Why targeted, nonhormonal male contraceptives?
Scientists have taken three main approaches to male contraception:
- A hormonal approach (along the lines of the female Pill), which is being studied for men in the form of implants and shots;
- A nonhormonal but systemic approach (such as the blood-pressure medication nifedipine), which is taken orally and affects the whole body;
- A nonsystemic approach, which targets the sperm directly without impacting the rest of the body.
All else being equal, it would seem logical to choose the most targeted method—the one that doesn’t have unknown effects on every system in the body. Hormonal manipulations have myriad consequences—consequences we still don’t fully understand even in women, despite decades of use of the Pill in younger women and hormone therapy in older women.
Systemic use of hormones can have unintended consequences.
The results of the Women’s Health Initiative study are a case in point. In July 2002, this study made front-page news and scared millions of women when it turned accepted wisdom on its head and told us that the popular combination of horse-derived estrogens (Premarin) plus the synthetic progestin MPA (medroxyprogesterone acetate) seems to lead to a slightly increased risk of heart disease, breast cancer and stroke, rather than preventing heart disease as was previously thought (Rossouw et al., 2002). (For details of the study, click here.)
Approved as pharmaceuticals in 1944, estrogens will probably have been on the market for 100 years before we understand the pros and cons of different estrogens, progestins, delivery systems, and timing. A parallel experiment, only this time with men as guinea pigs, would be a tragic demonstration that we have learned little from our past.
Hormonal methods can make optimal health care nearly impossible for today’s harried doctors. The effects of hormonal manipulations are too numerous to count, and it is difficult for most doctors to keep track of them all and watch for them in patients, even if doctors can get reimbursed for the necessary tests. For example, the estrogen in the Pill increases sex hormone binding globulin (SHBG), which binds up not just estrogen but also thyroid hormones, which are responsible for maintaining mood, energy, and the function of nearly every organ in the body. This can worsen the situation for the estimated 5-15% of women who already have thyroid disturbances (Wang & Crapo, 1997) and cause thyroid problems in women whose thyroid function is borderline. These subtle changes in mood and energy are likely to go undetected, especially since SHBG is not measured in the most common thyroid test.
Women also have a small natural supply of testosterone that is crucial for maintaining energy, muscle mass, and sexual desire. SHBG binds testosterone, resulting in a second contraceptive effect of female hormonal methods: women often lose interest in sex! (Sarajari et al., 2004) This side effect of the Pill is additional motivation for a significant percentage of the men who volunteer to take responsibility for contraception within their relationship.
Even nonhormonal methods can have effects throughout the body.
Nonhormonal methods that are still systemic avoid many of these unintended consequences, but they have potential pitfalls of their own. For example, the common blood pressure medication nifedipine is thought to have contraceptive effect and has already been extensively safety-tested in hypertensive men. Logically, however, one would want to be careful using a medication that lowers blood pressure in men who don’t have high blood pressure to start with.
Using a hormonal or systemic method can be effective, but it can also have unintended consequences. A more targeted approach is generally more appropriate, yet hormonal methods continue to draw a large share of research funding. To understand this, one must understand their advantages as subjects of study.
Hormonal methods have more advantages for their developers than their users.
Hormonal methods have three significant advantages to scientists, funders, and pharmaceutical companies: they are difficult to perfect, scientifically “sexy,” and potentially profitable. Not surprisingly, these are advantages to the research sector and not to the end user.
The difficulties in perfecting hormonal male contraception are legion: it is not easy to stop sperm at their source, with high enough accuracy, despite racial differences in effectiveness, and without side effects. And it is challenging to know which combination of hormones to use, in which dosage, via which delivery system. Pundits have been saying that hormonal male contraception would be on the market in “five to ten years” for more than 15 years now (e.g. Contraceptive Technology Update, 1989), and the goal will probably stay five to ten years out for many years to come. Thus scientists have a steady supply of research opportunities — and a steadier career path than for other methods — as long as public-private partnerships continue to provide funding.
In what sense is nonhormonal male contraceptive development not “sexy?” For scientists, there is very little professional respect to be gained from working on a common-sense contraceptive that focuses on the vas deferens, the tiny tube that all sperm flow through, or on even more low-tech methods. Research based on male anatomy is not as prestigious as immune, endocrine, or genetic approaches. It is much more intriguing to try to halt sperm production — and much easier to get funding to try to do so, especially given the profit factor. This factor is even more powerful now that a large percentage of the male contraceptive research done by the U.S. government is done in partnership with industry (CONRAD, 2002).
Profits and cost are factors.
Profit becomes a factor because a male “Pill” or monthly injection is patentable and needs to be purchased every month, over and over, by the end user, his insurance company, or his national health service. Like the female Pill, this type of formulation would lead to a huge, steady stream of profits for the company marketing it — which, unfortunately, means a steady stream of money out of the wallet of the man using it. (For an analogy, click here.)
A long-acting or low-cost male method thus not only holds little appeal for a pharmaceutical company but could actually be a net negative to profits — especially if the man is in a committed relationship and his partner stops buying her Pills from the company every month. Thus, it is illogical to expect pharmaceutical companies to develop such a contraceptive. Its development falls squarely on the shoulders of government agencies and the nonprofit sector.
Despite these powerful factors converging to make sure that almost all male contraceptive research is done on short-term hormonal or systemic methods, the men of the world deserve a nonsystemic, and certainly nonhormonal, long-term method. Men must not let the same path be laid out for them as was laid out for women.
For nearly three decades, women were unwitting subjects in a global hormonal experiment. They took a Pill that contained as much as seven times as much estrogen and ten times as much progestin as in the current formulation (Snider, 1990). Seven and a half million women were using oral contraceptives by the time researchers announced that half as much hormone would suffice, while causing fewer blood clots, heart attacks, and strokes! Though perhaps that type of grand experiment could be justified at the time based on the dearth of other options, repeating it on men is not justifiable, given that there are simpler, more elegant, safer methods to pursue.
For all these reasons, research must focus on targeted, nonhormonal approaches that affect a minimum number of body systems. Fortunately, several promising methods fit that description. We will first discuss methods that target the vas deferens, the tiny tube that carries sperm from the testes to the penis.
Next section: New Vas Deferens-based Methods of Male Contraception
