Articles on the Andropause

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	Reduced Testosterone activity is common in men from the age of 40 onwards.
	This causes the loss of energy, libido and potency which make up the "Male Menopause" or "Andropause".
	The Condition can usually be helped by carefully monitored Testosterone Replacement Therapy (TRT).
	TRT is as safe and effective as Hormone Replacement Therapy (HRT) for women.
	In addition to TRT, a wide range of other treatments to restore potency are available, especially Viagra.
	TRT is an important form of preventive medicine, probably slowing the ageing process in men.

Testosterone Replacement Therapy for Men (TRT)

TRT - HRT for men using Testosterone, has been shown to be dramatically effective in relieving symptoms and restoring drive, health, potency, and a sense of renewed vitality and virility when the right preparations are given to the right patients in the right doses at the right time.

To ensure its safety and effectiveness however it is essential that a full assessment or "work-up" of each patient is carried out before hormone replacement is started, and that the results of treatment are carefully monitored. For this purpose careful history-taking and examination and blood tests need to be carried out.

Both to establish the diagnosis and to monitor the treatment properly, laboratory measurements of the sex hormones and the complex range of factors regulating their action, together with tests of blood fat, liver, kidney, and prostate function and haematology profile, all need to be checked before treatment and at each follow-up assessment.

TRT is usually given in tablet or capsule form for the first three to six months. It can then be continued if necessary by mouth, transdermally, by injection, or by implantation of pellets of fused testosterone crystals into the buttock, under a local anaesthetic, at six monthly intervals.

Availability of Testosterone Preparations

In many parts of the world, the two main safe oral preparations, Testosterone Undecanoate (Andriol or Restandol made by Organon) and Mesterelone (Pro-Viron made by Scherring) are available, as well as Testosterone Pellet Implants, also made by Organon.  Transdermal Testosterone in the form of body or scrotal patches or creams is also available in most countries. In the USA, Testosterone is mainly available either by patches, or injectable forms such as Testosterone Enanthate, though it is hoped that Andriol may soon also be available there.

Availability of treatment

The availability of testosterone treatment is rapidly increasing world-wide, as more doctors become convinced of the benefits and safety of TRT for men. One of the aims of the Andropause Society is to accelerate this process by making doctors more aware of the problems associated with the Male Menopause, or andropause, and informing them of the latest research in its favour and providing training for them via the Web using the latest video conferencing technology.

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This is the commonest presenting problem in male sexual dysfunction clinics and peaks at the time when the andropause appears, that is the mid-forties onwards. It is a major health problem which is seldom adequately investigated or treated.

The Mechanics of Erection

Man's ability to have an erection, which has been worshipped from the earliest of times, is actually a recurring miracle of hydraulic engineering. It is brought about by a complex series of chemical changes and nerve reflexes, which work together to increase the amount of blood flowing into the penis and temporarily decrease the amount going out. Two elongated blood sacks, the corpora cavernosa, become engorged and create the erection. This event, which is achieved with effortless and sometimes embarrassing ease in the teens and twenties, usually becomes a more difficult feat in the thirties and forties, can be variable in the fifties and sixties, and is often a disappointingly brief and infrequent wonder in the seventies and beyond, especially in the 'hormonally challenged' andropausal male.

Testosterone and Erectile Function

Though it is difficult to say precisely what part testosterone plays in helping to produce erections, it certainly both primes the penis and triggers the chain of events which bring an erection about. It is surprising, but gratifying, how often when adequate testosterone therapy is given, all the symptoms of the andropause disappear within a few weeks or months, including erectile difficulties, particularly when other factors contributing to its onset or continuation are dealt with.

A statistically highly significant improvement in erectile function occurred in over 70 per cent of 1000 cases treated with a variety of different forms of testosterone. This was particularly marked with the more powerful oral preparation, Restandol (Andriol), which sometimes needed to be given in high but safe doses, and with the testosterone pellet implants.

Though this use of testosterone to help erection problems is controversial and not acknowledged by some authorities, which say it only increases frustration without giving back the means to perform, this is certainly not the experience in this large group of patients. The efficiency of testosterone in restoring potency is a common experience with doctors prepared to give it an adequate trial.

It was even recognised over 50 years ago in the article on the 'male climacteric' by Drs Heller and Myers in an article on"The Male Climacteric" in JAMA in 1944. They found that erectile function returned in nearly all of their testosterone deficient patients when they gave the hormone and went away again when they stopped.

Even though it is more difficult to restore function than desire, unless the source of the problems is obviously psychological or mechanical, it seems logical to investigate the testosterone balance of the patient, and restore it to normal as the first stage of treatment. Even if erections are not greatly improved by this alone, libido and confidence usually are. The most commonly used methods such as penile injections of prostaglandins, as in Caverject, then seem to work much better. Recent experience at in London has shown this to be particularly true when Viagra and Testosterone are combined to cure over 98% of impotence problems.

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Abstract 25.7.03

THE ADDITION OF TESTOSTERONE REPLACEMENT THERAPY TO TREAT ERECTILE DYSFUNCTION AFTER FAILURE OF SILDENAFIL ALONE IN MEN WITH ACQUIRED ANDROGEN DEFICIENCY SYNDROME

Brian Rosenthal, Phillip C. Ginsberg, Michael Metro, Richard C. Harkaway, Philadelphia PA

(The Journal of Urology, Vol. 169, No 4, Supplement, Tuesday, April 29, 2003)

INTRODUCTION AND OBJECTIVE: While Viagra (sildenafil citrate) is an affective treatment for erectile dysfunction, it does not always result in adequate potency. We evaluated whether combination therapy with Viagra and testosterone replacement theapy is effective in achieving adequate potency in patients who have failed with Viagra alone and were subsequently found to have low serum testosterone levels.

METHODS: Between July 2000 and June 2001, we evaluated 80 men who failed 3 months of Viagra therapy at maximum dosage with at least three attempts at intercourse during the three month period. 24 of the 80 men were found to have testosterone between 90 and 400mg/ml. Each of the 24 men was then started on testosterone replacement (Androgel 5mg daily) for 4 weeks, Viagra was subsequently restarted in combination therapy with the Androgel after 4 weeks of androgen replacement therapy. Potency was defined as the ability to have at least one episode of satisfactory intercourse during the treatment period.

RESULTS: At 4 weeks follow up, after the start of Hormone Replacement Therapy (HRT) alone, none of the men had regained potency. At 3 months follow up after combination therapy was started, 22 of the 24 men (92%) reported improved potency.

CONCLUSIONS: We recognize that this study lacks an adequate control group of men with prolonged use of HRT alone to determine the success of potency. However, our data shows promising results for the use of combination therapy with testosterone replacement therapy and Viagra in patients who have failed Viagra and were found to have low normal serum levels of testosterone. In addition, it underscores the number of men with low or low-normal testosterone levels who would benefit from testosterone screening when being evaluated for erectile dysfunction.

Source of funding: None

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Viagra – A Giant Leap for Mankind

In the treatment of erectile dysfunction (E.D.) Viagra is ‘a giant leap for mankind’. Probably more men care about putting the manhood back in the man than putting a man on the moon. In fact, this drug can put a man and woman over the moon by ending the dreaded ED and the misery this causes.

In terms of media attention, it seems to have caught the public imagination just as much, and not even NASA’s triumph made the cover of the two American magazines Time and Business week simultaneously, as Viagra did in 1998.

Does it deserve this degree of hype? It seems to do so, both as a major advance in a long neglected area of men’s health, and as the official dawn of a ‘New Era of Lifestyle Drugs’.

How Good is Viagra?

In over 4,000 patients in more than twenty different research studies World-wide, Viagra has been shown to be highly effective in ED of many different types, whether due to psychosocial problems, diabetes, or prostate cancer operations. The benefits are dose related, just over 60% responding to the 25mg dose, over 70% to 50mg, and 80% to 100mg.

How Bad is Viagra?

The side effects of Viagra are also dosage related, and the figures shown are on the strongest dose of 100mg. Fortunately, they are usually mild and short-lived, and with experience, its usually possible to adjust the dose for maximum action and minimum side effects. In the trials, only 2-3% withdrew because of unwanted reactions to Viagra, and generally it is considered a very safe drug.

Viagra and the Andropause

Viagra only treats one symptom of the male menopause or andropause, that of E.D. The others of low sex drive, reduced mental and physical energy, irritability and night sweats would all go untreated by Viagra alone. Also, all the research studies agree that it is not an aphrodisiac, and will not work if the desire is not there.

Testosterone is the hormonal basis of desire in both men and women, and if it is low, so is the libido. It is the desire and sexual excitement that generates the nitric oxide that increases genital blood flow and lubrication in both sexes, producing erections in the male, and by slowing its breakdown, Viagra prolongs these responses. This is why both in theory and in practice the two work better together.

Also, as was recorded in two key articles in the Journal of the American Medical Association over fifty years ago (Werner, A.A., JAMA, 1939 and Heller, C.G. and Myers,G.B. JAMA, 1944: 126:472), testosterone treatment on its own can restore potency in the majority of andropausal men.

In over a thousand such men studied in London over the last ten years, in 65% erectile function improved with the male HRT treatment alone to the point where intercourse was satisfactory. Only in the remainder, the group now most likely to receive additional benefit from Viagra, was treatment needed with methods such as the now thankfully largely superseded penile injections.

Also the initial findings of work on the combined treatment suggests not only a higher response rate (up to 98%), but that Viagra works at lower doses, and longer and stronger with additional testosterone.

Also of course Viagra has none of the preventive medical benefits of male HRT with testosterone, especially to the heart and circulation, muscles and bones. Like oestrogen, testosterone has recently been shown to increase nitric oxide production in blood vessels all over the body, which as in the penis relaxes them and improves blood flow. This is likely to be important in slowing aging changes in both heart and brain as papers presented at The First World Congress on the Aging Male held in Geneva February (1999) confirmed.

Viagra Plus Testosterone is the logical answer to the commonest cause of E.D., the andropause.

Testosterone replacement therapy has been widely available for over 60 years and has been used extensively to treat men with low levels of the hormone.   The aim of treatment is to return the level of testosterone in the blood to normal that is from a state of deficiency to sufficiency.   Such a concept is true for diabetes and other hormonal deficiency states such as an underactive thyroid gland as well of course as hormone replacement therapy for menopausal women.

Testosterone can increase the amount of red blood cells and the pigment haemaglobin however it is common to find that men with low levels of testosterone have low levels red cells and haemaglobin before treatment is started, infact some are clearly anaemic.  In such cases testosterone replacement therapy merely normalises their blood picture.

There has been great interest recently about the benefits of testosterone on the cardiovascular system.  It has been reported that men with abnormally low levels of testosterone may be at greater risk of cardiovascular disease^3,4,5.  Such men with heart disease when given TRT to normalise their testosterone levels gain cardiovascular benefit and one study has shown that blood flow in the coronary arteries is improved^4,5.  Other studies have shown that men with low levels of testosterone have an adverse cholesterol, blood sugar and blood clotting factor profile and therefore may be at greater risk of cardiac problems⁶.  Testosterone replacement therapy reverses these adverse profiles when they are present.

It has also been shown that men with abnormally low levels of testosterone are at greater risk of osteoporosis and fracture of the hip and that replacement may benefit the bones^7,8.

Depression and lack of well-being are also common associations with low testosterone levels and that treatment with testosterone improves symptoms⁹

Testosterone deficiency, like thyroid deficiency or diabetes is an abnormal state of affairs with physiological and psychological consequences.  As it is an abnormality it should be treated.

References

1.        Atkinson LE, Chang YL, Snyder P.  Long-term experience with testosterone replacement through scrotal skin.  In: Nieschlag E, Behre HM (eds)  Testosterone.  Action deficiency substitution. Springer-Verlag, Germany. 1998, 364-88.

2.        Schroder FH.  The prostate and androgens: the risk of supplementation.  In: Oddens B, Vermeulen A  (eds)  Androgens and the aging male. Parthenon publishing Group., New York, 1996, pp223-6.

3.        English KM, Mandour O,  Steeds RP et al.  Men with coronary artery diseas have lower levels of androgens than men with normal coronary angiograms.  Eur Heart J. 2000; 21: 890-4.

4.        Rosanno GMC, Leonardo F, Pagnotta P et al.  Acute anti-ischaemic effect of testosterone in men with coronary artery disease.  Circulation.  1999; 99: 1666-70.

5.        Webb CM, McNeill DCRR, Hayward CS et al.  Effect of testosterone on coronary vasomotor regulation in men with coronary heart disease.  Circulation.  1999, 100, 1690-6.

6.        Phillips GB, Pinkernell BH, Jing TY.  The association of hypotestosteronaemia with coronary artery disease in men.  Arterioscler Thromb.  1994; 14: 701-6.

7.        Jackson JA, Riggs MW, Spiekerman M.  Testosterone deficiency as a risk factor for hip fracture in men; a case control study.  Am J Med Sci.   1992; 304: 4-8.

8.        Finkelstein JS.  Androgens and bone metabolism.  In: Nieschlag E, Behre HM (eds). Testosterone.  Action deficiency substitution. Springer-Verlag, Germany. 1998, 187-207.

9.        Wang C, Alexander G, Berman N et al.  Testosterone replacement therapy improves mood in hypogonadal men -  a clinical research centre study.  J Clin Endocrinol Metab.  1996; 81: 3578-83.

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When we discuss estrogens as human hormones, we must include the many environmental and dietary sources of naturally occurring estrogenic compounds as well as the steroid hormones produced within, since all can activate receptors in human cells throughout the body. Environmental estrogens that may be synthesized for other purposes, such as DDT and other pesticides, are called xeno-estrogens. Plant estrogenic compounds are called phyto-estrogens. Many powerful herbal compounds belong to this category and have their effects mediated through activating estrogen receptors. All structurally similar molecules from these groups have at least some capability to occupy receptors and activate or block the activity programmed for that receptor, some more powerfully than the native hormone!

In humans, estrogen receptors have been found in every tissue. Two different estrogen receptors, ERa and ERb, have been identified, each switched on and controlled by a different gene. Both may be active in the same cells at different times of growth, development or "mature" cell activities. They are associated with different activating proteins which allow for great diversity of effects at different times. They control our brains, our immunity, our bones and our sexuality. In fact, they participate in every major function in the body. Why else would they be so widely distributed? It should become obvious by now that estrogens are essential for life and health.

So where does testosterone the "king" of the powerful hormones fit in to this schema. It is a "masculine" hormone of higher species that has specific receptors and effects. Testosterone can either activate androgen receptors, AR, or be converted to estradiol to activate estrogen receptors! This occurs in both sexes. We tend to think in terms of "male" or "female" when we discuss testosterone and estrogen. But what is becoming obvious is that these hormones are not sex specific, rather sex dominant, both being present in both sexes.

Biblically, in Genesis, the female is formed from the "marrow" or essence of the male. The Yin and the Yang principle also expresses a duality and an intertwined connection between the essence of male and female, testosterone and estrogen. What has not been recognized is the fact that all human estrogens are derived from "male" hormone precursors, particularly testosterone! This conversion takes place inside cells and tissues all around the body. In fact, many of the well known functions of testosterone are mediated through conversion first to estradiol, the primary estrogen. In particular, our sexuality is governed almost ironically by this "male" to "female" conversion! Both sexes seem to have this "androgynous" switching to activate the final receptors of sexuality, the ERa and ERb estrogen receptors. These may balance the classic androgen receptors, AR, that have been until now thought to be the major players in sexuality. So it comes as a shock to most males that estrogen may be the most powerful of all the "sex-hormones", the queen among kings!

Particularly, treatment with testosterone in high doses results in excessive conversion into estradiol essentially nullifying the benfits initially seen or looked for. Much of the confusion in the medical literature is the result of mis-understanding of this concept when large doses were tested for effects, particularly sexual function. With aging there is a general increase in conversion of androgens into estrogen. This problem may underlie the deficiency of testosterone through down regulation centrally or through down regulation of receptors at the cell itself. Treatment failure may be frequently reversed using aromatase inhibitors or non-aromatizable androgens. The delicate balance is the key to successful treatment with all hormone replacement strategies.

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ANA 126th Annual Meeting, Chicago, 30.9.2001

When doctors suppress testosterone levels in men with prostate cancer, they may inadvertently be increasing the level of a substance that appears to control the risk of Alzheimer's disease.

A recent study indicates that when testosterone levels go down, there is a dramatic increase in levels of a protein known as beta amyloid, the prime suspect in the death of nerve cells in Alzheimer's disease.

We believe this phenomenon may explain why Alzheimer's disease occurs in late life. People with a genetic predisposition to Alzheimer's may have borderline amyloid levels until menopause or the male equivalent. Andropause, reduces gonadal hormone secretions. Brain amyloid levels may then rise enough to cause amyloid accumulation to begin.

A number of studies have found that women on hormone replacement therapy in the menopause have half the risk for the disease, leading Gandy and his colleagues to speculate that gonadal hormones such as estrogen and testosterone might help to break down amyloid.

Although it has not been proven, a wealth of evidence suggests that the accumulation of amyloid into clumps called 'senile plaques' is toxic to nerve cells. On autopsy of Alzheimer's patients, doctors find especially high numbers of senile plaques in brain areas that underlie memory and reasoning, brain functions that deteriorate dramatically in the disease.

Previous studies by Gandy and his colleagues showed that brain concentrations of amyloid increased significantly in female guinea pigs whose ovaries had been removed. When the animals received hormone replacement therapy, their levels of amyloid dropped again.

The researchers realized that a natural experiment could be conducted with men whose testosterone levels are suppressed as part of their treatment for prostate cancer. In each of six men, when testosterone levels were suppressed, plasma amyloid rose two-fold over the six months' duration of the trial.

Other researchers have shown that people with higher levels of amyloid circulating in the blood are more likely to get Alzheimer's. For that reason, it will now be important to follow these measures for several years, while also administering serial cognitive function exams to determine whether any of the men develop Alzheimer's disease.

As for the effectiveness of hormone replacement therapy in preventing Alzheimer's, a large, ten-year study currently underway will yield five-year interim result in 2003.

If hormones are proven to be effective in this trial, then prevention of Alzheimer's disease may become a consideration in selecting candidates of both genders for hormone replacement therapy. 

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Probably the best current definition of the term andropause is that proposed by Tremblay and Morales as ‘when men exhibit several of the symptoms and/or clinical features of reduced testosterone availability to various systems or organ functions’¹. This key article goes on to give a detailed list of symptoms, which are strikingly similar both in content and frequency to those originally listed by Werner², and several other authors over the past sixty years^3;3;4;4-6;6.

This characteristic "identikit" pattern of andropause symptoms is the same as that seen in androgen deficient adult males generally, whether caused by testicular damage, suppression of testosterone by a prolactinoma, anti-androgens, or increases in sex hormone binding globulin (SHBG) caused by thyrotoxicosis or anticonvulsant drugs⁷.

It is also important to distinguish the symptoms of the andropause from those of male mid-life crisis. While the former most commonly starts in the 45-55 age group, and is brought on by androgen deficiency, the latter typically occurs age 35-45, and is a psychological, existential crisis. Though they are often confused in both lay and professional minds, to the detriment of the diagnosis and treatment of both conditions, they have widely different clinical pictures, which can and should be distinguished³.

Equally importantly in relation to the differential diagnosis, the symptoms are reversed by giving adequate doses of testosterone, as reported consistently in the above studies and numerous others over the last 50 years. Too often this group of symptoms is written off as inevitable ageing, even if it is occurring in forty or fifty year-olds, without adequate clinical and laboratory investigation or a therapeutic trial. This is in stark contrast to women suffering similar symptoms who have far easier access to their form of HRT.

Reference List

7. Toone BK, Wheeler M, Nanjee N, Fenwick P, Grant R. Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics. Journal of Neurology, Neurosurgery and Psychiatry 1983;46:824-6.
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