Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an

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 ...

and

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) medication which is used in the treatment of low testosterone levels in men,

delayed puberty Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormone, hormonal signs that puberty has begun. In the United States ...

in boys, at low doses as a component of menopausal hormone therapy for menopausal symptoms like hot flashes, osteoporosis, and low sexual desire in women, and to treat breast cancer in women. It is taken

by mouth 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 held in the cheek or under the tongue.

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 of methyltestosterone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire. It can also cause

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 ...

ic effects like fluid retention, breast tenderness, and breast enlargement in men and liver damage. The drug is a synthetic androgen and anabolic steroid 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 ...

(AR), 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 ...

and dihydrotestosterone (DHT). It has moderate

ic effects and moderate anabolic effects, which make it useful for producing masculinization. Methyltestosterone was discovered in 1935 and was introduced for medical use in 1936. It was made shortly after the discovery of

and was one of the first synthetic AAS to be developed. In addition to its medical use, methyltestosterone is used to improve physique and performance, although it is not as commonly used as other AAS for such purposes due to its androgenic effects, estrogenic effects, and risk of liver damage. The drug is a controlled substance in many countries and so non-medical use is generally illicit.

Uses

Medical

Methyltestosterone is or has been used in the treatment of

, hypogonadism, cryptorchidism, and

erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and

energy Energy () is the physical quantity, quantitative physical property, property that is transferred to a physical body, body or to a physical system, recognizable in the performance of Work (thermodynamics), work and in the form of heat and l ...

), postpartum breast pain and engorgement, and breast cancer in women. It is specifically approved in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

for the treatment of hypogonadism and delayed puberty in males and the treatment of advanced inoperable breast cancer in females. It was also approved in low doses in combination with esterified estrogens for the treatment of moderate to severe vasomotor symptoms associated with menopause in women in the United States, but this formulation was discontinued and hence is no longer used. Methyltestosterone is less effective in inducing masculinization than testosterone, but is useful for maintaining established masculinization in adults. The dosages of methyltestosterone used are 10 to 50 mg/day in men for common medical uses like hypogonadism and delayed puberty as well as physique- and performance-enhancing purposes and 2.5 mg/day in women for menopausal symptoms. Higher dosages of 50 to 200 mg/day have been used to treat women with inoperable breast cancer that has failed to respond to other therapies, although such dosages are associated with severe irreversible virilization.

Non-medical

Methyltestosterone is used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters, although it is not commonly used relative to other AAS for such purposes.

Available forms

Methyltestosterone is typically used as an oral medication. It is also available under the brand names Metandren and Oreton Methyl for use specifically by buccal or sublingual administration. Methyltestosterone is available in the form of 2, 5, 10, and 25 mg oral tablets. It was also available in combination with estrogens as esterified estrogens/methyltestosterone (0.625 mg/1.25 mg, 1.25 mg/2.5 mg) and conjugated estrogens/methyltestosterone (0.625 mg/5.0 mg, 1.25 mg/10 mg).

Contraindications

Methyltestosterone should be used with caution in women and children, as it can cause irreversible virilization. Due to its estrogenicity, methyltestosterone can also accelerate epiphyseal closure and thereby produce

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...

in children and adolescents. It can worsen symptoms in men with benign prostatic hyperplasia. Methyltestosterone should not be used in men with

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

, as androgens can accelerate tumor progression. The drug should be used with caution in patients with pre-existing hepatotoxicity, due to its own potential for hepatotoxicity.

Side effects

Adverse effects of methyltestosterone include

ic side effects like oily skin, acne, seborrhea, increased facial/ body hair growth, scalp hair loss, increased aggressiveness and sex drive, and spontaneous erections, as well as

ic side effects like breast tenderness, gynecomastia, fluid retention, and edema. In women, methyltestosterone can cause partially irreversible virilization, for instance voice deepening, hirsutism, clitoromegaly, breast atrophy, and muscle hypertrophy, as well as menstrual disturbances and reversible

infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...

. In men, the drug may also cause hypogonadism, testicular atrophy, and reversible infertility at sufficiently high dosages. Methyltestosterone can sometimes cause hepatotoxicity, for instance elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma, with extended use. It can also have adverse effects on the cardiovascular system. AAS like methyltestosterone stimulate erythropoiesis ( red blood cell production) and increase hematocrit levels and at high dosages can cause polycythemia (overproduction of red blood cells), which can greatly increase the risk of thrombic events such as embolism and

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and

Violent Violence is characterized as the use of physical force by humans to cause harm to other living beings, or property, such as pain, injury, disablement, death, damage and destruction. The World Health Organization (WHO) defines violence a ...

and even homicidal behavior,

hypomania Hypomania (literally "under mania" or "less than mania") is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome characterized essentially by an apparently non-contextual elevation of Mood (psychology), mood (i.e., euphoria) th ...

mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...

, depression, suicidality, delusions, and

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

have all been associated with very high dosages of AAS.

Interactions

Aromatase inhibitors can be used to reduce or prevent the

ic effects of methyltestosterone and 5α-reductase inhibitors can be used to reduce its virilizing effects and thereby improve its ratio of anabolic to

ic activity and reduce its rate of androgenic

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 ...

Pharmacology

Pharmacodynamics

As an AAS, methyltestosterone is an

of the

(AR), similarly to

s like

and dihydrotestosterone (DHT). It is a substrate for 5α-reductase like testosterone, and so is potentiated analogously 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 follicles, 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 ...

via transformation into the more potent AR agonist mestanolone (17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to

ic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS. Due to efficient aromatization into the potent and metabolism-resistant

methylestradiol (17α-methylestradiol), methyltestosterone has relatively high

icity and hence potential for

s such as gynecomastia and fluid retention. The drug possesses negligible progestogenic activity. Due to its combined disadvantages of a relatively poor ratio of anabolic to androgenic activity, unusually high estrogenicity, and the potential for hepatotoxicity (as with other 17α-alkylated AAS), methyltestosterone has not been used as commonly as many other AAS either in medicine or for physique- or performance-enhancing purposes.

Pharmacokinetics

Absorption

Methyltestosterone has dramatically improved oral bioavailability and metabolic stability relative to testosterone. This difference is due to the C17α methyl group, which results in steric hindrance and prevents

metabolism Metabolism (, from ''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 cellular processes; the co ...

. The oral bioavailability of methyltestosterone is about 70%, and it is well-absorbed from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. Methyltestosterone can also be taken buccally or sublingually. Although effective orally, methyltestosterone is more effective by these non-oral routes, which are said to approximately double its bioavailability and require half the oral dosage. Circulating levels of methyltestosterone with administration of 1.25 to 2.5 mg/day oral methyltestosterone in women are in the range of 20 to 30 ng/dL. For comparison to testosterone, methyltestosterone is at least as potent as an AAS. However, due to the large decrease in sex hormone-binding globulin (SHBG) levels and hence increase in free unbound testosterone caused by methyltestosterone, androgenic effects may be greater than reflected merely by methyltestosterone levels.

Distribution

Methyltestosterone is highly protein-bound, by approximately 98%. The medication has low but significant affinity for human serum sex hormone-binding globulin (SHBG), about 25% of that of testosterone and 5% of that of DHT.

Metabolism

The

biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

of methyltestosterone is approximately 3 hours (range 2.5–3.5 hours). The duration of action of methyltestosterone is said to be 1 to 3 days, and is described as relatively short among AAS.

Excretion

Methyltestosterone is excreted 90% in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

as conjugates and other metabolites, and 6% in

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

Chemistry

Methyltestosterone, also known as 17α-methyltestosterone or as 17α-methylandrost-4-en-17β-ol-3-one, is a synthetic, 17α-alkylated androstane

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 ...

of testosterone differing from it only in the presence of a methyl group at the C17α position. Close synthetic relatives of methyltestosterone include metandienone (17α-methyl-δ¹-testosterone) and fluoxymesterone (9α-fluoro-11β-hydroxy-17α-methyltestosterone).

Derivatives

Methyltestosterone and ethyltestosterone (17α-ethyltestosterone) are the parent structures of all 17α-alkylated AAS. Major 17α-alkylated AAS include the testosterone derivatives fluoxymesterone, metandienone (methandrostenolone), and methyltestosterone and the DHT derivatives oxandrolone, oxymetholone, and stanozolol.

Synthesis

A chemical synthesis of methyltestosterone from dehydroepiandrosterone (DHEA) with methandriol as an intermediate proceeds as follows: Methyltestosterone synthesis

History

Methyltestosterone was first synthesized in 1935 along with methandriol and mestanolone. It was the second synthetic AAS to be developed, following mesterolone (1α-methyl-DHT) in 1934, and was the first 17α-alkylated AAS to be synthesized. The drug was introduced for medical use in 1936.

Society and culture

Generic names

''Methyltestosterone'' is the , , , , and of the drug and its generic name in English and Japanese, while ''méthyltestostérone'' is its and French name and ''metiltestosterone'' is its and Italian name. The generic name of the drug is ''methyltestosterone'' in

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

, ''methyltestosteron'' in German, and ''metiltestosterona'' in Spanish. Methyltestosterone is also known by its former developmental code name ''NSC-9701''.

Brand names

Brand names under which methyltestosterone is or has been marketed for medical use include Afro, Agovirin, Android, Androral, Mesteron, Metandren, Methitest, Methyltestosterone, Methyl Testosterone, Oraviron, Oreton, Oreton Methyl, Testormon, Testovis, Testred, and Virilon, among others.

With an estrogen

Methyltestosterone is available at a low-dose in combination with esterified estrogens for the treatment of menopausal symptoms like hot flashes in women under the brand names Covaryx, Essian, Estratest, Menogen, and Syntest.

Availability

United States

Although it is not commonly used, methyltestosterone is one of the few AAS that remains available for medical use in the

. The others are

, testosterone cypionate, testosterone enanthate, testosterone undecanoate, oxandrolone, oxymetholone, and fluoxymesterone.

Other countries

Methyltestosterone has also been marketed in many other countries throughout the world.

Legal status

Methyltestosterone, along with other AAS, is a schedule III controlled substance in the

under the Controlled Substances Act and a schedule IV controlled substance in

Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...

under the Controlled Drugs and Substances Act.

References

External links

* {{Estrogen receptor modulators Anabolic–androgenic steroids Androstanes Aphrodisiacs Doping in sport Enones Erectile dysfunction drugs Female sexual dysfunction drugs Hepatotoxins Hormonal antineoplastic drugs Synthetic estrogens Tertiary alcohols Testosterone