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pharmacokinetics as T;and (4) MENT was recently shown to increase remyelination of neuronal cells (M. Schumacher, unpublished).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.
; 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.
|Mao, Baiping; Mruk, Dolores; Lian, Qingquan et al. (2018) Mechanistic Insights into PFOS-Mediated Sertoli Cell Injury. Trends Mol Med 24:781-793|
|Kannan, Athilakshmi; Bhurke, Arpita; Sitruk-Ware, Regine et al. (2018) Characterization of Molecular Changes in Endometrium Associated With Chronic Use of Progesterone Receptor Modulators: Ulipristal Acetate Versus Mifepristone. Reprod Sci 25:320-328|
|Xiao, Xiang; Ni, Ya; Yu, Chenhuan et al. (2018) Src family kinases (SFKs) and cell polarity in the testis. Semin Cell Dev Biol 81:46-53|
|Chen, Haiqi; Mruk, Dolores D; Lui, Wing-Yee et al. (2018) Cell polarity and planar cell polarity (PCP) in spermatogenesis. Semin Cell Dev Biol 81:71-77|
|Chen, Haiqi; Xiao, Xiang; Lui, Wing-Yee et al. (2018) Vangl2 regulates spermatid planar cell polarity through microtubule (MT)-based cytoskeleton in the rat testis. Cell Death Dis 9:340|
|Wen, Qing; Mruk, Dolores; Tang, Elizabeth I et al. (2018) Cell polarity and cytoskeletons-Lesson from the testis. Semin Cell Dev Biol 81:21-32|
|Li, Linxi; Mao, Baiping; Wu, Siwen et al. (2018) Regulation of spermatid polarity by the actin- and microtubule (MT)-based cytoskeletons. Semin Cell Dev Biol 81:88-96|
|Wen, Qing; Tang, Elizabeth I; Li, Nan et al. (2018) Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons. Methods Mol Biol 1748:229-243|
|Chen, Shuhua; Kumar, Narender; Mao, Zisu et al. (2018) Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain. Menopause 25:1138-1151|
|Chen, Haiqi; Lui, Wing-Yee; Mruk, Dolores D et al. (2018) Monitoring the Integrity of the Blood-Testis Barrier (BTB): An In Vivo Assay. Methods Mol Biol 1748:245-252|
Showing the most recent 10 out of 256 publications