In 2005 – just as in 1905, when the word hormone was first coined – there are two hormone ‘tracks’. Science-based endocrinology is one road, while the other is extravagant quackery, which, on the face of it, is making pretty much the same claims as were made a hundred years ago. The logic of today’s breed of rejuvenators is not dissimilar to that of Brown-Séquard, the pioneer of hormones, who ended an otherwise distinguished career by trying to restore that which was lost, by injections of semen. The gist of the rejuvenators’ argument is this: since the levels of many hormones are known to fall with age, restoring hormone levels to those of youth will hold back the years. The truth about hormones is not quite that obvious.
Trying to regain youth is a pursuit that is millennia old. The Bible tells us, rather indiscreetly, that King David had a significant loss of ‘heat’ as he reached his twilight years. A solution was found in the form of Abishag (surely a case of nominative determinism if ever there was one), a virgin from the Shunammite tribe. ‘Let her lie in thy bosom that my lord the king may get heat,’ said his counsellors, who possibly were hoping for the idea to catch on so that they too could have a maiden bed-warmer. Then there was Ponce de León, the sixteenth-century explorer whose extraordinary quest for the fountain of youth led to the discovery of Florida. And there have always been rich pickings for the devisers of aphrodisiac potions and lotions – anything that enables people (principally men) to enjoy the pleasures of firm flesh for longer.
With the growing knowledge about hormones, the testicles and their hormone testosterone came to be regarded as the sure return route to youth, and for a while, with Brown-Séquard’s liquide testiculaire storming the world, perhaps it was felt that time could be reversed. Certainly, there are many before and after pictures from the early 1900s, of jowly and solid citizens transforming before your very eyes into lithe dilettantes – all down to the restoring power of organotherapy. Autosuggestion and a bit of Vaseline on the lens is more like it.
A rejuvenation boom took place in the 1920s, led principally by the eminent Viennese physiologist, Professor Eugen Steinach (1861–1944). He began a series of experiments on the physiology of the sex organs. He showed that the sexual behaviour of an individual animal is dependent on the sex of the reproductive organs they have implanted, not on their original sex. Thus, ovaries placed in male rats produce feminine behaviours, despite the fact that the rats were male from birth. These experiments were immaculate in their design and conception but were popularized and distorted by the media. Steinach discovered the glandular cells – Leydig cells – that produce testosterone in the testicles; these he called the ‘puberty gland’. His experiment – introducing testicular implants into elderly rats – had produced a rejuvenating effect, with previously crumbly animals discovering new interest in female rats and living on average 25 per cent longer. The startling results of this work were all Steinach needed to persuade the world that rejuvenation science was now entirely respectable.
There followed a bizarre series of grafting experiments in which men agreed, apparently willingly, to have bits of testicles from other men stitched into their own genitalia, with the object of rejuvenation or, at the very least, restoration of ‘powers’. Donors became a problem, as they were far outnumbered by those who wanted treatment, and implants were soon coming from decidedly dubious sources such as, in the States, electrocuted prisoners and those killed in car crashes. Enthusiasm was fuelled by tales such as that of a football player who had had to be castrated following a sports injury. He received a transplant from the organ of a teenage boy and was said to need an ice pack to control the frequency of erections.
In fact, testosterone has little to do with the mechanics of penile enlargement – it’s the hormone of desire and libido, not of erections, which are largely controlled by alterations in the blood flow and the moment juste.
Steinach, who could see that glandular grafting would never move forwards while it relied on human donors, came up with an inspired solution. The vas deferens is a narrow tube which carries and stores sperm. There is one on each side of a man’s body, taking the sperm released from the testicle on that side along to the prostate gland, where the seminal fluid is added. A single tube then carries sperm and fluid out through the urethra during ejacuation. Male sterilization – a vasectomy – involves cutting both vas deferens before they get to the prostate gland, so that the man still ejaculates semen, but it contains no sperm. Steinach’s operation involved severing on vas deferens: you could call it a demivasectomy. He claimed that doing this increased the testosterone output of the Leydig cells. The rationale was that since sperm were no longer required, the sperm-producing cells shrank, providing more room for the testosterone-producing Leydig cells. Actually this is nonsense, for sperm continue to be produced after a vasectomy – they just can’t exit via the normal route and are reabsorbed by the body. The Steinach operation was performed one vas deferens at a time, which always left the option of a second operation (for a further hefty fee) if the results were not satisfactory. Those who’d had the surgery claimed they felt rejuvenated – a stark contrast to the feeling that men have today about vasectomy. The last thing you’d hear a man saying now is that a vasectomy was likely to increase their sex drive. A typical Steinach enthusiast was the poet W. B. Yeats. He had stopped writing poetry after the death of his companion and mentor Lady Gregory. He decided that the way back to creativity was through potency and opted for a Steinach operation, which was carried out in Harley Street in April 1934 when he was sixty-nine. The sexologist Norman Haire was the surgeon. Perhaps not coincidentally, in September of that year Yeats began a relationship with the young actress and poet Margot Ruddock, who was twenty-seven.
With testimonials from W. B. Yeats and with Steinach thundering ‘A man is as old as his endocrine glands’, it was perhaps hardly surprising that the Steinach operation became so popular. A vasectomy no more rejuvenates, however, than wearing a hat makes you invisible. The common thread between the work of Steinach and the other youth pedlars who followed him was testosterone. Yet it is hard to fathom why testosterone and the reversal of ageing were ever linked.
The Hormone of Ageing – Testosterone?
The evidence that testosterone is not associated with long life is all around us. Women live on average ten years longer than men. Indeed, male mortality is higher than female mortality at all ages. Some of this is cultural – men smoke more than women, for instance, and the mania of early adulthood ensures a high incidence of death by foolhardiness in those years. It is also a direct reflection of the effect of testosterone on the cardiovascular system, which pushes up rates of death from heart attacks and stroke in men. Then there is the evidence from eunuchs. Freed of their male hormones, they live almost as long as women.
Castrati were boys with outstanding singing voices, who were offered by their families for castration as a way of preserving those voices. Many came from very poor families and, although the practice was against the law, these children met with mysterious accidents with wild animals, with their testicles having to be subsequently removed because of ‘injury’. They sang female roles (it not being proper for women to tread the boards in the seventeenth and eighteenth centuries) but also male roles since the top parts called for the highest voices. Some, like Farinelli, became immensely famous. The last castrati died in 1922.
Some evidence, too, comes from modern studies of castration. Shockingly, in some US states in the early part of the twentieth century, castration was considered an acceptable way of dealing with those people considered ‘unfit’ – largely institutionalized men with mental retardation, who were forcibly sterilized in order to protect the American gene pool. In 1969, Dr James Hamilton compared the lifespans of castrated men in long-stay institutions in Kansas with those of age-matched controls at the same hospitals and found a 13.6-year difference in lifespan.
Nor is there much encouragement for testosterone as a youth elixir from the animal world. Some animals have chosen the nuclear option in terms of reproductive strategies. It’s literally do and die. The technical name for this is semelparous reproduction – and you are already familiar with one example, the Pacific salmon. They start their lives in nursery ponds way upstream, before making their way to the ocean, where they live for up to four years. Then, in a humbling display of driven determination, they return to their spawning grounds, battling upstream, dodging bears, and leaping impossible heights to overcome waterfalls. The females release eggs, the male their sperm and that’s it – they die.
There is but one example of a mammal that has chosen this same option. Antechinus is a type of marsupial shrew. A tiny and rather unremarkable Australian carnivore with a nasty nip, it could easily be overlooked in the grand scheme of things were it not for the fact that it is famous for death by too much sex. ‘Way to go’ is the usual, rather admiring comment. In late July the mating season begins and the male shrews seemingly become infected with an all-consuming mating mania. They use their teeth to fight off love rivals and also to subdue females, becoming tattered and wounded in the process – though they hardly seem to notice.
Once aboard the mate of their choice, a male Antechinus will thrust away for up to twelve hours, only releasing the female to pursue another. A dozen mates in succession and many for the full twelve-hour stretch is not unusual before they die, usually while still on the job. Way to go indeed.
In Antechinus as in the Pacific salmon, castration before sexual maturity extends life. Deprived of their sex hormones and of the urge to roger anything that moves, the male Antechinus will live twice as long – in fact to the same age as the females. It is a myth that they have more testosterone than adult human males – their blood testosterone is similar to that in other animals of their type – but the difference is that the Antechinus has none of the proteins that would normally mop up testosterone in the blood (sex hormone binding globulins), so it is exposed to full-on testosterone. This is not a pretty sight. Effectively they are doomed to die by their sex hormones. For continued hormone stimulation also means that their adrenal glands are at full stretch too, pumping out steroids. Normally the feedback system ensures that something is done to slow down production. This system seems to fail. Worse, under the influence of all that testosterone, the binding proteins which would normally mop up cortisone are also much reduced. You might think PMT or raging teenage hormones are scary. They have nothing on this.
Sustained hormonal onslaught means that these creatures start to fall apart – their bones become brittle, they develop trouble with their salt balance and become bloated, they get diabetes, their immune system falters, the skin thins and they start to lose their fur in clumps. Shrews don’t live long enough to develop cancers, but evidence suggests that they probably would if sex hadn’t finished them off first. If you think that these ailments have an all-too-familiar ring, sounding for all the world like the complaints of your granddad, you’re right. This is programmed ageing, engineered by hormones.
The concept of a testosterone deficiency state with age has become more accepted, despite the fact that, unlike the menopause, there is no catastrophic ‘andropause’ in which the level of testosterone plummets, rather a gradual wind-down. Many doubt the ‘deficiency’ model, particularly given that the level at which treatment is recommended drifts ever upwards, and consider it little more than pharmaceutical-company-inspired hype in which many internet youth pedlars, the silk suit merchants of Harley Street but also men themselves, are all complicit. The promise of improved libido and re-energized sexual activity is a siren call that few men can resist, even given its clear perils. Testosterone has an air of danger and notoriety that few other hormones can match.
Testosterone is powerfully anabolic (that is, it builds muscle), particularly if it is accompanied by resistance exercise. Even a low dose can give athletes a big performance boost, and in a surprisingly short time too, as little as three weeks. Testosterone use (and that of other synthetic anabolic steroids) is banned in competitive sport, but hormone use in sport has degenerated into a different kind of sport, scientists v. scientists, in which those who devise tests to detect the latest anabolic steroid are outwitted by yet more scientists who devise new, undetectable molecules.
There is also a high level of abuse amongst teenagers, anxious to boost their looks or improve their sports performance. A survey of US high school students suggests 3.5 per cent use steroids such as testosterone. Many alarming surveys have shown that athletes would be prepared to trade up to five years of their life, or even death within five years, if there was a substance they could take which would guarantee them a gold medal win.
Steroid abuse is hard to counter when the abusers are teenagers who think themselves invincible and athletes determined to win at all costs. The evidence is that in the short term, the medical dangers of androgen abuse are limited. They certainly cause sterility, along with male breasts and shrunken testicles, while they are being taken, but this seems to be reversible. They also drain the immune system’s ability to fight disease, causing a 20 per cent drop in numbers of a white blood cell critical to fighting infection, the natural killer cell. The long-term effects of abuse are more concerning. Almost certainly they include liver cancer, with oral use, as well as cardiovascular and kidney disease. Colon and prostate cancer are also suspected. Although almost four decades of steroid abuse have elapsed and the long-term effects should now have revealed themselves, they are hard to distinguish amongst the noise of general ageing. Also few will admit to steroid abuse and there is a suspicion that some athletes remain blissfully unaware of the true nature of ‘supplements’ given to them by their coaches and trainers.
The effects on behaviour, the so-called ‘roid rage’ which can occur in abusing athletes, are variable in the extreme and some people are much more affected than others. A reduction in empathy is very common, and aggressive, uncontrolled behaviour is often reported. Psychosis is less common. Addiction is claimed, although it is hard to know which drug – exercise itself or steroids – is at fault. The paradox is that steroids can adversely affect performance, while building muscle – a truth which is not generally acknowledged. What is certain is that steroid abuse will continue.
Hair Today, Gone Tomorrow
Nothing ages a man more than the loss of his hair. Grey hair can be dyed, but baldness cannot be hidden nearly as well. Here, too, testosterone is involved. The irritating thing about ageing is that while hair thins on top, it also begins to grow in all sorts of other most unwelcome places – ears, nostrils and back, for example. Women are not immune from this effect either, and they, too, get whiskery with age. Hair on men’s bodies is stimulated rather than inhibited by testosterone. Hair on their head can be a different matter altogether, particularly on the crown.
Male pattern baldness – also called by those who want to medicalize it, androgenetic alopecia – is male hormone driven, which, given that testosterone promotes hair growth, seems contradictory. Men who lose their hair in that temples-first, crown-next way, have inherited a gene that makes the hair follicles on their head especially susceptible to androgens, in particular the breakdown product of testosterone, dihydrotestosterone (DHT). This gene is a dominant one, meaning that only one copy is required to have an effect, making it highly likely that it will appear in every generation. At family gatherings, adolescents can hardly fail to notice what is in store for them as they look at the balding pates of their uncles and cousins and see their dad and granddad in all their shining domed glory. It is only of some comfort to dad to confirm to his son that he will be next.
Hair production is similar to that of egg production in women, in that all the hair follicles are present before birth, and there are a finite number, usually around the 100,000 mark. Follicles go through periods of activity and rest before becoming dormant. The hair falls out before starting to grow all over again. Male hormones are metabolized extensively in the scalp and dihydrotestosterone interacts with genetically sensitive hair follicles on the crown and temples. The onslaught of DHT causes the follicles on the crown to become progressively more and more tiny. The single hair that such a miniaturized follicle produces is so fine it can hardly be seen.
Bald men do not have low testosterone levels – in fact they have higher levels of DHT and testosterone in their blood and other scalp hair than those with a full head of hair. There is indeed truth in the old wives’ tale that bald men are more virile and likely to have hairier chests than the cranially hirsute.
The key is the enzyme 5-alpha reductase, which creates DHT from testosterone. Bald men have far more of this enzyme knocking about their scalps. A side effect of a drug developed for the treatment of prostate cancer, finasteride, which blocks the action of the enzyme 5-alpha reductase, thus reducing levels of DHT in the scalp, is hair growth and it is now more widely used as a hair restorer than a prostate restorer.
One curious discovery of recent years is that women who inherit polycystic ovary syndrome (PCOS), which causes ovarian hormones to run amok resulting in obesity, hirsutism and infrequent heavy periods (often resulting in infertility), seem to have more male relatives who are bald than one would expect. It’s been postulated that the same gene has different effects, depending on gender, causing PCOS in women but premature baldness in men. For some time after this research was revealed, I asked prematurely balding men if their mothers or sisters had period problems and difficulties in conceiving. Many began their replies ‘Funny you should say that …’
The Goat Gland Doctor
The world will probably never again see the like of John Romulus Brinkley, who made a $12 million fortune from gland grafting.
Brinkley claimed to be a doctor but, although he had spent three years at medical school in Chicago, he had in fact never graduated. Instead, he bought a $500 diploma from the Eclectic Medical University of Kansas which licensed him to practise in Arkansas and Kansas. His early career was spent as a snake oil salesman. He and a partner set themselves up as the Greenville Electro Medical Doctors, injecting people with coloured water for $25 a shot. In 1917, he was working as house doctor at the Swift Meat Packing company in Kansas where he was much struck by the rambunctious nature of the male Toggenborg goats waiting in the slaughterhouse yard. Legend has it that, a couple of years later, a farmer named Stittsworth came to see him, complaining of diminished libido. Remembering the goats, Brinkley is said to have joked, ‘What you need is some goat glands’ and when Stittsworth immediately replied, ‘So doc, put ’em in’, he did. Stittsworth was thrilled with the result and shortly afterwards fathered a baby, whom he predictably named Billy.
The stage was set. Brinkley knew of the work of Brown-Séquard, knew a money-making opportunity when he saw one and, as he had already demonstrated, was totally unprincipled. Thanks to Stittsworth, his business was soon booming. Brinkley charged an outrageous $750 an operation, the equivalent of more than $10,000 today. He was grossing $37,500 each and every month. Brinkley was a marketing genius – for instance, saying that his operation was most suited to the intelligent, and least suited to the stupid. This appealed to men’s vanity and had them queuing up, proving in the process what intelligent, forward-thinking men they were. He also craftily insisted that patients give up alcohol and tobacco, ensuring that the benifits of abstinence could be attributed to goat glands. Brinkley began to claim that goat glands cured everything from acne to insanity.
Gland grafting was not confined to the US. In Europe, Serge Voronoff, a French surgeon of Russian Jewish extraction, switched to transplant surgery in middle age. In 1921 he too was experiencing problems in obtaining human glands for transplant and decided to resort to animal donors. He preferred chimps, but resorted to monkeys when chimp testicles were not available. His tack was rejuvenation, rather than restoring ‘powers’. During the 1920s, Voronoff and monkey gland implants flourished to such an extent that the French government was forced to pass a law making monkey hunting in the French colonies illegal. These implants had a celebrity status in their day rather similar to that which more extreme plastic surgery has now.
The Hormone of Ageing:
DHEA?
There’s another hormone that falls significantly with age – dehydroepiandrosterone – thankfully more usually known as DHEA. It is an androgen produced by the cortex of the adrenal glands which sit atop your kidneys. DHEA is used by the body as a general building material to produce other steroid hormones like oestrogen and testosterone. Steroid production starts with cholesterol, and then goes through various permutations on the way to the end of the line, which is oestrogen. One of the ‘stops’ on the way is androstenedione (known as ‘andro’ and a common sports abuse drug). There are two forms of DHEA in the blood but the majority of it is in a sulphated form. DHEA supplements can be bought at any drugstore in the USA, but are prescription-only in Britain. They are manufactured from plant chemicals found in soy and wild yams. But please note: eating soya products does not mean ingestion of DHEA.
DHEA soars at puberty and peaks at around the age of twenty-four for women and thirty for men and declines to the low levels of childhood thereafter. At eighty, circulating DHEA is only about 5 per cent of its peak values. This process does not take place at a uniform rate: the majority of the fall is in middle age, flattening out at forty-fiveish. What excited interest in DHEA was some work in the 1980s which showed that levels of DHEA seem to be correlated with predicted lifespan. Also, numerous studies have associated low plasma DHEA with disease – diabetes, cancer and inflammatory disease among others and not necessarily in the elderly. A ten-year follow-up study in Sweden published in 1998 revealed that an older man’s chance of having a heart attack was inversely related to his level of DHEA.
If falling levels hasten mortality, then could rising levels extend lifespan? Internet touts were convinced they knew the answer. DHEA is marketed on the internet not only as an elixir for longer life but also for losing or (equally) gaining weight, preventing cancer, boosting the immune system and increasing muscle mass. Given half a chance, they’d claim it can raise the dead and get nasty stains out of carpets too. Given that DHEA is the supposed hormone of longevity, a slight bit of grit in the oyster is that current smokers have a 25 per cent higher DHEA than those who have never smoked. Nevertheless, DHEA-deficiency syndrome seems to be a new term for what most would call old age.
There is some evidence that DHEA is helpful in the treatment of those autoimmune diseases in which the body’s own immune system turns on itself. Much commoner in women than men, there’s an especially nasty one called lupus, whose main symptoms are extreme fatigue and disabling arthritis. Treatment with DHEA, though not effecting a cure, does allow patients to reduce the amount of other steroids they normally have to take to treat the disease. This is important because steroid drugs have many side effects, particularly at higher doses. DHEA is not without side effects itself and in women has unwanted masculinizing effects, like growth of whiskery hairs on the face, greasy skin and acne, and should therefore be treated with caution. In both men and women, DHEA can cause liver dysfunction. There are also question marks about its relation with breast and prostate cancer.
Like many of the products taken for muscle-boosting, the evidence that it actually does what is claimed is extremely limited. Most researchers agree that DHEA neither raises testosterone concentrations in the blood of men, nor increases their muscle strength. Clinical effects in the elderly are very modest.
There is some science underpinning a theoretical role of DHEA in countering neurological diseases like Alzheimer’s but the evidence that it actually has a role is thin on the ground. The most interesting feature of DHEA comes from studies showing high-dose administration to the elderly, who reported a much improved sense of well-being during a four-week study. Relief of mild depression would explain a lot about perceptions of DHEA as a miracle life-enhancer. Just because there are undoubtedly low levels of DHEA in certain disease states does not mean that it is causative or that DHEA is a treatment. There is also evidence from the Australian Sue Ismiel International Study into Women’s Health and Hormones, which documents how women’s hormones change with age, that DHEA starts to fall far more sharply and earlier in life than hitherto thought, and that significantly it doesn’t then alter across the menopause years. In other words, the pretty picture being presented of an increasing fall with age isn’t correct. Unproven, unregulated and don’t go there is my verdict.
GROWTH HORMONE?
Growth hormone is responsible for growth in childhood and thereafter for a host of body functions, including many aspects of metabolism. It reaches peak production when you are a teenager and thereafter declines steadily, so that the total amount of GH secreted by a sixty-year-old man is about half that secreted by a twenty year old. It is influenced by many things, including age, sex, exercise and food, especially that containing protein. Growth hormone exerts its effects via insulin-like growth factor (IGF-1), which is produced by the liver and by tissues sensitive to IGF-1, such as bone and muscle.
Many of the things that we don’t like about ageing – a decrease in lean body mass and an increase in body fat, brittler bones, thinner skin – are also features of adults who have growth hormone deficiency following car accidents or brain surgery for pituitary tumours. These people definitely benefit from regular shots of GH, substantially increasing their lean body mass, and, with longer treatment, their bone and muscle strength too.
You can probably guess what’s coming next. In 1990, the New England Journal of Medicine (NEJM), probably the world’s most prestigious medical journal, published a study by Dr Daniel Rudman and his associates from the Medical College of Wisconsin. The study involved twelve men, aged sixty-one to eighty-one, who were apparently healthy but who had (as one would expect) IGF-1 levels below that of young men. These men were given growth hormone injections at a dose twice that given to GH-deficient adults, three times a week for six months, and then compared with nine men who had received no treatment. The study reported a reduction in fat tissue and increase in lean body mass as well as an increase in skin thickness of 7 per cent. Despite these seemingly encouraging results, the study came with a health warning. This was a very short study, there were unpleasant side effects and, the Journal warned, nothing was known about the long-term implications.
Significantly, the study did not examine whether the men felt any better or whether they had improved their muscle strength or mobility. Subsequent studies showed that although GH does affect body composition, it does not improve function. The really bad news is that it causes insulin insensitivity, leading to diabetes, there are question marks over links to prostate cancer (a fourfold increased risk) and melanoma, and it can speed up the growth of breast tumours if they are already present. Growth hormone falls with age for a reason – probably because it is protective of some other crucial body function like insulin activity – and it’s plausible that low levels in older people are a better indicator of good health than high ones.
Nevertheless, the Rudman study was a call to arms for the anti-ageing industry – prompting in fact, the formation of the American Association of Anti Ageing Medicine, a completely unrecognized branch of medicine. Hundreds of websites sprang up offering oral and inhaled formulations of growth hormone. All protein hormones (and GH is one of them) are destroyed by gastric juice, so oral GH has no value whatsoever, but it didn’t stop it being marketed on the internet. If you look carefully you will discover that many of these products are not actually GH at all. A word that is used frequently is ‘secretagogues’, which is a genuine term for a substance that will prompt release of a hormone. The marketing of these products weaves fact with fiction in the most ingenious way. Here’s a typical example:
Product X contains the human unique growth hormone releasing formula used in the famous Rudman experiment. For many users this synergistic combination of arginine, pyroglutamate and lysine is the most potent HGH releaser, dramatically raising IGF-1 levels for a solid eight hours after use.
I sent one such product to a professor of endocrinology, who tried and tested it for me, using his full laboratory kit. There was not even the vaguest flicker of response from a product which cost £60 for a month’s supply.
Growth hormone is secreted in response to meals, particularly if they have a high protein content – it’s a throwback to our hunter gatherer days when protein wasn’t that common in the diet. When it does appear, your body needs to use it to the max, hence the need for a prompt. Arginine, which is naturally found in meat, is given intravenously by endocrinologists as a standard test of GH function. It should be followed by a spike in GH production. You can achieve the same effect less clinically with two tablespoons of Bovril in a quarter pint of hot water. The point is that this rise is short-lived and repeated doses produce decreasing levels of response.
The way that medical scams work is by including some small nugget of truth in the ‘sell’. So there was indeed a positive study in the NEJM, GH is produced in response to a test dose of arginine, and so on – but it’s not the whole truth. The NEJM found that the Rudman paper was getting more hits on its website than all their other 1990 papers put together. If you click on this reference now, you get a stern commentary from the editor, saying that anti-ageing therapy with growth hormone has not been proved effective and denouncing the way in which their paper has been hijacked by companies wanting to promote their products: ‘If people are induced to buy a human growth hormone releaser on the basis of research published in the Journal, they are being misled.’ Rudman, too, has been forced to publicly disassociate himself from the wilder claims of the growth hormone enthusiasts.
But the story of GH and its disciples is not quite over. In January 2003, the American Food and Drug Administration decided to get tough on the GH-pedlars and sent a warning letter to one company, objecting to their claims that their ‘Be Youthful’ GH product was effective against depression, fatigue and high blood pressure. In April 2003, another company, Nature’s Youth, was forced to destroy $500,000 worth of stock because they could not substantiate their claims. They cited the Rudman paper as their defence. ‘My secret is out, Nature’s Youth is how I stay “Good to go and ready to launch”,’ said the leading promoter of the Nature’s Youth product, right-wing shock jock and talkshow host, G. Gordon Liddy. Memories are short. Older people know him better as the man who served a five-year jail sentence for his part in the Watergate conspiracy, which ended with the resignation of President Richard Nixon.
The hype about growth hormone has claimed new victims – who are, in one sense, encouraged by the very people who are supposed to protect them. Athletes, and in particular bodybuilders, have been led to believe that GH is anabolic in adults – that is, it will build new muscle. The International Olympic Committee says it is ‘the most anabolic substance known’, which is odd because the evidence that short- or long-term administration of GH alone, with other steroids or in combination with training, has an effect on muscle protein manufacture, weight or strength in healthy young to middle-aged humans is very slim indeed.
Women, as I have said, consistently produce more GH than men in response to the same level of exercise, yet they are not more muscular than men. More GH is produced by the body in response to aerobic exercise than to resistance exercise, but it is resistance rather than aerobic exercise that bulks up muscle. Acromegalics, who have very high levels of GH all the time, are not muscular. So why is it so widely believed to have this effect?
Possibly because it does affect body water and connective tissue composition, which leads to greater muscle definition or ‘cut’. A bit like vitamins, one suspects that many athletes have a view that you can never have too much of a good thing. The truth is that the side effects of chronic use of growth hormone are deeply alarming – sudden heart attack, diabetes and colorectal cancer. Indeed, all those things that afflict people with acromegaly. Worse, because it is so much cheaper, the type of GH used by athletes may not be the genetically engineered safe variety, but instead the type sourced from cadavers, which is illegal in Britain and many other countries in the world because of the risk of transmission of CJD.
MELATONIN?
A potent marketing tool for many of the modern rejuvenators is the salivary assay. The idea is that your saliva is tested for levels of these various ‘anti-ageing’ hormones so that an individualized prescription based on your personal ‘deficiencies’ is prepared. Actually, salivary levels don’t always correlate with blood levels and in any case, whether one person’s levels can be said to be ‘better’ than another’s is a moot point in itself. As I’ve said many times before in this book, levels of the same hormone vary enormously between individuals, without any apparent effect on function. It’s what is normal for you that counts. Needless to say, these personalized prescriptions cost an arm and a leg. Several legs.
There’s another contender for the anti-ageing hormone: melatonin. This is the hormone produced by the pineal gland which is the slave of the body clock. Levels also fall with age. The steepest decline occurs from about the age of fifty, and by sixty, the pineal gland is producing half the amount of melatonin that it did at the age of twenty. In the words of the rejuvenators, ‘Not so coincidentally, as melatonin levels drop, we begin to exhibit serious signs of ageing.’ Oh really?
Sex is of course part of the picture. Melatonin does indeed prepare many animals for seasonal behaviours. It is thanks to its influence that, in many animals, the gonads increase in size during the breeding season, only to decrease afterwards. So the melatonin pushers contend that taking extra melatonin will keep a man’s tackle in unshrivelled condition, much like, er, the equipment of Prairie voles in spring. Also, since sexual dreams are a big part of fantasy, improving sleep (which melatonin may well do) will improve the quality of your sexual fantasy. Pardon?
But the greater enthusiasm for melatonin as an anti-ageing treatment is because it is also a powerful anti-oxidant which, in many different studies, has been shown to protect DNA from damage. It is theorized that decreased levels of melatonin, typically found in shift-workers who are exposed to light at night, may increase the initiation and growth of cancer. One of the first reports from the Nurses’ Health Study, based on questionnaires from more than 78,000 women, showed that those who had worked thirty or more years on night shifts, with at least three night shifts per month, had an almost 40 per cent greater risk of developing breast cancer compared with those who worked the usual nine-to-five shifts. It is thought this might be because lowered melatonin causes an increase in oestrogen. Another effect of melatonin seems to be inhibition of the enzyme telomerase, which is intimately involved in cell replication, making it more likely that any cancer cell will self-destruct rather than replicate.
It has also been suggested recently that one reason for the increases seen in childhood leukaemias might be because children go to bed later, and sleep with the light on, thus lowering their melatonin and increasing cancer rates. Take this with several pinches of salt, please.
At the moment, melatonin is being trialled as an adjunct to cancer therapies. Some small studies show promise but there is not enough evidence to make any sort of definitive statement. It is also being added to chemotherapy in the hope that it will reduce side effects. Although it seems to do this in some cases, it looks as though it does so at the expense of the effectiveness of the chemotherapy.
The gospel has been that melatonin falls with age but some recent work suggests that this view should be challenged. A study from the National Institute of Health, carried out at Harvard Medical School in 1999 by Dr Charles Czeisler compared thirty-four healthy older men and women over sixty with ninety-eight men under thirty, carefully controlling for confounders which would affect melatonin levels, including the simplest things like switching on the bathroom light if you get up in the middle of the night (which would cause melatonin to drop sharply), as well as drugs commonly used by older people which can lower melatonin, such as aspirin and beta blockers. When they then measured blood levels of melatonin, they found no difference between young and old.
The bad news about melatonin is that some studies suggest high doses could constrict blood vessels in the brain, causing stroke. By all means use it for jet lag – it works well for 50 per cent of those who take it. As for chronic use, there is no evidence of benefit and certainly none at all for clock-turning-back abilities – but there is some evidence of harm.
Having spent most of this chapter saying that hormones aren’t the key to longer life, let me now tell you how they might be. The conventional view of ageing is that it is due to an accumulation of random damage, with free radicals – the unwelcome and highly reactive by-products of chemical reactions within the body – the prime suspects. Many of the anti-ageing strategies involve taking vitamins and other supplements that mop up free radicals, although this is spectacularly unsuccessful (despite what you may read).
Radical calorie restriction, however, is known to extend life by up to half as long again in mice and worms and, once again, it is thought that this might work in humans because it will cut the number of free radicals produced over a lifetime. Recent work has shown that knocking out a gene called Daf2 extends lifespan even more than calorie restriction. Daf2 is a hormone receptor for IGF-1, the mediator of growth hormone which, as we have seen, has numerous roles throughout the body, including lessening the response of individual cells to stress. Hormones may indeed hold the key to extended life – in fact, one would be astonished if they were not involved – but we are a long way from even extending lifespan, let alone achieving immortality.
