Updates in Male Contraceptive Agents

Male contraceptive agents have been highly anticipated as the next step in contraception innovation. To date, several hormonal agents have been developed and tested for safety and efficacy, with three products: Nesterone with Testosterone gel (NES/T), 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MTNDC), and dimethandrolone undecanoate (DMAU). Currently, NES/T is leading in development and contraceptive ability.[1,2]

NES/T has been formulated as a gel containing Nesterone, also known as segesterone acetate (a “pure” progestin presently found in Annovera) in combination with testosterone. This product has passed phase I and phase IIa trials, and is currently in phase IIb trials with a predicted conclusion date for February 2021.[2] NES/T is formulated as a topical gel that can be applied to the shoulders daily with the drug action of sperm count/development suppression to thresholds that should translate to effective contraception with normal hormonal function.[2]

11β-MTNDC is a 28 day daily use oral tablet formulated to act as similarly to 28 day contraceptive regimens for females. The drug acts as a hormonal suppressant to impair spermatogenesis. It is currently in phase I trials, therefore its extent of efficacy and long term effects is still to be determined.[3]

DMAU is formulated as both a 28 day daily use oral tabletand a long acting injection (dosing frequency to be determined). DMAU has a similar action to 11β-MTNDC, and is also still under early investigation in phase I trials.[4]

Despite the difference in administration routes, these drugs have similar effects on male sex hormones. They suppress brain hormones called “gonadotropins,” which results in profound reduction of endogenous testosterone production. The low levels of testosterone thereby result in a reversible reduction in spermatogenesis within the testicles to the point of sperm development impairment, but not enough to cause lasting hormonal changes as of current trialing.[1] The drugs themselvesact as a supplement in place of the person’s own testosterone to maintain male hormonal functions. Current trialing has noted that each product does have the adverse of effect of minor acne at the beginning of treatment.[2,3,4] Participants also noted their concern with a lack of STI prevention.[5] However, with only low risk adverse effects demonstrated thus far in studies, and participants reporting these methods as “easy” treatment regimens to follow, these products appear acceptable for use in the eyes of the American male population.[2,3]

The utility of these products, if approved, is still being questioned. In one US survey participants stated that they would greatly consider the Nestorone topical gel as a first choice method of contraception. 6 However, based on previous contraceptive studies in the US and the United Arab Emirates, the percentages of men using methods of contraception is roughly 59% and 20% respectively.[7,8] According to a 2017 CDC study on contraception use in the U.S., approximately 42.5 million men (59% of the polled 72 million men in the study) engage in contraception practice.[7] With only just over half of the US male population reporting the use of contraception, it is understandable that drug marketing could be seen as risky to pharmaceutical companies if the products are still only in development.

The major obstacles to further drug development are marketing based support and acknowledgment. With only one major organization funding the research on these products, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, progress is very slow.[1] No major pharmaceutical marketing companies have made any public statements on male contraception as a new drug category, it may take longer than the full trialing time to hear more on product availability in the market.

These novel products, NES/T gel, oral DMAU and 11β-MNTDC, if proven to be effective contraceptive agents, would constitute a suitable alternative for couples that wish to participate in planned parenting, but wish to avoid or cannot use contraceptives indicated for females. Although the rate of progress is slow, it is substantial and the availability of male contraception agents may arrive within the next decade. For more information please follow the link to the Eunice Kennedy Shriver National Institute of Child Health and Human Development website (https://www.nichd.nih.gov/).

References

1. Long JE, Lee MS, Blithe DL. Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods. Clin Chem 2019;65(1):153-160.
2. Wang C, Page S, Nagia A, et al. Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception. https://clinicaltrials.gov/ct2/show/NCT03452111. Dec 11, 2019.
3. Wu S, Yuen F, Swerdloff RS, et al. Safety and Pharmacokinetics of Single-Dose Novel Oral Androgen 11β-Methyl-19-Nortestosterone-17β-Dodecyl carbonate in Men. J Clin Endocrinol Med 2019; 104(3):629-638.
4. Gava G, Meriggiola M. Update on male hormonal contraception. Ther Adv Endocrinol Metab. 2019;10.
5. Glasier A. Acceptability of contraception for men: a review. Contraception 2010; 82(5):453-456.
6. Roth M, Shih G, Ilani N, et al. Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial. Contraception 2014;90(4):407-412.
7. Daniels K., Amba J. Current Contraceptive Status Among Women Aged 15–49: United States, 2015–2017. CDC. https://www.cdc.gov/nchs/products/databriefs/db327.htm. Accessed December 22 2019.
8. Ghazal-Aswad S, Zaib-Un-Nisa S, Rizik DE, et al. A study on the knowledge and practice of contraception among men in the United Arab Emirates. J Fam Plann Reprod Health Care 2002; 28(4):196-200.
9.  

Photo by Anna Shvets on Pexels.com

About the Author

Steven Gonzalez, PharmD Candidate is a pharmacy student in the Chicago College of Pharmacy Class of 2022 at Midwestern University, with the dream of becoming a successful clinical pharmacist. In his time off, Steven enjoys spending time with his friends and family, going hiking, fishing, and watching classic movies.

Article reviewed by Brooke Griffin, PharmD, BCACP