Trengestone, sold under the brand names Reteroid, Retroid, and Retrone, is a progestin medication which was formerly used to treat

menstrual disorder A menstrual disorder is characterized as any abnormal condition with regards to a person's menstrual cycle. There are many different types of menstrual disorders that vary with signs and symptoms, including pain during menstruation, heavy bleeding ...

s but is now no longer marketed.http://www.micromedexsolutions.com It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of trengestone include headache, fatigue, and

breast tenderness Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...

among others. Trengestone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of progestogens like progesterone. It is not

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 or

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 ac ...

ic. Trengestone was introduced for medical use in 1974. It is no longer available.

Medical uses

Trengestone was used in the treatment of

s. It has also been used to induce ovulation, with about a 50% success rate on average.

Side effects

s of trengestone include headache, fatigue, and

among others. It is not

ic and does not cause

masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...

Pharmacology

Pharmacodynamics

Trengestone is a progestogen, or an agonist of the progesterone receptor. It is an atypical progestogen similarly to

dydrogesterone Dydrogesterone, sold under the brand name Duphaston & Dydroboon among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertil ...

. For instance, unlike other progestogens, trengestone and dydrogesterone do not increase

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

(i.e., have no hyperthermic effect). In addition, whereas other progestogens are antigonadotropic and inhibit

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...

, dydrogesterone is neither antigonadotropic nor progonadotropic and does not affect ovulation, and trengestone appears to be progonadotropic and can be used to induce ovulation. Similarly to dydrogesterone and progesterone, trengestone has no

ic or

ic activity.

Pharmacokinetics

Trengestone appears to be a prodrug of

20α-dihydrotrengestone 20α-Dihydrotrengestone (20α-DHTG), also known as 20α-hydroxytrengestone, as well as 6-chloro-20(''S'')-hydroxy-9β,10α-pregna-1,4,6-trien-3-one, is a progestin and the major active metabolite of trengestone. It appears that trengestone is a p ...

(20α-DHTG), as it is largely transformed into this major metabolite upon

oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...

. 20α-DHTG has potent progestogenic activity, with peak levels of this metabolite occurring at 2 to 4 hours following administration of trengestone and with a

biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of 8 to 14 hours. Trengestone is

excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

41 to 46% in

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

and up to 30% unchanged in feces, suggesting that a significant portion of the medication is not absorbed from the gastrointestinal tract. The

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

and pharmacokinetics of trengestone have been reviewed.

Chemistry

Trengestone, also known as 1,6-didehydro-6-chlororetroprogesterone or as 6-chloro-9β,10α-pregna-1,4,6-triene-3,20-dione, is a synthetic

pregnane Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally allop ...

steroid 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. ...

of progesterone and retroprogesterone. Retroprogesterone derivatives like trengestone are analogues of progesterone in which the

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...

atom at the 9th carbon has been switched from the α-position (below the plane) to the β-position (above the plane) and the

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...

at the 10th carbon has been switched from the β-position to the α-position. This results in a "bent" configuration in which the plane of rings A and B is orientated at a 60° angle below the rings C and D. Analogues of trengestone include

(6-dehydroretroprogesterone) and

Ro 6-3129 Ro 6-3129, also known as 16α-ethylthio-6-dehydroretroprogesterone or as 16α-ethylthio-9β,10α-pregna-4,6-diene-3,20-dione, as well as 16α-ethylthiodydrogesterone, is a progestogen of the retroprogesterone group which was developed by Roche ...

(16α-ethylthio-6-dehydroretroprogesterone).

History

Trengestone was synthesized in 1964 and was introduced for medical use by

Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

in 1974.

Society and culture

Generic names

''Trengestone'' is the generic name of the drug and its . It is also known by its former developmental code name ''Ro 4-8347''.

Brand names

Trengestone was marketed under the brand names Reteroid, Retroid, and Retrone.

Availability

Trengestone is no longer marketed and hence is no longer available in any country.

References

{{Progesterone receptor modulators Abandoned drugs Chloroarenes Diketones Fertility medicine Pregnanes Prodrugs Progestogens Progonadotropins