What are the next steps for male contraceptive research?

A concerted research effort in the following seven areas would ensure that a new male contraceptive is available sooner rather than later:

1. RISUG has been shown to provide years of contraception for men with a single ten-minute procedure. It is reversible in animals (including nonhuman primates) and is also likely to be reversible in humans. Now that syringe design problems have been resolved, the final phase of clinical trials is ramping up again in India. Indian health officials can support this work by continuing to support the clinical trial, publishing the results of previous follow-up studies sooner rather than later, and approving the reversal study that is currently stalled. Meanwhile, RISUG is being developed in the U.S., as “Vasalgel™”, by a small nonprofit foundation with a savvy, experienced consulting team. When the foundation finishes manufacturing Vasalgel and conducting basic toxicology and efficacy tests, larger foundation and government bodies can meet men’s demand for this contraceptive by teaming up with the small foundation on further development. Approval under the new harmonized U.S./European Union/Japanese regulations would open the door to approval in most of the rest of the world. The small foundation will not have enough funding to cover the entire $4-5 million project—an amount that is tiny compared to the potential savings in avoided unintended pregnancies and maternal mortality (not to mention the self-determination that will finally be available to men).
2. Studies are currently underway on ultrasound contraception in rats (University of North Carolina), monkeys (University of California), and dogs (an Italian university, for permanent sterilization). We already know enough from these studies to confirm that ultrasound works in rats and dogs and that Dr. Fahim’s results in the 1970’s were not a fluke. If these current studies, which are set to conclude in 2011, meet with continued success, it will be incumbent upon researchers and funders to explore the long-term effects of repeated use of this method. A simple, cheap contraceptive that can be either medium-term or permanent would be an incredible boon.
3. Dr. Christina Wang and Dr. Ronald Swerdloff’s studies on the effect of heat as a booster for hormonal methods should be encouraged and expanded, and Dr. Roger Mieusset and Dr. Louis Bujan’s proposed study on artificial cryptorchidism (or a similar study by Drs. Wang and Swerdloff) should be funded. Additional knowledge on how heat affects the testes and DNA (and whether it has any impact on hormones) might allow us to feel more confident in using artificial cryptorchidism, a method that is free and already available to men everywhere in the world.
4. Tripterygium wilfordii (TW) and Tripterygium hypoglaucum (TH) are readily available and known to have contraceptive effect; since they have been used for millennia, their side effects are well understood. In conjunction with Chinese researchers, the World Health Organization conducted research to successfully purify extracts of TW in the 1980s and 1990s. Rather than allowing this research to go to waste, systematic studies must clarify the optimal contraceptive dose.
5. Carica papaya, a plant-based contraceptive extract being studied in India, needs the input of a chemical synthesis team in order to move forward as a standardized product. A complete male contraception research program would include a center for research on plant-based contraceptives that would include enough chemical synthesis and purification people-power to study carica papaya, tripterygium wilfordii, and two to three others (possibly including oleanolic acid, from South Africa, and gandarusa, being studied in Indonesia) as well as running preclinical and small clinical trials.
6. It would not take much to get more information on High Intensity Focused Ultrasound (HIFU) as a vasectomy alternative. This extremely quick nonsurgical procedure (under one minute) has already been shown feasible in dogs. It would take $1-2 million to revive the startup company working on it, acquire the intellectual property, refine the equipment, and conduct preliminary human trials.
7. If all the methods above-- most of which have been shown to work in either humans or dogs-- were fully funded, a concerted effort in male contraception would then include slightly earlier-stage research such as gamendazole and RAR-antagonists.

What about intriguing early leads such as CatSper? Adding new methods to the pipeline is also important. However, our current research environment makes it easier to spend money on dozens of early leads than to finish clinical trials on the methods already known to work. Though it is tempting to pursue the next great discovery around the corner, it is not acceptable to spend money doing so if we do not plan to finish the jobs already started.

Universities, government agencies, and research organizations each tend to specialize in a particular stage of research. All too often, no one agency keeps track of the big picture. Ongoing projects can thus run out of money at the halfway point at the same time as new projects are being funded.

Not only do highly-advanced methods such as RISUG need funding, a further crop of methods (vitamin A receptor antagonists, l-CDB-4022, gamendazole…) has been shown to work in animals. Further basic contraceptive research cannot be justified until we show that we have a fully functioning, integrated system by taking the above contraceptives as far as they can go — which will, hopefully, be to market and to end users. Only then can we justify spending limited funds on basic research or on looking for nontoxic variants of additional compounds. Only then will we know that it is not destined to be research in a vacuum. And only then will we know that this new research will not also be abandoned halfway.

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