Dimethandrolone undecanoate (DMAU), also known by its developmental code name CDB-4521, is an

experimental An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs whe ...

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 development as a potential

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. 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 ...

, but can also be given by injection into muscle.

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 DMAU include mild

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs ...

and mild decreases in levels of HDL cholesterol. It may also cause low estrogen levels and associated

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 such as reduced sexual function and decreased bone mineral density. DMAU 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, DMAU has antigonadotropic effects. These effects result in reversible suppression of sperm production and are responsible for the

contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...

effects of DMAU in men. The medication 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. DMAU is a

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. DMAU was first described in 2002. 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 ...

Medical uses

DMAU is an experimental medication and is not currently approved for medical use. It is under development for use as a potential male hormonal contraceptive, specifically as a

for men. The medication has been found to profoundly and rapidly reversibly suppress testicular

production in men when taken by mouth once per day for a month. The circulating levels of testosterone achieved with oral DMAU were equivalent to those seen on average with surgical castration (13.4 ng/dL for DMAU, 15 ng/dL for castration). Following discontinuation of DMAU, testosterone levels began to recover within days and reached normal levels within a month. Testicular testosterone production is essential for

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...

and

fertility Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...

in men. Suppression of spermatogenesis and the actual

effects of DMAU in men have not yet been clinically assessed, but future studies are being planned to confirm the contraceptive effectiveness of the medication. In addition to male contraception, there has also been interest in the potential use of DMAU 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 low testosterone levels in men.

Side effects

In a clinical study, DMAU was found to be well tolerated when administered to men for a month.

s included mild

(between 3 and 9 pounds) and mild decreases in levels of HDL cholesterol. No major or serious

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 were observed. Because DMAU is not 5α-reduced, in contrast to

, it may have less risk of

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 h ...

Low estrogen levels

Because DMAU suppresses testosterone levels and by extension

levels in men but has no estrogenic activity of its own, it may pose a risk of

s of low estrogen levels such as

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction ...

(e.g., decreased sex drive, reduced erectile function) and

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

. Reduced sexual function and decreased

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to opti ...

have been observed with the closely related medication trestolone, which has low estrogenicity similarly to DMAU.

Liver toxicity

Unlike testosterone but similarly to 17α-alkyated AAS like

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 ...

(17α-methyltestosterone), DMAU has been found to produce some effects indicative of potential

liver toxicity 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 ...

when it was administered orally to animals. However, the effects were significantly less than those of methyltestosterone. Both DMAU and trestolone (7α-methyl-19-nortestosterone) showed potential signs of liver toxicity whereas

11β-methyl-19-nortestosterone 17β-dodecylcarbonate 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 ...

showed few to no such effects, suggesting that the C7α methyl group of DMAU and trestolone could be an important contributing factor to their liver toxicity potential. In any case, however, in a clinical study, DMAU was found to be safe in terms of

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

function when administered to men for a month.

Pharmacology

Pharmacodynamics

DMAU is an androgen ester, specifically 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 ...

of dimethandrolone, and acts as a

of dimethandrolone in the body. As such, it is an AAS, or an

of the

, and is also a

, or an agonist of the

. Due to these activities, DMAU has potent antigonadotropic effects, and is able to powerfully suppress

levels. This results in suppression of

and is responsible for its

hormonal contraceptive Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...

effects in men. The medication is not aromatized and has no

ic activity. In addition, it is not 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 and hence is not potentiated or inactivated in tissues that express 5α-reductase like

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 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 betwee ...

s, and the

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 ...

. As such, DMAU may have a reduced risk of

s and

androgen-dependent condition An androgen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of androgenic activity in the body. Known androgen-dependent conditions include acne ...

s such as

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, ...

, pattern scalp hair loss, body hair growth,

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 ...

, and

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, ...

relative to testosterone and certain other AAS.

Pharmacokinetics

pharmacokinetic 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 subs ...

study of DMAU in men found that only 2 to 3% of the drug was

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...

into dimethandrolone when it was administered orally in the form of powder in capsules. In contrast, hydrolysis of

testosterone undecanoate Testosterone undecanoate, sold under the brand name Nebido among others, is an androgen and anabolic steroid (AAS) medication that is used mainly in the treatment of low testosterone levels in men, It is taken by mouth or given by injection ...

into

is rapid and appears to be complete. The difference in conversion efficiency with DMAU relative to testosterone undecanoate is attributed to

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivi ...

in DMAU caused by its additional C7α and C11β

methyl group 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 a ...

s. Although the hydrolysis of DMAU into dimethandrolone was very limited, it was still sufficient to produce dose-dependent biological effects at the dosages assessed, including reversible suppression of

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

and

levels. A subsequent pharmacokinetic study found that the conversion of DMAU into dimethandrolone was improved when the drug was delivered orally in

castor oil Castor oil is a vegetable oil pressed from castor beans, the seeds of the plant ''Ricinus communis''. The seeds are 40 to 60 percent oil. It is a colourless or pale yellow liquid with a distinct taste and odor. Its boiling point is and its den ...

/ benzyl benzoate or a self-emulsifying drug delivery system contained in capsules as opposed to powder in capsules.

Chemistry

Dimethandrolone undecanoate, also known as 7α,11β-dimethyl-19-nortestosterone 17β-undecanoate or as 7α,11β-dimethylestr-4-en-17β-ol-3-one 17β-undecanoate, 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 non- 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 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 phenylpropionat ...

. It is the C17β undecanoate (undecylate)

of dimethandrolone (7α,11β-dimethyl-19-nortestosterone). Other esters of dimethandrolone, such as dimethandrolone buciclate (CDB-4386A) and dimethandrolone dodecylcarbonate (CDB-4730), have also been developed. Analogous esters of closely related AAS include trestolone acetate (7α-methyl-19-nortestosterone 17β-acetate) and

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. DMAU was developed under the code name CDB-4521 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 ...

. The first clinical studies of DMAU in men were published in 2014 (single-dose), 2015 (single-dose), and 2018 (continuous for one month).

References

{{Progesterone receptor modulators Androgen esters Anabolic–androgenic steroids Antigonadotropins Contraception for males Estranes Experimental drugs Experimental methods of birth control Enones Progestogen esters Progestogens Undecanoate esters