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 "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects ...

(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 bod ...

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 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 ag ...

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 ...

, 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 sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

. 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. Pro ...

, 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 ...

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 majo ...

. Due to its androgenic and progestogenic activity, dimethandrolone 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. It has no

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

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 The ''Eunice Kennedy Shriver'' National Institute of Child Health and Human Development (NICHD) is one of the National Institutes of Health (NIH) in the United States Department of Health and Human Services. It supports and conducts research aime ...

, an agency in the

United States government The federal government of the United States (U.S. federal government or U.S. government) is the national government of the United States, a federal republic located primarily in North America, composed of 50 states, a city within a feder ...

. An

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

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 dru ...

of dimethandrolone,

dimethandrolone undecanoate Dimethandrolone undecanoate (DMAU), also known by its developmental code name CDB-4521, is an experimental androgen/anabolic steroid (AAS) and progestogen medication which is under development as a potential birth control pill for men. It is tak ...

(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. The pill contains two important hormones: progesti ...

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 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 or SARMs are a class of androgen receptor ligands that maintain some of the desirable effects of androgens, such as preventing osteoporosis and muscle loss while reducing risks of developing prostate cance ...

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

of the

(AR). Unlike

and various other AAS, dimethandrolone is not

metabolized Metabolism (, from el, μεταβολή ''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 cell ...

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 o ...

. 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 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 both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and phys ...

. 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, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

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, inability to urinate, or loss o ...

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 su ...

, pattern scalp hair loss, and

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

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 many ...

, and for this reason, is not converted into the corresponding

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

A- ring

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

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 spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

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

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 seen ...

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 is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

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 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 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 ...

and a non-17α-alkylated

nandrolone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

(19-nortestosterone).

Esters

Aside from the C17β

undecanoate Undecylic acid (systematically named undecanoic acid) is a carboxylic acid with chemical formula C H3(CH2)9C OOH. It is often used as an antifungal agent, to treat ringworm and athlete's foot, for example. Like decanoic acid, it has a distinct ...

of dimethandrolone, DMAU (CDB-4521), a few other esters, such as

dimethandrolone buciclate Dimethandrolone buciclate (developmental code name CDB-4386A), or dimethandrolone bucyclate, also known as 7α,11β-dimethyl-19-nortestosterone 17β-buciclate, is a synthetic anabolic–androgenic steroid (AAS) and a derivative of nandrolone (19- ...

(CDB-4386A) and dimethandrolone dodecylcarbonate (CDB-4730), have also been developed.

Analogues

Other AAS that are closely related to dimethandrolone (besides nandrolone) include

trestolone Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and in ...

(also known as 7α-methyl-19-nortestosterone (MENT)) and

11β-methyl-19-nortestosterone 11β-Methyl-19-nortestosterone (11β-MNT) is a synthetic and orally active anabolic–androgenic steroid (AAS) and a derivative of nandrolone (19-nortestosterone) which was developed by the Contraceptive Development Branch (CDB) of the National I ...

(11β-MNT) and their respective C17β esters

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–andro ...

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 enabling disclosure of the invention."A ...

for dimethandrolone was filed in 1997 and was granted in 1999. Subsequently, a patent for DMAU and

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

, one of the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...

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 U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is ...

References

{{Progesterone receptor modulators Cyclopentanols Androgens and anabolic steroids Contraception for males Estranes Experimental drugs Experimental methods of birth control Enones Progestogens