Testosterone for men
What about the men?
- the andropause
Although it is fair to say that preventative medicine has neglected men in the last 50 years even though they die 7 years on average earlier than women, traditional treatment over the centuries has focussed upon men and male virility. Even from Egyptian days 4000 years ago the interest in what we will now call "endocrinology" was based upon improving the sex life of men and avoiding pregnancy in women. There were all sorts of weird ways of preventing pregnancy, the most famous and eccentric being a vaginal pessary of honey and crocodile dung but for the men the secret seemed to be the eating of testicles of various animals recognising that puberty, virility and fertility were somehow related to these organs.
In the last 19th century, Brown Sequard, a distinguished French physician and the founder of endocrinology created a cocktail of sheep's testis which he claimed improved his mental ability, energy and "increased the arc of his urine". There were many such other anecdotal and non-scientific claims over the next half century. The male hormone, testosterone, was believed to be the vital chemical and the isolation of testosterone was a race between scientists from the companies Organon, Schering and Ciba. It was isolated in 1935 with the Nobel Prize for Medicine going to the Organon scientists. The clinical trials of testosterone starting two years later were mostly on women for no other reason than that the principal doctors interested in the new hormones, oestrogen and testosterone, were gynaecologists. When it was possible to measure these hormones it became clear that testosterone existed in women as well as men but in lesser amounts and even existed in normal young women in levels twice as high as the traditionally recognised female hormone, oestrogen. It is thus untrue to think that testosterone is a male hormone. Oestrogen and testosterone are both hormones and treatment with either or both hormones may be appropriate for men or women.
The role of testosterone in women is now clearly established but it is regrettable that in spite of the logic for its use in men and in some circles, and enthusiasm for such treatment, there are very, very few scientific trials to support its use. Logically it should be hugely beneficial but we need clinical trials to convince the sceptics in the same way it was necessary 30 years ago to conduct proper trials on oestrogen to firmly establish which were the symptoms of oestrogen deficiency and which were the result of ageing or disease and independent of any hormone levels.
The ageing male usually has a decrease in testosterone but not as invariably as in women whose plasma oestrogen levels always decline at the time of the menopause. There are also increasing problems with health with age and the dilemma is to decide whether these changes are  determined by age, genetics and lifestyle factors or  whether there is a hormonal component to these disorders which is coincidental and does not respond to treatment and  whether there is a treatable hormonal component that will prevent or ameliorate many of the symptoms and illnesses of the ageing male.
So far a couple of acronyms have been devised :- ADAM - Androgen Decline in the Ageing Male or PEDAM - the Partial Endocrine Deficiency in the Adult Male. Most 60 year old men, the author included, would rather be regarded as "adult" than "ageing". My feeling is that PEDAM wins this competition even if only for the choice of a kinder adjective.
Although living longer, there is a greater period of dependency. In 1927 the average life span was around 47 years and death resulted usually from acute disease or trauma. Hospitalisation and/or dependency lasted only days of at the most weeks. In 1950 the average life span was about 58 years and hospitalisation or dependency lasted for weeks or months. In 1999 the average life span is about 80 years and death results from long-term chronic diseases such as cancer, degenerative diseases, or organ failure. Hospitalisation or dependency in 1999 may last for many years.
Thus there is the greatly increased life expectancy in the Western world with a slightly increased health expectancy. In the UK this is 71.8 and 58.7 years respectively giving an average 13 years of less than good health. In the USA the difference is 14.6 years of physical decline and less than healthy life. The major health problems are cardiovascular disease including coronary artery disease and heart failure and strokes. Various forms of cancer are another major problem. Lung cancer has the highest mortality, also common are stomach, liver, colon, rectum, oesophagus and also the prostate which has the highest prevalence in old age. The chronic disabling conditions with age include the decline in most physiological functions, ageing of the male endocrine system, problems with prostatic hypertrophy with urine/bladder problems. There is also erectile dysfunction and decreased sexuality. There is osteoporosis and also a decrease in muscle mass. Problems of mental health are more common with dementia occurring in 4-7% of men over the age of 65 and depression occurring in 10-15% with about 3% having severe depression. Suicide is more common. There are sleep disorders of insomnia, early waking and sleep apnoea. As in the female menopause, the challenge is to find out how many of these things are related to hormonal changes and can perhaps be treated or prevented by testosterone therapy.
There is a decline in testosterone levels particularly the free (active) testosterone with age. The normal values of total testosterone are between 11 and 30 nmol/l and testosterone levels below this normal range occur in 20% of men aged 60-80 and 33% aged over 80.
It is believed that testosterone levels of about 11nmol/l are critical for sexual function. These low levels are also related to decline in stamina and muscle mass. It is for this body building function that younger athletes often take testosterone or other anabolic steroids illegally. It certainly works for them but the evidence is less clear whether the aged male has an improvement in body mass when he takes more modest physiological doses of testosterone. Apart from ageing there is also evidence that stress, both physical and psychological, excess alcohol, excess smoking, and obesity all lower testosterone levels.
The symptoms of low testosterone in ageing/adult men are typically flushes and sweats, depression, nervousness and insomnia. There is also decreased libido and problems with maintaining an erection. The men are easily fatigued, have poor concentration and memory and complain of being easily cross and bad tempered. Yes, there are many reasons for all of these varied problems and just as in the female menopause it is important to tease out those symptoms due to hormone deficiency and those due to personality, environment, bad marriage, or other items of physical or mental pathology. Unfortunately the clinical trial on the alleged symptoms of the male climacteric and the response to testosterone have not been done - nor, I think, has it even been attempted seriously.
Let us now consider testosterone and heart attacks. It is an old joke that testosterone causes world wars and heart attacks because allegedly it produces aggression and, as more men have heart attacks than women, the assumption is that it is due to testosterone. I am not sure whether either part of this statement is correct. Over the last five years there has been so much work showing an association of low testosterone levels in men with coronary artery disease as shown by clinical heart attacks or by radiological angiographic studies. This does not mean that the association is causative as there is no proof that the low testosterone causes the coronary heart disease but we can, I think, now exclude the view that high testosterone is associated with heart attacks and that testosterone, either the man's own testosterone or treatment with testosterone, produces more heart attacks. This work comes from Italy, from Bristol, from Leeds and is very highly regarded. It is turning our views on hormones and heart attacks in the male upside down.
Peter Collins from the Brompton Hospital has been studying the effects of oestrogens on the physiology of the coronary arteries in women showing that addition of oestrogen dilates the coronary arteries and increases coronary blood flow. To his surprise, the same thing occurred when testosterone was added to this experimental model and he has now shown that testosterone dilates the coronary arteries and increases blood flow in men as well as women
Thus, I believe we can be reassured that there is no evidence that testosterone causes heart attacks but there is an increasing body of good scientific work indicating that testosterone is probably protective in the male against heart attacks. It is important that we reject the prejudice that links testosterone with increased heart attacks as we try to determine whether testosterone therapy in men is clinically sensible and safe in certain endocrine disorders or for certain groups of symptoms.
What then do you do with a man who has no symptoms of testosterone deficiency but on repeated blood tests does have a low testosterone? Are we justified in treating him? The problem is that if one checked the sort of blood profile in men that I measure in women who come to my menopause clinic, one will find significant abnormalities. These tests include haemoglobin for anaemia, liver function, kidney function, calcium, the lipids cholesterol and triglyceride, blood sugar as well as the hormones measuring thyroid function, oestradiol and FSH (important for women) and testosterone and LH important (important for men). Many men and women would have abnormal cholesterol levels and a few would have a high blood sugar and a few would have abnormal thyroid function. No-one would dispute that it is important to treat those findings but what about the men with low testosterone?
Certainly in middle aged men lifestyle changes must be seen to be as important as any hormone therapy. This would include loss of weight, treatment of hypertension, not smoking, a sensible low fat diet, reduce alcohol consumption and regular exercise. When all of these are done, do we treat men with andropausal symptoms with testosterone and do we treat men with low testosterone without symptoms with testosterone? I believe you do treat although it must be said that the data are not there to support a strong statement on this. However, it does help a lot of men and it is probably harmless. As a gynaecologist, I do not treat too many men but I have over the last five years treated about 40 middle aged men with testosterone . This is apparently helpful because they all come back every five or six months for further treatment by a testosterone implant convinced that they feel the psychological and physical benefit of this replacement therapy. A breakdown of the results of 20 of these before and after therapy has been reported to the British Menopause Society and the North American Menopause Society by members of my team. The results show that there were significant reductions in symptoms of depression, anxiety, libido, erectile dysfunction, fatigue and concentration, three months after treatment. There were no statistical differences in their symptoms of sleep disturbances and sweats. We could also not establish a correlation between testosterone levels and symptom improvement but there is a need larger numbers for a worthwhile study.
One of the clear risks of testosterone therapy is growth of any small occult prostatic cancer that might be present. As this is such a common tumour in older men it is essential that before giving testosterone a rectal examination is performed to assess the size of the prostate and also the prostatic antigen, PSA, is measured. This is a useful, but not totally reliable, screening test for prostatic cancer. Testosterone should not be given before a high reading is investigated by a urologist.
Hormone replacement therapy
There are several ways of replacing hormones. The first is to stimulate the cells of the testes into producing more testosterone by giving LH and FSH in the form of HcG (Profasi). This is normally a pituitary hormone which in women stimulates the ovarian follicles to grow and thus to facilitate ovulation and release of ova. In the man it stimulates the Leydig cells of the testis to produce testosterone.
Injections of five or ten thousand units given each week for five weeks which may produce an increase in plasma testosterone if the ageing testes are responsive to these stimulating hormones. If, however, the man already has a high LH level in the blood indicating some degree of testicular failure, it is unlikely to be effective. This, of course, is analogous to the menopausal woman with a high FSH who is trying to stimulate the ovary to ovulate. No amount of extra FSH will produce more oestrogen or facilitate ovulation in these women.
I find that an injection of testosterone proprionate, Sustanon 250 mgs, is a useful diagnostic test dose which works within 24 hours and lasts 2-3 weeks. Taken together with the symptomatology and the results of the hormone tests, it does give a reasonable indication whether long-term testosterone therapy will be helpful.
Testosterone patches are about to come on to the market but have not been very successful. The manufacturers came up with the idea of putting the patch on the scrotum. As the scrotum is normally a wrinkly, hairy area it is necessary to shave but the patch often falls off. It has been shown to be fairly ineffective in increasing plasma testosterone levels, improving symptoms or increasing bone density. It may have a future but it will require more efficient transfer of testosterone from the patch through the skin and a more sensible siting of the patch on the body.
Oral testosterone is available in the form of testosterone undeconoate (Restandol). There has always been a theoretical danger that oral testosterone can damage the liver but the only problems have been in female to male transexuals taking huge doses of methyltestosterone. In the appropriate small dose, oral testosterone does not cause liver damage. I prefer hormone implants. As with women, this is a very simple procedure but, of course, the dose is higher - 100 mgs is the usual dose for women but men have 600-800 mgs implants. This is the route of administration also much preferred by my patients who will have short-term Sustanon injections followed by long-term testosterone implants.
There are of course side-effects of any treatment that works. An increase in heart attacks is unlikely but could be one of them in spite of the additional fears about testosterone. Fears that this is associated with high testosterone levels. The one certain problem is that of polycythaemia which is an increase in haemoglobin and total mass of red cells because of stimulation by testostosterone of the red blood forming hormone, erythropoetin. This has theoretical long-term problems of venous thrombosis and may, although I have never had such a patient, require removal of a pint of blood every two weeks by a technique called venesection. Weight gain is theoretically a problem although this should be due to increased muscle bulk rather than fat round the middle of the body. Sleep apnoea is allegedly another complication of testosterone therapy. This may develop because the loss of oxygen experienced if men stop breathing for forty to sixty seconds during the night can produce the polycythaemia which is also a direct complication of testosterone therapy.
The great fear of course is a growth of a small undiagnosed prostate cancer and this s the reason why most andrologists are, for the timebeing, opposed to the concept of testosterone replacement therapy. They see that an effective treatment of advanced prostate cancer is removal of testosterone by drugs or even removal of the testis so it seems inconceivable to them that the administration of testosterone can be anything but dangerous for the prostate. However, the truth of that controversy is not at all clear. For the timebeing annual measurement of the prostatic cancer antigen (PSA) is the best we can offer.
We are starting a proper scientific study of testosterone which will treat about 60 men randomised into a testosterone treatment group and placebo treatment group. The study will be of their symptoms, hormone levels, bone density and most of all the symptoms of flushes, sweats, insomnia, tiredness, loss of libido and erection. Many of these men in the study will be husbands of my menopausal patients but other interested men will be welcome to be considered for the study. It is fair to say that as we have no funding for the study and volunteers will be charged a modest amount to cover the costs.
In conclusion the apparent neglect of men's ageing and sexual problems is, for the most part, our own fault. Women have gynaecologists and are usually willing to discuss menstrual, sexual problems with their general practitioner or their friends. They are much better communicators than men who, on the other hand, have great trouble discussing sexual matters without either embarrassment or exaggeration. Perhaps men need "andrologists" to discuss all of these health, sexual and marital issues that they normally internalise, being far too manly to have to discuss these important issues with a stranger. We have seen this in our studies over the last 30 years in that women will answer the most detailed and intimate sexual questionnaires in some of our studies on sexual response to hormone therapy. The same questions, transcribed for male sexuality, bring out embarrassed incomprehension. In short, men have trouble telling the truth about their sex lives but they still need our help. It may be in the form of testosterone replacement therapy.