Estradiol valerate/hydroxyprogesterone caproate

Last updated
Estradiol valerate /
hydroxyprogesterone caproate
Estradiol valerate.svg
Hydroxyprogesterone caproate.svg
Estradiol valerate (top) and hydroxy­progesterone caproate (bottom)
Combination of
Estradiol valerate Estrogen
Hydroxyprogesterone caproate Progestogen
Clinical data
Trade names Gravibinon, Injectable No. 1, others
Other namesEV/OHPC; NSC-77622
Routes of
administration 		Intramuscular injection
Identifiers
CAS Number
PubChem CID
UNII

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 and progestogen medication which is used in the treatment of threatened miscarriage and other indications (e.g., as a means of pseudopregnancy) [1] [2] [3] and as a form of combined injectable birth control to prevent pregnancy. [4] [5] [6] It contains estradiol valerate (EV), an estrogen, and hydroxyprogesterone caproate (OHPC), a progestin. [7] [4] [5] The medication is given by injection into muscle once a day to once a month depending on the indication. [1] [4] [5]

Contents

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 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 European pharmaceutical 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]

See also

Related Research Articles

<span class="mw-page-title-main">Estradiol valerate</span> Chemical compound

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova 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 for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

<span class="mw-page-title-main">Gestonorone caproate</span> Chemical compound

Gestonorone caproate, also known as gestronol hexanoate or norhydroxyprogesterone caproate and sold under the brand names Depostat and Primostat, is a progestin medication which is used in the treatment of enlarged prostate and cancer of the endometrium. It is given by injection into muscle typically once a week.

<span class="mw-page-title-main">Hydroxyprogesterone caproate</span> Medication

Hydroxyprogesterone caproate, sold under the brand names Proluton and Makena 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 manufacturer, Covis Pharma, agreed to withdraw the drug from the US market. The approvals of Makena and its generics were withdrawn by the US Food and Drug Administration (FDA) in April 2023.

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.

<span class="mw-page-title-main">Algestone acetophenide</span> Chemical compound

Algestone acetophenide, also known more commonly as dihydroxyprogesterone acetophenide (DHPA) and sold under the brand names Perlutal and Topasel among others, is a progestin medication which is used in combination with an estrogen as a form of long-lasting injectable birth control. It has also been used alone, but is no longer available as a standalone medication. DHPA is not active by mouth and is given once a month by injection into muscle.

<span class="mw-page-title-main">Norethisterone enanthate</span> Chemical compound

Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of hormonal birth control which is used to prevent pregnancy in women. It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women. Each dose of this form lasts two months with only up to two doses typically recommended.

<span class="mw-page-title-main">Estradiol enantate</span> Chemical compound

Estradiol enantate, also spelled estradiol enanthate and sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control for women. It is formulated in combination with dihydroxyprogesterone acetophenide, a progestin, and is used specifically as a combined injectable contraceptive. Estradiol enantate is not available for medical use alone. The medication, in combination with DHPA, is given by injection into muscle once a month.

<span class="mw-page-title-main">Estradiol dipropionate</span> Chemical compound

Estradiol dipropionate (EDP), sold under the brand names Agofollin, Di-Ovocylin, and Progynon DP among others, is an estrogen medication which has been used in hormone therapy for menopausal symptoms and low estrogen levels in women and in the treatment of gynecological disorders. It has also been used in feminizing hormone therapy for transgender women and in the treatment of prostate cancer in men. Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today. It appears to remain in use only in Japan, Macedonia, and Australia. Estradiol dipropionate is given by injection into muscle at intervals ranging from once or twice a week to once every week and a half to two weeks.

<span class="mw-page-title-main">Estradiol hexahydrobenzoate</span> Chemical compound

Estradiol hexahydrobenzoate (EHHB), sold under a number of brand names including Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, and Tardoginestryl, is an estrogen medication which was previously used for indications such as menopausal hormone therapy and gynecological disorders. EHHB is given by injection into muscle at regular intervals, for instance once every few weeks.

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 contraceptives, they contain only a progestogen without an estrogen, and include two progestin preparations:

<span class="mw-page-title-main">Estradiol benzoate/progesterone</span> Drug combination

Estradiol benzoate/progesterone (EB/P4), sold under the brand names Duogynon and Sistocyclin among others, is a combination medication of estradiol benzoate (EB), an estrogen, and progesterone (P4), a progestogen. It has been formulated both as short-acting oil solutions and long-acting microcrystalline aqueous suspensions and is given by injection into muscle either once or continuously at regular intervals.

<span class="mw-page-title-main">Estradiol valerate/norethisterone enantate</span> Combination drug

Estradiol valerate/norethisterone enantate (EV/NETE), sold under the brand name Mesigyna among others, is a form of combined injectable birth control which is used to prevent pregnancy in women. It contains estradiol valerate (EV), an estrogen, and norethisterone enantate (NETE), a progestin. The medication is given once a month by injection into muscle.

<span class="mw-page-title-main">Estradiol enantate/algestone acetophenide</span> Pharmaceutical combination

Estradiol enantate/algestone acetophenide, also known as estradiol enantate/dihydroxyprogesterone acetophenide (E2-EN/DHPA) and sold under the brand names Perlutal and Topasel among others, is a form of combined injectable birth control which is used to prevent pregnancy. It contains estradiol enantate (E2-EN), an estrogen, and algestone acetophenide, a progestin. The medication is given once a month by injection into muscle.

<span class="mw-page-title-main">Estradiol benzoate/hydroxyprogesterone caproate</span> Combination drug

Estradiol benzoate/hydroxyprogesterone caproate (EB/OHPC), sold under the brand name Primosiston among others, is a combined estrogen and progestogen medication which is used to treat gynecological disorders and habitual abortion. It contains estradiol benzoate (EB), an estrogen, and hydroxyprogesterone caproate (OHPC), a progestin. The medication is given by injection into muscle.

<span class="mw-page-title-main">Methenmadinone caproate</span> Chemical compound

Methenmadinone caproate is a progestin medication which was developed in Czechoslovakia in the 1960s and was studied for potential use in combined injectable contraceptives in the 1970s but was never marketed. It was studied as a combined injectable contraceptive in combination with estradiol valerate at doses of 60 mg and 10 mg, respectively, once a month by intramuscular injection. MMC is the C17α caproate (hexanoate) ester of methenmadinone and an analogue of methenmadinone acetate. In addition to MMA, analogues of MMC include chlormadinone caproate, gestonorone caproate, hydroxyprogesterone caproate, medroxyprogesterone caproate, and megestrol caproate.

<span class="mw-page-title-main">Chlormadinone caproate</span> Chemical compound

Chlormadinone caproate (CMC) is a progestin and a progestogen ester which was studied for potential use in combined injectable contraceptives but was never marketed. It was assessed in combination with estradiol valerate at doses of 80 mg and 3 mg, respectively. In addition to chlormadinone acetate (CMA), analogues of CMC include gestonorone caproate, hydroxyprogesterone caproate, medroxyprogesterone caproate, megestrol caproate, and methenmadinone caproate.

<span class="mw-page-title-main">Lynestrenol phenylpropionate</span> Chemical compound

Lynestrenol phenylpropionate (LPP), also known as ethynylestrenol phenylpropionate, is a progestin and a progestogen ester which was developed for potential use as a progestogen-only injectable contraceptive by Organon but was never marketed. It was assessed at doses of 25 to 75 mg in an oil solution once a month by intramuscular injection. LPP was associated with high contraceptive failure at the low dose and with poor cycle control. The medication was found to produce estrogenic effects in the endometrium in women due to transformation into estrogenic metabolites.

<span class="mw-page-title-main">Estradiol valerate/methenmadinone caproate</span> Combination drug

Estradiol valerate/methenmadinone caproate (EV/MMC), known by the tentative brand name Lutofollin, is a combination medication of estradiol valerate (EV), an estrogen, and methenmadinone caproate, a progestin, which was developed for potential use as a once-a-month combined injectable contraceptive but was never marketed. It contained 10 mg EV and 60 mg MMC in 1 mL oil solution and was intended for administration by intramuscular injection once every 4 weeks.

Estradiol benzoate/estradiol valerate/hydroxyprogesterone caproate (EB/EV/OHPC), sold under the brand name Sin-Ol, is a combination medication of estradiol benzoate (EB), an estrogen, estradiol valerate (EV), an estrogen, and hydroxyprogesterone caproate (OHPC), a progestin, which was reportedly used as a combined injectable contraceptive in women in the early 1970s. It contained 1 mg EB, 10 mg EV, and 250 mg OHPC in oil solution, was provided in the form of 3 mL ampoules, and was administered by intramuscular injection at regular intervals. The medication was manufactured by the pharmaceutical company Reuffer in Mexico.

<span class="mw-page-title-main">Estradiol valerate/megestrol acetate</span> Combination drug

Estradiol valerate/megestrol acetate (EV/MGA) is a combined injectable contraceptive which was developed in China in the 1980s but was never marketed. It is an aqueous suspension of microcapsules containing 5 mg estradiol valerate (EV) and 15 mg megestrol acetate (MGA). It was also studied at doses of EV ranging from 0.5 to 5 mg and at doses of MGA ranging from 15 to 25 mg.

References

  1. 1 2 3 Göretzlehner G, Lauritzen C, Göretzlehner U (1 January 2007). "Störungen des Menstrual Zyklus und ihre Therapie". Praktische Hormontherapie in der Gynäkologie. Walter de Gruyter. pp. 117, 337, 385, 391–392. ISBN   978-3-11-020864-1.
  2. 1 2 Schindler AE (June 2001). "[Treatment of high risk pregnancy with gravibinon]". Zentralblatt für Gynakologie. 123 (6): 353–356. doi:10.1055/s-2001-16285. PMID   11488163. S2CID   71374491.
  3. 1 2 Schindler AE (January 2004). "First trimester endocrinology: consequences for diagnosis and treatment of pregnancy failure". Gynecological Endocrinology. 18 (1): 51–57. doi:10.1080/09513590310001651795. PMID   15106366. S2CID   20910537.
  4. 1 2 3 4 5 6 7 Garza-Flores J (April 1994). "Pharmacokinetics of once-a-month injectable contraceptives". Contraception. 49 (4): 347–359. doi:10.1016/0010-7824(94)90032-9. PMID   8013219.
  5. 1 2 3 4 5 6 7 8 9 Sang GW (April 1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–385. doi:10.1016/0010-7824(94)90033-7. PMID   8013220.
  6. 1 2 3 4 5 6 7 8 9 10 11 Toppozada MK (April 1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. doi:10.1016/0010-7824(94)90029-9. PMID   8013216.
  7. 1 2 3 4 Muller (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 561–. ISBN   978-3-7692-2114-5.
  8. ↑ Lim CE, Ho KK, Cheng NC, Wong FW (September 2013). "Combined oestrogen and progesterone for preventing miscarriage". The Cochrane Database of Systematic Reviews. 2013 (9): CD009278. doi:10.1002/14651858.CD009278.pub2. hdl: 10453/117991 . PMC   7389506 . PMID   24068368.
  9. 1 2 Göretzlehner G, Lauritzen C, Römer T, Rossmanith W (1 January 2012). "Hormontherapien bei gynäkologischen Erkrankungen". Praktische Hormontherapie in der Gynäkologie. Walter de Gruyter. pp. 227–228. ISBN   978-3-11-024568-4.
  10. 1 2 Ulrich 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. PMID   7835827. S2CID   260169203.
  11. 1 2 Ulrich 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. ISSN   0932-8610.
  12. 1 2 3 Toppozada MK (1983). "Monthly Injectable Contraceptives". In Goldsmith A, Toppozada M (eds.). Long-Acting Contraception. pp. 93–103. OCLC   35018604.
  13. 1 2 3 4 5 Spinola PG (11 December 2001). "Benefits of injectable contraception to women's health". In Artini PG, Genazzani AR, Petraglia F (eds.). Advances in Gynecological Endocrinology. CRC Press. pp. 101–102. ISBN   978-1-84214-071-0.
  14. ↑ 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. PMID   8370495. S2CID   71261744. 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).
  15. ↑ Acta Europaea Fertilitatis. Morgagni Edizioni Scientifiche. 1969. p. 662,665.
  16. ↑ Belgium (1969). Belgisch staatsblad. p. 4798.
  17. ↑ Pundel JP (1971). "[Prolonged amenorrhea after abortion during intensive treatment with progestagens]". Gynécologie Pratique (in French). 22 (2): 77–85. PMID   5562318.
  18. ↑ "Facts about once-a-month injectable contraceptives: memorandum from a WHO meeting". Bulletin of the World Health Organization. 71 (6): 677–689. 1993. PMC   2393537 . PMID   8313486.
  19. 1 2 del Carmen Cravioto M (15 September 1995). "Combined injectable preparations and introduction as a new method". In Bringer J, Hedon B (eds.). Fertility and Sterility: A Current Overview. CRC Press. pp. 47–. ISBN   978-1-85070-694-6.
  20. 1 2 3 Toppozada M (June 1977). "The clinical use of monthly injectable contraceptive preparations". Obstetrical & Gynecological Survey. 32 (6): 335–347. doi:10.1097/00006254-197706000-00001. PMID   865726.
  21. 1 2 "Hydroxyprogesterone injection Uses, Side Effects & Warnings". drugs.com.
  22. 1 2 3 4 Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2082. ISBN   978-0-85369-840-1.
  23. 1 2 3 4 "Micromedex Products: Please Login".
  24. 1 2 PDR Generics. Medical Economics. 1996. p. 1171. ISBN   978-1-56363-151-1.
  25. 1 2 Kleemann A, Engel J (2001). Pharmaceutical Substances: Syntheses, Patents, Applications. Thieme. p. 1033. ISBN   978-3-13-558404-1.
  26. 1 2 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; International Agency for Research on Cancer (1 January 1999). Hormonal Contraception and Post-menopausal Hormonal Therapy (PDF). IARC. p. 65. ISBN   978-92-832-1272-0. Archived from the original (PDF) on 28 August 2021. Retrieved 18 September 2018.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.