Some early-stage products target sperm motility and hold potential as an on-demand contraceptive, says Daniel S. Johnston, PhD, chief of the Contraception Research Branch with the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, MD.
“If a man wants to be infertile for six hours, or if it lasts a couple of days, it’s a fascinating concept,” Johnston says.
These are some of the male contraceptive methods now under study:
Nonhormonal, reversible options. In the past decade, various genes and proteins have been identified that are expressed in the male reproductive tract with deletion phenotypes that can lead to male infertility in mice. These phenotypes can arrest teratozoospermia, asthenozoospermia, globozoospermia, spermatogenesis, abnormal spermiation, and other outcomes.1
“You see a couple of on-demand, nonhormonal ones that have the possibility of being contraceptives if they can be successfully developed,” Johnston says. One candidate is in preclinical stages at Weill Cornell Medicine. (See story on potential on-demand male pill in this issue.)
Another possibility targets EPPIN, which is a surface protein on human spermatozoa. It is a sperm-surface drug target for male contraception. This androgen-dependent gene is expressed in the testis and epididymis, vas deferens, seminal vesicle, and adrenal gland.2,3 “These are trying to work their way to clinical trials,” Johnston says.
Gel, Pill Under Consideration
Male contraceptive gel. A clinical trial is underway for a male contraceptive gel that combines daily nestorone (NES) and testosterone.4
Study participants apply 2.5 mL of contraceptive gel to each shoulder and upper arm after showering in the morning. It is left on the skin for at least four hours before washing. Men and their female partners are enrolled in the study. In the efficacy phase, the sperm concentration is reduced, and participants continue to apply the gel so sperm concentrations are maintained at 1 million/mL or less. Enrolled couples agree to stop using other forms of contraception and only depend on the gel for pregnancy prevention. (More information is available at: https://www.malecontraception.center/nes-t-gel.)
Male birth control pill. Daily oral dimethandrolone undecanoate (DMAU) is an active ingredient hydrolyzed to DMA, a novel derivative of 19-nortestosterone. It binds to progesterone receptors and androgen. (More information is available at: https://www.malecontraception.center/dimethandrolone.)
Another single-agent male hormonal contraceptive possibility is 11 b methyl nortestosterone, which binds to the androgen and progestin receptors in vitro. (Find out more at: https://www.malecontraception.center/11-v-methyl-nortestosterone.)
Researchers also are working on a new molecule derivative of 19-nortestosterone. Early research suggested it could suppress testosterone and was well-tolerated in men when given in oral doses with food.4
Vas occlusion. “Vas occlusion [methods] are interesting,” says Heather Vahdat, MPH, executive director of the Male Contraceptive Initiative of Durham, NC. “It’s beneficial to think of a reversible transition from vasectomy. Our partners in that space are developing different polymers injected into the vas.”
The injected polymers act like an implant and is administered in a similar way to vasectomy, which should make it easy for urologists to learn, she notes.
One option is Vasalgel, a multiyear contraceptive that is similar to a no-scalpel vasectomy. A gel is injected into the vas deferens. When a man wishes to restore the flow of sperm, the polymer can be dissolved and flushed out. (Find out more at: https://www.parsemus.org/vasalgel/.) Another version, Echo-VR, uses a polymer hydrogel that is implanted inside the vas deferens. (Find out more at: http://www.contraline.com/product/.) It is minimally invasive outpatient surgery that prevents sperm from traveling through the vas deferens, Vahdat says.
“They compare it more to an IUD [intrauterine device] because it’s in the reproductive organ, and it’s a physical thing that can be removed,” she explains. “These products are being designed to last for multiple years, fitting the role of a mid- to long-acting method.”
This contraceptive possibility could appeal to younger people who want to delay parenthood. “It is a set-it-and-forget-it mentality,” she says. “When you’re young, you don’t want to think about taking a pill every day, so it’s a great option.”
RISUG, developed in India, is another intravasal injectable male contraceptive that can make men sterile for 10 to 15 years. Animal models show that it is completely reversible.5
Recently, RISUG was approved in India, but as a permanent contraceptive solution and not as a reversible contraceptive. “You inject it, and it becomes a permanent plug,” Vahdat says. “Downstream, they plan to make it reversible, but they got it to market as a permanent contraceptive.”
- Kent K, Johnston M, Strump N, et al. Toward development of the male pill: A decade of potential non-hormonal contraceptive targets. Front Cell Dev Biol 2020;8:61.
- O’Rand MG, Silva EJR, Hamil KG. Non-hormonal male contraception: A review and development of an Eppin based contraceptive. Pharmacol Ther 2016;157:105-111.
- Mariani NAP, Camara AC, Silva AAS, et al. Epididymal protease inhibitor (EPPIN) is a protein hub for seminal vesicle-secreted protein SVS2 binding in mouse spermatozoa. Mol Cell Endocrinol 2020;506:110754.
- Gava G, Meriggiola MC. Update on male hormonal contraception. Ther Adv Endocrinol Metab 2019;10:2042018819834846.
- Lohiya NK, Alam I, Hussain M, et al. RISUG: An intravasal injectable male contraceptive. Indian J Med Res 2014;140(Suppl 1):S63-S72.