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 when a ...

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 (AAS) and progestogen 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. The pill contains two important hormones: progesti ...

for men. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

, but can also be given by injection into muscle.

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 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 w ...

and mild decreases in levels of

HDL cholesterol High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

. It may also cause low estrogen levels and associated symptoms such as reduced sexual function and decreased bone mineral density. DMAU is an AAS, and hence is an agonist of the androgen receptor, 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, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. Due to its androgenic and progestogenic activity, DMAU has antigonadotropic effects. These effects result in reversible suppression of

sperm production 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 tubules ...

and are responsible for the contraceptive effects of DMAU in men. The medication 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. DMAU is a prodrug 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 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 ...

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 A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testosteron ...

production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stati ...

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 Inguinal orchiectomy (also named orchidectomy) is a specific method of orchiectomy whereby one or both testicles and the full spermatic cord are surgically removed through an incision in the lower lateral abdomen (the "inguinal region"). The p ...

(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 and

fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...

in men. Suppression of spermatogenesis and the actual contraceptive 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 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

. No major or serious

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

, it may have less risk of scalp hair loss.

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 symptoms 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 a ...

(e.g., decreased sex drive, reduced erectile function) and osteoporosis. Reduced sexual function and decreased bone mineral density 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 (17α-methyltestosterone), DMAU has been found to produce some effects indicative of potential liver toxicity 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 I ...

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 organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

function when administered to men for a month.

Pharmacology

Pharmacodynamics

DMAU is an

androgen ester An androgen or anabolic steroid ester is an ester of an androgen/anabolic steroid (AAS) such as the natural testosterone or dihydrotestosterone (DHT) or the synthetic nandrolone (19-nortestosterone). Esterification renders AAS into metabolism-re ...

, specifically 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 a ...

of dimethandrolone, and acts as a prodrug of dimethandrolone in the body. As such, it is an AAS, or an agonist of the androgen receptor, and is also a progestogen, or an agonist of the progesterone receptor. Due to these activities, DMAU has potent antigonadotropic effects, and is able to powerfully suppress

levels. This results in suppression of spermatogenesis and is responsible for its hormonal contraceptive effects in men. The medication is not

aromatized 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 ...

and has no

ic activity. In addition, it is not a substrate 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 de ...

, hair follicles, and the

prostate gland 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 physio ...

. 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 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 ...

, 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, inability to urinate, or loss o ...

, and prostate cancer relative to testosterone and certain other AAS.

Pharmacokinetics

A pharmacokinetic study of DMAU in men found that only 2 to 3% of the drug was hydrolyzed 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 names Andriol and Aveed among others, is an androgen and anabolic steroid (AAS) medication that is used mainly in the treatment of low testosterone levels in men, including hormone therapy for tran ...

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 a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

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 . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...

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 (GnRH) ...

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. It is a colourless or pale yellow liquid with a distinct taste and odor. Its boiling point is and its density is 0.961 g/cm3. It includes a mixture of triglycerides in which about ...

benzyl benzoate Benzyl benzoate is an organic compound which is used as a medication and insect repellent. As a medication it is used to treat scabies and lice. For scabies either permethrin or malathion is typically preferred. It is applied to the skin as a ...

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 synthetic

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, fo ...

steroid and a non- 17α-alkylated

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. ...

of 19-nortestosterone. It is the C17β undecanoate (undecylate)

of dimethandrolone (7α,11β-dimethyl-19-nortestosterone). Other esters of dimethandrolone, 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.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 (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 enabling disclosure of the invention."A ...

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

was filed in 2002 and was granted to the

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

, 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 late ...

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 ...

. 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