Normethandrone, also known as methylestrenolone or methylnortestosterone and sold under the brand name Metalutin among others, is 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. ...

and

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) medication which is used in combination with an

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 ...

in the treatment of

amenorrhea Amenorrhea or amenorrhoea is the absence of a menstrual period in a female organism who has reached reproductive age. Physiological states of amenorrhoea are most commonly seen during pregnancy and lactation (breastfeeding). In humans, it is wher ...

and

menopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s 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 ...

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 normethandrone 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 a medical term commonly used in three medical a ...

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

, increased hair growth, voice changes, and increased

sexual desire Sexual desire is an emotion and motivational state characterized by an interest in sexual objects or activities, or by a drive to seek out sexual objects or to engage in sexual activities. It is an aspect of sexuality, which varies significantly ...

. It can also cause

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground glas ...

. Normethandrone is a progestin, 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 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 ...

, 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

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 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 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 ...

. It is also a

AAS and hence is an

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

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 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). It has some

ic activity as well and no other important

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

activity. Normethandrone was introduced for medical use by 1957. It is available only in a few countries, including

Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...

Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...

, and

Venezuela Venezuela, officially the Bolivarian Republic of Venezuela, is a country on the northern coast of South America, consisting of a continental landmass and many Federal Dependencies of Venezuela, islands and islets in the Caribbean Sea. It com ...

, and is available only in combination with methylestradiol or

estradiol valerate Estradiol valerate (EV), sold for use oral administration, by mouth under the brand name Progynova and for use by injection (medicine), injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen (medication), es ...

Medical uses

Normethandrone is used in combination with an

, either methylestradiol or

, in the treatment of

and

s in women. It has also been used to treat

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...

in women. Normethandrone has been used successfully to inhibit

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 ...

in men with sexual deviance. Although normethandrone can be classified as an AAS and has strong such effects at sufficiently high doses, it is not typically used as such and is instead used medically only as a progestin. This is because it is so highly progestogenic in comparison.

Available forms

Normethandrone is marketed in combination with methylestradiol in the form of

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

tablets containing 5 mg normethandrone and 0.3 mg methylestradiol.

Side effects

Normethandrone has been associated with

s of

and

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

Pharmacology

Pharmacodynamics

Normethandrone shows high

ic activity. With

sublingual administration Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue. Many drugs are absorbed through sublingual a ...

in women, it has at least 150 times the

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

of sublingual

and 50 times the potency of sublingual

ethisterone Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecologica ...

. It also has 10 times the potency of injected progesterone via this route. The oral potency of normethandrone in terms of endometrial transformation is similar to that of

norethisterone Norethisterone, also known as norethindrone and sold under the brand name Norlutin among others, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medicatio ...

. It has been reported to inhibit

ovulation Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

in women. In addition to its progestogenic activity, normethandrone has

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 ...

and

ic activity and can produce effects associated with this activity. It has a high ratio of anabolic to androgenic activity. The anabolic

of normethandrone is similar to that of

norethandrolone Norethandrolone, sold under the brand names Nilevar and Pronabol among others, is an androgen and anabolic steroid (AAS) medication which has been used to promote muscle growth and to treat severe burns, physical trauma, and aplastic anemia but ...

and is much greater than that of

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 ...

metandienone Metandienone, also known as methandienone or methandrostenolone and sold under the brand name Dianabol (D-Bol) among others, is an androgen and anabolic steroid (AAS) medication which is mostly no longer prescribed. It is also used non-medically ...

. It is also greater than that of ethylestrenol. Normethandrone has been found to increase

nitrogen retention In human physiology, nitrogen balance is the net difference between bodily nitrogen intake (ingestion) and loss (excretion). It can be represented as the following: \mbox = - Nitrogen is a fundamental chemical component of amino acids, the mole ...

, a measure of anabolic effect, at a dosage of 30 mg/day. Analogously to nandrolone and

, 5α-dihydronormethandrone, the 5α-reduced

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 ...

of normethandrone, shows reduced

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

relative to normethandrone. Its affinity for the androgen receptor is specifically about 33 to 60% of that of normethandrone. Normethandrone has

ic activity via

aromatization Aromatization is a chemical reaction in which an aromaticity, aromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion of cycl ...

into methylestradiol.

Pharmacokinetics

Normethandrone is

metabolized 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 ...

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 ...

into methylestradiol in small quantities, similarly to

methyltestosterone Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low ...

and

. The metabolites of normethandrone have not been well-studied, but 5α-dihydronormethandrone is a likely metabolite formed by 5α-reductase. The

pharmacokinetics 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 su ...

of normethandrone have been reviewed.

Chemistry

Normethandrone, also known as 17α-methyl-19-nortestosterone or as 17α-methylestr-4-en-17β-ol-3-one, is a

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, for i ...

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 17α-alkylated

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 ...

(19-nortestosterone; 19-NT). It is specifically the 17α-

methyl 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 as ...

derivative of nandrolone as well as the 17α-methyl variant of

(17α-ethyl-19-NT) and

(17α-ethynyl-19-NT).

Synthesis

Chemical syntheses of normethandrone have been published.

History

Normethandrone has been marketed for medical use since 1957. The combination of normethandrone and methylestradiol was introduced by at least 1966.

Society and culture

Generic names

Normethandrone has not been assigned an or other formal name designations. It is also known as ''methylestrenolone'', ''methylnortestosterone'', ''normethandrolone'', and ''normethisterone''.

Brand names

Brand names of normethandrone include Batynid, Ginecosid, Ginecoside, Gynomin, Lutenin, Matronal, Mediol, Metalutin, Methalutin, Orgasteron, Orosteron, and Renodiol.

Availability

Normethandrone is marketed in

, and

in combination with methylestradiol or

References

{{Navboxes , title =

Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Estrogen receptor modulators {{Progesterone receptor modulators 1-Methylcyclopentanols Anabolic–androgenic steroids Estranes Hepatotoxins Enones Progestogens Synthetic estrogens