Had there been a male contraceptive pill in 1976, I might not be here to write this. That year my mum – may she rest in peace – was told by her doctor to come off the pill, after 12 years, because of health worries. “She said to the doctor, ‘I’ll get pregnant,’” my dad recalls. “And in a very short while, she was.” He explains, much to my discomfort, that although my parents switched to condoms, I was conceived because “sometimes you feel reckless”. But if a male pill had existed, my dad says, he would definitely have used it.
So why didn’t it? It certainly wasn’t because of a lack of scientific interest. Gregory Pincus, who co-invented the female pill, first tested the same hormonal approach on men in 1957, and various hormonal and non-hormonal methods have been explored since. Although attitudes among those who might use a male pill were once considered a daunting obstacle, it’s now clear that many men want a new option.
But we’re still waiting. Developing a method that men would accept has brought decades of frustration, yet researchers are confident that they are close to overcoming the scientific barriers. But, crucially, drug makers’ commitment to contraceptives has always been tentative, particularly with products for men – and today, the whole contraceptive industry is struggling. So who is actually going to make the male pill happen?
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In the 1970s, when my dad might have used the pill, prospects seemed better in some ways. Male fertility control was an active research field, with governments backing various ideas to limit overcrowding on Earth. One product my dad might have been interested in – a non-hormonal drug called gossypol – was being tested on a scale unmatched since. At the UN’s 1974 World Population Conference, Elsimar Coutinho, today a famous sex and fertility doctor in Brazil, was promoting the drug, which he was testing on men at the Federal University of Bahia. However, attitudes surrounding sex and reproduction can be unpredictable, and not everyone was convinced of its worth.
“The conference hall was full of women,” Coutinho says on the phone, his gravelly voice matching his website’s picture of a suave doctor with slicked-back grey hair. “I was going to tell them, ‘Now you don’t have to take pills if you don’t want.’” Yet, having determined their own fertility through the contraceptive pill for little more than a decade, his female audience were determined not to relinquish control. “To my surprise, I was shouted down and booed out.”
Despite such reactions, poorer countries with fast-growing populations found gossypol appealing because it could be extracted cheaply from cotton farming waste. Coutinho also worked with the Chinese government, which in 1972 ran gossypol trials with 8,806 men. Daily doses successfully reduced sperm counts enough to satisfy researchers, but side-effects were a cause for concern. One notable problem was that 66 of the men had low potassium in their blood. More importantly, sperm levels in many men didn’t return to normal when they stopped taking the drug.
Researchers continued tests for years, showing that, in rats, gossypol doesn’t just stop sperm moving, but also damages the lining of epididymis ducts, which store sperm. Eventually, an October 1986 symposium in Wuhan, China – whose sponsors included the Chinese government and the World Health Organization (WHO) – concluded that gossypol was “of little interest”.
The science is difficult but not impossible. What the field really lacks is a champion with lots of money and enthusiasm
Attempts to revive interest in Brazil after fresh trials put the potassium problem down to the Chinese diet also foundered, and in 2001 the gossypol saga came to an end. Coutinho mischievously suggests machismo in government may have been a contributing factor. “We worked on this for many years and realised men are very afraid of losing virility,” he says. “Maybe those judging our application were among them.”
But my dad would not have seen a male pill as a threat to his virility, and I too would be interested in rather than threatened by the idea – I believe it would benefit, rather than harm, the sex my partner and I have. Are we unusual?
In fact, plenty of men are interested in a male pill. A 2005 study found that more than half of 9,000 men from across the world were keen. In 2011, Susan Walker at Anglia Ruskin University in Chelmsford published a study of 54 men in an unnamed town in England. Twenty-six of them said they would take it. “They were not concerned about losing fertility – as long as they could be sure of regaining it,” Walker stresses.
The rest, split between “no” and “don’t know”, showed some gender-based reluctance. “It’s a strange idea,” one man said. “I’m so used to women taking the pill.” Those who were unsure were more concerned about side-effects, Walker notes. “They said: ‘I’ve seen what the pill does to my girlfriend’, ‘What would the long-term effects on my fertility be?’, ‘Could I be sure my fertility would return?’ – that kind of really quite sensible concern.”
The survey also included 134 women, roughly half of whom would let their partners use a male pill. However, more than half were worried that men would forget to take it; just one in six of the men had this worry. But, says Richard Anderson, a professor of reproductive science at the University of Edinburgh: “Whenever there’s a study published, a radio journalist will walk up and down the high street in their local town and ask women whether they would trust a man to take a pill, and of course they all run for the hills. But if you ask a woman if they would trust their partner – who they share children, their bank account and a bed every night with – then you’re going to get a different answer.”
A single crumpled piece of A4 paper on an almost-bare wall in Anderson’s office illustrates how hormonal male contraceptives work, reducing men to brain and balls. In the brain, it picks out the hypothalamus and pituitary gland. In the testicles it shows cells that make testosterone, and the tubules they neighbour, where sperm are made. Progestogen hormones like those used in female pills can stop the glands in a man’s brain making luteinising hormone and follicle-stimulating hormone. The absence of these hormones stops the testicles producing sperm and testosterone. Testosterone replacement is given, along with progestogens, to avoid undesirable effects such as weaker muscles and reduced sex drive.
The Edinburgh trials attracted a lot of media attention. “‘100% success’ for male pill trial”, trumpeted the BBC in 2000, reporting on the suppression of sperm production in 30 men – reportedly without side-effects – from a combined progestogen pill and testosterone-releasing implant. Both hormones came from the Dutch drug company Organon, which, after what Anderson calls “a lot of persuading”, began to pay attention. But a larger clinical trial with Germany’s Schering threw up “adverse events” such as acne, sweating and effects on weight, mood and sex drive. Some of these were serious and even life-threatening, including one attempted suicide.
This would prove to be the pinnacle of big pharma’s interest. Herjan Coelingh Bennink, global executive vice-president in Organon’s reproductive medicine programme until 2000, echoed Coutinho’s account of his experience with gossypol. “At board level it was only middle-aged white males,” Coelingh Bennink recalls. “I tried to explain how important it could be, but they never got further than saying to each other, ‘Would you do it?’ ‘No, I wouldn’t do it.’ It was not considered male behaviour to take responsibility for contraception.”
Since then, he and others have continued in the field, but low profit margins have kept drug companies away. According to Anderson, the biggest obstacles are not scientific. “Getting male fertility down to acceptable levels is difficult but not impossible, and there have been many years of experience of how to do that,” he says. “What the field has really lacked is a champion with lots of money and enthusiasm. Thereafter you get industrial involvement.”
Lately, one particularly striking approach has been taken by Nnaemeka Amobi from King’s College London, who is developing a non-hormonal “instant male pill”. Also known as the “dry orgasm pill”, Amobi’s contraceptive stops men releasing semen and the sperm it contains. He stresses that otherwise the normal physical processes of a man’s orgasm are unaffected.
“The movement of semen from the testes to where it stays until ejaculation happens long before climax,” Amobi says. “As soon as you’re aroused, spermatic fluid is moved towards the seminal vesicles and prostate. Our pill stops that initial movement by inactivating the tubes that propel fluid from the testes to the prostate.”
Amobi and his fellow researchers started from two existing drugs that had caused dry orgasms as an undesirable side-effect. They redesigned the drugs to remove the original intended actions and focus on this. Animal tests suggest they have succeeded. “We used rams because rats and rabbits don’t have seminal fluid like humans,” Amobi says. “We tried boars, which produce 250ml of semen. Can you imagine that? Rams have 1ml, closer to humans’ 2-5ml.”
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These tests show the method could become effective within 3-4 hours, and wear off after a day. “A woman can say, ‘Here’s the pill – let me see you take it’,” Amobi says. And as well as avoiding pregnancy, preventing semen emission should help reduce sexual transmission of semen-borne diseases, such as HIV.
One potential backer interested in the drug was the Parsemus Foundation, a small private organisation based in Berkeley, California. Ultimately, though, its founder, Elaine Lissner, faced a tough choice between funding Amobi’s research and another promising new male contraceptive technology. She chose to spend the foundation’s limited cash on the latter. Amobi isn’t bitter because, in his opinion, Lissner is the main reason people still talk about male contraception. But she still has regrets. “It’s shocking that they can’t get backing for the first new idea about HIV transmission-prevention in ages.”
Lissner dislikes hormonal approaches because of their side-effects, and also dislikes risk. She is therefore researching a “hydrogel” that can be injected into the vas deferens – the tube linking the epididymis to the penis.
Called Vasalgel, it lets through semen but not sperm, and is intended to be washed out by another injection when men want the use of their sperm back. The blocked sperm are cleared from the epididymis and eaten up by immune cells, as happens normally if a man hasn’t had an orgasm for a while. Lissner publicises Vasalgel energetically, and one glance at its thriving Facebook page should dispel any doubts that men would be interested. “People are crazy for Vasalgel, desperate for it,” she says. “We have over 32,000 people on the mailing list waiting to hear about clinical trials.”
One man who is keen to try it is Justin Terry, a married 30-year-old machinist who makes vehicle parts in Alabama. He and his wife don’t have children, and she is taking the contraceptive pill. “We’ve been married 10 years,” Terry says. “She doesn’t want kids and neither do I, really. She wants to get off the pill.” It gives her tender breasts, and she is concerned about adverse effects of continuing to take it. Terry has also considered vasectomy (as have I), but has hesitated because it is more invasive and not completely reversible. “Vasalgel sounds like it will be reversible and would involve much less invasive surgery,” he says.
Parsemus’s efforts have been helped by the David and Lucile Packard Foundation, also based in California, which provided $ 50,000 to help them test Vasalgel in baboons. “We expected to be out of money last year and we’re not,” Lissner says. “But the clinical trial is half a million dollars, so that’s a different scale. Beyond that, it’s multimillions.” The trial will involve about 30 men and will test Vasalgel as a vasectomy alternative, without looking at reversibility.
Knowing the field’s status, Lissner is not relying on government or the pharmaceutical industry. Instead, she is looking for backing from wealthy social investors – and potential users – and is publicising what might be possible in the field to bring interested parties together. “The difference is that we have built an infrastructure where the public is able to channel its support,” she says.
On Blithe’s suggestion, I watch a Channel 4 documentary called The Great Sperm Race, which shows the journey sperm make through a woman’s uterus to her fallopian tube. It has people dressed in white as sperm, and they die in vast numbers. From the millions of sperm ejaculated, 20-100 get close enough to the egg to try to fertilise it.
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As I watch, I imagine the white-clad actors instead represent the many possible male pills. There have been, and still are, masses of ideas – far more than I have been able to mention here. And yet, like the unsuccessful sperm, many have fallen by the wayside. I think of the contraceptive drug industry’s current status and I can’t help think we have missed its fertile period. If the perfect idea were to fight its way through development today, there is only a tiny chance that there would be a partner to meet it and eventually produce a fully formed male pill from it.
It seems obvious that if a new male contraceptive does make it to maturity, it will be thanks to the efforts of people such as Blithe and Lissner. They, as much as anyone, are trying to create environments where the right technology can take seed. But without keen interest from the traditional contraceptive industry, that will require an enormous effort. Lissner’s energetic attempts to consolidate support from men like Justin Terry, my dad and me could prove critical.
Lissner is adamant that the ideas that seem to have faltered are not dead – they’re just resting. “We keep collecting new methods, and never finish the ones we have,” she fumes. “Pick one and make something! Finish the job!”
• A longer version of this article first appeared in Mosaic and is republished here under a Creative Commons licence.
What happened to the male contraceptive pill?
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