It has taken almost 20 years and hundreds of thousands of pounds' worth of research by the best medical brains in the world, but at last the Holy Grail of contraceptive science, a 'Pill' for men, is nigh. The prodigious turnover of the male reproductive system - a 100 million sperm are made in the testes every day - has been conquered. The latest clinical trial designed to test the efficacy of the male 'Pill' (not a pill at all but an injection of testosterone administered weekly) is drawing to a close, and the World Health Organisation will publish the results in October. The preliminary data is looking good.
More than 700 couples from nine countries have taken part in two WHO trials since 1986. The first trial showed the male Pill to be more effective than the female oral contraceptive pill. Between 60 and 70 per cent of European men on it stopped producing sperm (the figure is 95 per cent for Chinese and Indonesian men), and in the remainder sperm production fell to less than 3 million per millilitre of semen, a level generally designated as infertile.
The second trial focused on the men who continued to produce sperm despite being on the Pill. The data is expected to show that its contraceptive effect was at least as good as existing methods, according to Dr Fred Wu, a senior lecturer in medicine at Manchester University and a key figure in the WHO trials.
A prerequisite for people who have neither started nor finished having children is that a contraceptive method should be reversible, and the male Pill does not disappoint here either. Within four to six months of stopping it, the testes are producing sperm with their usual vigour. The next stage is a bigger trial involving thousands of couples. If earlier successes are repeated, then scientists say the male Pill could hit the marketplace within two to five years.
To achieve this a substantial commitment from the pharmaceutical industry is needed for the large-scale manufacture and supply of the male Pill. One would assume that drug companies would be falling over themselves to obtain commercial rights to such an effective contraceptive which comes with a high-profile. They are not; they are steadfastly ignoring trial results and calls by eminent scientists to get involved.
Earlier this year, Professor Dennis Lincoln of the Medical Research Council's Centre for Reproductive Biology, took the unusual step of appealing for industry backing. At the International Science Festival in April, he said there was a need for 'major investment to refine the technology' of the male Pill. 'There has been a modicum of interest since then,' he says.
Dr David Griffin, a scientist with the WHO's Human Reproductive Program, says that 'one or two companies' were interested but acknowledges that 'they are making enough money from existing methods . . . there is only limited profitability attached to (the male Pill)'. Tom Delaney, spokesman for a consortium of female Pill manufacturers in Britain who have wide experience of reproductive physiology, says there is little interest in a male Pill. 'One of the companies says it's looking at something, another says it was but not any more,' he says.
Tony Eaton, spokesman for Roussel Laboratories which makes the abortion pill RU486 and is pioneering new female contraceptive technologies, says that on a purely pragmatic level 'it is easier to control one egg a month than millions of sperm each day'.
There are several reasons for this lack of commercial enthusiasm. First, a weekly injection is not particularly appealing for users. The injection acts on the pituitary gland in the brain, blocking production of two other hormones that stimulate the testes to produce sperm. It takes 10 weeks to have an effect, and has been tagged a male Pill by scientists because it works like the female pill, temporarily suppressing fertility. Dr Wu and colleagues at WHO have, however, a longer-acting formulation in the pipeline, which would work for three or four months at a time.
Second, there are concerns about product liability. Pharmaceutical companies had their fingers burnt with the female Pill, and the periodic health scares, particularly breast cancer and blood clots. Now, powerful consumer and health advocacy lobbies make them reluctant to take another step into what, according to one industry figure, is a 'liability minefield' with unknown financial returns. 'Fear of litigation, particularly in America, has driven some companies traditionally involved with contraception out of this area of the business,' according to Tony Eaton.
The WHO trials have so far failed to identify any major side-effects of the testosterone injection, apart from acne, weight gain and oily skin. A slight increase in libido was a problem for some participants. However, the trials so far have been relatively small. There is some concern about heart disease - testosterone can raise levels of unfavourable blood fats - and increased aggression. Then there is the spectre of prostate disease which has been linked with changes in levels of naturally circulating testosterone. It is unlikely that an injection would have the same effect, but until large numbers of men have used it over many years, the potential for trouble remains.
A small trial has just started at St Mary's Hospital, Manchester, which seeks to address some of the problems, by giving men a tablet containing progestogens, which would allow smaller doses of testosterone to be injected. Progestogens occur in both sexes but are associated with female reproduction. They will not cause feminisation in men but metabolic effects (such as weight gain) have to be investigated. Professor Lincoln accepts that including progestogen in a male contraceptive could pose a marketing problem. Men who see sperm production as an indication of their virility might consider it the final straw.
There is a third major problem: who will use the male Pill? Dr Wu says it is impossible to pre-judge what the market will be but believes there is a huge demand for male contraception, as shown by an estimated 60 million vasectomies and 60 billion condoms used each year.
Development agencies and family planning organisations see a male Pill as one of the answers to the population explosion. However, these worthy intentions cannot be reconciled with the demands of the corporate balance sheet. Developed countries are where the money lies but there is a limited market. The most suitable candidates for a male Pill are men in their thirties and forties in stable relationships, who have completed their families or do not want children. Their partners may be unable or unwilling to take the Pill. They may be reluctant to have a vasectomy. Would a hormonal preparation be any more attractive to them?
In addition, despite the avowed commitment to a male Pill by WHO, Dr Griffin estimates a figure of only dollars 5m committed to research over 20 years. A spokeswoman for the Medical Research Council says male Pill research is 'very active' but funding far from substantial in comparison with other reproductive projects.
If contraception were really to become an equitable reality between male and female - an argument that supporters of the male Pill frequently offer as a good reason for forging ahead with research - the target group would need to be younger men who may have several relationships before wanting to father children. And despite cultural changes cited by scientists, with more men willing to share the burden of contraception, how many women would trust a man who told her that he was on the Pill?
Dr Pramilla Senanayake, assistant secretary general of the International Planned Parenthood Federation, believes that any new contraceptive method for men must be a 'breakthrough'. In the end, however, the male Pill may turn out to be more of a white elephant than Holy Grail. At a time when the need for better contraception to stem population growth and protect against the Aids virus has never been greater, there is a danger it may prove to have been no more than a challenging brain-teaser for scientists.
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