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

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) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low doses as a component of menopausal hormone therapy for menopausal

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 like hot flashes,

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

, and low sexual desire in women, and to treat breast cancer in women. It is taken by mouth or held in the cheek or under the tongue. Side effects of methyltestosterone include

s of

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 ...

like acne, increased hair growth, voice changes, and increased sexual desire. It can also cause estrogenic effects like fluid retention, breast tenderness, and breast enlargement in men and liver damage. The drug is 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 ...

androgen and anabolic steroid 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 ...

(AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has moderate androgenic 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 testosterone 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 delayed puberty, hypogonadism, cryptorchidism, and

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

in males, and in low doses to treat

menopausal symptom Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...

s (specifically for

, hot flashes, and to increase libido and energy), postpartum

breast pain 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 ...

and engorgement, and breast cancer in women. It is specifically approved in the United States for the treatment of hypogonadism and delayed puberty in males and the treatment of advanced inoperable breast cancer in females.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/083976s031lbl.pdf It was also approved in low doses in combination with esterified estrogens for the treatment of moderate to severe vasomotor

s 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.http://www.micromedexsolutions.com/micromedex2 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

athlete An athlete (also sportsman or sportswoman) is a person who competes in one or more sports that involve physical strength, speed, or endurance. Athletes may be professionals or amateurs. Most professional athletes have particularly well-devel ...

s, 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 Conjugated estrogens/methyltestosterone (CEEs/MT), sold under the brand name Premarin with Methyltestosterone, is a combination of conjugated estrogens (CEEs), an estrogen, and methyltestosterone (MT), an androgen and anabolic steroid (AAR), whic ...

(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 The epiphyseal plate (or epiphysial plate, physis, or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, with ...

and thereby produce short stature 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 cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

, 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 androgenic side effects like oily skin, acne, seborrhea, increased facial/

body hair Body hair, or androgenic hair, is the terminal hair that develops on the human body during and after puberty. It is differentiated from the head hair and less visible vellus hair, which is much finer and lighter in color. The growth of androge ...

growth Growth may refer to: Biology * Auxology, the study of all aspects of human physical growth * Bacterial growth * Cell growth * Growth hormone, a peptide hormone that stimulates growth * Human development (biology) * Plant growth * Secondary growth ...

scalp hair loss Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

, increased aggressiveness and sex drive, and

spontaneous erection An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, vascular, a ...

s, as well as estrogenic side effects like breast tenderness, gynecomastia, fluid retention, and

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

. 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 Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...

. 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 Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metab ...

, peliosis hepatis, hepatomas, and

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

, with extended use. It can also have adverse effects on the

cardiovascular system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

. 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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

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

. Violent and even homicidal behavior, hypomania/

mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wit ...

, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS.

Interactions

Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and

5α-reductase inhibitor 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 ...

s can be used to prevent its potentiation in so-called "androgenic" tissues and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects. Antiandrogens like bicalutamide and cyproterone acetate can block both the anabolic and androgenic effects of AAS like methyltestosterone.

Pharmacology

Pharmacodynamics

As an AAS, methyltestosterone is an

of the

(AR), similarly to androgens like testosterone and dihydrotestosterone (DHT). It is 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 ...

like testosterone, and so is potentiated analogously 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 via transformation into the more potent AR agonist

mestanolone Mestanolone, also known as methylandrostanolone and sold under the brand names Androstalone and Ermalone among others, is an androgen and anabolic steroid (AAS) medication which is mostly no longer used. It is still available for use in Japan ...

(17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to androgenic 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 estrogen methylestradiol (17α-methylestradiol), methyltestosterone has relatively high estrogenicity and hence potential for estrogenic side effects such as gynecomastia and fluid retention. The drug possesses negligible

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. ...

ic 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 Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

relative to testosterone. This difference is due to the C17α methyl group, which results in steric hindrance and prevents metabolism. 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 digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

. 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 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 as conjugates and other

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 ...

s, and 6% in

feces Feces ( or faeces), known colloquially and in slang as poo and poop, 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 large intestine. Feces contain a relati ...

Chemistry

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

, 17α-alkylated androstane

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 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 Ethyltestosterone, or 17α-ethyltestosterone, also known as 17α-ethylandrost-4-en-17β-ol-3-one or 17α-pregn-4-en-17-ol-3-one, is a synthetic, orally active anabolic–androgenic steroid (AAS) of the 17α-alkylated group related to methylte ...

(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

. 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 French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...

name and ''metiltestosterone'' is its and Italian name. The generic name of the drug is ''methyltestosterone'' in Latin, ''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 United States. The others are testosterone, 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 United States under the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

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

References

External links

Methyltestosterone - William Llewellyn's Anabolic.org
{{Estrogen receptor modulators Androgens and anabolic steroids Androstanes Aphrodisiacs Bodybuilding Doping in sport Enones Erectile dysfunction drugs Female sexual dysfunction drugs Hepatotoxins Hormonal antineoplastic drugs Synthetic estrogens Tertiary alcohols Testosterone World Anti-Doping Agency prohibited substances