Testosterone – The Good News Stories in Medicine

At a conference on ‘Testosterone in Health and Disease’  being held at The Royal Society of Medicine on 29^th and 30^th March, leading international researchers will be giving the good news on the part that these hormones, the androgens, can play in preventing and treating many increasingly common health problems.

Good News in Sexual Health for Women and Men

     Desire disorders in women and erection problems are two of the areas where lack of testosterone can play a key role.  Professor Abdul Traish from Boston University will be talking about androgen deficiency and ‘Female Arousal Disorder and Sexual Function’, as well as its part in causing ‘Erectile Dysfunction’.  Two experienced physicians, Dr Adrian Zentner from Australia, and Dr Clement Williams from Canada, will be discussing their clinical work with testosterone replacement in women.  To wet the appetite further, and give the theoretical background, Professor Focko Rommerts from Rotterdam University will be giving an illustrated talk between courses at the conference dinner on ‘Eating, Smelling, Love and Sex’.

Good News for Alzheimer’s Disease and Dementia.

     Professor Robert Tan from Houston provides the latest evidence about ‘The impact of Testosterone on Alzheimer’s Disease’, and Professor Ralph Martins from Western Australia, will be giving the encouraging news on its early diagnosis, and possibilities in predicting and preventing this increasingly common condition.  Professor Eva Hogervorst from Loughborough University, will be describing the association of testosterone levels with well-being and memory, and Dr Monique Cherrier the improvements in brain function which testosterone treatment can produce.    

Good News on Testosterone being a Tonic for the Heart

     Professor Kevin Channer from Sheffield will be controversially describing testosterone as a ‘Tonic for the Heart’. Professor Ben-Shlomo from Bristol University will be giving the latest evidence linking stress, low testosterone and coronary heart disease, and Dr. Ewa Jankowska, Imperial College, on hormones and heart failure.

Good News in Diabetes and Conditions linked to Obesity

     Professor Adrian Dobs from John’s Hopkins University in the USA, Professor Kevin Channer, and Professor Stefan Arver from Karolinska University, in Stockholm will be talking about the important part that testosterone deficiency can play in obesity and diabetes, and how treatment can help these conditions and improve the quantity, and more importantly the quality, of later life.

Good News that testosterone treatment is safe and does not cause prostate cancer

     The excellent safety record of testosterone treatment, especially in relation to the prostate, will be emphasized by Professor Alvaro Morales from Ontario, and the Chairman of the conference’s charity, Mr Mark Feneley of The Institute of Urology.

Good News on the Early Detection of Testosterone Deficiency

     Laboratory blood tests to detect testosterone deficiency are very unreliable, especially in women according to Dr Tom Trinick.  Dr Malcolm Carruthers, President of the Society for the Study of Androgen Deficiency, will be explaining why instead doctors need to rely more on the characteristic symptoms for diagnosis.  This can result from age, obesity and genetic factors causing the body to fail to respond properly to the hormone, the newly described ‘Androgen Resistance Syndrome’.

The Full Conference Programme is on www.andropause.org.uk. For more details of the different topics and abstracts from these and other speaker’s papers, contact the Society Conference Organiser, Jean Coleman on androjean@aol.com or 01189815234

Testosterone-Good News in Sexual Health for Women and Men

Female Arousal Disorder and Function with Androgen Insufficiency

Professor Abdul Traish, is Director of Urology Research, Boston University School of Medicine, Massachusetts.

Summary: Female sexual dysfunction is a highly prevalent, multicausal, and multidimensional medical problem that has a major impact on quality of life and interpersonal relationships. It is hypothesized that genital arousal disorder is caused by diminished arterial blood flow within the hypogastric arterial bed. This hypothesis may explain the pathophysiologic mechanisms in older patients with vascular risk factors, but it does not account for either the prevalence or the mechanisms of arousal disorders seen in young women with no vascular risk factors. Hormonal imbalances may be important contributing factors to the pathophysiologic mechanisms involved in female arousal disorders. Androgens modulate the growth and function of female genital sexual organs included the labia, vagina, and clitoris. This article discusses the potential role for androgens in facilitating female genital sexual arousal

Clinical Experiences with Testosterone Replacement in Women

Dr Adrian Zentner is a Primary Care Physician and Medical Director of the Wellmen and Women Too Programme, is based in Perth, and operates regular clinics in 5 capital cities across Australia. He is author of the book ‘Raising the Fig-leaf’ published this year.  Dr Clement Williams, is Medical Director, Dudarave Medical Clinic, West Vancouver, Canada.

Summary:   Androgen deficiency in women is a poorly defined yet well recognized condition characterized by otherwise unexplained fatigue, lethargy, depression, cognitive changes and loss of libido.  The causes and significance of testosterone deficiency in women are reviewed and cases presented to illustrate the precautions required and the benefits that may accrue when treating women with testosterone.

Links Between Testosterone Deficiency, Metabolic Syndrome and Erectile Dysfunction.

Dr Farid Saad Male Healthcare, Schering AG Berlin / Germany & Research Department, Gulf Medical College School of Medicine, Ajman / UAE

Summary: Testosterone is pivotal in erectile physiology. Erectile dysfunction (ED) and the metabolic syndrome share the same risk factors and hypogonadism is often part of the metabolic syndrome. Testosterone may be the common denominator. ED may be the first symptom prompting men to seek medical advice. The time has come to view ED no longer as an entity in itself but as an expression of multiple underlying pathologies which require medical attention promoting general health and therewith also sexual functioning.

Eating, Smelling, Love and Sex.

Professor Focko Rommerts, of the Department of Internal Medicine, Erasmus Medical College, Rotterdam, The Netherlands, will be telling us all we wanted to know about these subtle anatomical, hormonal and psychological links in sexual life.

Testosterone - Good News for Alzheimer’s Disease and Dementia.

Professor Robert Tan, Clinical Director and Chief of Geriatrics, University of Texas, Houston, will give the latest findings on ‘The impact testosterone on Alzheimer’s Disease’.

     Professor Ralph Martins, who holds the Inaugural Chair at the Centre for Ageing and Alzheimer’s Disease, Edith Cowan University, Perth, Western Australia, will be talking about ‘Genetic Factors in androgen deficiency and Alzheimer’s Disease’.

     Professor Eva Hogervorst from the Department of Human Sciences at Loughborough University, will be describing a ‘Longitudinal analysis of the association of testosterone levels with well-being and memory’.

     Dr Monique Cherrier from the Department of Psychiatry and Behavioural Sciences, Washington State University in Seattle will talking about ‘Testosterone replacement and cognitive functioning’.

     Professor Nancy Sicotte, of the Neurology Department UCLA School of Medicine, will be talking about ‘Testosterone and Multiple Sclerosis’.

     Professor Christian Pike from the Adrus Gerontology Centre, University of Southern California will be speaking on ‘Androgen regulation of neuropathy in Alzheimer’s Disease’.

     Professor Molly Shores from the Department of Veterans Affairs, Seattle will be talking about ‘Testosterone and mortality in older men’.

Androgens in General Practice

In 2005 Professor Shabsigh of presented evidence to suggest that the symptoms of erectile dysfunction and hypogonadism may be early warning markers of important men's health issues, such as cardiovascular disease, diabetes, metabolic syndrome, depression and benign prostatic hyperplasia (Shabsigh, 2005).
This means that early detection of erectile dysfunction (ED) may be a key factor in early diagnosis and treatment of these serious disorders.
Unlike the female of the species, men have always put their health at risk by a macho avoidance of the doctor. Often, by the time a man decides to consult his GP, his condition is already too advanced for successful treatment. Since the arrival of Viagra, Cialis and Levitra, this has changed to a degree in that it has now become slightly more acceptable for men to discuss the problem of ED and perhaps also to talk to a doctor about it.
It has now been established that the probability of men suffering from erectile dysfunction increases rapidly with age.
Low testosterone levels, or inability to make use effectively of higher levels, results in changes in the penile tissues causing erectile dysfunction (Shabsigh, 2006, Traish, 2006, Foresta 2004). Moderate to long term hormone replacement can reverse these changes and may avert the need for use of more expensive drugs (Yassin, 2006). Shabsigh suggests that symptoms of sexual dysfunction may be the manifestation that presents an opportunity to detect other disorders and hopefully implement changes to improve men's health.

Defining a normal level of testosterone
Testosterone replacement has continued to be viewed as a controversial treatment for a number of reasons. Definition of the normal pattern of blood levels has remained a stumbling block as many patients exhibiting symptoms of androgen deficiency have apparently normal levels of blood testosterone. However, it is now generally recognised that three factors undermine the use of total testosterone as an indicator of hormonal sufficiency.
Firstly, the level of available and usable testosterone is reduced increasingly with age by the accumulation of sex hormone binding globuline (SHBG) which inactivates the hormone. Other proteins also have a binding effect. To overcome this difficulty, Calculated Free Testosterone is now used as a more accurate alternative (Vermuelen, 1971, 1998).
Secondly, Recent papers have revealed the extreme difficulty of obtaining accurate measure of both testosterone and oestrogen using current laboratory techniques. There are large inter-laboratory and inter-method discrepancies which render results unreliable.
Another factor which can influence results is the state of the patient at the time of testing. A heavy drinking bout the night before can lower testosterone. If the patient is fasting, the level will be raised.
Finally, variations in the androgen receptor also radically affect the effective use of the hormone in the tissues. The androgen receptor is the most mutated receptor in the body. CAG repeat polymorphism can dramatically change the body's reactions to testosterone. Short chain repeats increase the effects of the hormone, long chain repeats require higher levels to trigger a reaction in the tissues.
Hence, an apparently normal level of testosterone in the blood may be ineffective for those with a mutated CAG repeat chain.

Cardiovascular Disease
Cardiovascular disease has a similar pathogenesis to ED and a growing body of research now challenges many traditional views concerning the role of androgens in relation to heart disease. Testosterone has long been considered a dangerous hormone, damaging to the circulatory system, albeit with little evidence. To the contrary, evidence from clinical and laboratory research associates testosterone with cardiovascular health Physiological androgen activity may actually be a tonic for the heart and protect the circulatory system against complications that appear associated with declining serum testosterone (Channer, 2007).
Testosterone replacement therapy is safe, with no excess adverse events, improving functional capacity and symptoms in hypogonadal men with moderately severe heart failure (Malkin et al, 2006). Testosterone does not increase the risk of thrombosis (Smith et al, 2005) Testosterone improves ischaemic threshold and quality of life in hypogonadal men with angina (Malkin, Channer et al, 2004) and low doses of transdermal Testosterone therapy improve the angina threshold in men with chronic, stable angina (English et al, 2000) Age-related decline in testosterone could contribute to the atheroschlerotic process and the immune-modulation properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome (Malkin et al, 2003; Jones et al, 2005)
Resistance to insulin occurs in chronic heart failure and relates to prognosis. Testosterone improves this, suggesting a favorable effect on an important metabolic component of chronic heart failure (Malkin, Channer et al, 2007) Low testosterone levels in young men can be detected using measurements of finger length ratios and it has been suggested, could be used to predict those at risk of later circulatory problems and the possible need for replacement in later life (Fink, Manning & Neave, 2006).

Alzheimer's Disease
It is now predicted that cases of dementia could rise from 700,000 to 1.7 million by the year 2050. The Alzheimer's Society refers to this as 'a time bomb' and calls for resources and strategies for care and support.
An increasing number of studies suggest that Testosterone replacement is a major possibility in treatment of many of these cases.
Available testosterone depletion is a normal consequence of aging in men. Testosterone is frequently lower in AD patients, and one consequence of this is an increased risk for the development of AD (Pike et al, 2006, Rosario 2004). Testosterone plays a role in regulating toxic beta-amyloid (Abeta) levels but also has both neurotrophic and neuroprotective functions.
Sufferers also may have distortions of the androgen receptor which result in a decreased capacity to use such levels of testosterone as are available to them. So that even apparently normal levels of the hormone are inadequate to protect (Lehmann, Hogervorst et al, 2004) . Overproduction of Abeta peptide is believed to be a key factor in the development of AD. It is neurotoxic probably due to its capacity to cause oxidative stress. The reproductive hormones help to reduce the damaging effects of Abeta (Barron et al 2006).
Oxidative stress has been implicated in AD pathogenesis as well as in other illnesses such as atherosclerosis and Parkinson's (Sicotte, 2006). Many studies show that oestrogen, progesterone, testosterone and luteinizing hormone have a neuroprotective role. Decreasing levels of these hormones during aging are thought to increase risk of AD as a result of reduced protection against oxidation (Hogervorst, 2004).
These findings have led to trials evaluating androgen-based therapies for the prevention and treatment of AD (Lim et al, 2003, Tan R., 2003). Initial findings suggest that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease. Enhancement of testosterone levels may be an effective method of preventing or ameliorating the disease (Tan R., 2003).

Metabolic syndrome
Metabolic syndrome (which has also been shown to be an indicator of later Alzheimer's disease) is set to reach epidemic proportions. The metabolic syndrome is a cluster of the most dangerous heart risk factors: diabetes and prediabetes, abdominal obesity, dyslipidaemia, high blood pressure, and hypercoagulability. The global prevalence is 25% in adults and up to 80% of sufferers of diabetes will die of cardiovascular disease. Again, low testosterone levels (or possibly ineffective use of available testosterone due to genetic changes in the androgen receptors or increased levels of SHBG), has been flagged up as a factor in this type of illness (Svartberg, 2006).
Androgen replacement has given encouraging results as a method of treatment in this area. Zitzmann (2006) found in several small intervention studies that normalization of testosterone levels reduces fat mass and inflammatory markers, increases lean body mass and shows an overall improvement in the risk factors for the metabolic syndrome and cardiovascular diseases in patients with visceral obesity, cardiovascular diseases and diabetes type 2.
Kapoor, Channer et al (2006) concludes that testosterone replacement reduces resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. In addition, improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity represent a reduced cardiovascular risk.

Prostate Cancer and Safety Issues
A series of recent publications examining the link with prostate cancer supports the current consensus that testosterone may exacerbate prostate cancer that is already present, with many reasons to doubt the role of testosterone in the initiation of biologically significant cancer (Raynauld, 2006; Feneley, 2006; Morales, 2007; Chen at al, 2003). In fact, there is evidence that high levels of testosterone and adrenal androgens may be associated with lesser risk of aggressive prostate cancer, whereas androgen levels are not associated with non-aggressive disease (Severi et al, 2006). Aside from potential adverse safety concerns with inappropriate or unmonitored testosterone replacement, overwhelming evidence supports testosterone replacement as one of the safest forms of pharmacology. A survey all forms of testosterone treatment reported to the Medicines Control Agency from 1963 to 2002, gives no adverse reactions in the first 15 years of reporting. Over the next 29 years a total of 214 possible reactions were reported in 185 patients, some having more than one reaction. Of these reactions, half were minor skin reactions, pain at injection sites or loss of pellet implants. There were only three fatalities reported, including one suicide, one overdose and one sarcoma of unknown site. These, of course may or may not have been due to the testosterone. More recent studies (Feneley 2006, Raynaud, 2006) confirm these safety findings.
It should also be noted that low testosterone has now been found to be associated with increased mortality (Shores, 2006).

Future use of Testosterone
The use of testosterone purely as a cosmetic, anti ageing technique is not acceptable to many practitioners. Nor is the prescribing of testosterone to younger men as an aphrodisiac or a sports aid in any way warranted. But medicine in the 21st century faces a different series of challenges. The ageing population is set to increase markedly over the next few decades. Responsible testosterone replacement may be a way to reduce the predicted large numbers of dependent elderly who are likely to need care from the health services. The watershed which doctors face in the 21st century, of metabolic disease, Alzheimer's disease, cardiovascular disease and depression is likely to overwhelm existing health resources. Preventative measures together with the help of these new hormonally based approaches may be part of the solution.

Information:Prof. A. Traish, Prof. A. Yassin, Dr. Andrea Garolla, Prof. K. Channer, Prof. C. Pike, Prof. E. Hogervorst, Prof. N. Sicotte, Prof. R. Tan, Dr. Michael Zitzmann Mr. Mark Feneley, and Professor Alvaro Morales, will be presenting papers at the 5th International Conference of the Society for the Study of Androgen Deficiency on March 29th & 30th (Sessional Rates available) at the Royal Society of Medicine, London.

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