Estradiol valerate/gestonorone caproate (EV/GC), known by the developmental code names SH-834 and SH-8.0834, is a high-dose

combination medication A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

estradiol valerate Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 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 fo ...

(EV), an

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 a ...

, and

gestonorone caproate 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 end ...

(GC; norhydroxyprogesterone caproate), 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. Pro ...

, which was developed and studied by Schering in the 1960s and 1970s for potential use in the treatment of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

in women but was ultimately never marketed. It contained 90 mg EV and 300 mg GC in each 3 mL of

oil solution An oil is any nonpolar chemical substance A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent C ...

and was intended 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 ...

once a week. The combination has also been studied incidentally in the treatment of

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

. Both high-dose estrogens and high-dose progestogens have been found to be independently effective in the treatment of breast cancer in women. High-dose estrogens show greater and more consistent effectiveness than high-dose progestogens for this indication. The combination of an estrogen and progestogen, specifically

estradiol benzoate Estradiol benzoate (EB), sold under the brand name Progynon-B among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in ...

and

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 ma ...

, was first studied in breast cancer in rodents and women by

Charles Huggins Charles Brenton Huggins (September 22, 1901 – January 12, 1997) was a Canadian-American physician, physiologist and cancer researcher at the University of Chicago specializing in prostate cancer. He was awarded the 1966 Nobel Prize for Physio ...

and colleagues in 1962. Initially progesterone and

hydroxyprogesterone caproate Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication which is used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological diso ...

were used as the progestogen component in such studies; the need for a more

potent Potent may refer to: * for the heraldic fur *Warren Potent for the Australian Olympic medalist in shooting See also: *Potency (disambiguation) Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biologica ...

progestogen in such combinations led to the development of EV/GC, which was first reported in the treatment of breast cancer in women in 1966. GC is a relatively pure progestogen that has about 5- to 10-fold the progestogenic potency of hydroxyprogesterone caproate in humans. New reports on EV/GC in breast cancer continued until 1976. Both progesterone and hydroxyprogesterone caproate, which are relatively pure progestogens, have been found to have modest or negligible effectiveness when employed by themselves in the treatment of breast cancer in women. Conversely, progestins with

off-target In pharmacology, an antitarget (or off-target) is a receptor, enzyme, or other biological target that, when affected by a drug, causes undesirable side-effects. During drug design and development, it is important for pharmaceutical companies to e ...

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verte ...

and/or

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

ic activity, such as

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of b ...

megestrol acetate Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014 ...

, and

19-nortestosterone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

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. ...

s, have been found to have greater and more clinically useful effectiveness in comparison. This has raised the possibility that the beneficial therapeutic effects of progestogens in breast cancer may be more related to their off-target activity than their progestogenic activity. In accordance, a study found that the effectiveness of an estrogen alone and the combination of EV/GC in the treatment of breast cancer in women was not significantly different. This was the last study of EV/GC to be published.

References

Abandoned drugs Combined estrogen–progestogen formulations {{Genito-urinary-drug-stub