Dimethandrolone (DMA), also known by its developmental code name CDB-1321, is an experimental

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 is under investigation for potential clinical use. Dimethandrolone 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, dimethandrolone has antigonadotropic effects. It has no

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 activity. Dimethandrolone was first described in 1997. It was developed by the Contraceptive Development Branch of the National Institute of Child Health and Human Development, an agency in the

United States government The Federal Government of the United States of America (U.S. federal government or U.S. government) is the Federation#Federal governments, national government of the United States. The U.S. federal government is composed of three distinct ...

. An

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

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 dimethandrolone, dimethandrolone undecanoate (DMAU) (CDB-4521), is under development for potential use as a

birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. It is the oral form of combined hormonal contra ...

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 men.

Side effects

Pharmacology

Pharmacodynamics

Dimethandrolone is an AAS, though it has also been described as a

selective androgen receptor modulator Selective androgen receptor modulators (SARMs) are a class of drugs that tissue selectivity, selectively activate the androgen receptor in specific tissue (biology), tissues, promoting muscle and bone growth while having less effect on male re ...

(SARM). As an AAS, it is a potent

of the

(AR). Unlike

and various other AAS, dimethandrolone is not

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 ...

by 5α-reductase. In addition, the 5α-reduced derivative of dimethandrolone, 5α-dihydrodimethandrolone (5α-DHDMA), possesses only 30 to 40% of the potency of dimethandrolone as an agonist of the AR, indicating that dimethandrolone does not require potentiation by 5α-reductase for its activity as an AAS and that even if it were 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 (aquatic environment), the earthy material that exi ...

for 5α-reductase, it would not be potentiated in 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 ...

and

prostate 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, dimethandrolone and ester prodrugs of it like DMAU are thought to have a reduced risk 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 ...

s and conditions such as

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, urinary retention, inability t ...

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, ...

, pattern scalp hair loss, and

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, ...

relative to testosterone and certain other AAS. Dimethandrolone is not 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 for this reason, is not converted into the corresponding

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

A-

ring (The) Ring(s) may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell Arts, entertainment, and media Film and TV * ''The Ring'' (franchise), 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 ...

7α,11β-dimethylestradiol, a potent

. As such, dimethandrolone is not estrogenic. This is in contrast to nandrolone, which, although its rate of aromatization into the estrogen

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

is reduced relative to that of testosterone, is still converted to a significant extent. Similarly to nandrolone and other 19-nortestosterone derivatives, dimethandrolone is a potent progestogen in addition to AAS. This property may serve to augment its antigonadotropic activity, which in turn may improve its effectiveness as an antispermatogenic agent and male contraceptive. This is salient and potentially beneficial as male contraceptives based on androgens alone have failed to produce satisfactory

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 see ...

in around one-third of men. Dimethandrolone has shown minimal potential for

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 ...

in animal studies, which is in accordance with the fact that it is not a 17α-alkylated AAS.

Chemistry

Dimethandrolone, also known as 7α,11β-dimethyl-19-nortestosterone or as 7α,11β-dimethylestr-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 non-17α-alkylated

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).

Esters

Aside from the C17β undecanoate

of dimethandrolone, DMAU (CDB-4521), a few other esters, such as dimethandrolone buciclate (CDB-4386A) and dimethandrolone dodecylcarbonate (CDB-4730), have also been developed.

Analogues

Other AAS that are closely related to dimethandrolone (besides nandrolone) include trestolone (also known as 7α-methyl-19-nortestosterone (MENT)) and 11β-methyl-19-nortestosterone (11β-MNT) and their respective C17β esters trestolone acetate and 11β-MNT dodecylcarbonate (11β-MNTDC).

History

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

for dimethandrolone was filed in 1997 and was granted in 1999. Subsequently, a patent for DMAU and dimethandrolone buciclate was filed in 2002 and was granted to the

in 2003. Dimethandrolone was developed under the code name CDB-1321 by the Contraceptive Development Branch of the National Institute of Child Health and Human Development, one of the

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

in the

United States Department of Health and Human Services The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the US federal government created to protect the health of the US people and providing essential human services. Its motto is ...

References

{{Progesterone receptor modulators Cyclopentanols Anabolic–androgenic steroids Contraception for males Estranes Experimental drugs Experimental methods of birth control Enones Progestogens