Regulatory challenges of new male contraceptive methods.
androgen
hormonal male contraception
non‐hormonal male contraception
progestin
semen analysis
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
revised:
26
06
2024
received:
13
02
2024
accepted:
19
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
Progress in male contraception development faces the challenge of a lack of regulatory precedent and guidelines on the evidence (trial design and primary endpoint) required for marketing approval. Moreover, the development of a male contraceptive is complicated by the fact that the clinical treatment effect; prevention of pregnancy, is not measured in the patient receiving the intervention. Regulatory precedent and guidelines exist for female hormonal contraceptives but their applicability to male contraceptive products likely varies based on the mode of action and the anticipated pharmacodynamic effects of the product. The unique attributes of male contraceptives, including the frequent delay between the intervention (e.g., vasectomy and hormonal methods) and ultimate contraceptive effect, sperm suppression near azoospermia, and pregnancy prevention need to be addressed. This article describes the regulatory challenges faced by developers of male contraceptive products and offers proposals, paving the way for the development of both hormonal methods and non-hormonal approaches. Our article intends to suggest the directions but cannot substitute for the advice of regulatory agencies.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 American Society of Andrology and European Academy of Andrology.
Références
Food and Drug Administration. Establishing effectiveness and safety for hormonal drug products intended to prevent pregnancy guidance for industry. 2019. Available from: https://www.fda.gov/regulatory‐information/search‐fda‐guidance‐documents/establishing‐effectiveness‐and‐safety‐hormonal‐drug‐products‐intended‐prevent‐pregnancy‐guidance
European Medicines Agency. Clinical investigation of steroid contraceptives in women—scientific guideline. 2005. Available from: https://www.ema.europa.eu/en/clinical‐investigation‐steroid‐contraceptives‐women‐scientific‐guideline
Food and Drug Administration. FDA guidelines: the extent of population exposure to assess clinical safety: for drugs intended for long‐term treatment of non‐life‐threatening conditions. 1995. Available from: https://www.fda.gov/regulatory‐information/search‐fda‐guidance‐documents/e1a‐extent‐population‐exposure‐assess‐clinical‐safety‐drugs‐intended‐long‐term‐treatment‐non‐life
European Medicines Agency. ICH Topic E 1 population exposure: the extent of population exposure to assess clinical safety. 1995. Available from: https://www.ema.europa.eu/en/documents/scientific‐guideline/ich‐e‐1‐population‐exposure‐extent‐population‐exposure‐assess‐clinical‐safety‐step‐5_en.pdf
Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30:2‐13.
McLachlan RI, O'Donnell L, Meachem SJ, et al. Hormonal regulation of spermatogenesis in primates and man: insights for development of the male hormonal contraceptive. J Androl. 2002;23(2):149‐162.
World Health Organization Task Force on the Regulation of Male Fertility. Contraceptive efficacy of testosterone‐induced azoospermia and oligozoospermia in normal men. Fertil Steril. 1996;65(4):821‐829.
Aaltonen P, Amory JK, Anderson RA, et al. 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. J Androl. 2007;28(3):362‐363.
Wang C, Meriggiola MC, Amory JK, et al. Practice and Development of Male Contraception: European Academy of Andrology and American Society of Andrology Guidelines. Andrology; 2023. doi:10.1111/andr.13525. Epub ahead of print.
Behre HM, Zitzmann M, Anderson RA, et al. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab. 2016;101(12):4779‐4788.
Mommers E, Kersemaekers WM, Elliesen J, et al. Male hormonal contraception: a double‐blind, placebo‐controlled study. J Clin Endocrinol Metab. 2008;93(7):2572‐2580.
Mahabadi V, Amory JK, Swerdloff RS, et al. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009;94(7):2313‐2320.
Ilani N, Roth MY, Amory JK, et al. A new combination of testosterone and nestorone transdermal gels for male hormonal contraception. J Clin Endocrinol Metab. 2012;97(10):3476‐3486.
Roth MY, Ilani N, Wang C, 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.
Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C; Hormonal Male Contraception Summit Group. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412‐1420.
Trussell J, Portman D. The creeping Pearl: why has the rate of contraceptive failure increased in clinical trials of combined hormonal contraceptive pills? Contraception. 2013;88(5):604‐610.
Campbell MJ, Lotti F, Baldi E, et al. Distribution of semen examination results 2020 – a follow up of data collated for the WHO semen analysis manual 2010. Andrology. 2021;9(3):817‐822. doi:10.1111/andr.12983
O'Rand MG, Silva EJ, Hamil KG. Non‐hormonal male contraception: a review and development of an Eppin based contraceptive. Pharmacol Ther. 2016;157:105‐111. doi:10.1016/j.pharmthera.2015.11.004
Mauck CK, Vincent KL. The postcoital test in the development of new vaginal contraceptives†. Biol Reprod. 2020;103(2):437‐444. doi:10.1093/biolre/ioaa099
Gruber FS, Johnston ZC, Barratt CL, Andrews PD. A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity. eLife. 2020;9. doi:10.7554/eLife.51739
USFDA. Investigational device exemption (IDE). 2022. Available from: https://www.fda.gov/medical‐devices/premarket‐submissions‐selecting‐and‐preparing‐correct‐submission/investigational‐device‐exemption‐ide
Official Journal of the European Union. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Available from: http://data.europa.eu/eli/reg/2017/745/oj
Noman MAA, Kyzer JL, Chung SSW, Wolgemuth DJ, Georg GI. Retinoic acid receptor antagonists for male contraception: current status. Biol Reprod. 2020;103(2):390‐399.
Matzuk MM, McKeown MR, Filippakopoulos P, et al. Small‐molecule inhibition of BRDT for male contraception. Cell. 2012;150(4):673‐684.
Lishko PV, Kirichok Y. The role of Hv1 and CatSper channels in sperm activation: hv1 and CatSper channels in sperm activation. J Physiol. 2010;588(23):4667‐46672.
Balbach M, Rossetti T, Ferreira J, et al. On‐demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun. 2023;14(1):637.
Salicioni AM, Gervasi MG, Sosnik J, et al. Testis‐specific serine kinase protein family in male fertility and as targets for non‐hormonal male contraception†. Biol Reprod. 2020;103(2):264‐274.
Chang Z, Qin W, Zheng H, et al. Triptonide is a reversible non‐hormonal male contraceptive agent in mice and non‐human primates. Nat Commun. 2021;12(1):1253.