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ITHS Interview Profile: Diving into Male Contraception Research with Dr. John Amory

ITHS Interview Profile: Diving into Male Contraception Research with Dr. John Amory

The ITHS interview series is meant to shine a deserving spotlight on individuals who are doing critical work across the vast spectrum of translational science.

In our June installment of this series, we sat down with Dr. John Amory, a renowned researcher in the field of male contraception and the Deputy Director and Associate Principal Investigator of the Institute of Translational Health Sciences (ITHS). He also co-directs the KL2 Multidisciplinary Clinical Research Career Development Program at ITHS. In addition to his role at ITHS, Dr. Amory is a physician at the General Internal Medicine Center at the University of Washington Medical Center, a professor of medicine at the University of Washington, and the section head of General Internal Medicine at the University of Washington.

Dr. Amory spoke to ITHS about his research journey in the burgeoning field of male contraception, what still surprises him, and what breakthroughs he thinks might be just around the corner.

Let’s start at the beginning! Will you give us an overview of the male contraceptive research you are currently involved in?

JA: Our current research focuses on both clinical and preclinical approaches, including hormonal and non-hormonal methods. We are currently conducting a large-scale study involving 450 couples from around the world. This study investigates the hormonal approach to male contraception. This approach, pioneered by Bill Bremner and his colleagues in the 1980s, draws parallels with female contraceptives that use estrogen and progesterone. In male hormonal contraception, we administer testosterone and progesterone to men. This combination suppresses the normal production of testosterone and subsequently stops sperm production in approximately 80% to 90% of men. While it demonstrates decent contraceptive efficacy, there are two challenges we encounter. Firstly, not all men can achieve the required suppression of sperm counts for effective contraception, and the underlying reasons for this are unknown at this time. This has been a persistent challenge in the field.

Secondly, the administration of testosterone and progesterone to men, especially the progesterone component, can lead to side effects such as weight gain and mood changes. The combination of these factors has impeded the progress of hormonal approaches toward reaching the market. Nevertheless, we are currently undertaking a significant Phase 2 study in couples who rely exclusively on a daily testosterone progesterone gel as their contraceptive method. This approach proves effective for men who successfully suppress their sperm production, although it is important to note that not all men achieve this outcome.

Can you share insight into the background work that led to this stage of research?

JA: The story behind the development of male hormonal contraception is quite intriguing. Testosterone was first discovered in the 1930s, and formulations for its use became available in the 1950s. Men began using it, and over time, it was realized that testosterone administration could impact sperm production. Extensive research and experimentation followed, leading to the hormonal approach we are pursuing today. The path to understanding the intricacies of male contraception has involved many scientific efforts and collaborative endeavors.

Reflecting back to my medical school days, advance treatments for ailments such as AIDS, Hepatitis C, and even obesity seemed unattainable. However, we now live in an age of miracles. Look at the CAR T-cell revolution or what Nora Disis is doing with tumor vaccines.

Do you anticipate major breakthroughs in your research within the next 10 years?

JA: In the field of male contraception, there has been a running joke that it is always “five years away” for the past three decades. I can confidently say that progress is being made on multiple fronts. On the hormonal side, we are at an advanced clinical stage, and there are

Novel Inhibitors Bound to ALDH1A2: The Drug Development for Male Contraception

discussions about moving into pretrial phases to seek approval, which would be a significant milestone. This represents a major class of male contraceptives. Additionally, there is a great deal of excitement surrounding non-hormonal approaches. One promising avenue we are exploring is blocking retinoic acid biosynthesis, which shows considerable potential. It is worth noting that several other research groups worldwide are also working on reversible blockage techniques. Earlier this year, a notable study emerged where an enzyme critical for sperm motility was successfully blocked, generating significant attention. It is challenging to predict which approach will be the first to market and achieve substantial success. While my personal goal of having long-acting reversible male contraceptives available for my two sons before they attend college has not yet been realized, I remain hopeful that future generations will have that option.

Can you share how you secure funding for your research?

JA: Funding for our work primarily comes from the National Institutes of Health (NIH), specifically the National Institute of Child Health and Human Development. Within the NIH, there is a dedicated branch called the Contraceptive Development Branch, which focuses on the development of innovative contraceptives. We submit our funding applications to this branch. They have a substantial budget allocated for such research endeavors. In addition to government funding, we also receive support from private sources such as the Gates Foundation and the Male Contraceptive Institute. Furthermore, over the years, I have collaborated with several companies that have provided funding for our projects.

Have you observed a lack of interest from pharmaceutical companies regarding male contraceptives?

JA: Unfortunately, yes.  However, we remain hopeful that this situation will change as we continue to demonstrate excellent efficacy and safety in our research. Developing male contraceptives presents unique challenges in the pharmaceutical industry. The tolerance for side effects in contraception is considerably low compared to other areas of medicine. When developing treatments for conditions like cancer, people are more willing to accept side effects. However, in contraception, we are dealing with otherwise healthy individuals who are taking drugs.

Female contraception is known to cause significant side effects in women, and in rare cases, there have been instances of fatalities. Though the occurrence of such events is minimal, the risks were always justified due to the significantly higher risk of unintended pregnancies. For sexually active women who wish to avoid pregnancy, the benefits of contraception far outweigh the risks involved. However, the same argument cannot be made for men, as they do not face the physical risks associated with unintended pregnancies.

Is there still a significant disparity in funding between female contraceptives and male contraceptives, despite the potential risks involved in female contraception?

JA: Yes, there is indeed a greater amount of funding allocated to female birth control. The risk trade-off is considered more evident in female contraception due to the potential medical complications and even mortality associated with unintended pregnancies. This has posed challenges in the field of male contraceptives. To address this, my colleague in Bioethics is Dr. Gina Campelia and I proposed the concept of “shared risk.” We calculated the risks borne by couples, where the woman’s contraceptive use carries a certain level of risk specific to her. In comparison, if a man uses a contraceptive with associated risks, the shared risk for the couple is lower than that for the woman. Even a small amount of risk, such as one in a million, could be acceptable, considering the significantly higher risk of unintended pregnancies.

How do you see the role of male contraceptives evolving in the future?

JA: The role of male contraception is expected to evolve in the future with the aim of significantly reducing unintended pregnancies. I think the progress of basic science innovations drives translational science, which in turn advances pharmaceutical science leading to the discovery of novel drugs. Reflecting back to my medical school days, advance treatments for ailments such as AIDS, Hepatitis C, and even obesity seemed unattainable. However, we now live in an age of miracles. Look at the CAR T-cell revolution or what Nora Disis is doing with tumor vaccines. I mean, it is so exciting to be a physician-researcher right now.

In addition to male contraceptives, it is crucial to focus on improving sex education for young individuals and addressing affordability and accessibility barriers to contraceptives. By providing comprehensive education and removing outdated requirements, we can empower individuals, especially teenagers, to make informed decisions about contraception. Furthermore, when men have more contraceptive options, it promotes shared responsibility between partners in preventing pregnancies, ultimately benefiting couples and their relationships.

All photos courtesy of Dr. John Amory. Interview by Mihila Gomes and Lisa Stromme Warren. If you have a story suggestion for the ITHS Interview Profile series, please send your ideas to Lisa Stromme Warren.