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 and
Latin America.[1][2][8][3] The combination has also been used as a form of
pseudopregnancy (high-dose estrogen/progestogen therapy), for instance to treat
osteopenia due to
hypogonadism, to induce
feminization in hypogonadism/
delayed puberty, and as a means of hormonal breast enhancement to produce
breast enlargement.[9][10][11] 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.[9][10][11]
EV/OHPC is used as a
combined injectable contraceptive to prevent
pregnancy in women under the brand name Injectable No. 1 (or Chinese Injectable No. 1) in
China as well.[4][5][6] When used as a combined injectable contraceptive, EV/OHPC is given twice in the first month and then once per month thereafter.[6][12][13]
Available forms
EV/OHPC is available for general use (e.g., as Gravibinon) in the form of
ampoules containing 5 to 10 mg
estradiol valerate (EV) and 250 to 500 mg
hydroxyprogesterone caproate (OHPC).[7] It is available for use as a combined injectable contraceptive specifically at a dose of 5 mg EV and 250 mg OHPC.[4][5][6]
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 (short and hence fast cycles).[6][12] This may be unacceptable to many women.[6] Twice-monthly administration of half doses has not been found to improve
breakthrough bleeding, though cycle length increased to 20 to 24 days.[12]
History
EV/OHPC was reportedly first introduced for medical use in 1955.[14] The medication was developed by
Schering and marketed under the brand name Gravibinon for the treatment of
habitual abortion in
Europe by the late 1960s.[15][16][17]
EV/OHPC was the first combined injectable contraceptive to be studied.[13][6] It was first evaluated by Siegel and colleagues in 1963.[13][6] The doses used in their study were 10 mg EV and 500 mg OHPC.[13] 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
China under the brand name Injectable No. 1 (or Chinese Injectable No. 1).[6][13] The formulation was also reported to be marketed in a few countries neighboring China.[18] EV/OHPC was also studied at the same dose by a "major
Europeanpharmaceutical company" 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.[5] As a result of these
menstrual disturbances, the company abandoned development of the formulation.[5]
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.[19][20] The others were
estradiol enanthate/algestone acetophenide (E2-EN/DHPA; brand names Perlutal, Topasel), which had been marketed in
Spain and
Latin America, and
estradiol cypionate/medroxyprogesterone acetate (EC/MPA; code name Cyclo-Provera), which was still experimental by 1976 and did not become formally available for clinical use until the 1990s.[20][6] 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.[20][6]
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.[19]
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.[21][22][23][7][24][25] It has been marketed under the brand name Injectable No. 1 or Chinese Injectable No. 1 for use as a combined injectable contraceptive.[4][5]
Availability
EV/OHPC is marketed under the brand names Gravidinona in
Mexico and Gestadinona in
Brazil for threatened abortion.[21][22][23] It was also marketed under the brand name Gravidinona in
Chile but was discontinued in this country.[22][23] EV/OHPC was also marketed under the brand names Gravibinon (
Schering) in
Austria,
Belgium, and
Germany and Gravibinan (Schering) in
France,
Italy, and
Turkey for threatened abortion as well, but has been discontinued in these countries.[22][23][7][24][25] 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
China.[4][5]
Usage
It was estimated in 1995 that EV/OHPC had been used as a combined injectable contraceptive in China by about 1 million women.[26] 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.[26]
^
abUlrich U, Pfeifer T, Lauritzen C (September 1994). "Rapid increase in lumbar spine bone density in osteopenic women by high-dose intramuscular estrogen-progestogen injections. A preliminary report". Hormone and Metabolic Research. 26 (9): 428–431.
doi:
10.1055/s-2007-1001723.
PMID7835827.
S2CID260169203.
^
abUlrich U, Pfeifer T, Buck G, Keckstein J, Lauritzen C (1995). "High-dose estrogen-progestogen injections in gonadal dysgenesis, ovarian hypoplasia, and androgen insensitivity syndrome: Impact on bone density". Adolescent and Pediatric Gynecology. 8 (1): 20–23.
doi:
10.1016/S0932-8610(12)80156-3.
ISSN0932-8610.
^Kaiser R (July 1993). "[Gestagen-estrogen combinations in gynecology. On the history, dosage and use of a hormone principle]" [Progestogen-Estrogen Combinations in Gynecology. History, Dosage, and Use of a Hormone Principle]. Geburtshilfe und Frauenheilkunde. 53 (7): 503–513.
doi:
10.1055/s-2007-1022924.
PMID8370495.
S2CID71261744. Zur kombinierten Anwendung von Gestagen en und Östrogenen stand en zunächst ölgelöstes Östradiolbenzoat und Progesteron zur Verfügung. Das erste derartige Mischpräparat kam in Deutschland 1950 auf den Mark t. Dem Wunsch nach verlän gerter Wirkungsdauer entsprach en dann Kristallmischsuspension en verschiedener Korngröße aus Östradiolmonobenzoat + Progesteron, deren Anwendung sich auf klinische Untersuchungen besch ränkte (83). Ölgelöste Depotpräparate mit Östradiolbenzoat oder -valerat + 17-hydroxyprogesteroncaproat wurden ab 1955 in die Therapie eingeführt (45.46).
^Pundel JP (1971). "[Prolonged amenorrhea after abortion during intensive treatment with progestagens]". Gynécologie Pratique (in French). 22 (2): 77–85.
PMID5562318.
^
abcdSweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2082.
ISBN978-0-85369-840-1.