At last week’s Spotlight on Male Methods of Contraception webinar, hosted by the Community of Practice on Method Choice, we invited Dr. Stephanie Page, Head of the Division of Metabolism, Endocrinology, and Nutrition and Co-Director of UW Medicine Diabetes Institute and Dr. Logan Nickels, Director of Operations and Programs at the Male Contraceptive Initiative to share their insights on the future of hormonal and non-hormonal methods of male contraception. See below for their full presentations, and read on for an additional Q&A.
The following has been edited for length and clarity.
WHAT ABOUT EXISTING METHODS?
What is the regulatory pathway/benefit/risk profile of male condoms?
LN: Male condoms are regulated by the FDA as Class II medical devices. As such, they don’t face a deep regulatory scrutiny, but there are some controls in place. In general, they have little risk to the user, and provide a great benefit in the prevention of pregnancy and STIs. Their efficacy rate is low compared to other modern methods of contraception, but they certainly hold a place in the method mix as a male-controlled, on-demand method with STI prevention.
SP: Male condoms are critical tools for reproductive health for both men and women. However, they have a 14% failure rate, and the failure rate during the first year of use is much higher (important when thinking about adolescent health and contraception).
Should we collectively put efforts toward revitalizing non-scalpel vasectomy?
LN: Non-scalpel vasectomy is certainly one of the best ways that we can engage men today, and we should make efforts to promote its acceptability and awareness in key demographics. This, of course, can be done concurrently with the development of new male methods. Promotion of vasectomy can help create an environment of male engagement where, by the time new methods hit the market, men are literate, interested, and primed to use them.
NEW METHODS IN DEVELOPMENT & HOW THEY WORK
What are your thoughts on self-administration of an injectable male contraceptive?
SP: That is the goal for any injectable contraceptive—for men and women. This is currently being explored with Depo Provera for women. An ideal male injectable would be either self-administered or done in the clinic, based upon user/couple preference and availability of providers
How does the contraceptive gel work? Does it also focus on limiting sperm maturity?
SP: The gel is a combination of testosterone and a progesterone that is absorbed through the skin. It is a hormonal contraceptive gel for men and blocks the maturation of sperm. It takes about 4–8 weeks to be effective and about the same amount of time for the man’s sperm count to return to normal.
Regarding testosterone at two times the physiologic dose—have there been studies on the impact on mood changes and behavior? And if so, did they question partner(s) about any increase in intimate partner violence/discord?
SP: The studies with higher doses of testosterone were done in the 1980s, and changes in mood were not evaluated—nor were there surveys of female partners’ or couples’ perceptions of their relationship. Increases in partner violence were neither reported nor assessed. Current hormonal male methods in development use physiologic doses of testosterone to avoid any health impacts of abnormal hormone levels, and we are evaluating impacts on both partners. Issues of aggression and rage associated with testosterone/androgens have generally been reported in association with high doses of anabolic steroids, which contain much more androgen than men are normally exposed to.
WHY NEW DEVELOPMENTS IN MALE CONTRACEPTION TAKE SO LONG
Can you provide some information on when some of these promising hormonal and non-hormonal methods may reach the market?
LN: As for non-hormonal methods, vasectomy alternatives like vas-occlusive devices could take between 5–10 years. Drug-based non-hormonal contraceptives are likely 15–20 years from market approval.
SP: We hope to have a hormonal male contraceptive available by 2030. This is realistic if current studies go very well and the path toward regulatory approval is reasonable.
Tell us about the regulatory concerns and challenges for both hormonal and non-hormonal methods. Why would this be different from other hormonal contraceptives for women?
LN: There are a few factors at play here. Since we’ll be treating what is presumably a young, healthy population for a very long time, the safety and efficacy barriers will likely be high. Furthermore, since contraceptive use by men doesn’t mitigate any health risks in the user, it remains unclear how side effects and their health risks will be tolerated by regulatory authorities. This is a new pathway with little precedence, and questions will need to be addressed as they arise.
SP: All of what Dr. Nickels has stated is important and accurate. When we think about novel methods for men, it’s important to note that they may use them periodically, just as women do. Few individuals use one method for life. Nonetheless, long term safety issues are important for all healthy individuals.
What have conversations with manufacturers been like, and which manufacturers are engaged for hormonal and non-hormonal methods?
LN: The pharmaceutical industry has largely stayed out of contraception in recent years, presumably due to a strict dollars and cents calculation. Despite the supporting data, there are questions surrounding the potential market. It’s assumed that the development risks associated with creating a drug that has comparatively high safety and efficacy barriers (compared to other areas like oncology) has also made it difficult for the industry to commit to the field.
Why is the development of male contraceptive methods that addresses sperm motility MORE complicated (or slower to progress) than hormonal methods that affect sperm maturation?
LN: Just as it took years of research to illustrate that a sperm count below 1 million/mL was considered infertile, it will take some time to determine the relationship between motility and contraceptive effect. Moreover, sperm remain viable in the female tract for some time after ejaculation, and any drug will need to overcome this barrier in development.
SP: A lot of work has already gone into both developing male hormonal contraceptives and, importantly, understanding the physiological impacts of testosterone. Exogenous testosterone is given to men for other health conditions (i.e. genetic absence of testosterone, surgery causing lack of testosterone, etc.), so we know a lot from other parts of medicine about how to give testosterone and what it does in the body.
CHANGING ATTITUDES TOWARD MALE CONTRACEPTION
How can some of the barriers to vasectomy—other than reversibility—be addressed by newer non-hormonal male contraceptives?
LN: We can mitigate barriers to vasectomy uptake like lack of knowledge, provider bias, and stigma by increasing the number of male methods on the market. When we avail more options to more men, we can create an environment where they are realistically considered as contraceptive users. Creating avenues for men to participate in contraception ensures that they are not considered secondary stakeholders in sexual and reproductive health, which can ultimately increase awareness while decreasing stigma and bias.
What about acceptability? Will women accept—or trust—men’s use of contraception?
LN: Although the data is older, there are studies that support women’s trust of their male partners in contraception use. It seems reasonable that in long-term, monogamous relationships, there would be a degree of partner trust that would facilitate men’s use of contraception. Ultimately, this trust will be very relationship-dependent. As the degree of established partner history and trust decreases, it seems reasonable that women would not—nor should they—trust a male partner to take on sole contraceptive responsibility, as women ultimately bear the majority of risks from pregnancy, health, etc.
Does all this data show that we now need a major focus on male attitudes, knowledge and practices for hormonal and non-hormonal male methods?
LN: Undoubtedly. There has been a lack of focus on men in the past, and much of the data that does exist is outdated and not completely reflective of the ever-changing world in which we live. Attitudes and opinions are also multi-faceted, and a deep illustration of male attitudes, knowledge, and practice could certainly inform developers and industry as we move toward new contraceptive products for men.
WATCH THE FULL PRESENTATION
For more on new and emerging methods of male contraception, check out the full presentation to the Community of Practice on Method Choice.
Curious about future methods of female contraception? Join our mailing list for details on our upcoming webinars.