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 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 product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

medication used for

progestogen Progestogens, also sometimes written 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 progestogen in the body. ...

ic indications. It has been formulated both alone and in together with

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

s, androgens/

anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone (medication), testosterone as well as synthetic androgens that are structurally related ...

s, and other

s in several combination preparations (brand names Tocogestan,

Trioestrine Retard Estradiol diundecylate/hydroxyprogesterone heptanoate/testosterone cyclohexylpropionate (EDU/OHPH/TCHP), sold under the brand name Trioestrine Retard, is an injectable combination medication of estradiol diundecylate (EDU), an estrogen, hydroxypr ...

, and Triormon Depositum). OHPH is given by

injection into muscle Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...

at regular intervals. OHPH is a progestin, or a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

, and hence is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

, the biological target of progestogens like

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

. It appears to have similar

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

to that of the closely related medication hydroxyprogesterone caproate (OHPC). OHPH was first described by 1954 and was introduced for medical use by 1957. It has been used clinically in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...

and

Monaco Monaco (; ), officially the Principality of Monaco (french: Principauté de Monaco; Ligurian: ; oc, Principat de Mónegue), is a sovereign city-state and microstate on the French Riviera a few kilometres west of the Italian region of Lig ...

in the past but is no longer marketed.

Medical uses

OHPH is a

and was used in situations in which progestogens were indicated.

Available forms

OHPH was provided as a 125 mg/1 mL

oil solution An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...

for use by

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

. In addition to single-drug preparations, OHPH has also been used in a number of multi-drug formulations. It was used in Tocogestan, a combination of 50 mg

, 200 mg OHPH, and 250 mg α-tocopherol palmitate (

vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...

) in

for use by intramuscular injection. It was also used in Triormon Depositum (

estradiol dibutyrate Estradiol dibutyrate (EDBu), or estradiol dibutanoate, is an estrogen medication and an estrogen ester – specifically, a diester of estradiol – which is no longer used. It was a component of Triormon Depositum, a combination formulation of e ...

, testosterone caproate, and OHPH) and

(

estradiol diundecylate Estradiol diundecylate (brand name Estrolent), or estradiol diundecanoate, also known as 17β-estradiol 3,17β-diundecylate, is an estrogen and an estrogen ester – specifically, the 3,17β-di undecylate ester of estradiol – which has been ma ...

testosterone cyclohexylpropionate Testosterone cyclohexylpropionate (TCHP; brand names Andromar, Femolone, Telipex Retard) is an androgen and anabolic steroid and a testosterone ester. See also * Estradiol diundecylate/hydroxyprogesterone heptanoate/testosterone cyclohexylpropio ...

, and OHPH). OHPH was a component of the experimental preparation

Trophobolene Estrapronicate/hydroxyprogesterone heptanoate/nandrolone undecanoate (EPC/OHPH/NU), tentative brand name Trophobolene or Trophoboline, is an injectable combination medication of estrapronicate (EPC; estradiol nicotinate propionate), an estrogen, ...

(or Trophoboline), which also contained

estrapronicate Estrapronicate (), also known as estradiol nicotinate propionate is an estrogen medication and estrogen ester which was never marketed. It was studied as a component of the experimental tristeroid combination drug Trophobolene, which contained n ...

(estradiol nicotinate propionate) and

nandrolone undecanoate Nandrolone undecanoate (NU), also known as nandrolone undecylate, and sold under the brand names Dynabolon, Dynabolin, and Psychobolan, is an androgen and anabolic steroid medication and a nandrolone ester. It was developed in the 1960s, and was ...

, as well.

Pharmacology

Pharmacodynamics

OHPH is a progestin, or a

, and hence is an

of the

, the biological target of progestogens like

. The progestogenic potency of OHPH in the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

is equal to or greater than that of

when administered by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...

in animals.Junkmann, K. (1959). Über Entwicklungen auf dem Gestagengebiet. 15. In Meeting Gen. Assembly of the Japan Medical Congr., Tokyo (Vol. 1, pp. 697-706). Its potency in animals likewise appears to be similar to that of hydroxyprogesterone caproate.

Pharmacokinetics

OHPH shows a pronounced

depot effect A depot injection is a term for an injection formulation of a medication which releases slowly over time to permit less frequent administration of a medication. They are designed to increase medication adherence and consistency, especially in pa ...

when administered by

in animals, similarly to the closely related medication hydroxyprogesterone caproate. The

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

activity of OHPH in animals does not appear to have been assessed.

Chemistry

OHPH, also known as hydroxyprogesterone enanthate (OHPE), as well as 17α-hydroxyprogesterone heptanoate or 17α-hydroxypregn-4-ene-3,20-dione 17α-heptanoate, is a

pregnane

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

and

17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many ot ...

. It is a

progestogen ester A progestogen ester is an ester of a progestogen or progestin (a synthetic progestogen). The prototypical progestogen is progesterone, an endogenous sex hormone. Esterification is frequently employed to improve the pharmacokinetics of steroids, i ...

; specifically, it is the C17α

heptanoate Enanthic acid, also called heptanoic acid, is an organic compound composed of a seven-carbon chain terminating in a carboxylic acid functional group. It is a colorless oily liquid with an unpleasant, rancid odor. It contributes to the odor of som ...

(enanthate)

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

of 17α-hydroxyprogesterone. Analogues of OHPH include the more well-known medications

hydroxyprogesterone acetate Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine. It has reportedly also been used in bi ...

and hydroxyprogesterone caproate (hydroxyprogesterone hexanoate). The C3

benzilic acid Benzilic acid is an organic compound with formula or ()2(HO)C(COOH). It is a white crystalline aromatic acid, soluble in many primary alcohols. Preparation Benzilic acid can be prepared by a heating mixture of benzil, ethanol, and potassium hy ...

hydrazone Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. ...

of OHPH, hydroxyprogesterone heptanoate benzilic acid hydrazone (OHPHBH), is known and has been studied in animals. In terms of

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...

, OHPH is very similar to hydroxyprogesterone caproate, differing from it only in having one additional

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...

in its

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...

chain A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A c ...

History

OHPH was first described, along with hydroxyprogesterone caproate and

, by Karl Junkmann of

Schering AG Schering AG was a research-centered German multinational pharmaceutical company headquartered in Wedding, Berlin, which operated as an independent company from 1851 to 2006. In 2006, it was bought by Bayer AG and merged to form the Bayer subsi ...

in 1954. It was introduced for medical use by 1957. OHPH was commercialized by Roussel and Théramex, and has been used clinically in

and

but is no longer marketed.

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.

Availability

OHPH was previously marketed in

and

but is no longer available.https://www.micromedexsolutions.com/

References

{{Progesterone receptor modulators Abandoned drugs Diketones Enanthate esters Enones Esters Pregnanes Progestogen esters Progestogens