Estradiol/megestrol acetate

{{Short description|Pharmaceutical combination}}

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| image = Estradiol.svg

| width = 225px

| caption =

| image2 = Megestrol acetate.svg

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| caption2 = Estradiol (top) and
megestrol acetate (bottom)

| type = combo

| drug_name = Estradiol /
megestrol acetate

| component1 = Estradiol

| class1 = Estrogen

| component2 = Megestrol acetate

| class2 = Progestogen

| tradename = Mego-E, Chinese injectable No. 2

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| routes_of_administration = Intramuscular injection

| CAS_number = 88923-79-9

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| ATCvet =

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| synonyms = E2/MGA

}}

Estradiol/megestrol acetate (E2/MGA), sold under the brand names Mego-E and Chinese injectable No. 2, is a form of combined injectable birth control which is used in the People's Republic of China.{{cite journal | vauthors = De-Wei Z | title = Research activities in the field of oral contraceptives in the People's Republic of China | journal = Acta Obstet Gynecol Scand | issue = Suppl | volume = 105 | pages = 51–60 | date = 1982 | pmid = 6952745 | doi = 10.3109/00016348209155319 | s2cid = 44858028 }}{{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 | issue = Suppl 1 | pages = S1–34 | date = 1994 | pmid = 12290848 | doi = 10.3109/01443619409027641 }}{{cite journal | vauthors = Garza-Flores J | title = Pharmacokinetics of once-a-month injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 347–59 | date = April 1994 | pmid = 8013219 | doi = 10.1016/0010-7824(94)90032-9 }}{{cite journal | vauthors = Sang GW | title = Pharmacodynamic effects of once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 361–85 | date = April 1994 | pmid = 8013220 | doi = 10.1016/0010-7824(94)90033-7 }}{{cite journal | vauthors = Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S | title = Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control | journal = World J Pharm Pharm Sci | volume = 3 | issue = 10 | pages = 364–392 | year = 2014 | issn = 2278-4357 | url = http://www.wjpps.com/download/article/1412071798.pdf}}{{cite journal | vauthors = Toppozada MK | title = Existing once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 293–301 | date = April 1994 | pmid = 8013216 | doi = 10.1016/0010-7824(94)90029-9 }}{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=International Agency for Research on Cancer|title=Hormonal Contraception and Post-menopausal Hormonal Therapy|date=1 January 1999|publisher=IARC|isbn=978-92-832-1272-0|page=65|url=https://monographs.iarc.fr/wp-content/uploads/2018/06/mono72.pdf|access-date=16 September 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828080855/https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono72.pdf|url-status=dead}}; {{google books|id=F8hrAAAAMAAJ|title=Hormonal Contraception and Post-menopausal Hormonal Therapy}} It contains 3.5 mg estradiol (E2), an estrogen, and 25 mg megestrol acetate (MGA), a progestin. It is a microcrystalline aqueous suspension with a defined particle size range. The medication is given once per month by injection into muscle.

Studies of E2/MGA have been published.{{cite journal | vauthors = Yian JH, Min HD, Hu YT, Pan JX | title = "美尔伊"避孕针的临床观察及实验研究 | trans-title = Mego-E injectable contraceptive: Analysis of clinical observations and laboratory findings | date = 1983 | journal = Reproduction & Contraception | volume = 3 | issue = 4 | pages = 16–20 | issn = 0253-357X | url = http://new.oversea.cnki.net/kcms/detail/detail.aspx?filename=SZBB198304003&dbname=CJFD1983 }}{{cite journal | vauthors = Ding J, Guo Q, Pan J, Yan Y | title = 避孕针剂"美尔伊"作用原理的探讨 | trans-title = Study on the Mechanism of Injectable Contraceptive Mego-E. | journal = Universitatis Medicinalis Secondae Shanghai | date = 1985 | issue = 5 | pages = 320–323+385 | issn = 0258-5898 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=SHEY198505004 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Chu YH, Li Q, Zhao ZF | title = 育龄妇女肌注复方甲地孕酮避孕针的药代动力学 | trans-title = Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive | date = April 1986 | journal = The Chinese Journal of Clinical Pharmacology | issue = 4 | pages = 224–229 | doi = 10.13699/j.cnki.1001-6821.1986.04.004 | issn = 1001-6821 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=GLYZ198604003}}{{cite journal | vauthors = Zheng H, Tan Y, Bao Y, Ding Y, Wang L, Jiang X, Zhu L, Zhang Z | title = 复方甲地孕酮注射液的遗传学效应研究. | trans-title = A study on the genetic effects of "compound megestrol injection" | journal = Genetics and Diseases | date = 1986 | issue = 3 | pages = 149–153 | issn = 1003-9406 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZHYC198603005 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Pan J | title = 复方甲地孕酮避孕针临床研究进展. | trans-title = Progress in clinical research of compound megestrol acetate injectable needle. | journal = Journal of Shanghai Second Medical University | date = 1987 | issue = S1 | pages = 71–73 | issn = 0258-5898 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbname=CJFD8589&filename=SHEY1987S1029 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Yan Y, Pan J, Zhang Y, Kang J | title = The effect of monthly injectable contraceptive megestrol acetate compound on pituitary-ovarian function. | journal = Journal of Shanghai Second Medical University | date = 1987 | issue = 2 | pages = 7–12 | issn = 1001-6686 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=SHEI198702001 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Pan J, Yan Y, Li X, Zhang Y, Li M | title = 潘家骧,严隽鸿,黎小燕,张亚琴,李明光. | trans-title = Effects of injection Mego-E on blood glucose and serum insulin levels. | journal = Journal of Shanghai Second Medical University | date = 1987 | issue = 2 | pages = 48–55 | issn = 1001-6686 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=SHEI198702008 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Zhang L, Qi Y, Zhang H | title = 血浆甲地孕酮的高效液相色谱测定法. | trans-title = HLPC determination of megestrol in blood plasma. / Determination of plasma megestrol by high performance liquid chromatography. | journal = Pharmaceutical Industry | date = 1987 | issue = 7 | pages = 311–313 | doi = 10.16522/j.cnki.cjph.1987.07.006 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFD&filename=ZHOU198707005 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Zhou M, Zhang L, Qi Y | title = 醋酸甲地孕酮与血浆蛋白的结合. | trans-title = Studies on plasma protein binding of megestrol acetate. | journal = Journal of Shanghai Medical University | date = 1988 | issue = 1 | pages = 13–17 | issn = 0257-8131 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=SHYK198801003 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Cheng XF, Shao HZ, Chen ZP | title = 复方甲地孕酮避孕针对人凝血、抗凝血、纤溶及血小板聚集性的影响 | trans-title = Effect of megestrol acetate compound (injectable contraceptive) on human blood coagulation, anticoagulation activity, fibrinolysis and platelet aggregation | language = zh | journal = Shengzhi Yu Biyun | volume = 8 | issue = 1 | pages = 22–6 | date = 1988 | issn = 0253-357X | pmid = 12315407 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&filename=SZBB198801004}} The elimination half-life of MGA in this formulation is 14.35 ± 9.1 days. The plasma protein binding of MGA to albumin is 82.4%, while none is bound to sex hormone-binding globulin. Following an injection of E2/MGA, estradiol increased after 24 hours and persisted at high levels for 5 days, thereafter decreasing to low levels.

In 1969, MGA was studied in China as an aqueous suspension for parenteral administration in animals.{{cite journal | vauthors = Cheng X, Shao H, Yang J, Zhi L, Wang H, Wang Z, etal | date = September 1977 | title = 复方甲地孕酮避孕针的药理研究 | trans-title = Pharmacological studies on the contraceptive injection of megestrol acetate. | journal = Acta Zoologica Sinica | volume = 23 | issue = 3 | pages = 231–237 | issn = 0001-7302 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?filename=BEAR197703000&dbname=CJFD7984 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }} The next year, it was studied in women as a progestogen-only injectable contraceptive, with a dosing interval of once every 3 months by intramuscular injection. It was effective as a contraceptive but was associated with menstrual irregularities. Starting in 1973, a combination of estradiol cypionate (EC) and MGA was studied in women as a combined injectable contraceptive over a period of 3 years.{{cite book | author = Mokhtar K. Toppozada | chapter = Monthly Injectable Contraceptives | pages = 93–103 | veditors = Goldsmith A, Toppozada M | title = Long-Acting Contraception | year = 1983 | oclc = 35018604 | url = https://scholar.google.com/scholar?cluster=14664537528797672080}} E2/MGA, an "improvement" of EC/MGA, was studied in China in large clinical trials from 1977 to 1979 and was approved for use in this country in 1980. By 1987, production of E2/MGA had reached 9 million units per year and had spread to over 22 Chinese provinces and cities. E2/MGA appears to have been discontinued sometime between 2005 and 2008.{{cite journal | vauthors = Gallo MF, Grimes DA, Lopez LM, Schulz KF, d'Arcangues C | title = Combination injectable contraceptives for contraception | journal = The Cochrane Database of Systematic Reviews | volume = 3 | pages = CD004568 | date = 2013 | pmid = 23641480 | url = https://pubmed.ncbi.nlm.nih.gov/23641480 }}

A follow-up product consisting of 5 mg estradiol valerate (EV) and 15 mg MGA encapsulated in 50 to 80 μm-diameter microspheres as an aqueous suspension for use by intramuscular injection was developed and studied in China as well but was never marketed.{{cite journal | vauthors = Han Z, Xiao R | title = 复方甲地孕酮微囊注射液四种配伍量的临床选择. | trans-title = Clinical evaluation of intramuscular injection of microencapsulated compound megestrol acetate. | journal = Journal of Sichuan Medical College | date = 1982 | issue = 1 | pages = 93–99 | issn = 1672-173X | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD7984&filename=HXYK198201015 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Han ZY, Xiao RQ | title = Clinical evaluation of intramuscular injection of microencapsulated compound megestrol acetate | journal = Int J Gynaecol Obstet | volume = 22 | issue = 4 | pages = 319–24 | date = August 1984 | pmid = 6152804 | doi = 10.1016/0020-7292(84)90091-2 | s2cid = 72806071 }}{{cite journal | vauthors = Han ZY, Xiao RQ | title = A follow-up study of the efficacy and safety of injectable microencapsulated megestrol acetate and a discussion on its contraceptive mechanism | journal = Int J Gynaecol Obstet | volume = 23 | issue = 3 | pages = 207–11 | date = June 1985 | pmid = 2865183 | doi = 10.1016/0020-7292(85)90106-7 | s2cid = 74276439 }}{{cite journal | vauthors = Lu B, Li TL, Guan Q, Yang HL | title = 微囊化与未微囊化复方甲地孕酮注射液动物肌内残留率的对比研究 | trans-title = Comparative study of the residual rates of microencapsulated and unmicroencapsulated compound megestrol acetate injection in animal muscle | language = zh | journal = Sichuan Yi Xue Yuan Xue Bao | volume = 16 | issue = 1 | pages = 44–8 | date = March 1985 | issn = 1672-173X | pmid = 4012589 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=HXYK198501010}}{{cite journal | vauthors = Lu B, Meng JX, Xie ZY, Pu JX | title = 复方甲地孕酮微囊注射液溶出度的研究 | trans-title = Study on dissolution rate of injection of microencapsulated compound megestrol acetate | language = zh | journal = Hua Xi Yi Ke da Xue Xue Bao | volume = 20 | issue = 1 | pages = 81–84 | date = March 1989 | pmid = 2793150 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=HXYK198901033}}{{cite journal | vauthors = Xu LZ, Han ZY, Yue YC, Yang SZ | title = 复方甲地孕酮微囊注射液肌注后血药浓度及对垂体-卵巢功能影响的探讨 | trans-title = Blood levels of megestrol acetate following injection of the microencapsulated compound megestrol acetate and its effect on pituitary-ovarian function | language = zh | journal = Hua Xi Yi Ke da Xue Xue Bao | volume = 19 | issue = 1 | pages = 97–101 | date = March 1988 | issn = 1672-173X | pmid = 3391610 | url = http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CJFQ&dbname=CJFD8589&filename=HXYK198801035}} Following an injection, levels of MGA were higher than 2 ng/mL after a day, reached a peak of 3.2 ng/mL after 8 days, remained at levels of 2 ng/mL after 27 days, remained at 1 to 2 ng/mL after 27 to 45 days, and were below 1 ng/mL after 45 to 51 days (0.71 ng/mL on the 51st day).