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 whe ...

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

anabolic steroid Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor (AR). Anabolism, Anaboli ...

(AAS) and

progestogen Progestogens, also sometimes written progestins, 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 progestoge ...

medication which has been under development for potential use as a form of hormonal birth control for men and in

androgen replacement therapy Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced. It typically involves the administration of tes ...

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 and

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

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

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s Trestolone is an AAS, and hence is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

, 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 male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

. It is also 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. ...

, or a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

progestogen, and hence is an agonist 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 resi ...

, 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 ma ...

. Due to its androgenic and progestogenic activity, trestolone has antigonadotropic effects. These effects result in reversible suppression of sperm production and are responsible for the

contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...

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 re ...

, a

non-profit A nonprofit organization (NPO), also known as a nonbusiness entity, nonprofit institution, not-for-profit organization, or simply a nonprofit, is a non-governmental (private) legal entity organized and operated for a collective, public, or so ...

non-governmental organization A non-governmental organization (NGO) is an independent, typically nonprofit organization that operates outside government control, though it may get a significant percentage of its funding from government or corporate sources. NGOs often focus ...

dedicated to

reproductive health Sexual and reproductive health (SRH) is a field of research, health care, and social activism that explores the health of an individual's Human reproductive system, reproductive system and sexual well-being during all stages of their life. Se ...

.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

for low testosterone levels. The medication has been studied and developed for use as a

subcutaneous implant In medicine, a subcutaneous implant is an implant (medicine), implant that is delivered under the skin into the subcutaneous tissue, subcutaneous tissue (biology), tissue by surgery or injection (medicine), injection and is used to deliver a drug ...

. An androgen ester and

of trestolone, trestolone acetate, has also been developed, for use via

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

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 ...

(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

of the

(AR), similarly to

s like

and

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...

(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 ...

hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction betwee ...

s, and

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

. As such, it has a high ratio of

anabolic Anabolism () is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catab ...

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 man ...

and hence produces the

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

7α-methylestradiol as a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

. 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

ic 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; : spermatozoa; ) is a motile sperm cell (biology), cell produced by male animals relying on internal fertilization. A spermatozoon is a moving form of the ploidy, haploid cell (biology), cell that is ...

are produced in the

testes A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

of males in a process called

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

. In order to render a man infertile, a hormone-based male contraceptive method must stop spermatogenesis by interrupting the release of gonadotropins from the

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

. 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 (G ...

(LH) and

follicle stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, ...

(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 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. Normally, an inadequate testosterone level causes undesirable effects such as

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

, loss of

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

mass, reduced

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

, 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 Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...

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%. H ...

and short

elimination half-life Biological half-life (elimination half-life, pharmacological 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 blood plasma. ...

, make it unsuitable for

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

or long-term

. As such, trestolone must be administered

parenteral In pharmacology and toxicology, a route of administration 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

transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific Dose (biochemistry), dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over ot ...

, or topical gel. Trestolone acetate, a

of trestolone, can be administered via

Chemistry

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

estrane

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

and a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

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

(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 (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

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 compound, synthetic AAS, for example, nandrolone (19-nortestosterone). Dehydroepia ...

of trestolone) and dimethandrolone (7α,11β-dimethyl-19-nortestosterone) (the C11β methylated derivative of trestolone), as well as mibolerone (7α,17α-dimethyl-19-nortestosterone) and dimethyltrienolone (7α,17α-dimethyl-δ^9,11-19-nortestosterone). The

tibolone (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 and

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 Anabolic–androgenic steroids Antigonadotropins Contraception for males Estranes Experimental methods of birth control Hormonal contraception Cyclic ketones Progestogens Synthetic estrogens Hydroxyketones