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

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) 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 body. ...

medication which is under development as a potential birth control pill for men. It is taken by mouth, but can also be given by

injection into muscle Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...

. Side effects of DMAU include mild weight gain and mild decreases in levels of HDL cholesterol. It may also cause low estrogen levels and associated

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 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 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 ...

, the biological target of androgens like testosterone. 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 product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

, 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 o ...

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 m ...

. Due to its androgenic and progestogenic activity, DMAU 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. 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 unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

effects of DMAU in men. The medication has no estrogenic activity. DMAU is a

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 drug ...

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.

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 Male contraceptives, also known as male birth control, are methods of preventing pregnancy that solely involve the male physiology. The most common kinds of male contraception include condoms, outercourse, and vasectomy. In domestic animals, cas ...

, specifically as a birth control pill for men. The medication has been found to profoundly and rapidly reversibly suppress testicular testosterone 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 testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...

and fertility 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) or hormone replacement therapy (HRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced exogenously ...

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. Side effects included mild weight gain (between 3 and 9 pounds) and mild decreases in levels of HDL cholesterol. No major or serious side effects were observed. Because DMAU is not 5α-reduced, in contrast to testosterone, 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 ha ...

Low estrogen levels

Because DMAU suppresses testosterone levels and by extension estrogen 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 (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 bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

. 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 optica ...

have been observed with the closely related medication

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 i ...

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

when it was administered orally to animals. However, the effects were significantly less than those of methyltestosterone. Both DMAU and

(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 and kidney function when administered to men for a month.

Pharmacology

Pharmacodynamics

DMAU is an androgen ester, specifically an ester 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

effects, and is able to powerfully suppress testosterone 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 origin ...

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

and hence is not potentiated or inactivated in tissues that express 5α-reductase like 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 the prostate gland. As such, DMAU may have a reduced risk of androgenic side effects and androgen-dependent conditions such as acne, pattern scalp hair loss,

body hair growth Body may refer to: In science * Physical body, an object in physics that represents a large amount, has mass or takes up space * Body (biology), the physical material of an organism * Body plan, the physical features shared by a group of anim ...

, benign prostatic hyperplasia, and

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 ...

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 determining the fate of substances administered ...

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 hydrolysis ...

into dimethandrolone when it was administered orally in the form of powder in capsules. In contrast, hydrolysis of testosterone undecanoate into testosterone is rapid and appears to be complete. The difference in conversion efficiency with DMAU relative to testosterone undecanoate is attributed to steric hindrance in DMAU caused by its additional C7α and C11β methyl groups. 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 and testosterone levels. A subsequent pharmacokinetic study found that the conversion of DMAU into dimethandrolone was improved when the drug was delivered orally in castor oil/ benzyl benzoate or a self-emulsifying drug delivery system contained in capsules as opposed to powder in capsules.Ayoub, R. J., Page, S. T., Swerdloff, R. S., Liu, P. Y., Amory, J. K., Leung, A., ... & Wang, C. (2015) SAT-121: Comparison of the Pharmacokinetics (PK) and Safety of Three Oral Formulations of Dimethandrolone Undecanoate (DMAU): A Potential Male Oral Contraceptive.

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

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 non- 17α-alkylated derivative of

19-nortestosterone 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 ...

. It is the C17β

undecanoate Undecylic acid (systematically named undecanoic acid) is a carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is o ...

(undecylate) ester of dimethandrolone (7α,11β-dimethyl-19-nortestosterone). Other esters of dimethandrolone, such as dimethandrolone buciclate (CDB-4386A) and

dimethandrolone dodecylcarbonate Dimethandrolone dodecylcarbonate (developmental code name CDB-4730), or dimethandrolone dodecanoylcarbonate, also known as 7α,11β-dimethyl-19-nortestosterone 17β-dodecylcarbonate, is a synthetic and orally active anabolic–androgenic stero ...

(CDB-4730), have also been developed.Blye, Richard, and Hyun Kim. "Methods of making and using 7a, 11b-dimethyl-17b-hydroxy-4-estren-3-one 17b-trans-4-n-butylcyclohexane carboxylate and 7a, 11b-dimethyl-17b-hydroxyestr-4-en-3-one 17-undecanoate." U.S. Patent Application No. 10/260,854.Blye, Richard P., and Hyun K. Kim. "Nandrolone 17β-carbonates." U.S. Patent No. 7,820,642. 26 Oct. 2010. Analogous esters of closely related AAS include

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–androg ...

(7α-methyl-19-nortestosterone 17β-acetate) and

History

A patent for dimethandrolone was filed in 1997 and was granted in 1999.Cook, C. E., Kepler, J. A., Lee, Y. W., & Wani, M. C. (1999). U.S. Patent No. 5,952,319. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US5952319A/en Subsequently, a patent for DMAU and dimethandrolone buciclate was filed in 2002 and was granted to the United States government in 2003.Blye, Richard, and Hyun Kim. "Methods of making and using 7a, 11b-dimethyl-17b-hydroxy-4-estren-3-one 17b-trans-4-n-butylcyclohexane carboxylate and 7a, 11b-dimethyl-17b-hydroxyestr-4-en-3-one 17-undecanoate." U.S. Patent Application 10/260,854, filed April 10, 2003. https://patents.google.com/patent/US20030069215A1/en 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 in the United States Department of Health and Human Services. 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 Androgens and anabolic steroids Antigonadotropins Contraception for males Estranes Experimental drugs Experimental methods of birth control Enones Prodrugs Progestogens Undecanoate esters