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THERE’S always a Charlie Chaplin or a Warren Beatty siring children well into
their sixties and seventies, belying the fact that sex is not an option for an
astoundingly large number of men in their middle years and beyond. Whatever you
choose to call it—the “male menopause”, “andropause” or
“viropause”—or even if you don’t feel such terms are appropriate, men and
their reproductive systems age, big time.

Erectile dysfunction is one of the most common and upsetting aspects of that
process. Then there are lacklustre libidos and symptoms more usually associated
with the female menopause, such as osteoporosis, ample midriffs, muscle fading
from the arms and legs, fatigue and sleep disturbances. And accompanying all
these changes is a slow and steady declines in testosterone and other
hormones.

To the uninitiated, the solution may seem obvious: testosterone is supposedly
the “male” hormone, so supplement its flagging supply and the health of many
ageing men will be restored. Testosterone replacement therapy (TRT) does indeed
look like being the next big thing for the pharmaceuticals industry. Although
testosterone supplements have been around for a while in the US, they have
usually been given by painful injections or skin patches that can cause
dermatitis. Last month, however, a user-friendly testosterone gel, AndroGel, was
launched on the massive American market, and the ripple effect is likely to
increase demand for TRT around the world.

Some are predicting that the widespread use of TRT will end up being as much
of a boon to middle-aged men as HRT has been for some menopausal women. But
others fear that pushing TRT in all but exceptional circumstances will become a
racket and possibly a dangerous one at that.

The fashionable, bustling terraces of Harley Street in London are home to at
least two clinics that enthusiastically promote TRT. “Female HRT was one of the
greatest advances in preventative medicine in the 20th century,” says Malcolm
Carruthers, a chemical pathologist who runs the Andropause Clinic at the Gold
Cross Medical Centre. “TRT will be the greatest in the 21st century.”

Carruthers’s evaluation of the still controversial female HRT may be a bit
overblown, but women have certainly had more success than men when it comes to
getting their age-related hormonal deficiencies taken seriously. The female
menopause, which is caused by a relatively abrupt decline in the level of female
sex hormones, is clearly signalled by the cessation of decades of periods. It
kicks in on average in the early fifties, and no one is exempt.

But in men, reproductive function and age have an altogether murkier
relationship—hence the ongoing debate about whether the “male menopause”
is close enough to its female version to warrant the name. Testosterone levels,
libido and the ability to maintain a usable erection decline with age, but to
vastly different degrees in different men. That variation, plus the blunderbuss
nature of the male reproductive strategy—the limited research so far
suggests that sperm counts also fall with age, but it still only takes one to
cause a pregnancy—means that some men can carry on reproducing into their
twilight years.

On average, blood testosterone falls from 23 nanomoles per litre at around 40
years old to 13 nanomoles per litre for the over-75s. And as testosterone levels
go down, so too do erections, says Richard Petty, medical director of the
WellMan Clinic, just off Harley Street. According to the Massachusetts Male
Aging Study—or MMAS, the best study on the topic to date—30 per cent
of men at 50 years old, 50 per cent at 60, and 70 per cent at 70 suffer some
type of erectile dysfunction. Only a fraction of these are completely
impotent—roughly 8 per cent at 50 years old and 30 per cent at
70—but even moderate impotence, where erections are infrequent or
unreliable, can severely cramp a man’s sex life.

Under the skin

Figures like these and that fact that when Petty prescribes TRT, as
subcutaneous implants, many of his patients report improvements in their
erections, sex drive and general well-being, convince Petty that TRT works. He
is also swayed by the 50 or more clinical trials that appear to show that in
older men testosterone supplements can increase bone density and strength,
decrease the amount of fat on the trunk, and improve mood, libido and some
aspects of cognitive function. Other studies suggest that men who naturally have
higher levels of the stuff are more hale and hearty, with fewer heart attacks
and less obesity. “Fifty-five per cent of men over the age of 50 are affected
somehow or another by low testosterone levels,” estimates Petty.

That attitude angers John McKinlay, the epidemiologist who headed the MMAS
and director of the New England Research Institute in Watertown. Many of the
clinical trials of TRT for ageing men are so small and so poorly designed they
are worthless, he says, while the few that are well run provide only slim
evidence that TRT can improve some aspects of ageing men’s health—and then
often only in men whose testosterone levels are below the normal level for their
age. As for the idea that testosterone is a general cure-all for everything from
impotence to middle-aged spread, forget it, says McKinlay. “A drug that is good
for everything is usually good for nothing.”

J. Lisa Tenover, a geriatrician at Emory University in Atlanta, and the lead
researcher on one of the TRT trials, begs to differ. In a three-year
placebo-controlled study, she has given fortnightly testosterone injections to
70 men over 65 years old who had testosterone levels at or just below the lower
end of the normal range. At the outset, the men were certainly not profoundly
“hypogonadal”—a term generally taken to mean that the testes produce next
to no testosterone, so that muscles become severely wasted, body hair is lost,
libido plummets, and sometimes even the testes shrink and breasts develop.
Nonetheless, for the men who received TRT, muscle mass increased, body fat
dropped, and at least one index of strength improved, namely hand grip, she told
the Second International Congress on the Aging Male in Geneva earlier this year.
And, she points out, the changes were statistically significant.

But what really impressed Tenover was the effect TRT had on bone mineral
density. This increased by 10 per cent in the men’s spines, and 3.5 per cent in
their hips: improvements equivalent to those seen in post-menopausal women on
oestrogen. That’s important because, contrary to popular perceptions,
osteoporosis is common in older men—they suffer about one-third of all hip
fractures, and they are more likely to die as a result. TRT “may be a reasonable
therapy for osteoporosis in men”, Tenover says.

Of course, most middle-aged men and their partners are going to be far more
interested in what TRT can do for their sex lives. And, unfortunately, it’s in
the erection department that testosterone’s benefits are least certain. True, on
average both testosterone and the quality of erection fall off with age, but the
MMAS found no causal relationship between the two.

Indeed, even without any testosterone to speak of, a man’s sex life doesn’t
inevitably go down the tubes. Up to 95 per cent of a man’s testosterone comes
from his testes, but a few 18th-century castrati are reputed to have managed
sexual intercourse, as have some men who have been castrated to treat prostate
cancer.

But testosterone does play a key role in libido, and a libido that has been
flattened by insufficient testosterone is going to dramatically reduce the
number of erections a man gets.

Tenover has yet to release the results of her clinical trial of TRT’s effect
on sexual function. But she says TRT has helped a number of her patients who
have true libido problems (generally a small fraction of the total number with
erectile dysfunction), who were not depressed, and who had levels of
testosterone towards the low end of the normal range. “About 5 per cent of
erectile dysfunction in men over the age of 50 is due to low testosterone,” she
says.

For the vast majority of patients with erectile dysfunction, the root cause
is not low libido but circulatory problems (see “Penile barometer”) or nerve
damage, often due to diabetes. The rest can usually be put down to psychological
factors or physical trauma (excessive bike riding is one of the prime culprits).
And apart from some cases of trauma, Viagra is the best bet for treating these
patients. The drug slows the breakdown of a substance that relaxes smooth muscle
in the penis, encouraging it to fill up with blood. But Viagra is expensive, not
particularly convenient—it has to be taken an hour before sexual
activity—and doesn’t work for everyone. A cheaper option for some men may
be exercise. Physical activity, even just walking briskly for a few miles a day,
reduces the risk of erectile dysfunction by 20 per cent compared with men who
are sedentary, according to a study by McKinlay’s group. Men who exercised more
had a nearly 50 per cent lower rate of erectile dysfunction.

Which is perhaps why McKinlay is particularly disturbed by what he sees as an
increasing tendency to push TRT. His team has conducted a rough-and-ready survey
of 153 clinical endocrinologists who treat patients in Europe, Australasia and
the US to find out when they consider a man suffers from hypogonadism. The
majority, says McKinlay, quoted blood levels under 9 nanomoles per
litre—about 4 per cent of the over-40s. In the US, however, the level at
which a man is considered to have hypogonadism has drifted upwards over the past
few years to nearer 12 nanomoles per litre, increasing the potential market
several fold, he says.

Nonetheless, McKinlay is quick to acknowledge that true hypogonadism exists,
and in many cases should be treated with testosterone. AndroGel was approved by
the US Food and Drug Administration for men of all ages with severe testosterone
lack due, for example, to a genetic disorder that stopped their testes
developing. What worries him is that demand from older patients with
testosterone levels at the lower end of the normal range, or with symptoms such
as tiredness or low libido that may be caused by other disorders, including
depression, will quickly create a large and lucrative “off-label” market for
AndroGel. “The genie is out the bottle and most people will go along with it,”
he says.

Sexual taboo

Carruthers, Petty and others argue that just as significant in determining
who gets TRT are the taboos that have long meant that men’s sexual health is
neglected by doctors. “There is a tendency to ignore these people, to say, `you
are too old for help’,” says Alvaro Morales, a urologist and oncologist at
Queen’s University in Kingston, Ontario. To this day, older men who are brave
enough to seek treatment for flagging sex drives or uncooperative penises may
still be told to concentrate on their golf instead. Arguably, that was not bad
advice before the technical breakthrough of Viagra and the possibility of TRT,
when the main options were vacuum devices, penile injections or implants.

Even when doctors are willing to help, there’s still a lot of confusion about
the best way to decide whether TRT is worth trying. First, there is the sticky
issue of how to diagnose testosterone deficiency. Most definitions of
hypogonadism use measurements of “total” testosterone in the blood. But some
endocrinologists worry that this means many men in need of TRT are missed. Not
only does the total amount of testosterone decrease with age, the amount of a
blood protein that binds to the hormone increases. And because bound
testosterone cannot interact with its target organs such as the brain, muscle
and bone, the combined effect is to reduce the amount of biologically active
testosterone by as much as 50 per cent between the ages of 25 and 75 years.

What’s more, testosterone is unlikely to be the whole story. Other hormones
decrease with age—including DHEA, which is produced both in the adrenal
glands and by the breakdown of testosterone in the liver, growth hormone,
insulin-like growth factor 1 and leptin. Any of these may also have an impact on
libido, muscle mass, sleep disturbances and so on. “One of the big problems is
that people have concentrated on testosterone. We have to look at the wider
picture,” says Morales.

Then there’s the issue of whether TRT could prove dangerous. “The only thing
we’ve learnt from medical history,” says McKinlay, “is that we never learn.” In
the 1940s and 50s, the sledgehammer approach to treating the menopause was to
give women high doses of “unopposed” oestrogen—that is oestrogen without
progestin, a second hormone that counteracts some of oestrogen’s effects. The
result was a massive six to eightfold increase in the risk of developing cancer
of the endometrium, the lining of the uterus. Unopposed testosterone could
increase the risk of prostate cancer, predicts McKinlay, but “we’re about to
start handing out testosterone willy-nilly”. And not only is prostate cancer
life-threatening, a common side effect of its treatment is, ironically,
impotence.

But once again the jury is still out. The Atlanta study uncovered a tendency,although not a statistically significant one, towards enlarged prostate glands
in men taking TRT. Tenover, however, points out that it’s too soon to say
whether TRT will up the risk of prostate cancer; not enough men on TRT have been
studied to know the answer. Nonetheless, she says, as a precautionary measure
any doctor contemplating prescribing TRT should screen patients for risk factors
such as high levels of prostate specific antigens (PSA).

Just as important is measuring the concentration of red blood cells.
Testosterone can increase their numbers to dangerous levels—indeed,
testosterone was once a common treatment for severe forms of
anaemia—increasing the risk of strokes. And there’s even a possibility
that higher testosterone levels may be linked to an increased risk of heart
attacks. Most studies suggest that TRT would actually protect against heart
disease, but enough suggest otherwise to warrant caution. “Heart disease is the
major killer of men,” points out Tenover, who gets some research funding from
ALZA Corporation, which makes a testosterone skin patch, “so even if you change
the risk a little in a negative direction, that would be a major reason not to
use TRT.”

With all these unknowns to juggle, it’s easy to see why academic researchers
are throwing their hands up in horror at the very idea of a simple testosterone
replacement therapy. As one wag put it at a recent urology meeting: “If you’re
not confused, you’re not informed.”

Andrologists and geriatricians, on the other hand, who face patients whose
lives are diminished by low libido and other symptoms of male ageing, sometimes
feel differently. Although there’s no consensus about the pros and cons of TRT,
it’s not just Harley Street physicians who are doling it out. And sometimes even
patients whose blood testosterone levels are merely shifted towards the lower
end of the normal range for their age are being treated.

Morales, like Tenover, is already prescribing TRT, albeit cautiously. Both
doctors base their decision on whether to prescribe on a combination of
testosterone levels, symptoms of deficiency, and any contraindications such as a
high risk of prostate cancer. When they prescribe TRT they try it for a few
months to see if the symptoms improve. The method is far from foolproof, admits
Morales, because “the placebo effect is extremely high with sexual function”.
But that is still better than leaving patients untreated, he says.

“It’s a quality of life issue,” he concludes. “In 10 years’ time there will
be marvellous hormone replacement therapy for men. But until then, even with all
the confusion surrounding [TRT], it’s still worth a try.”

THE quality of an erection—roughly speaking, how stiff the penis gets
and for how long—could be the best barometer for cardiovascular health
there is. The blood vessels that are needed to make the penis stiffen can easily
become furred with atherosclerotic plaques, the same fatty deposits that will
eventually block blood flow in larger vessels, causing strokes and heart
attacks. Before they do that, however, such plaques usually reduce blood flow to
a man’s penis, to the detriment of his erections. The penis “is like the
pressure valve on a boiler”, says David Handelsman, an andrologist at the
University of Sydney. “It’s the first thing that gives out.”

Other conditions, such as neural damage due to diabetes, can cause erection
problems. Nonetheless, the Massachusetts Male Aging Study, which followed 1156
men over nine years, found that men with erectile problems at the beginning of
the study were significantly more likely to suffer coronary disease during the
study, even after taking into account other contributory factors such as weight
and smoking.

All too often, however, doctors dismiss patients’ concerns about their
erections, putting impotence down to normal ageing. That practice should change,
says John McKinlay, director of the New England Research Institute in Watertown
and head of the Massachusetts Male Aging Study. “Erectile dysfunction is angina
of the penis,” he says. “This is the most significant bio-behavioural marker of
the most common killer of older men.”