Myers C, Jones R, Upadhyay U. Predicted changes in abortion access and incidence in a post-roe world. Contraception. 2019;100(5):367–73. https://doi.org/10.1016/j.contraception.2019.07.139.
Kimport K, Rasidjan MP. Exploring the emotional costs of abortion travel in the United States due to legal restriction. Contraception. 2023;120:109956. https://doi.org/10.1016/j.contraception.2023.109956.
Page ST, Blithe D, Wang C. Hormonal male contraception: getting to market. Front Endocrinol (Lausanne). 2022;13:891589. https://doi.org/10.3389/fendo.2022.891589.
Kimport K. More than a physical burden: women’s mental and emotional work in preventing pregnancy. J Sex Res. 2018;55(9):1096–105. https://doi.org/10.1080/00224499.2017.1311834.
Kimport K. Talking about male body-based contraceptives: the counseling visit and the feminization of contraception. Soc Sci Med. 2018;201:44–50. https://doi.org/10.1016/j.socscimed.2018.01.040.
Alspaugh A, Barroso J, Reibel M, Phillips S. Women’s contraceptive perceptions, beliefs, and attitudes: an integrative review of qualitative research. J Midwifery Womens Health. 2020;65(1):64–84. https://doi.org/10.1111/jmwh.12992.
Sundaram A, Vaughan B, Kost K, Bankole A, Finer L, Singh S, et al. Contraceptive failure in the United States: estimates from the 2006–2010 national survey of family growth. Perspect Sex Reprod Health. 2017;49(1):7–16. https://doi.org/10.1363/psrh.12017.
Vaughan B, Trussell J, Kost K, Singh S, Jones R. Discontinuation and resumption of contraceptive use: results from the 2002 national survey of family growth. Contraception. 2008;78(4):271–83. https://doi.org/10.1016/j.contraception.2008.05.007.
Bearak J, Popinchalk A, Ganatra B, Moller AB, Tunçalp Ö, Beavin C, et al. Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990–2019. Lancet Glob Health. 2020;8(9):e1152–e61. https://doi.org/10.1016/s2214-109x(20)30315-6.
Finer LB, Zolna MR. Shifts in intended and unintended pregnancies in the United States, 2001–2008. Am J Public Health. 2014;104(Suppl 1):43–8. https://doi.org/10.2105/ajph.2013.301416.
Heinemann K, Saad F, Wiesemes M, White S, Heinemann L. Attitudes toward male fertility control: results of a multinational survey on four continents. Hum Reprod. 2005;20(2):549–56. https://doi.org/10.1093/humrep/deh574.
Eberhardt J, van Wersch A, Meikle N. Attitudes towards the male contraceptive pill in men and women in casual and stable sexual relationships. J Fam Plann Reprod Health Care. 2009;35(3):161–5. https://doi.org/10.1783/147118909788707986.
Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25(2):271–85. https://doi.org/10.1016/j.beem.2010.08.006.
Nieschlag E. 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. October 22–23, 2006. Contraception. 2007;75(3):166-7. doi: https://doi.org/10.1016/j.contraception.2006.12.001.
Klein CE. The hypothalamic-pituitary-gonadal Axis. In: Kufe DWPR, Weichselbaum RR, et al. editors. Holland-Frei Cancer Medicine. Online: BC Decker Inc; 2003. https://www.ncbi.nlm.nih.gov/books/NBK13386/.
Litwack G. Polypeptide Hormones. In: Human Biochemistry. 2nd ed. Online: Andre Gerhard Wolff, Elsevier Inc. 2022. p. 475–516. doi: https://doi.org/10.1016/B978-0-323-85718-5.00013-3.
von Eckardstein S, Noe G, Brache V, Nieschlag E, Croxatto H, Alvarez F, et al. A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J Clin Endocrinol Metab. 2003;88(11):5232–9. https://doi.org/10.1210/jc.2002-022043.
Walton MJ, Kumar N, Baird DT, Ludlow H, Anderson RA. 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with etonogestrel implants for spermatogenic suppression in healthy men. J Androl. 2007;28(5):679–88. https://doi.org/10.2164/jandrol.107.002683.
García-Becerra R, Ordaz-Rosado D, Noé G, Chávez B, Cooney AJ, Larrea F. Comparison of 7α-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation. Reproduction. 2012;143(2):211–9. https://doi.org/10.1530/rep-11-0171.
Pavlou SN, Brewer K, Farley MG, Lindner J, Bastias MC, Rogers BJ, et al. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab. 1991;73(6):1360–9. https://doi.org/10.1210/jcem-73-6-1360.
Bagatell CJ, Matsumoto AM, Christensen RB, Rivier JE, Bremner WJ. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab. 1993;77(2):427–32. https://doi.org/10.1210/jcem.77.2.8345047.
Handelsman DJ, Wishart S, Conway AJ. Oestradiol enhances testosterone-induced suppression of human spermatogenesis. Hum Reprod. 2000;15(3):672–9. https://doi.org/10.1093/humrep/15.3.672.
Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab. 2003;88(10):4659–67. https://doi.org/10.1210/jc.2003-030107.
Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab. 1996;81(11):4113–21. https://doi.org/10.1210/jcem.81.11.8923869.
Kamischke A, Diebäcker J, Nieschlag E. Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function. Clin Endocrinol (Oxf). 2000;53(3):351–8. https://doi.org/10.1046/j.1365-2265.2000.01097.x.
Kamischke A, Heuermann T, Krüger K, von Eckardstein S, Schellschmidt I, Rübig A, et al. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab. 2002;87(2):530–9. https://doi.org/10.1210/jcem.87.2.8218.
Meriggiola MC, Costantino A, Saad F, D’Emidio L, Morselli Labate AM, Bertaccini A, et al. Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate. J Clin Endocrinol Metab. 2005;90(4):2005–14. https://doi.org/10.1210/jc.2004-1852.
Behre HM, Zitzmann M, Anderson RA, Handelsman DJ, Lestari SW, McLachlan RI, et al. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab. 2016;101(12):4779–88. https://doi.org/10.1210/jc.2016-2141.
WHO Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet. 1990;336(8721):955–9. https://doi.org/10.1016/0140-6736(90)92416-F.
WHO Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril. 1996;65(6):821. https://doi.org/10.1016/S0015-0282(16)58221-1.
McLachlan RI, McDonald J, Rushford D, Robertson DM, Garrett C, Baker HWG. Efficacy and acceptability of testosterone implants, alone or in combination with a 5α-reductase inhibitor, for male hormonal contraception. Contraception. 2000;62(2):73–8. https://doi.org/10.1016/S0010-7824(00)00139-6.
Gu Y-Q, Wang X-H, Xu D, Peng L, Cheng L-F, Huang M-K, et al. A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy chinese men. J Clin Endocrinol Metab. 2003;88(2):562–8. https://doi.org/10.1210/jc.2002-020447.
Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in chinese men. J Clin Endocrinol Metab. 2009;94(6):1910–5. https://doi.org/10.1210/jc.2008-1846.
Handelsman DJ, Conway AJ, Boylan LM. Suppression of human spermatogenesis by testosterone implants. J Clin Endocrinol Metab. 1992;75(5):1326–32. https://doi.org/10.1210/jcem.75.5.1430094.
Nieschlag E, Hoogen H, Bölk M, Schuster H, Wickings EJ. Clinical trial with testosterone undecanoate for male fertility control. Contraception. 1978;18(6):607–14. https://doi.org/10.1016/0010-7824(78)90045-8.
Blithe D, Myer K. Study of daily application of Nestorone® (NES) and testosterone (T) combination gel for male contraception. ClinicalTrials.gov: 2023 https://ClinicalTrials.gov/show/NCT03452111.
Amory JK, Blithe DL, Sitruk-Ware R, Swerdloff RS, Bremner WJ, Dart C, et al. Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone). Contraception. 2023:110064. https://doi.org/10.1016/j.contraception.2023.110064.
Anawalt BD, Roth MY, Ceponis J, Surampudi V, Amory JK, Swerdloff RS, et al. Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men. Andrology. 2019;7(6):878–87. https://doi.org/10.1111/andr.12603.
Ilani N, Roth MY, Amory JK, Swerdloff RS, Dart C, Page ST, et al. A new combination of testosterone and nestorone transdermal gels for male hormonal contraception. J Clin Endocrinol Metab. 2012;97(10):3476–86. https://doi.org/10.1210/jc.2012-1384.
Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, et al. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009;94(7):2313–20. https://doi.org/10.1210/jc.2008-2604.
Wang C, Page S. Injectable DMAU for male contraception in healthy male volunteers (CCN015); 2023. https://ClinicalTrials.gov/show/NCT02927210.
Wang C, Page S. Study of spermatogenesis suppression with DMAU alone or with LNG versus placebo alone in normal men. https://ClinicalTrials.gov/show/NCT03455075; 2020.
Thirumalai A, Ceponis J, Amory JK, Swerdloff R, Surampudi V, Liu PY, et al. Effects of 28 days of oral dimethandrolone undecanoate in healthy men: a prototype male pill. J Clin Endocrinol Metab. 2019;104(2):423–32. https://doi.org/10.1210/jc.2018-01452.
Ayoub R, Page ST, Swerdloff RS, Liu PY, Amory JK, Leung A, et al. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology. 2017;5(2):278–85. https://doi.org/10.1111/andr.12303.
Surampudi P, Page ST, Swerdloff RS, Nya-Ngatchou JJ, Liu PY, Amory JK, et al. Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive. Andrology. 2014;2(4):579–87. https://doi.org/10.1111/j.2047-2927.2014.00216.x.
Yuen F, Thirumalai A, Fernando FA, Swerdloff RS, Liu PY, Pak Y, et al. Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men. Andrology. 2021;9(5):1526–39. https://doi.org/10.1111/andr.13025.
Yuen F, Thirumalai A, Pham C, Swerdloff RS, Anawalt BD, Liu PY, et al. Daily oral administration of the novel androgen 11β-MNTDC markedly suppresses serum gonadotropins in healthy men. J Clin Endocrinol Metab. 2020;105(3):e835–47. https://doi.org/10.1210/clinem/dgaa032.
Wu S, Yuen F, Swerdloff RS, Pak Y, Thirumalai A, Liu PY, et al. Safety and pharmacokinetics of single-dose novel oral androgen 11β-methyl-19-nortestosterone-17β-dodecylcarbonate in men. J Clin Endocrinol Metab. 2019;104(3):629–38. https://doi.org/10.1210/jc.2018-01528.
Kumar N, Koide SS, Tsong Y, Sundaram K. Nestorone: a progestin with a unique pharmacological profile. Steroids. 2000;65(10–11):629–36. https://doi.org/10.1016/s0039-128x(00)00119-7.
Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, et al. Nestorone® as a novel progestin for nonoral contraception: structure-activity relationships and brain metabolism studies. Endocrinology. 2017;158(1):170–82. https://doi.org/10.1210/en.2016-1426.
Sitruk-Ware R, Nath A. The use of newer progestins for contraception. Contraception. 2010;82(5):410–7. https://doi.org/10.1016/j.contraception.2010.04.004.
Fraser IS, Weisberg E, Kumar N, Kumar S, Humberstone AJ, McCrossin L, et al. An initial pharmacokinetic study with a Metered Dose Transdermal System for delivery of the progestogen nestorone as a possible future contraceptive. Contraception. 2007;76(6):432–8. https://doi.org/10.1016/j.contraception.2007.08.006.
FDA News Release. : FDA approves new vaginal ring for one year of birth control. https://www.fda.gov/news-events/press-announcements/fda-approves-new-vaginal-ring-one-year-birth-control (2018). Accessed 2023.
Archer DF, Merkatz RB, Bahamondes L, Westhoff CL, Darney P, Apter D, et al. Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials. Lancet Glob Health. 2019;7(8):e1054–e64. https://doi.org/10.1016/s2214-109x(19)30265-7.
Virro JJ, Besinque K, Carney CE, Gross D, Bernick B, Mirkin S. Long-lasting, patient-controlled, procedure-free contraception: a review of Annovera with a pharmacist perspective. Pharm (Basel). 2020;8(3). https://doi.org/10.3390/pharmacy8030156.
Liu PY, Swerdloff RS, Anawalt BD, Anderson RA, Bremner WJ, Elliesen J, et al. Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis. J Clin Endocrinol Metab. 2008;93(5):1774–83. https://doi.org/10.1210/jc.2007-2768.
Roth MY, Ilani N, Wang C, Page ST, Bremner WJ, Swerdloff RS, et al. Characteristics associated with suppression of spermatogenesis in a male hormonal contraceptive trial using testosterone and nestorone(®) gels. Andrology. 2013;1(6):899–905. https://doi.org/10.1111/j.2047-2927.2013.00135.x.
Roe AH, Bartz DA, Douglas PS. Combined estrogen-progestin contraception: Side effects and health concerns. In: Crowley WF, Schreiber CA, editors.Online: UpToDate. 2023. https://www.uptodate.com/contents/combined-estrogen-progestin-contraception-side-effects-and-health-concerns. Accessed 20 April 2023.
Roth MY, Shih G, Ilani N, Wang C, Page ST, Bremner WJ, et al. Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial. Contraception. 2014;90(4):407–12. https://doi.org/10.1016/j.contraception.2014.05.013.
Attardi BJ, Hild SA, Reel JR. Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity. Endocrinology. 2006;147(6):3016–26. https://doi.org/10.1210/en.2005-1524.
Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR. Dimethandrolone (7alpha,11beta-dimethyl-19-nortestosterone) and 11beta-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase. J Steroid Biochem Mol Biol. 2008;110(3–5):214–22. https://doi.org/10.1016/j.jsbmb.2007.11.009.
Sharma S, Ahire D, Basit A, Lajoie M, Wang C, Lee MS, et al. Dimethandrolone, a potential male contraceptive pill, is primarily metabolized by the highly polymorphic UDP-glucuronosyltransferase 2B17 enzyme in human intestine and liver. Drug Metab Dispos. 2022;50(12):1493–500. https://doi.org/10.1124/dmd.122.001041.
Hild SA, Attardi BJ, Koduri S, Till BA, Reel JR. Effects of synthetic androgens on liver function using the rabbit as a model. J Androl. 2010;31(5):472–81. https://doi.org/10.2164/jandrol.109.009365.
Hild SA, Marshall GR, Attardi BJ, Hess RA, Schlatt S, Simorangkir DR, et al. Development of l-CDB-4022 as a nonsteroidal male oral contraceptive: induction and recovery from severe oligospermia in the adult male cynomolgus monkey (Macaca fascicularis). Endocrinology. 2007;148(4):1784–96. https://doi.org/10.1210/en.2006-1487.
Attardi BJ, Marck BT, Matsumoto AM, Koduri S, Hild SA. Long-term effects of dimethandrolone 17β-undecanoate and 11β-methyl-19-nortestosterone 17β-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats. J Androl. 2011;32(2):183–92. https://doi.org/10.2164/jandrol.110.010371.
NIDDK. Androgenic Steroids. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases. 2020. https://www.ncbi.nlm.nih.gov/books/NBK548931/.
Thirumalai A, Yuen F, Amory JK, Hoofnagle AN, Swerdloff RS, Liu PY, et al. Dimethandrolone undecanoate, a novel, nonaromatizable androgen, increases P1NP in healthy men over 28 days. J Clin Endocrinol Metab. 2021;106(1):e171–e81. https://doi.org/10.1210/clinem/dgaa761.
Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, et al. The potent synthetic androgens, dimethandrolone (7α,11β-dimethyl-19-nortestosterone) and 11β-methyl-19-nortestosterone, do not require 5α-reduction to exert their maximal androgenic effects. J Steroid Biochem Mol Biol. 2010;122(4):212–8. https://doi.org/10.1016/j.jsbmb.2010.06.009.
Mu E, Kulkarni J. Hormonal contraception and mood disorders. Aust Prescr. 2022;45(3):75–9. https://doi.org/10.18773/austprescr.2022.025.
de Wit AE, Booij SH, Giltay EJ, Joffe H, Schoevers RA, Oldehinkel AJ. Association of use of oral contraceptives with depressive symptoms among adolescents and young women. JAMA Psychiatry. 2020;77(1):52–9. https://doi.org/10.1001/jamapsychiatry.2019.2838.
Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry. 2016;73(11):1154–62. https://doi.org/10.1001/jamapsychiatry.2016.2387.
Frost JJ, Lindberg LD, Finer LB. Young adults’ contraceptive knowledge, norms and attitudes: associations with risk of unintended pregnancy. Perspect Sex Reprod Health. 2012;44(2):107–16. https://doi.org/10.1363/4410712.
Noman MAA, Kyzer JL, Chung SSW, Wolgemuth DJ, Georg GI. Retinoic acid receptor antagonists for male contraception: current status†. Biol Reprod. 2020;103(2):390–9. https://doi.org/10.1093/biolre/ioaa122.
Schleif MC, Havel SL, Griswold MD. Function of retinoic acid in development of male and female gametes. Nutrients. 2022;14(6). https://doi.org/10.3390/nu14061293.
Heller CG, Moore DJ, Paulsen CA. Suppression of spermatogenesis and chronic toxicity in men by a new series of bis(dichloroacetyl) diamines. Toxicol Appl Pharmacol. 1961;3:1–11. https://doi.org/10.1016/0041-008x(61)90002-3.
Chung SS, Wang X, Roberts SS, Griffey SM, Reczek PR, Wolgemuth DJ. Oral administration of a retinoic acid receptor antagonist reversibly inhibits spermatogenesis in mice. Endocrinology. 2011;152(6):2492–502. https://doi.org/10.1210/en.2010-0941.
Chung SS, Wang X, Wolgemuth DJ. Prolonged oral administration of a pan-retinoic acid receptor antagonist inhibits spermatogenesis in mice with a rapid recovery and changes in the expression of influx and efflux transporters. Endocrinology. 2016;157(4):1601–12. https://doi.org/10.1210/en.2015-1675.
Amory JK, Muller CH, Shimshoni JA, Isoherranen N, Paik J, Moreb JS, et al. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl. 2011;32(1):111–9. https://doi.org/10.2164/jandrol.110.010751.
Chung SS, Cuellar RA, Wang X, Reczek PR, Georg GI, Wolgemuth DJ. Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo. ACS Med Chem Lett. 2013;4(5):446–50. https://doi.org/10.1021/ml300365k.
Cochran AG, Conery AR, Sims RJ 3. Bromodomains: a new target class for drug development. Nat Rev Drug Discov. 2019;18(8):609–28. https://doi.org/10.1038/s41573-019-0030-7.
Fujisawa T, Filippakopoulos P. Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat Rev Mol Cell Biol. 2017;18(4):246–62. https://doi.org/10.1038/nrm.2016.143.
Wisniewski A, Georg GI. BET proteins: investigating BRDT as a potential target for male contraception. Bioorg Med Chem Lett. 2020;30(6):126958. https://doi.org/10.1016/j.bmcl.2020.126958.
Shang E, Nickerson HD, Wen D, Wang X, Wolgemuth DJ. The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation. Development. 2007;134(19):3507–15. https://doi.org/10.1242/dev.004481.
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, et al. Small-molecule inhibition of BRDT for male contraception. Cell. 2012;150(4):673–84. https://doi.org/10.1016/j.cell.2012.06.045.
Ayoub AM, Hawk LML, Herzig RJ, Jiang J, Wisniewski AJ, Gee CT, et al. BET bromodomain inhibitors with one-step synthesis discovered from virtual screen. J Med Chem. 2017;60(12):4805–17. https://doi.org/10.1021/acs.jmedchem.6b01336.
Law RP, Atkinson SJ, Bamborough P, Chung CW, Demont EH, Gordon LJ, et al. Discovery of tetrahydroquinoxalines as bromodomain and extra-terminal domain (BET) inhibitors with selectivity for the second bromodomain. J Med Chem. 2018;61(10):4317–34. https://doi.org/10.1021/acs.jmedchem.7b01666.
Yu Z, Ku AF, Anglin JL, Sharma R, Ucisik MN, Faver JC, et al. Discovery and characterization of bromodomain 2-specific inhibitors of BRDT. Proc Natl Acad Sci U S A. 2021;118(9). https://doi.org/10.1073/pnas.2021102118.
Guan X, Cheryala N, Karim RM, Chan A, Berndt N, Qi J, et al. Bivalent BET bromodomain inhibitors Confer increased potency and selectivity for BRDT via protein conformational plasticity. J Med Chem. 2022;65(15):10441–58. https://doi.org/10.1021/acs.jmedchem.2c00453.
Salicioni AM, Gervasi MG, Sosnik J, Tourzani DA, Nayyab S, Caraballo DA, et al. Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception†. Biol Reprod. 2020;103(2):264–74. https://doi.org/10.1093/biolre/ioaa064.
Xu B, Hao Z, Jha KN, Zhang Z, Urekar C, Digilio L, et al. Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency. Dev Biol. 2008;319(2):211–22. https://doi.org/10.1016/j.ydbio.2008.03.047.
Nayyab S, Gervasi MG, Tourzani DA, Caraballo DA, Jha KN, Teves ME, et al. TSSK3, a novel target for male contraception, is required for spermiogenesis. Mol Reprod Dev. 2021;88(11):718–30. https://doi.org/10.1002/mrd.23539.
Spiridonov NA, Wong L, Zerfas PM, Starost MF, Pack SD, Paweletz CP, et al. Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility. Mol Cell Biol. 2005;25(10):4250–61. https://doi.org/10.1128/mcb.25.10.4250-4261.2005.
Zhang H, Su D, Yang Y, Zhang W, Liu Y, Bai G, et al. Some single-nucleotide polymorphisms of the TSSK2 gene may be associated with human spermatogenesis impairment. J Androl. 2010;31(4):388–92. https://doi.org/10.2164/jandrol.109.008466.
Shetty J, Sinville R, Shumilin IA, Minor W, Zhang J, Hawkinson JE, et al. Recombinant production of enzymatically active male contraceptive drug target hTSSK2 – localization of the TSKS domain phosphorylated by TSSK2. Protein Expr Purif. 2016;121:88–96. https://doi.org/10.1016/j.pep.2016.01.009.
Hawkinson JE, Sinville R, Mudaliar D, Shetty J, Ward T, Herr JC, et al. Potent pyrimidine and pyrrolopyrimidine inhibitors of testis-specific serine/threonine kinase†|2 (TSSK2). ChemMedChem. 2017;12(22):1857–65. https://doi.org/10.1002/cmdc.201700503.
Dcunha R, Hussein RS, Ananda H, Kumari S, Adiga SK, Kannan N, et al. Current insights and latest updates in sperm motility and associated applications in assisted reproduction. Reprod Sci. 2022;29(1):7–25. https://doi.org/10.1007/s43032-020-00408-y.
O’Rand MG, Widgren EE, Hamil KG, Silva EJ, Richardson RT. Functional studies of eppin. Biochem Soc Trans. 2011;39(5):1447–9. https://doi.org/10.1042/bst0391447.
O’Rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, et al. Reversible immunocontraception in male monkeys immunized with eppin. Science. 2004;306(5699):1189–90. https://doi.org/10.1126/science.1099743.
O’Rand MG, Hamil KG, Adevai T, Zelinski M. Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive. PLoS ONE. 2018;13(4):e0195953. https://doi.org/10.1371/journal.pone.0195953.
Silva AAS, Raimundo TRF, Mariani NAP, Kushima H, Avellar MCW, Buffone MG, et al. Dissecting EPPIN protease inhibitor domains in sperm motility and fertilizing ability: repercussions for male contraceptive development. Mol Hum Reprod. 2021;27(12). https://doi.org/10.1093/molehr/gaab066.
Balbach M, Ghanem L, Rossetti T, Kaur N, Ritagliati C, Ferreira J, et al. Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization. Mol Hum Reprod. 2021;27(9). https://doi.org/10.1093/molehr/gaab054.
Miller M, Rossetti T, Ferreira J, Ghanem L, Balbach M, Kaur N, et al. Design, synthesis, and pharmacological evaluation of second-generation soluble adenylyl cyclase (sAC, ADCY10) inhibitors with slow dissociation rates. J Med Chem. 2022;65(22):15208–26. https://doi.org/10.1021/acs.jmedchem.2c01133.
Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, et al. On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun. 2023;14(1):637. https://doi.org/10.1038/s41467-023-36119-6.
Ramos-Espiritu L, Kleinboelting S, Navarrete FA, Alvau A, Visconti PE, Valsecchi F, et al. Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase. Nat Chem Biol. 2016;12(10):838–44. https://doi.org/10.1038/nchembio.2151.
Ritagliati C, Ayoub S, Balbach M, Buck J, Levin LR. In vivo characterization of sAC null sperm. Front Cell Dev Biol. 2023;11:1134051. https://doi.org/10.3389/fcell.2023.1134051.
Rahban R, Nef S, CatSper. The complex main gate of calcium entry in mammalian spermatozoa. Mol Cell Endocrinol. 2020;518:110951. https://doi.org/10.1016/j.mce.2020.110951.
Li H, Ding X, Guan H, Xiong C. Inhibition of human sperm function and mouse fertilization in vitro by an antibody against cation channel of sperm 1: the contraceptive potential of its transmembrane domains and pore region. Fertil Steril. 2009;92(3):1141–6. https://doi.org/10.1016/j.fertnstert.2008.07.1751.
Rennhack A, Schiffer C, Brenker C, Fridman D, Nitao ET, Cheng YM, et al. A novel cross-species inhibitor to study the function of CatSper ca(2+) channels in sperm. Br J Pharmacol. 2018;175(15):3144–61. https://doi.org/10.1111/bph.14355.
Carlson AE, Burnett LA, del Camino D, Quill TA, Hille B, Chong JA, et al. Pharmacological targeting of native CatSper channels reveals a required role in maintenance of sperm hyperactivation. PLoS ONE. 2009;4(8):e6844. https://doi.org/10.1371/journal.pone.0006844.
Curci L, Carvajal G, Sulzyk V, Gonzalez SN, Cuasnicú PS. Pharmacological inactivation of CatSper blocks sperm fertilizing ability independently of the capacitation status of the cells: implications for non-hormonal contraception. Front Cell Dev Biol. 2021;9:686461. https://doi.org/10.3389/fcell.2021.686461.
Carlson EJ, Francis R, Liu Y, Li P, Lyon M, Santi CM, et al. Discovery and characterization of multiple classes of human CatSper blockers. ChemMedChem. 2022;17(15):e202000499. https://doi.org/10.1002/cmdc.202000499.
Chávez JC, Ferreira JJ, Butler A, De La Vega Beltrán JL, Treviño CL, Darszon A, et al. SLO3 K + channels control calcium entry through CATSPER channels in sperm. J Biol Chem. 2014;289(46):32266–75. https://doi.org/10.1074/jbc.M114.607556.
Tan Z, Garcia TX. SLO3 in the fast lane: the latest male contraceptive target with a promising small-molecule inhibitor. Proc Natl Acad Sci U S A. 2023;120(8):e2221758120. https://doi.org/10.1073/pnas.2221758120.
Schreiber M, Wei A, Yuan A, Gaut J, Saito M, Salkoff L. Slo3, a novel pH-sensitive K + channel from mammalian spermatocytes. J Biol Chem. 1998;273(6):3509–16. https://doi.org/10.1074/jbc.273.6.3509.
Santi CM, Martínez-López P, de la Vega-Beltrán JL, Butler A, Alisio A, Darszon A, et al. The SLO3 sperm-specific potassium channel plays a vital role in male fertility. FEBS Lett. 2010;584(5):1041–6. https://doi.org/10.1016/j.febslet.2010.02.005.
Zeng XH, Yang C, Kim ST, Lingle CJ, Xia XM. Deletion of the Slo3 gene abolishes alkalization-activated K + current in mouse spermatozoa. Proc Natl Acad Sci U S A. 2011;108(14):5879–84. https://doi.org/10.1073/pnas.1100240108.
Lyon M, Li P, Ferreira JJ, Lazarenko RM, Kharade SV, Kramer M, et al. A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function. Proc Natl Acad Sci U S A. 2023;120(4):e2212338120. https://doi.org/10.1073/pnas.2212338120.
Guha SK, Singh G, Ansari S, Kumar S, Srivastava A, Koul V, et al. Phase II clinical trial of a vas deferens injectable contraceptive for the male. Contraception. 1997;56(4):245–50. https://doi.org/10.1016/s0010-7824(97)00142-x.
Sharma RS, Mathur AK, Singh R, Das HC, Singh GJ, Toor DPS, et al. Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): a clinical experience. Indian J Med Res. 2019;150(1):81–6. https://doi.org/10.4103/ijmr.IJMR_635_18.
Lohiya NK, Ansari AS, Sadasukhi TC, Pachera S, Khilwani B, Dhaked RK. RISUG® offers early contraception: an experience during phase III clinical trials. J Reprod Healthc Med. 2022;3:11. https://doi.org/10.25259/JRHM_8_2022.
Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G. Azoospermia in rabbits following an intravas injection of Vasalgel ™. Basic Clin Androl. 2016;26:6. https://doi.org/10.1186/s12610-016-0033-8.
Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G. Reversibility of Vasalgel™ male contraceptive in a rabbit model. Basic Clin Androl. 2017;27:8. https://doi.org/10.1186/s12610-017-0051-1.
Colagross-Schouten A, Lemoy MJ, Keesler RI, Lissner E, VandeVoort CA. The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys. Basic Clin Androl. 2017;27:4. https://doi.org/10.1186/s12610-017-0048-9.
Zhao SC, Zhang SP, Yu RC. Intravasal injection of formed-in-place silicone rubber as a method of vas occlusion. Int J Androl. 1992;15(6):460–4. https://doi.org/10.1111/j.1365-2605.1992.tb01138.x.
Zhao SC, Lian YH, Yu RC, Zhang SP. Recovery of fertility after removal of polyurethane plugs from the human vas deferens occluded for up to 5 years. Int J Androl. 1992;15(6):465–7. https://doi.org/10.1111/j.1365-2605.1992.tb01139.x.
Eisenfrats K, Lawrentschuk N, Contraline. Safety evaluation of the ADAM system. https://www.clinicaltrials.gov/ct2/show/NCT05134428; 2023.
Thirumalai A, Amory JK. Emerging approaches to male contraception. Fertil Steril. 2021;115(6):1369–76. https://doi.org/10.1016/j.fertnstert.2021.03.047.
Long JE, Lee MS, Blithe DL. Update on novel hormonal and nonhormonal male contraceptive development. J Clin Endocrinol Metab. 2021;106(6):e2381–e92. https://doi.org/10.1210/clinem/dgab034.
Service CA, Puri D, Hsieh TC, Patel DP. Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options. Ther Adv Reprod Health. 2023;17:26334941221138323. https://doi.org/10.1177/26334941221138323.
Add Comment