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| Other names | Dimethandrolone undecylate; DMAU; CDB-4521; Dimethylnandrolone undecanoate; 7α,11β-Dimethyl-19-nortestosterone 17β-undecanoate; 7α,11β-Dimethylestr-4-en-17β-ol-3-one 17β-undecanoate |
| Routes of administration | By mouth,intramuscular injection[1] |
| Drug class | Androgen;Anabolic steroid;Androgen ester;Progestogen |
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| Chemical and physical data | |
| Formula | C31H50O3 |
| Molar mass | 470.738 g·mol−1 |
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Dimethandrolone undecanoate (DMAU), also known by its developmental code nameCDB-4521, is anexperimentalandrogen/anabolic steroid (AAS) andprogestogen medication which is under development as a potentialbirth control pillfor men.[2][3][4] It is takenby mouth, but can also be given byinjection into muscle.[2][3][1]
Side effects of DMAU include mildweight gain and mild decreases in levels ofHDL cholesterol.[5][6] It may also causelow estrogen levels and associatedsymptoms such asreduced sexual function anddecreased bone mineral density.[7][8] DMAU is an AAS, and hence is anagonist of theandrogen receptor, thebiological target of androgens liketestosterone.[2][3] It is also aprogestin, or asynthetic progestogen, and hence is an agonist of theprogesterone receptor, the biological target of progestogens likeprogesterone.[2][3] Due to its androgenic and progestogenic activity, DMAU hasantigonadotropic effects.[2][3] These effects result in reversible suppression ofsperm production and are responsible for thecontraceptive effects of DMAU in men.[2][3] The medication has noestrogenic activity.[7] DMAU is aprodrug ofdimethandrolone.[2][3]
DMAU was first described in 2002.[9] It was developed by the Contraceptive Development Branch of theNational Institute of Child Health and Human Development, an agency in theUnited States government.[2][3][4]
DMAU is an experimental medication and is not currently approved for medical use.[5] It is under development for use as a potentialmale hormonal contraceptive, specifically as abirth control pill for men.[2][3][4] The medication has been found to profoundly and rapidly reversibly suppresstesticulartestosteroneproduction in men when taken by mouth once per day for a month.[5][10] The circulating levels of testosterone achieved with oral DMAU were equivalent to those seen on average withsurgical castration (13.4 ng/dL for DMAU, 15 ng/dL for castration).[10][11] Following discontinuation of DMAU, testosterone levels began to recover within days and reached normal levels within a month.[10][12] Testicular testosterone production is essential forspermatogenesis andfertility in men.[13] Suppression of spermatogenesis and the actualcontraceptive 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.[5][10] In addition to male contraception, there has also been interest in the potential use of DMAU inandrogen replacement therapy forlow testosterone levels in men.[14][2][15]
In a clinical study, DMAU was found to bewell tolerated when administered to men for a month.[5][16]Side effects included mildweight gain (between 3 and 9 pounds) and mild decreases in levels ofHDL cholesterol.[5][16][6] No major or seriousside effects were observed.[12][16]
Because DMAU is not5α-reduced, in contrast totestosterone, it may have less risk ofscalp hair loss.[17]
Because DMAU suppresses testosterone levels and by extensionestrogen levels in men but has no estrogenic activity of its own, it may pose a risk ofsymptoms oflow estrogen levels such assexual dysfunction (e.g.,decreased sex drive,reduced erectile function) andosteoporosis.[18][19][14][8] Reduced sexual function and decreasedbone mineral density have been observed with the closely related medicationtrestolone, which has low estrogenicity similarly to DMAU.[14][20][8]
Unlike testosterone but similarly to17α-alkyated AAS likemethyltestosterone (17α-methyltestosterone), DMAU has been found to produce some effects indicative of potentialliver toxicity when it was administered orally to animals.[21] However, the effects were significantly less than those of methyltestosterone.[21] Both DMAU andtrestolone (7α-methyl-19-nortestosterone) showed potential signs of liver toxicity whereas11β-methyl-19-nortestosterone 17β-dodecylcarbonate 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.[21] In any case, however, in a clinical study, DMAU was found to be safe in terms ofliver andkidney function when administered to men for a month.[5]
DMAU is anandrogen ester, specifically anester ofdimethandrolone, and acts as aprodrug of dimethandrolone in the body.[2][3] As such, it is an AAS, or anagonist of theandrogen receptor, and is also aprogestogen, or an agonist of theprogesterone receptor.[2] Due to these activities, DMAU has potentantigonadotropic effects, and is able to powerfully suppresstestosterone levels.[2][5][10] This results in suppression ofspermatogenesis and is responsible for itshormonal contraceptive effects in men.[2] The medication is notaromatized and has noestrogenic activity.[7] In addition, it is not asubstrate for5α-reductase and hence is not potentiated or inactivated intissues that express 5α-reductase likeskin,hair follicles, and theprostate gland.[15] As such, DMAU may have a reduced risk ofandrogenicside effects andandrogen-dependent conditions such asacne,pattern scalp hair loss,body hair growth,benign prostatic hyperplasia, andprostate cancer relative to testosterone and certain other AAS.[15]
Apharmacokinetic study of DMAU in men found that only 2 to 3% of the drug washydrolyzed into dimethandrolone when it was administered orally in the form of powder incapsules.[3] In contrast, hydrolysis oftestosterone undecanoate intotestosterone is rapid and appears to be complete.[3] The difference in conversion efficiency with DMAU relative to testosterone undecanoate is attributed tosteric hindrance in DMAU caused by its additional C7α and C11βmethyl groups.[3] 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 ofluteinizing hormone andtestosterone levels.[3] A subsequent pharmacokinetic study found that the conversion of DMAU into dimethandrolone was improved when the drug was delivered orally incastor oil/benzyl benzoate or aself-emulsifying drug delivery system contained in capsules as opposed to powder in capsules.[22]
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 asyntheticestranesteroid and a non-17α-alkylatedderivative of19-nortestosterone.[2] It is the C17βundecanoate (undecylate)ester ofdimethandrolone (7α,11β-dimethyl-19-nortestosterone).[2] Other esters of dimethandrolone, such asdimethandrolone buciclate (CDB-4386A) anddimethandrolone dodecylcarbonate (CDB-4730), have also been developed.[9][23] Analogous esters of closely related AAS includetrestolone acetate (7α-methyl-19-nortestosterone 17β-acetate) and11β-methyl-19-nortestosterone 17β-dodecylcarbonate.[2][15]
Apatent fordimethandrolone was filed in 1997 and was granted in 1999.[24] Subsequently, a patent for DMAU anddimethandrolone buciclate was filed in 2002 and was granted to theUnited States government in 2003.[9] DMAU was developed under the code name CDB-4521 by the Contraceptive Development Branch of theNational Institute of Child Health and Human Development, one of theNational Institutes of Health in theUnited States Department of Health and Human Services.[2][3][4] The first clinical studies of DMAU in men were published in 2014 (single-dose), 2015 (single-dose), and 2018 (continuous for one month).[3][22][5]
The castrate level was defined as testosterone being less than 50 ng/dL (1.7 nmol/L), many years ago. However contemporary laboratory testing methods showed that the mean value after surgical castration is 15 ng/dL [1]. Thus, recently the level is defined as being less than 20 ng/dL (1 nmol/L).
However, also lumbar spine bone mineral density decreased in both groups, most probably because of insufficient MENT aromatization [104], limiting its potential for hormonal substitution in hypogonadal men.