Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an

experimental An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...

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 ...

/ anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and in androgen replacement therapy for low testosterone levels in men but has never been marketed for medical use. It is given as an implant that is placed into fat. As trestolone acetate, an

androgen ester An androgen or anabolic steroid ester is an ester of an androgen/anabolic steroid (AAS) such as the natural testosterone or dihydrotestosterone (DHT) or the synthetic nandrolone (19-nortestosterone). Esterification renders AAS into metabolism-re ...

and prodrug of trestolone, the medication can also be given by injection into muscle.

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 trestolone include low estrogen levels and associated symptoms such as reduced sexual function and decreased bone mineral density among others. Trestolone is an AAS, and hence is an agonist of the androgen 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 androgens like

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

. It is also a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. Due to its androgenic and progestogenic activity, trestolone has antigonadotropic effects. These effects result in reversible suppression of

sperm production Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules ...

and are responsible for the contraceptive effects of trestolone in men. Trestolone was first described in 1963. Subsequently, it was not studied again until 1990. Development of trestolone for potential clinical use started by 1993 and continued thereafter. No additional development appears to have been conducted since 2013. The medication was developed by the

Population Council The Population Council is an international, nonprofit, non-governmental organization. The Council conducts research in biomedicine, social science, and public health and helps build research capacities in developing countries. One-third of its res ...

, a

non-profit A nonprofit organization (NPO) or non-profit organisation, also known as a non-business entity, not-for-profit organization, or nonprofit institution, is a legal entity organized and operated for a collective, public or social benefit, in co ...

non-governmental organization A non-governmental organization (NGO) or non-governmental organisation (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences) is an organization that generally is formed independent from g ...

dedicated to

reproductive health Sexual and reproductive health (SRH) is a field of research, healthcare, and social activism that explores the health of an individual's reproductive system and sexual wellbeing during all stages of their life. The term can also be further de ...

.MENT
– project information from the Population Council

Medical uses

Trestolone is an experimental medication and is not currently approved for medical use. It has been under development for potential use as a male hormonal contraceptive and in androgen replacement therapy for low testosterone levels. The medication has been studied and developed for use as a subcutaneous implant. An

and prodrug of trestolone, trestolone acetate, has also been developed, for use via intramuscular injection.

Side effects

Trestolone may cause

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...

(e.g., decreased sex drive, reduced erectile function) and decreased bone mineral density due to estrogen deficiency.

Pharmacology

Pharmacodynamics

As an AAS, trestolone is an agonist of the androgen receptor (AR), similarly to

s like

and

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includ ...

(DHT). Trestolone is not a substrate for 5α-reductase and hence is not potentiated or inactivated in so-called "androgenic" tissues like the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...

, hair follicles, and

prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...

. As such, it has a high ratio of

anabolic Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking ...

ic activity, similarly to other nandrolone derivatives. Trestolone is a substrate for

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...

and hence produces the

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 ...

7α-methylestradiol as a metabolite. However, trestolone has only weak

ic activity and an amount that would appear to be insufficient for replacement purposes, as evidenced by decreased bone mineral density in men treated with it for hypogonadism. Trestolone also has potent progestogenic activity. Both the androgenic and progestogenic activity of trestolone are thought to be involved in its antigonadotropic activity.

Mechanism of action

Spermatozoa A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromos ...

are produced in the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...

of males in a process called spermatogenesis. In order to render a man infertile, a hormone-based male contraceptive method must stop spermatogenesis by interrupting the release of

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...

s from the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

. Even in low concentrations, trestolone is a potent inhibitor of the release of the gonadotropins,

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...

(LH) and follicle stimulating hormone (FSH). In order for spermatogenesis to occur in the testes, both FSH and testosterone must be present. By inhibiting release of FSH, trestolone creates an endocrine environment in which conditions for spermatogenesis are not ideal. Manufacture of sperm is further impaired by the suppression of LH, which in turn drastically curtails the production of testosterone. Sufficient regular doses of trestolone cause severe

oligozoospermia Terms oligospermia, oligozoospermia, and low sperm count refer to semen with a low concentration of sperm and is a common finding in male infertility. Often semen with a decreased sperm concentration may also show significant abnormalities in sperm ...

or azoospermia, and therefore infertility, in most men. Trestolone-induced infertility has been found to be quickly reversible upon discontinuation. When LH release is inhibited, the amount of testosterone made in the testes declines dramatically. As a result of trestolone's gonadotropin-suppressing qualities, levels of serum testosterone fall sharply in men treated with sufficient amounts of the medication. Testosterone is the main hormone responsible for maintenance of male

secondary sex characteristics Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...

. Normally, an inadequate testosterone level causes undesirable effects such as fatigue, loss of skeletal muscle mass, reduced

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...

, and weight gain. However, the androgenic and anabolic properties of trestolone largely ameliorate this essentially, trestolone replaces testosterone's role as the primary male hormone in the body.

Pharmacokinetics

The pharmacokinetic properties of trestolone, such as poor oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

and short

elimination 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 ...

, make it unsuitable for

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 ...

or long-term intramuscular injection. As such, trestolone must be administered

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

ly via a different and more practical route such as subcutaneous implant,

transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medica ...

, or

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...

. Trestolone acetate, a prodrug of trestolone, can be administered via intramuscular injection.

Chemistry

Trestolone, also known as 7α-methyl-19-nortestosterone (MENT) or as 7α-methylestr-4-en-17β-ol-3-one, is a synthetic

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...

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. ...

nandrolone 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 ...

(19-nortestosterone). It is a modification of nandrolone with a

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 C7α position. Closely related AAS include 7α-methyl-19-norandrostenedione (MENT dione, trestione) (an

androgen prohormone An androgen prohormone, or proandrogen, is a prohormone (or prodrug) of an anabolic-androgenic steroid (AAS). They can be prohormones of testosterone or of synthetic AAS, for example, nandrolone (19-nortestosterone). Dehydroepiandrosterone (DHEA) ...

of trestolone) and dimethandrolone (7α,11β-dimethyl-19-nortestosterone) (the C11β methylated derivative of trestolone), as well as

mibolerone Mibolerone, also known as dimethylnortestosterone (DMNT) and sold under the brand names Cheque Drops and Matenon, is a synthetic compound, synthetic, oral administration, orally active, and extremely potency (pharmacology), potent anabolic–andr ...

(7α,17α-dimethyl-19-nortestosterone) and dimethyltrienolone (7α,17α-dimethyl-δ^9,11-19-nortestosterone). The progestin

tibolone Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated ...

(7α-methyl-17α-ethynyl-δ⁵⁽¹⁰⁾-19-nortestosterone) is also closely related to trestolone.

History

Trestolone was first described in 1963. However, it was not subsequently studied again until 1990. Development of trestolone for potential use in

male hormonal contraception Male contraceptives, also known as male birth control, are methods of preventing pregnancy that solely involve the male physiology. The most common kinds of male contraception include condoms, outercourse, and vasectomy. In domestic animals, cast ...

and androgen replacement therapy was started by 1993, and continued thereafter. No additional development appears to have been conducted since 2013. Trestolone was developed by the

, a

dedicated to

Society and culture

Generic names

''Trestolone'' is the generic name of the drug and its . It is also commonly known as ''7α-methyl-19-nortestosterone'' (''MENT'').

References

{{Progesterone receptor modulators Abandoned drugs Secondary alcohols Androgens and anabolic steroids Antigonadotropins Contraception for males Estranes Experimental methods of birth control Hormonal contraception Ketones Progestogens Synthetic estrogens