Chemical compound
Hydroxyprogesterone heptanoate
Trade names H.O.P, Hydroxyprogesterone, Lutogil A.P., Lutogyl A.P., others Other names OHPH; 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 class
Progestogen ;
Progestin ;
Progestogen ester
ATC code
[(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 InfoCard
100.022.724
Formula C 28 H 42 O 4
Molar mass 442.640 g·mol−1 3D model (
JSmol )
CCCCCCC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C)C(=O)C
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
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]
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
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
^
a
b
c
d
e
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^
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"Neonatal neuroblastoma and in utero exposure to progestagens" . International Journal of Risk and Safety in Medicine . 11 (2): 121–128.
^
a
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e 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.
^
a
b
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ISSN
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^
a
b
c
Excerpta medica. Section 8, Neurology and neurosurgery . 1981. p. 10.
^
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ISBN
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^
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ISBN
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^
a
b Krówczyński L (1987).
Extended Release Dosage Forms . CRC Press. p. 12.
ISBN
978-0-8493-4307-0 . Progestogens. [...] Hydroxyprogesterone heptanoate. Hydroxyprogesterone (Theramex). Oily solution for injection.
^
a
b
c Schindler AE (July 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 .
PMID
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S2CID
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c Bińkowska M, Woroń J (June 2015).
"Progestogens in menopausal hormone therapy" . Przeglad Menopauzalny = Menopause Review . 14 (2): 134–143.
doi :
10.5114/pm.2015.52154 .
PMC
4498031 .
PMID
26327902 .
^
a
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c Posaci C, Smitz J, Camus M, Osmanagaoglu K, Devroey P (June 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 .
PMID
10928425 .
^
a
b
c
d
e
f 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 .
^
a
b
c
d
e
f Junkmann K (1954). "Über protrahiert wirksame Gestagene". Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie . 223 (3).
doi :
10.1007/BF00246995 .
S2CID
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^
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c Junkmann K (1959). Über Entwicklungen auf dem Gestagengebiet. 15 . General Assembly of the Japan Medical Congress, Tokyo. Vol. 1. pp. 697–706.
^
"Formulation" .
^
a
b 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 .
^ Shipley EG (1962).
"Anti-gonadotropic steroids, inhibition of ovulation and mating" . In Dorfman RI (ed.). Methods in Hormone Research . Vol. 2. Elsevier. pp. 252–.
ISBN
978-1-4832-7276-4 .
^ 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
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PMID
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^
"OHPH" . micromedexsolutions.com .
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins:
6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
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Levonorgestrel esters (e.g.,
levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g.,
norethisterone acetate ,
norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids:
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
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Bolandione
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Dienolone
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Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g.,
nandrolone decanoate ,
nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g.,
trenbolone acetate ,
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Trendione
Trestolone
Trestolone acetate
Mixed (
SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )