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Estradiol cypionate/medroxyprogesterone acetate (EC/MPA), sold under the brand name Cyclofem among others, is a form of
combined injectable birth control Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy. CICs are different from progestoge ...
. It contains
estradiol cypionate Estradiol cypionate (EC), sold under the brand name Depo-Estradiol among others, is an estrogen (medication), estrogen medication which is used in Hormone replacement therapy, hormone therapy for menopausal symptoms and hypoestrogenism, low estrog ...
(EC), an
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
, and
medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...
(MPA), a
progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
. It is recommended for short-term use and is given once a month by
injection into a muscle Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles ha ...
. Common
side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s of EC/MPA include irregular menstrual periods which typically improves with time. Other side effects include
blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
, headache, hair loss, depression, nausea, and breast pain. Use during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
is not recommended. Use during
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
is likely safe. It works mainly by preventing
ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
. EC/MPA came into medical use in 1993 with approval in the United States in 2000. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. The medication is approved for use in 18 countries. It is used in Mexico, Thailand, and Indonesia, among other countries. It is no longer commercially available in the United States.


Medical uses

EC/MPA is used as a once-monthly
combined injectable contraceptive Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy. CICs are different from progestoge ...
to prevent
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
in women.


Available forms

EC/MPA is available in the form of a
microcrystalline A microcrystalline material is a crystallized substance or rock that contains small crystals visible only through microscopic examination. There is little agreement on the range of crystal sizes that should be regarded as microcrystalline, but th ...
aqueous suspension In chemistry, a suspension is a Mixture#Homogeneous and heterogeneous mixtures, heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be macroscopic, visible to the naked eye, usual ...
of 5 mg EC and 25 mg MPA given in a 0.5 mL
aqueous solution An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be re ...
for
intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
once per month. It is provided in the form of single-dose
vial A vial (also known as a phial or flacon) is a small glass or plastic vessel or bottle, often used to store medication as liquids, powders or capsules. They can also be used as scientific sample vessels; for instance, in autosampler devices i ...
s and
ampoule An ampoule (also ampul and ampule) is a small sealed vial which is used to contain and preserve a sample, usually a solid or liquid. Ampoules are usually made of glass. Modern ampoules are most commonly used to contain pharmaceuticals and chem ...
s. The
particle size Particle size is a notion introduced for comparing dimensions of solid particles ('' flecks''), liquid particles ('' droplets''), or gaseous particles ('' bubbles''). The notion of particle size applies to particles in colloids, in ecology, in ...
s of the formulation are 93% within a range of 5 to 16 μm.


History

Depot MPA (DMPA) and EC/MPA were developed by
Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...
in the 1960s. DMPA (brand name Depo-Provera) was introduced for use as a
progestogen-only injectable contraceptive Progestogen-only injectable contraceptives (POICs) are a form of hormonal contraception and progestogen-only contraception that are administered by injection and providing long-lasting birth control. As opposed to combined injectable contracepti ...
for the first time outside of the United States in 1969 and was subsequently approved for use in birth control in the United States in 1992. A variety of preliminary studies on EC/MPA as a contraceptive were published between 1968 and 1978. In the late 1970s, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) began an initiative known as the Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP) to develop combined injectable contraceptives as part of its efforts to increase the availability and choices of birth control for women and men throughout the world. They sought to remedy the side effect of
menstrual irregularity Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods). The possible causes of irregular menstruation may vary. The common factors of ...
that is the major reason for discontinuation of progestogen-only injectable contraceptives like DMPA via incorporation of an estrogen. Funding for the initiative was provided by the
United Nations Development Programme The United Nations Development Programme (UNDP)french: Programme des Nations unies pour le développement, PNUD is a United Nations agency tasked with helping countries eliminate poverty and achieve sustainable economic growth and human dev ...
(UNDP),
United Nations Population Fund The United Nations Population Fund (UNFPA), formerly the United Nations Fund for Population Activities, is a UN agency aimed at improving reproductive and maternal health worldwide. Its work includes developing national healthcare strategies ...
(UNFPA), and
World Bank The World Bank is an international financial institution that provides loans and grants to the governments of low- and middle-income countries for the purpose of pursuing capital projects. The World Bank is the collective name for the Interna ...
. In 1980, the WHO conducted a
pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
study of
estradiol cypionate Estradiol cypionate (EC), sold under the brand name Depo-Estradiol among others, is an estrogen (medication), estrogen medication which is used in Hormone replacement therapy, hormone therapy for menopausal symptoms and hypoestrogenism, low estrog ...
,
estradiol valerate Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy fo ...
, and
estradiol benzoate Estradiol benzoate (EB), sold under the brand name Progynon-B among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in t ...
to determine which ester(s) would be most suitable for use in combined injectable contraceptives. Following the initial development of the medication by Upjohn under the code name Cyclo-Provera previously, EC/MPA was developed as a combined injectable contraceptive by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
under the code name HRP-112 in the 1980s and early 1990s. The WHO also developed estradiol valerate/norethisterone enantate (code name HRP-102) as a combined injectable contraceptive. Development of EC/MPA was completed by the early 1990s and the medication was licensed to the WHO/HRP-established
Concept Foundation The Concept Foundation is a non-profit foundation which was established by the UNDP/UNFPA/WHO/WB Special program in Reproductive Health (WHO/HRP), PATH, the World Bank in 1989 in Bangkok, Thailand, "as a mechanism through which WHO’s rights ass ...
as well as several
pharmaceutical companies The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate symptoms. ...
. EC/MPA was introduced for use as a combined injectable contraceptive under the brand name Cyclofem and others in
Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...
,
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is bo ...
, and
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania between the Indian and Pacific oceans. It consists of over 17,000 islands, including Sumatra, Java, Sulawesi, and parts of Borneo and New Guine ...
in 1993. It was available in 18 countries, mostly in
Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
and
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
, by 1998. In late 2000, EC/MPA was introduced for use as a combined injectable contraceptive by Upjohn under the brand name Lunelle in the United States. However, the formulation was discontinued in the United States in late 2003.


Society and culture


Generic names

EC/MPA was originally known as ''Cyclo-Provera'' (or ''Cycloprovera''), and is also known by its former developmental code name ''HRP-112''.


Brand names

Brand names of EC/MPA include Ciclofem, Ciclofemina, Cyclofem, Cyclofemina, Cyclogeston, Femelin, Femydrol, Gestin, Harmonis, Lunella, Lunelle, and Novafem.


Availability

EC/MPA has been approved for use in at least 18 countries. It is or has been used in
Bolivia , image_flag = Bandera de Bolivia (Estado).svg , flag_alt = Horizontal tricolor (red, yellow, and green from top to bottom) with the coat of arms of Bolivia in the center , flag_alt2 = 7 × 7 square p ...
,
Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
,
Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the east a ...
,
China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
,
Colombia Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the Car ...
,
Costa Rica Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...
, the
Dominican Republic The Dominican Republic ( ; es, República Dominicana, ) is a country located on the island of Hispaniola in the Greater Antilles archipelago of the Caribbean region. It occupies the eastern five-eighths of the island, which it shares wit ...
,
Ecuador Ecuador ( ; ; Quechua: ''Ikwayur''; Shuar: ''Ecuador'' or ''Ekuatur''), officially the Republic of Ecuador ( es, República del Ecuador, which literally translates as "Republic of the Equator"; Quechua: ''Ikwadur Ripuwlika''; Shuar: ''Eku ...
,
El Salvador El Salvador (; , meaning " The Saviour"), officially the Republic of El Salvador ( es, República de El Salvador), is a country in Central America. It is bordered on the northeast by Honduras, on the northwest by Guatemala, and on the south b ...
,
Guatemala Guatemala ( ; ), officially the Republic of Guatemala ( es, República de Guatemala, links=no), is a country in Central America. It is bordered to the north and west by Mexico; to the northeast by Belize and the Caribbean; to the east by H ...
,
Hong Kong Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China ( abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delt ...
,
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania between the Indian and Pacific oceans. It consists of over 17,000 islands, including Sumatra, Java, Sulawesi, and parts of Borneo and New Guine ...
,
Malaysia Malaysia ( ; ) is a country in Southeast Asia. The federation, federal constitutional monarchy consists of States and federal territories of Malaysia, thirteen states and three federal territories, separated by the South China Sea into two r ...
,
Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...
,
Panama Panama ( , ; es, link=no, Panamá ), officially the Republic of Panama ( es, República de Panamá), is a transcontinental country spanning the southern part of North America and the northern part of South America. It is bordered by Cos ...
,
Peru , image_flag = Flag of Peru.svg , image_coat = Escudo nacional del Perú.svg , other_symbol = Great Seal of the State , other_symbol_type = Seal (emblem), National seal , national_motto = "Fi ...
,
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is bo ...
, the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, and
Zimbabwe Zimbabwe (), officially the Republic of Zimbabwe, is a landlocked country located in Southeast Africa, between the Zambezi and Limpopo Rivers, bordered by South Africa to the south, Botswana to the south-west, Zambia to the north, and Mozam ...
, among other countries. The medication is no longer available in the United States.


See also

* Combined injectable birth control § Available forms * Conjugated estrogens/medroxyprogesterone acetate * Estradiol/medroxyprogesterone acetate *
List of combined sex-hormonal preparations This is a list of known combined sex-hormonal formulations. Brand names and developmental code names are in parentheses. Androgens Injection Marketed * Nandrolone decanoate/nandrolone phenylpropionate (Dinandrol) * Testosterone propionate/ ...
*
List of sex-hormonal aqueous suspensions This is a list of known sex-hormonal crystalline aqueous suspension formulations. Brand names and developmental code names are in parentheses. Single-drug formulations Androgens * Androstanolone * Methandriol (Notandron, Protandren) * Testost ...


References

{{DEFAULTSORT:Estradiol Cypionate Medroxyprogesterone Acetate Combined injectable contraceptives World Health Organization World Health Organization essential medicines Wikipedia medicine articles ready to translate