Estradiol valerate/hydroxyprogesterone caproate (EV/OHPC), sold under the brand names Gravibinon and Injectable No. 1 (or Chinese Injectable No. 1) among others, is a combined

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

and

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

medication which is used in the treatment of threatened miscarriage and other indications (e.g., as a means of

pseudopregnancy In mammalian species, pseudopregnancy is a physical state whereby all the signs and symptoms of pregnancy are exhibited, with the exception of the presence of a fetus, creating a false pregnancy. The corpus luteum (the remains of an ovulated ovar ...

) and as a form of combined injectable birth control to prevent

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. It contains

estradiol valerate Estradiol valerate (EV), sold for use oral administration, by mouth under the brand name Progynova and for use by injection (medicine), injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen (medication), es ...

(EV), an estrogen, and

hydroxyprogesterone caproate Hydroxyprogesterone caproate, sold under the brand name Delalutin among others, is a medication used to reduce the risk of preterm birth in women pregnant with one baby who have a history of spontaneous preterm birth. In March 2023, the manuf ...

(OHPC), 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

. The medication is given by injection into muscle once a day to once a month depending on the indication.

Medical uses

EV/OHPC has been used in the treatment of threatened miscarriage (habitual abortion) and for other indications under the brand name Gravibinon among others in

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

and

Latin America Latin America is the cultural region of the Americas where Romance languages are predominantly spoken, primarily Spanish language, Spanish and Portuguese language, Portuguese. Latin America is defined according to cultural identity, not geogr ...

. The combination has also been used as a form of

(high-dose estrogen/progestogen therapy), for instance to treat

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop o ...

due to

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

, to induce feminization in hypogonadism/

delayed puberty Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormone, hormonal signs that puberty has begun. In the United States ...

, and as a means of hormonal breast enhancement to produce

breast enlargement Breast enlargement is the enlargement of the breasts. It may occur naturally as in mammoplasia or may occur artificially through active intervention. Many women regard their breasts, which are female secondary sex characteristics, as important to t ...

. EV/OHPC is administered daily to once per week or less often for the treatment of threatened miscarriage, for use as a form of pseudopregnancy, and for other indications. EV/OHPC is used as a

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 progestog ...

to prevent

in women under the brand name Injectable No. 1 (or Chinese Injectable No. 1) in

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

as well. When used as a combined injectable contraceptive, EV/OHPC is given twice in the first month and then once per month thereafter.

Available forms

EV/OHPC is available for general use (e.g., as Gravibinon) in the form of

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 containing 5 to 10 mg

(EV) and 250 to 500 mg

(OHPC). It is available for use as a combined injectable contraceptive specifically at a dose of 5 mg EV and 250 mg OHPC.

Side effects

EV/OHPC as a combined injectable contraceptive has a relatively short duration and is associated with a high incidence of menstrual irregularity, for instance

polymenorrhea Polymenorrhea, also known as frequent periods, frequent menstruation, or frequent menstrual bleeding, is a menstrual disorder in which menstrual cycles are shorter than 21days in length and hence where menstruation occurs more frequently than usu ...

(short and hence fast cycles). This may be unacceptable to many women. Twice-monthly administration of half doses has not been found to improve

breakthrough bleeding Intermenstrual bleeding (IMB), or metrorrhagia, is vaginal bleeding at irregular intervals between expected menstrual periods. It may be associated with bleeding with sexual intercourse. The term metrorrhagia, in which metro means measure and ...

, though cycle length increased to 20 to 24 days.

History

EV/OHPC was reportedly first introduced for medical use in 1955. The medication was developed by Schering and marketed under the brand name Gravibinon for the treatment of habitual abortion in

by the late 1960s. EV/OHPC was the first combined injectable contraceptive to be studied. It was first evaluated by Siegel and colleagues in 1963. The doses used in their study were 10 mg EV and 500 mg OHPC. Around the same time as the Siegel study, a half-dose formulation containing 5 mg EV and 250 mg OHPC was developed and subsequently marketed for use in

under the brand name Injectable No. 1 (or Chinese Injectable No. 1). The formulation was also reported to be marketed in a few countries neighboring China. EV/OHPC was also studied at the same dose by a "major

pharmaceutical company The pharmaceutical industry is a Medicine, medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications and medical devices. Medications are then administered to (or Self-medicate, self-administered b ...

" in 1971, but was found to produce short menstrual cycles of 17 to 18 days with once-monthly administration and 20 to 24 days with twice-monthly administration. As a result of these

menstrual disturbance A menstrual disorder is characterized as any abnormal condition with regards to a woman's menstrual cycle. There are many different types of menstrual disorders that vary with signs and symptoms, including pain during menstruation, heavy bleeding, ...

s, the company abandoned development of the formulation. EV/OHPC was one of only two combined injectable contraceptives to have been marketed by 1976, and was one of only three combined injectable contraceptives with considerable clinical experience by 1976. The others were estradiol enanthate/algestone acetophenide (E2-EN/DHPA; brand names Perlutal, Topasel), which had been marketed in

Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...

and

, and

estradiol cypionate/medroxyprogesterone acetate Estradiol cypionate/medroxyprogesterone acetate (EC/MPA), sold under the brand name Cyclofem among others, is a form of combined injectable birth control. It contains estradiol cypionate (EC), an estrogen, and medroxyprogesterone acetate (MPA), ...

(EC/MPA; code name Cyclo-Provera), which was still experimental by 1976 and did not become formally available for clinical use until the 1990s. By 1994, at which point EC/MPA (brand names Cyclofem and later Lunelle) and estradiol valerate/norethisterone enanthate (EV/NETE; brand name Mesigyna) had been introduced, EV/OHPC had been in use for many years. EV/OHPC and E2-EN/DHPA have been referred to as first-generation combined injectable contraceptives, while EC/MPA and EV/NETE have been referred to as second-generation combined injectable contraceptives.

Society and culture

Brand names

EV/OHPC has been marketed under the brand names Deluteval (or Deluteval 2X), Gravibinon, Gravibinan, Gravidinona, and Gestadinona for the treatment of threatened abortion and other general uses. It has been marketed under the brand name Injectable No. 1 or Chinese Injectable No. 1 for use as a combined injectable contraceptive.

Availability

EV/OHPC is marketed under the brand names Gravidinona in

Mexico Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...

and Gestadinona in

Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...

for threatened abortion. It was also marketed under the brand name Gravidinona in

Chile Chile, officially the Republic of Chile, is a country in western South America. It is the southernmost country in the world and the closest to Antarctica, stretching along a narrow strip of land between the Andes, Andes Mountains and the Paci ...

but was discontinued in this country. EV/OHPC was also marketed under the brand names Gravibinon ( Schering) in

Austria Austria, formally the Republic of Austria, is a landlocked country in Central Europe, lying in the Eastern Alps. It is a federation of nine Federal states of Austria, states, of which the capital Vienna is the List of largest cities in Aust ...

Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...

, and

Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...

and Gravibinan (Schering) in

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

, and

Turkey Turkey, officially the Republic of Türkiye, is a country mainly located in Anatolia in West Asia, with a relatively small part called East Thrace in Southeast Europe. It borders the Black Sea to the north; Georgia (country), Georgia, Armen ...

for threatened abortion as well, but has been discontinued in these countries. EV/OHPC is marketed for use as a combined injectable contraceptive under the brand name Injectable No. 1 or Chinese Injectable No.1 in the

Usage

It was estimated in 1995 that EV/OHPC had been used as a combined injectable contraceptive in China by about 1 million women. However, combined injectable contraceptives like EV/OHPC are unlikely to constitute a large proportion of contraceptive use in the countries in which they are available.

References

{{DEFAULTSORT:Estradiol valerate hydroxyprogesterone caproate Combined estrogen–progestogen formulations Combined injectable contraceptives

Medical uses

Available forms

Side effects

History

Society and culture

Brand names

Availability

Usage

See also

References