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

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 ...

(AAS) and

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. ...

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) or hormone replacement therapy (HRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced exogenously ...

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 Trestolone acetate (; developmental code names CDB-903, NSC-69948, U-15614; also known as 7α-methyl-19-nortestosterone 17β-acetate (MENT acetate) and 7α-methylestr-4-en-17β-ol-3-one 17β-acetate) is a synthetic and injected anabolic–andr ...

, an androgen ester and

prodrug A prodrug is a 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 used to improve how the drug ...

of trestolone, the medication can also be 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 ...

. Side effects of trestolone include low estrogen levels and associated

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s such as reduced sexual function and decreased bone mineral density among others. Trestolone is an AAS, 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

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

, 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 ...

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 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 ...

. Due to its androgenic and progestogenic activity, trestolone has

antigonadotropic An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituita ...

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 unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

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, a non-profit, non-governmental organization dedicated to reproductive health.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 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, cas ...

and in

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

subcutaneous implant In medicine, a subcutaneous implant, or subcutaneous pellet, is an implant that is delivered under the skin into the subcutaneous tissue by surgery or injection and is used to deliver a drug for a long period of time. Examples of drugs that can ...

. An androgen ester and

of trestolone,

, has also been developed, for use via

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 ...

Side effects

Trestolone may cause sexual dysfunction (e.g., decreased sex drive, reduced erectile function) and decreased

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...

due to

estrogen deficiency Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiov ...

Pharmacology

Pharmacodynamics

As an AAS, trestolone is an

of the

(AR), similarly to androgens like testosterone and dihydrotestosterone (DHT). Trestolone is not a

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

for

5α-reductase 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...

and hence is not potentiated or inactivated in so-called "androgenic" tissues like the skin,

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 between h ...

s, and prostate gland. As such, it has a high ratio of anabolic to androgenic activity, similarly to other nandrolone derivatives. Trestolone is a substrate for aromatase and hence produces the estrogen 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 estrogenic activity and an amount that would appear to be insufficient for replacement purposes, as evidenced by decreased

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

activity.

Mechanism of action

Spermatozoa are produced in the testes 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 testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...

. 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. Even in low concentrations, trestolone is a potent inhibitor of the release of the gonadotropins, luteinizing hormone (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, an ...

(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 Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen ...

, 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 describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, loss of

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

mass, reduced libido, 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 determining the fate of substances administered ...

properties of trestolone, such as poor oral bioavailability and short elimination half-life, make it unsuitable for oral administration or long-term

. As such, trestolone must be administered parenterally via a different and more practical route such as

, transdermal patch, or topical gel.

Trestolone acetate Trestolone acetate (; developmental code names CDB-903, NSC-69948, U-15614; also known as 7α-methyl-19-nortestosterone 17β-acetate (MENT acetate) and 7α-methylestr-4-en-17β-ol-3-one 17β-acetate) is a synthetic and injected anabolic–andr ...

, 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 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 of nandrolone (19-nortestosterone). It is a modification of nandrolone with a methyl group at the C7α position. Closely related AAS include 7α-methyl-19-norandrostenedione (MENT dione, trestione) (an androgen prohormone of trestolone) and

dimethandrolone Dimethandrolone (DMA), also known by its developmental code name CDB-1321, is an experimental androgen/anabolic steroid (AAS) and progestogen medication which is under investigation for potential clinical use. Dimethandrolone is an AAS, and he ...

(7α,11β-dimethyl-19-nortestosterone) (the C11β methylated derivative of trestolone), as well as mibolerone (7α,17α-dimethyl-19-nortestosterone) and

dimethyltrienolone Dimethyltrienolone (developmental code name RU-2420) is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and 17α-alkylated 19-nortestosterone (nandrolone) derivative which was never marketed for medical ...

(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 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, ca ...

and

was started by 1993, and continued thereafter. No additional development appears to have been conducted since 2013. Trestolone was developed by the Population Council, a non-profit, non-governmental organization dedicated to reproductive health..

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