Hydroxyprogesterone heptanoate

Hydroxyprogesterone heptanoate (OHPH), also known as hydroxyprogesterone enanthate (OHPE) and sold under the brand names H.O.P., Lutogil A.P., and Lutogyl A.P. among others, is a progestin medication used for progestogenic indications.[1][2][3][4] It has been formulated both alone and in together with estrogens, androgens/anabolic steroids, and other progestogens in several combination preparations (brand names Tocogestan, Trioestrine Retard, and Triormon Depositum).[4][5][6][7][8][9][10] OHPH is given by injection into muscle at regular intervals.[11][9]

Not to be confused with 17α-Hydroxyprogesterone, Hydroxyprogesterone acetate, or Hydroxyprogesterone caproate.
Hydroxyprogesterone heptanoate
Clinical data
Trade namesH.O.P, Hydroxyprogesterone, Lutogil A.P., Lutogyl A.P., others
Other namesOHPH; Hydroxyprogesterone enanthate; OHPE; 17α-Hydroxyprogesterone heptanoate; 17α-Hydroxyprogesterone heptylate; 17α-Hydroxypregn-4-ene-3,20-dione 17α-heptanoate; 17α-Heptyloylpregn-4-ene-3,20-dione
Routes of
administration		Intramuscular injection
Drug classProgestogen; Progestin; Progestogen ester
ATC code
Identifiers
IUPAC name
  • [(8R,9S,10R,13S,14S,17R)-17-Acetyl-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] heptanoate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.022.724
Chemical and physical data
FormulaC28H42O4
Molar mass442.640 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C)C(=O)C
InChI
  • InChI=1S/C28H42O4/c1-5-6-7-8-9-25(31)32-28(19(2)29)17-14-24-22-11-10-20-18-21(30)12-15-26(20,3)23(22)13-16-27(24,28)4/h18,22-24H,5-17H2,1-4H3/t22-,23+,24+,26+,27+,28+/m1/s1
  • Key:NKJYZYWCGKSMSV-BDPSOKNUSA-N

OHPH is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[12][13][14] It appears to have similar pharmacology to that of the closely related medication hydroxyprogesterone caproate (OHPC).[15][16][17]

OHPH was first described by 1954[16] and was introduced for medical use by 1957.[6] It has been used clinically in France and Monaco in the past but is no longer marketed.[2][3][4]

Medical uses

OHPH is a progestogen and was used in situations in which progestogens were indicated.[12][13][14]

Available forms

OHPH was provided as a 125 mg/1 mL oil solution for use by intramuscular injection.[3][11] In addition to single-drug preparations, OHPH has also been used in a number of multi-drug formulations.[4][5][6][7][8][9][10] It was used in Tocogestan, a combination of 50 mg progesterone, 200 mg OHPH, and 250 mg α-tocopherol palmitate (vitamin E) in oil solution for use by intramuscular injection.[18][4][5] It was also used in Triormon Depositum (estradiol dibutyrate, testosterone caproate, and OHPH) and Trioestrine Retard (estradiol diundecylate, testosterone cyclohexylpropionate, and OHPH).[6][7] OHPH was a component of the experimental preparation Trophobolene (or Trophoboline), which also contained estrapronicate (estradiol nicotinate propionate) and nandrolone undecanoate, as well.[8][9][10]

Pharmacology

Pharmacodynamics

OHPH is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[15][12][13][14] The progestogenic potency of OHPH in the uterus is equal to or greater than that of progesterone when administered by subcutaneous injection in animals.[15][16][17] Its potency in animals likewise appears to be similar to that of hydroxyprogesterone caproate.[15][16][17]

Pharmacokinetics

OHPH shows a pronounced depot effect when administered by subcutaneous injection in animals, similarly to the closely related medication hydroxyprogesterone caproate.[15][16] The oral activity of OHPH in animals does not appear to have been assessed.[15]

Chemistry
See also: List of progestogens, Progestogen ester, and List of progestogen esters

OHPH, also known as hydroxyprogesterone enanthate (OHPE),[19] as well as 17α-hydroxyprogesterone heptanoate or 17α-hydroxypregn-4-ene-3,20-dione 17α-heptanoate, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.[1][2] It is a progestogen ester; specifically, it is the C17α heptanoate (enanthate) ester of 17α-hydroxyprogesterone.[1][2] Analogues of OHPH include the more well-known medications hydroxyprogesterone acetate and hydroxyprogesterone caproate (hydroxyprogesterone hexanoate).[1][2] The C3 benzilic acid hydrazone of OHPH, hydroxyprogesterone heptanoate benzilic acid hydrazone (OHPHBH), is known and has been studied in animals.[20][21] In terms of chemical structure, OHPH is very similar to hydroxyprogesterone caproate, differing from it only in having one additional carbon in its fatty acid ester chain.[1][2]

History

OHPH was first described, along with hydroxyprogesterone caproate and hydroxyprogesterone acetate, by Karl Junkmann of Schering AG in 1954.[16][19] It was introduced for medical use by 1957.[6] OHPH was commercialized by Roussel and Théramex, and has been used clinically in France and Monaco but is no longer marketed.[2][3][4]

Society and culture

Brand names

OHPH has been marketed alone under a number of brand names including H.O.P, Hydroxyprogesterone, Lutogil A.P., and Lutogyl A.P.[1][2][3][4]

Availability

OHPH was previously marketed in France and Monaco but is no longer available.[2][3][22]

See also

References
  1. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 665–. ISBN 978-1-4757-2085-3.
  2. Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 532–. ISBN 978-3-88763-075-1.
  3. Muller (19 June 1998). European Drug Index: European Drug Registrations, Fourth Edition. CRC Press. pp. 612–. ISBN 978-3-7692-2114-5.
  4. Axel Kleemann; Jürgen Engel (2001). Pharmaceutical Substances: Syntheses, Patents, Applications. Thieme. p. 1033. ISBN 978-3-13-558404-1.
  5. Sasco AJ, Gendre I, Verbier-Naneix C, Soulier JL, Raffi F, Satgé D, Robert E (1998). "Neonatal neuroblastoma and in utero exposure to progestagens". International Journal of Risk and Safety in Medicine. 11 (2): 121–128.
  6. Ermiglia, G; Valli, P (1957). "Triormon depositum in climacteric syndrome. Curves of excretion of catabolites and duration of the therapeutic effect". Quaderni Clin. Ostet. E Ginecol. 12: 284–93. Triormon depositum (estradiol dibutyrate 3, testosterone caprylate 50, and hydroxyprogesterone heptanoate 30 mg.), administered in castor oil-benzyl benzoate soln. or polyvinylpyrrolidone suspension to 21 women in climacteric, was followed by estradiol, pregnanediol, and 17-keto steroid urinary curves, most with a peak at the 4th day, and approaching starting values at the 8-10th day. The therapeutic efficacy of the drug was satisfactory.
  7. Bordier, Philippe (1963). "Cure of fifteen osteoporosis cases by a delayed effect of hormonal association". Semaine des Hopitaux. 39 (2): 81–4. ISSN 0037-1777. The patients (females) received intramuscularly, every 10 days for 2-3 months, estradiol diundecyleate 2.25, testosterone cyclohexylpropionate 67.5, and hydroxyprogesterone heptylate 100 mg. ("trioestrine retard"). Their av. calcuria decreased 30.5% (0-69%) and asthenia, anorexia, and muscular activity improved.
  8. Excerpta medica. Section 8, Neurology and neurosurgery. 1981. p. 10.
  9. Testosterone Congeners—Advances in Research and Application: 2013 Edition: ScholarlyBrief. ScholarlyEditions. 21 June 2013. pp. 137–. ISBN 978-1-4816-9288-5.
  10. Alberto Frigerio (1981). Chromatography in Biochemistry, Medicine and Environmental Research: Proceedings of the ... International Symposium on Chromatography in Biochemistry, Medicine and Environmental Research. Elsevier Scientific Publishing Company. p. 99. ISBN 9780444420169.
  11. Leszek Krówczyński (1987). Extended Release Dosage Forms. CRC Press. p. 12. ISBN 978-0-8493-4307-0. Progestogens. [...] Hydroxyprogesterone heptanoate. Hydroxyprogesterone (Theramex). Oily solution for injection.
  12. Schindler, Adolf E. (2014). "The "newer" progestogens and postmenopausal hormone therapy (HRT)". The Journal of Steroid Biochemistry and Molecular Biology. 142: 48–51. doi:10.1016/j.jsbmb.2013.12.003. ISSN 0960-0760. PMID 24333799. S2CID 32126275.
  13. Bińkowska, Małgorzata; Woroń, Jarosław (2015). "Progestogens in menopausal hormone therapy". Menopausal Review. 2 (2): 134–143. doi:10.5114/pm.2015.52154. ISSN 1643-8876. PMC 4498031. PMID 26327902.
  14. Posaci, C.; Smitz, J.; Camus, M.; Osmanagaoglu, K.; Devroey, P. (2000). "Progesterone for the luteal support of assisted reproductive technologies: clinical options". Human Reproduction. 15 (suppl 1): 129–148. doi:10.1093/humrep/15.suppl_1.129. ISSN 0268-1161. PMID 10928425.
  15. Neumann, F; Elger, W; Salloch, RR; Tube, O; Neumann, HF (1969). "Besonderheiten der Wirkungen der einzelnen Gestagene auf Morphologie und Funktion des Genitaltraktes bei Säugetieren" [Special features of the effects of the individual gestagens on the morphology and function of the genital tract in mammals]. Die Gestagene [Progestogens]. Vol. 2. Springer-Verlag. pp. 50–131. ISBN 978-3-662-00826-3.
  16. Junkmann K (1954). "Über protrahiert wirksame Gestagene". Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie. 223 (3). doi:10.1007/BF00246995. S2CID 33591186.
  17. Junkmann, K. (1959). Über Entwicklungen auf dem Gestagengebiet. 15. In Meeting Gen. Assembly of the Japan Medical Congr., Tokyo (Vol. 1, pp. 697-706).
  18. "Formulation".
  19. Batres, E.; Gomez, R.; Rosenkranz, G.; Sondheimer, F. (1956). "Notes - Steroids. LXXVI. Synthesis of Long Chain Carboxylic Acid Esters of 17α-Hydroxyprogesterone". The Journal of Organic Chemistry. 21 (2): 240–241. doi:10.1021/jo01108a601. ISSN 0022-3263.
  20. Ralph I. Dorfman (3 February 2016). Bioassay. Elsevier. pp. 252–. ISBN 978-1-4832-7276-4.
  21. Gleason CH, Parker JM (1959). "The duration of activity of the benziloyl hydrazones of testosterone-17-heptanoate, estrone-3-heptanoate and 17α-hydroxy-progesterone-17-heptanoate". Endocrinology. 65 (3): 508–511. doi:10.1210/endo-65-3-508. ISSN 0013-7227. PMID 13828402.
  22. https://www.micromedexsolutions.com/
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