {{cite book|author=United States. Congress. Senate. Committee on Labor and Public Welfare|title=Hearings, Reports and Prints of the Senate Committee on Labor and Public Welfare|url=https://books.google.com/books?id=Fto1AAAAIAAJ|year=1976|publisher=U.S. Government Printing Office|quote=Megestrol was never marketed in the United States for contraceptive use because in 1972, FDA took prompt action to discontinue investigational studies on megestrol after dogs exposed to the drug for four years In a chronic toxicity study developed benign breast tumors.}}
120. ^1 {{cite book|author1=Benno Clemens Runnebaum|author2=Thomas Rabe|author3=Ludwig Kiesel|title=Female Contraception: Update and Trends|url=https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA134|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73790-9|pages=134–}}
121. ^1 {{cite journal | vauthors = Bakke OM, Wardell WM, Lasagna L | title = Drug discontinuations in the United Kingdom and the United States, 1964 to 1983: issues of safety | journal = Clin. Pharmacol. Ther. | volume = 35 | issue = 5 | pages = 559–67 | date = May 1984 | pmid = 6713769 | doi = | url = }}
122. ^{{cite book|title=Modern Veterinary Practice|url=https://books.google.com/books?id=2K0iAQAAIAAJ|year=1971|quote=Your Q & A concerning megestrol acetate (Oct MVP, p 27), a product containing this compound (Ovarid: Glaxo) has been commercially available for controlling estrus in bitches in the UK for nearly 2 years.}}
123. ^{{cite book|title=VM/SAC, Veterinary Medicine/small Animal Clinician|url=https://books.google.com/books?id=lBIjAQAAIAAJ|year=1977|publisher=Veterinary Medicine Publishing Company|quote=In England, where megestrol acetate has been marketed for eight years, it is recommended to treat false pregnancy and estrogen-dependent mammary tumors in dogs. It has also been used successfully to treat hypersexuality in male dogs, and miliary dermatitis and eosinophilic granulomas in cats. In 1974, megestrol acetate was approved in the United States for postponement of es- trus and treatment of false pregnancy in dogs.}}
124. ^{{cite book|author=Upjohn Company|title=Proceedings of the Symposium on Cheque® for Canine Estrus Prevention, Brook Lodge, Augusta, Michigan, March 13-15, 1978|url=https://books.google.com/books?id=wPFUAAAAYAAJ|year=1978|publisher=Upjohn Company|quote=In 1974, Sobering marketed megestrol acetate3 (Figure 1) under the trade name of Ovaban® (Ovarid® in Europe).}}
125. ^{{cite journal | vauthors = KISTNER RW | title = Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium | journal = Cancer | volume = 12 | issue = | pages = 1106–22 | date = 1959 | pmid = 14409476 | doi = | url = }}
126. ^{{cite journal|last1=Geisler|first1=Hans E.|title=The use of megestrol acetate in the treatment of advanced malignant lesions of the endometrium|journal=Gynecologic Oncology|volume=1|issue=4|year=1973|pages=340–344|issn=0090-8258|doi=10.1016/0090-8258(73)90026-7}}
127. ^{{cite journal | vauthors = Wait RB | title = Megestrol acetate in the management of advanced endometrial carcinoma | journal = Obstet Gynecol | volume = 41 | issue = 1 | pages = 129–36 | date = January 1973 | pmid = 4682608 | doi = | url = }}
128. ^{{cite journal | vauthors = Taylor SG, Morris RS | title = Hormones in breast metastasis therapy | journal = Med. Clin. North Am. | volume = 35 | issue = 1 | pages = 51–61 | date = January 1951 | pmid = 14796108 | doi = | url = }}
129. ^{{cite journal | vauthors = Gordon D, Horwitt BN, Segaloff A, Murison PJ, Schlosser JV | title = Hormonal therapy in cancer of the breast. III. Effect of progesterone on clinical course and hormonal excretion | journal = Cancer | volume = 5 | issue = 2 | pages = 275–7 | date = March 1952 | pmid = 14905411 | doi = | url = }}
130. ^{{cite journal | vauthors = Stoll BA | title = Progestin therapy of breast cancer: comparison of agents | journal = Br Med J | volume = 3 | issue = 5561 | pages = 338–41 | date = August 1967 | pmid = 6029163 | pmc = 1841969 | doi = | url = }}
131. ^{{cite journal | vauthors = Ansfield FJ, Davis HL, Ellerby RA, Ramirez G | title = A clinical trial of megestrol acetate in advanced breast cancer | journal = Cancer | volume = 33 | issue = 4 | pages = 907–10 | date = April 1974 | pmid = 4819220 | doi = | url = }}
132. ^1 {{cite journal | vauthors = Lundgren S | title = Progestins in breast cancer treatment. A review | journal = Acta Oncol | volume = 31 | issue = 7 | pages = 709–22 | date = 1992 | pmid = 1476750 | doi = | url = }}
133. ^{{cite journal | vauthors = Pannuti F, Martoni A, Lenaz GR, Piana E, Nanni P | title = A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate | journal = Cancer Treat Rep | volume = 62 | issue = 4 | pages = 499–504 | date = April 1978 | pmid = 350387 | doi = | url = }}
134. ^{{cite journal | vauthors = Alexieva-Figusch J, van Gilse HA, Hop WC, Phoa CH, Blonk-van der Wijst J, Treurniet RE | title = Progestin therapy in advanced breast cancer: megestrol acetate--an evaluation of 160 treated cases | journal = Cancer | volume = 46 | issue = 11 | pages = 2369–72 | date = December 1980 | pmid = 7438013 | doi = | url = }}
135. ^{{cite journal | vauthors = Bines J, Dienstmann R, Obadia RM, Branco LG, Quintella DC, Castro TM, Camacho PG, Soares FA, Costa ME | title = Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial | journal = Ann. Oncol. | volume = 25 | issue = 4 | pages = 831–6 | date = April 2014 | pmid = 24615412 | doi = 10.1093/annonc/mdu015 | url = }}
136. ^{{cite journal | vauthors = Gutierrez R | title = New horizons in the surgical management of carcinoma of the prostate gland | journal = Am. J. Surg. | volume = 78 | issue = 2 | pages = 147–69 | date = August 1949 | pmid = 18135629 | doi = | url = }}
137. ^Maltry, E. (1970). Use of megestrol acetate (a new progestational agent) in the treatment of carcinoma of the prostate. In Proceedings of the Kimbrough Urological Seminar, 18th Annual Meeting (pp. 135-137).
138. ^1 {{cite journal | vauthors = Johnson DE, Kaesler KE, Ayala AG | title = Megestrol acetate for treatment of advanced carcinoma of the prostate | journal = J Surg Oncol | volume = 7 | issue = 1 | pages = 9–15 | date = 1975 | pmid = 1177459 | doi = | url = }}
139. ^1 {{cite journal | vauthors = Geller J, Albert J, Yen SS | title = Treatment of advanced cancer of prostate with megestrol acetate | journal = Urology | volume = 12 | issue = 5 | pages = 537–41 | date = November 1978 | pmid = 153029 | doi = | url = }}
140. ^{{cite book|author=Nicholas Vogelzang|title=Comprehensive Textbook of Genitourinary Oncology|url=https://books.google.com/books?id=WIsiGZnZ_mgC&pg=PA317|year=2006|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4984-8|pages=317–}}
141. ^1 {{cite book|author1=Barry Kinzbrunner|author2=Neil J. Weinreb|author3=Joel S. Policzer|title=20 Common Problems: End-of-Life Care|url=https://books.google.com/books?id=ZPgawhewn2gC|year=2002|publisher=McGraw Hill Professional|isbn=978-0-07-034883-7}}
142. ^1 {{cite journal | vauthors = Tchekmedyian NS, Tait N, Moody M, Greco FA, Aisner J | title = Appetite stimulation with megestrol acetate in cachectic cancer patients | journal = Semin. Oncol. | volume = 13 | issue = 4 Suppl 4 | pages = 37–43 | date = December 1986 | pmid = 3798127 | doi = | url = }}
143. ^{{cite journal | vauthors = Tchekmedyian NS, Tait N, Moody M, Aisner J | title = High-dose megestrol acetate. A possible treatment for cachexia | journal = JAMA | volume = 257 | issue = 9 | pages = 1195–8 | date = March 1987 | pmid = 3806918 | doi = | url = }}
144. ^{{cite journal | vauthors = Aisner J, Tchekmedyian NS, Tait N, Parnes H, Novak M | title = Studies of high-dose megestrol acetate: potential applications in cachexia | journal = Semin. Oncol. | volume = 15 | issue = 2 Suppl 1 | pages = 68–75 | date = April 1988 | pmid = 3285486 | doi = | url = }}
145. ^{{cite journal | vauthors = Aisner J, Parnes H, Tait N, Hickman M, Forrest A, Greco FA, Tchekmedyian NS | title = Appetite stimulation and weight gain with megestrol acetate | journal = Semin. Oncol. | volume = 17 | issue = 6 Suppl 9 | pages = 2–7 | date = December 1990 | pmid = 2259925 | doi = | url = }}
146. ^1 {{cite book|author1=Guido Eibl|author2=Mouad Edderkaoui|title=Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets|url=https://books.google.com/books?id=G0gsCQAAQBAJ&pg=PA96|date=22 April 2015|publisher=Frontiers Media SA|isbn=978-2-88919-468-1|pages=96–}}
147. ^{{cite journal | vauthors = Porche DJ | title = Megestrol acetate oral suspension | journal = J Assoc Nurses AIDS Care | volume = 5 | issue = 4 | pages = 35–6, 44 | date = 1994 | pmid = 7948971 | doi = | url = }}
148. ^1 2 {{cite book |author=Ian Morton |author2=Ian K. M. Morton |author3=Judith M. Hall | title = Concise Dictionary of Pharmacological Agents: Properties and Synonyms | url = https://books.google.com/books?id=mqaOMOtk61IC&pg=PA173 | accessdate = 2 June 2012 | year = 1999 | publisher = Springer | isbn = 978-0-7514-0499-9 | page = 173}}
149. ^1 2 3 4 5 6 7 https://www.drugs.com/international/megestrol.html
150. ^1 {{cite book|author1=V. Unzeitig|author2=Rick H.W. van Lunsen|title=Contraceptive Choices and Realities: Proceedings of the 5th Congress of the European Society of Contraception|url=https://books.google.com/books?id=-FliV0TxtEEC&pg=PA73|date=15 February 2000|publisher=CRC Press|isbn=978-1-85070-067-8|pages=73–}}
151. ^1 {{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA434|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|pages=44}}
152. ^{{cite journal|last1=Frick|first1=J.|title=Control of spermatogenesis in men by combined administration of progestin and androgen|journal=Contraception|volume=8|issue=3|year=1973|pages=191–206|issn=0010-7824|doi=10.1016/0010-7824(73)90030-9}}
153. ^{{cite journal | vauthors = Romatowski J | title = Use of megestrol acetate in cats | journal = J. Am. Vet. Med. Assoc. | volume = 194 | issue = 5 | pages = 700–2 | date = March 1989 | pmid = 2647696 | doi = | url = }}
154. ^1 {{cite book|author=Bonnie V. G. Beaver|title=Canine Behavior: Insights and Answers|url=https://books.google.com/books?id=S6o5ypyRPQEC&pg=PA128|date=1 January 2009|publisher=Elsevier Health Sciences|isbn=1-4160-5419-7|pages=128–}}
155. ^1 {{cite journal | vauthors = Simpson BS, Papich MG | title = Pharmacologic management in veterinary behavioral medicine | journal = Vet. Clin. North Am. Small Anim. Pract. | volume = 33 | issue = 2 | pages = 365–404, vii | date = March 2003 | pmid = 12701517 | doi = 10.1016/S0195-5616(02)00130-4 | url = }}

Further reading

{{div col|colwidth=30em}}
  • {{cite journal | vauthors = Canetta R, Florentine S, Hunter H, Lenaz L | title = Megestrol acetate | journal = Cancer Treat. Rev. | volume = 10 | issue = 3 | pages = 141–57 | date = September 1983 | pmid = 6352021 | doi = | url = }}
  • {{cite journal | vauthors = Sedlacek SM | title = An overview of megestrol acetate for the treatment of advanced breast cancer | journal = Semin. Oncol. | volume = 15 | issue = 2 Suppl 1 | pages = 3–13 | date = April 1988 | pmid = 3285483 | doi = | url = }}
  • {{cite journal | vauthors = Aisner J, Tchekmedyian NS, Tait N, Parnes H, Novak M | title = Studies of high-dose megestrol acetate: potential applications in cachexia | journal = Semin. Oncol. | volume = 15 | issue = 2 Suppl 1 | pages = 68–75 | date = April 1988 | pmid = 3285486 | doi = | url = }}
  • {{cite journal | vauthors = Schacter L, Rozencweig M, Canetta R, Kelley S, Nicaise C, Smaldone L | title = Megestrol acetate: clinical experience | journal = Cancer Treat. Rev. | volume = 16 | issue = 1 | pages = 49–63 | date = March 1989 | pmid = 2471590 | doi = 10.1016/0305-7372(89)90004-2 | url = }}
  • {{cite journal | vauthors = Romatowski J | title = Use of megestrol acetate in cats | journal = J. Am. Vet. Med. Assoc. | volume = 194 | issue = 5 | pages = 700–2 | date = March 1989 | pmid = 2647696 | doi = | url = }}
  • {{cite journal | vauthors = Venner P | title = Megestrol acetate in the treatment of metastatic carcinoma of the prostate | journal = Oncology | volume = 49 Suppl 2 | issue = | pages = 22–7 | date = 1992 | pmid = 1461622 | doi = 10.1159/000227123 | url = }}
  • {{cite journal | vauthors = Tchekmedyian NS | title = Treatment of anorexia with megestrol acetate | journal = Nutr Clin Pract | volume = 8 | issue = 3 | pages = 115–8 | date = June 1993 | pmid = 8289758 | doi = 10.1177/0115426593008003115 | url = }}
  • {{cite journal | vauthors = Strang P | title = The effect of megestrol acetate on anorexia, weight loss and cachexia in cancer and AIDS patients (review) | journal = Anticancer Res. | volume = 17 | issue = 1B | pages = 657–62 | date = 1997 | pmid = 9066597 | doi = | url = }}
  • {{cite journal | vauthors = Vyzula R | title = [Current views on use of megestrol acetate in oncology practice] | language = Czech | journal = Vnitr Lek | volume = 43 | issue = 4 | pages = 250–5 | date = April 1997 | pmid = 9601846 | doi = | url = }}
  • {{cite journal | vauthors = Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M | title = Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature | journal = Arch. Intern. Med. | volume = 157 | issue = 15 | pages = 1651–6 | date = 1997 | pmid = 9250225 | doi = | url = }}
  • {{cite journal | vauthors = Berstein LM | title = [Megestrol acetate as hormone therapy in oncology] | language = Russian | journal = Vopr Onkol | volume = 44 | issue = 2 | pages = 142–8 | date = 1998 | pmid = 9615815 | doi = | url = }}
  • {{cite journal | vauthors = Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC | title = Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate | journal = Semin. Oncol. | volume = 25 | issue = 2 Suppl 6 | pages = 45–52 | date = April 1998 | pmid = 9625383 | doi = | url = }}
  • {{cite journal | vauthors = Chang AY | title = Megestrol acetate as a biomodulator | journal = Semin. Oncol. | volume = 25 | issue = 2 Suppl 6 | pages = 58–61 | date = April 1998 | pmid = 9625385 | doi = | url = }}
  • {{cite journal | vauthors = Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC | title = Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms | journal = Crit Rev Oncog | volume = 9 | issue = 2 | pages = 99–106 | date = 1998 | pmid = 9973244 | doi = | url = }}
  • {{cite journal | vauthors = Stockheim JA, Daaboul JJ, Yogev R, Scully SP, Binns HJ, Chadwick EG | title = Adrenal suppression in children with the human immunodeficiency virus treated with megestrol acetate | journal = J. Pediatr. | volume = 134 | issue = 3 | pages = 368–70 | date = March 1999 | pmid = 10064680 | doi = | url = }}
  • {{cite journal | vauthors = Farrar DJ | title = Megestrol acetate: promises and pitfalls | journal = AIDS Patient Care STDS | volume = 13 | issue = 3 | pages = 149–52 | date = March 1999 | pmid = 10375262 | doi = 10.1089/apc.1999.13.149 | url = }}
  • {{cite journal | vauthors = Bonte J | title = Third generation aromatase inhibitors in metastatic breast cancer patients failing tamoxifen. Randomized comparisons with megestrol acetate: a critical review | journal = Eur. J. Gynaecol. Oncol. | volume = 21 | issue = 6 | pages = 555–9 | date = 2000 | pmid = 11214609 | doi = | url = }}
  • {{cite journal | vauthors = Karcic E, Philpot C, Morley JE | title = Treating malnutrition with megestrol acetate: literature review and review of our experience | journal = J Nutr Health Aging | volume = 6 | issue = 3 | pages = 191–200 | date = May 2002 | pmid = 12152625 | doi = | url = }}
  • {{cite journal | vauthors = Ruiz-García V, Juan O, Pérez Hoyos S, Peiró R, Ramón N, Rosero MA, García MA | title = [Megestrol acetate: a systematic review usefulness about the weight gain in neoplastic patients with cachexia] | language = Spanish| journal = Med Clin (Barc) | volume = 119 | issue = 5 | pages = 166–70 | date = July 2002 | pmid = 12200017 | doi = | url = }}
  • {{cite journal | vauthors = Thomas DR | title = Incidence of venous thromboembolism in megestrol acetate users | journal = J Am Med Dir Assoc | volume = 5 | issue = 1 | pages = 65–6; author reply 66–7 | date = 2004 | pmid = 14726802 | doi = 10.1097/01.JAM.0000105070.61741.9D | url = }}
  • {{cite journal | vauthors = Pascual López A, Roqué i Figuls M, Urrútia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M | title = Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome | journal = J Pain Symptom Manage | volume = 27 | issue = 4 | pages = 360–9 | date = April 2004 | pmid = 15050664 | doi = 10.1016/j.jpainsymman.2003.09.007 | url = }}
  • {{cite journal | vauthors = Femia RA, Goyette RE | title = The science of megestrol acetate delivery: potential to improve outcomes in cachexia | journal = BioDrugs | volume = 19 | issue = 3 | pages = 179–87 | date = 2005 | pmid = 15984902 | doi = | url = }}
  • {{cite journal | vauthors = Wentling GK, Sevin BU, Geiger XJ, Bridges MD | title = Benign metastasizing leiomyoma responsive to megestrol: case report and review of the literature | journal = Int. J. Gynecol. Cancer | volume = 15 | issue = 6 | pages = 1213–7 | date = 2005 | pmid = 16343217 | doi = 10.1111/j.1525-1438.2005.00190.x | url = }}
  • {{cite journal | vauthors = Mateen F, Jatoi A | title = Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients | journal = Clin Nutr | volume = 25 | issue = 5 | pages = 711–5 | date = October 2006 | pmid = 16867306 | doi = 10.1016/j.clnu.2006.05.009 | url = }}
  • {{cite journal | vauthors = | title = Megestrol acetate NCD oral suspension -- Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2 | journal = Drugs in R&D | volume = 8 | issue = 4 | pages = 251–4 | date = 2007 | pmid = 17596111 | doi = | url = }}
  • {{cite journal | vauthors = Yeh SS, Schuster MW | title = Megestrol acetate in cachexia and anorexia | journal = Int J Nanomed | volume = 1 | issue = 4 | pages = 411–6 | date = 2006 | pmid = 17722275 | pmc = 2676640 | doi = | url = }}
  • {{cite journal | vauthors = Leśniak W, Bała M, Jaeschke R, Krzakowski M | title = Effects of megestrol acetate in patients with cancer anorexia-cachexia syndrome--a systematic review and meta-analysis | journal = Pol. Arch. Med. Wewn. | volume = 118 | issue = 11 | pages = 636–44 | date = November 2008 | pmid = 19140567 | doi = | url = }}
  • {{cite journal | vauthors = Fox CB, Treadway AK, Blaszczyk AT, Sleeper RB | title = Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly | journal = Pharmacotherapy | volume = 29 | issue = 4 | pages = 383–97 | date = April 2009 | pmid = 19323618 | doi = 10.1592/phco.29.4.383 | url = }}
  • {{cite journal | vauthors = Argilés JM, Anguera A, Stemmler B | title = A new look at an old drug for the treatment of cancer cachexia: megestrol acetate | journal = Clin Nutr | volume = 32 | issue = 3 | pages = 319–24 | date = June 2013 | pmid = 23395103 | doi = 10.1016/j.clnu.2013.01.004 | url = }}
  • {{cite journal | vauthors = Greenberg M, Lawler D, Zawistowski S, Jöchle W | title = Low-dose megestrol acetate revisited: a viable adjunct to surgical sterilization in free roaming cats? | journal = Vet. J. | volume = 196 | issue = 3 | pages = 304–8 | date = June 2013 | pmid = 23499239 | doi = 10.1016/j.tvjl.2013.01.038 | url = }}
  • {{cite journal | vauthors = Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S | title = Megestrol acetate for treatment of anorexia-cachexia syndrome | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD004310 | date = March 2013 | pmid = 23543530 | doi = 10.1002/14651858.CD004310.pub3 | url = }}
  • {{cite journal | vauthors = Smith CS, Logomarsino JV | title = Using megestrol acetate to ameliorate protein-energy wasting in chronic kidney disease | journal = J Ren Care | volume = 42 | issue = 1 | pages = 53–9 | date = March 2016 | pmid = 26537025 | doi = 10.1111/jorc.12138 | url = }}
  • {{cite journal | vauthors = Wazny LD, Nadurak S, Orsulak C, Giles-Smith L, Tangri N | title = The Efficacy and Safety of Megestrol Acetate in Protein-Energy Wasting due to Chronic Kidney Disease: A Systematic Review | journal = J Ren Nutr | volume = 26 | issue = 3 | pages = 168–76 | date = May 2016 | pmid = 26776251 | doi = 10.1053/j.jrn.2015.11.002 | url = }}
{{div col end|2}}{{Navboxes
| title = Medical uses
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| titlestyle = background:#ccccff
| list1 ={{Androgen receptor modulators}}{{Glucocorticoid receptor modulators}}{{Progesterone receptor modulators}}
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18 : Acetate esters|Alcohols|Androgens and anabolic steroids|Antiemetics|Antigonadotropins|Appetite stimulants|Dienes|Diketones|Drugs with unknown mechanisms of action|Glucocorticoids|Hormonal antineoplastic drugs|Hormonal contraception|Pregnanes|Progestogen esters|Progestogens|Prostate cancer|Steroidal antiandrogens|Veterinary drugs
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