The proprietary androgen, 7a-methyl-19-nortestosterone (MENT?) in combination with DMPA progestin is being investigated for male contraception. MENT is 10 fold more effective than testosterone (T) in suppressing gonadotropins and maintaining muscle mass. Therefore, it is possible to deliver a dose of MENT via silastic implants that will be effective in suppressing gonadotropins and spermatogenesis. In addition, MENT will have potential health benefits on prostate, bone and muscle mass and myelin regeneration based on the results of in vitro and animal studies. For example, (1) MENT is resistant to 5a-reduction, therefore, it is less stimulatory on the prostate at a comparable replacement dose;(2) MENT is aromatized to a potent estrogen, thereby, maintains sexual behavior in animals and men;(3) MENT does not bind to sex hormone binding globulin (SHBG) and has similar pharmacokinetics as T;and (4) MENT was recently shown to increase remyelination of neuronal cells (M. Schumacher, unpublished). Hence the long-term use of MENT in men is expected to be superior to T with added health benefits. First generation exogenous treatment regimens using testosterone injection, gel or biodegradable pellet or MENT acetate (MENT Ac) silastic implant showed limited efficacy in male contraceptive clinical trials. Second generation regimens using androgen in combination with a progestin such as levonorgestrel, etonogestrel or DMPA showed higher efficacy in suppressing spermatogenesis. In this research project, we will use a regimen of three MENT Ac implants (releasing ~ 1500 pg/day of MENT Ac) in combination with either a single DMPA injection at the start or multiple injections at 3 month intervals. MENT Ac implants will be manufactured, and the clinical trial will commence during the next funding cycle (pending approval). In addition, pharmacological and mechanistic studies will be conducted to determine the safety and health benefits of MENT and DMPA use. MENT Ac is an acetylated derivative of MENT and is used in implant manufacturing for optimal release rates. MENT and MENT Ac are used interchangeably since MENT Ac released from implants is rapidly hydrolyzed to the active MENT. Depo Provera (DMPA, Pfizer) injectable is an approved female contraceptive and is being investigated for male contraception. Depo provera releases an active progestin, medroxyprogesterone acetate (MPA). MPA will be used in animal and in vitro studies.

Public Health Relevance

; Even though, women have several contraceptive choices, nearly half of them will discontinue use for various reasons. Surveys have indicated that men are willing to participate in contraceptive clinical trials and will use them if safe and effective methods are available. Development of a hormonal male contraceptive method based on MENT Ac implants in combination with DMPA injectable formulation will be particularly relevant for couples to control unintended pregnancy.

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El-Etr, Martine; Rame, Marion; Boucher, Celine et al. (2015) Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex. Glia 63:104-17
Huang, YongMei; Jensen, Jeffrey T; Brache, Vivian et al. (2014) A randomized study on pharmacodynamic effects of vaginal rings delivering the progesterone receptor modulator ulipristal acetate: research for a novel estrogen-free, method of contraception. Contraception 90:565-74
Mok, Ka-Wai; Mruk, Dolores D; Cheng, C Yan (2014) rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9. J Cell Sci 127:4870-82
Xiao, Xiang; Mruk, Dolores D; Wong, Chris K C et al. (2014) Germ cell transport across the seminiferous epithelium during spermatogenesis. Physiology (Bethesda) 29:286-98
Xiao, Xiang; Mruk, Dolores D; Tang, Elizabeth I et al. (2014) N-wasp is required for structural integrity of the blood-testis barrier. PLoS Genet 10:e1004447
Qian, Xiaojing; Mruk, Dolores D; Cheng, Yan-Ho et al. (2014) Actin binding proteins, spermatid transport and spermiation. Semin Cell Dev Biol 30:75-85
Wan, H T; Mruk, Dolores D; Tang, Elizabeth I et al. (2014) Role of non-receptor protein tyrosine kinases in spermatid transport during spermatogenesis. Semin Cell Dev Biol 30:65-74
Gungor-Ordueri, N Ece; Tang, Elizabeth I; Celik-Ozenci, Ciler et al. (2014) Ezrin is an actin binding protein that regulates sertoli cell and spermatid adhesion during spermatogenesis. Endocrinology 155:3981-95
Xiao, Xiang; Mruk, Dolores D; Wong, Elissa W P et al. (2014) Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated trafficking events at the Sertoli cell blood-testis barrier: an in vitro study. Am J Physiol Endocrinol Metab 307:E553-62
Gungor-Ordueri, N Ece; Celik-Ozenci, Ciler; Cheng, C Yan (2014) Fascin 1 is an actin filament-bundling protein that regulates ectoplasmic specialization dynamics in the rat testis. Am J Physiol Endocrinol Metab 307:E738-53

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