Association Between Circulating Levels of C-Reactive Protein and Interleukin-6...
The male menopause—does it exist?Adverse secular trends in male reproductive health association between serum testosterone level been reported association between serum testosterone level be reflected in increased testicular steroid use and testosterone levels risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function. The objective of the study was to examine whether an age-independent time trend in male serum testosterone levels exists. Testosterone and SHBG were analyzed in male serum samples from four large Danish population surveys conducted in —, —, —, and — Free testosterone levels were calculated. The effects of age, year of birth, and time period on hormone levels were estimated in a general linear statistical model. Testosterone, SHBG, and calculated free testosterone levels in Danish men in relation to age, study period, and year of birth were measured.
The role of hypogonadism in Klinefelter Syndrome
Adding to the growing debate about men's health, Duncan Gould and Richard Petty argue that some patients need investigation and treatment with testosterone. Howard Jacobs, however, is not convinced. It is not an inevitability but may occur mainly in middle aged and elderly men when testosterone production and plasma concentrations fall.
There seems to be a threshold plasma concentration below which symptoms may become apparent. Testosterone concentrations found to be critical for sexual functioning in men lie around An abnormally low concentration of testosterone hypotestosteronaemia may occur because of testicular dysfunction primary hypogonadism or hypothalamic-pituitary dysfunction secondary hypogonadism and may be congenital or acquired.
The presence of obesity is associated with lower concentrations of bioavailable testosterone, and insulin concentrations have been found to be indirectly correlated with sex hormone binding globulin and testosterone concentrations. Ageing is usually associated with a decline in sexual interest and potency. Affective symptoms have long been associated with hypotestosteronaemia: Fatigue may occur with hypotestosteronaemia.
During one prospective study symptoms significantly improved with supplementation and decreased during androgen withdrawal, another showed significant improvements in energy levels and tiredness.
Male ageing is associated with an increase in central and upper body fat deposition and reduced muscle mass and strength. This could be explained by an age associated decline in growth hormone concentrations, which itself is associated with an increase in sex hormone binding globulin and therefore a reduction in bioavailable testosterone. Vasomotor disturbance and night sweats occasionally occur, their association with testosterone deficiency and relief by testosterone replacement being noted as far back as the s.
Hypogonadism like hypothyroidism is a pathological state and is associated with several other comorbid factors such as the presence of cardiovascular risk factors obesity, higher waist: Whatever the nomenclature, be it male menopause or climacteric or age related hypotestosteronaemia, men presenting with symptoms outlined in the box should be investigated. Investigations should include assessments of concentrations of plasma gonadotrophin, prolactin, and sex hormone binding globulin and early morning concentrations of testosterone.
Men with hypotestosteronaemia with unequivocal signs and symptoms of androgen deficiency, and when reversible causes of testosterone deficiency and contraindications have been excluded, should be offered treatment with testosterone replacement therapy in line with the current WHO guidelines —this is, however, a specialty beyond the scope of this article.
In the ageing man reduction in testosterone concentration is due mainly to a decline in Leydig cell mass in the testicles or a dysfunction in hypothalamic-pituitary homeostatic control, or both, leading to abnormally low secretion of luteinising hormone with resultant low testosterone production. It is well recognised that with normal male ageing mean plasma testosterone concentrations decline, albeit with considerable variability between individuals and with a broad range in age related values.
Cross sectional and prospective studies show a decline that starts in early middle age and then progresses in a linear fashion.
We thank Dr Pierre Bouloux, reader in endocrinology, centre for neuroendocrinology, Royal Free Hospital School of Medicine, London, for reviewing this manuscript and assisting in its preparation. The normal menopause—that is, the final cessation of menstruation—is caused by primary ovarian failure.
The oestrogen deficiency that results often causes vasomotor instability flushing and sweating attacks , genital atrophy vaginal dryness and discomfort , and bladder irritability, together with difficulties in cognition and loss of a general feeling of wellbeing. This climacteric syndrome, readily reversible by oestrogen treatment, is obviously sex specific.
We have to ask whether it really provides a helpful analogy for the features Jaques described as the penultimate age of man In thinking about this we do well to consider how many of the changes in men as they pass from middle to old age should be attributed to the passage of years and how many to a decline in hormone concentrations. It is easy to see the attraction of an endocrine explanation because it raises the possibility of hormone treatment for symptoms that occur at this time of life.
Careful review of the literature is at best suggestive. There is, I am afraid, still a way to go. Firstly, what are the hormonal changes that occur in ageing men? Certainly gonadal function wanes: The key difference from the menopause, however, is the gradual nature of the change in men compared with the precipitate fall of oestrogen concentration in women. Secondly, what are the biological changes that can be related to these endocrine alterations? The association of a symptom with a particular hormone concentration does not indicate causation.
Therefore before attributing to testosterone deficiency the reduction in sexual activity, the decline in muscle bulk to which Jaques referred, and the decline in skeletal mineralisation that may all occur in elderly men, we are obliged to prove that hormone replacement therapy in physiological doses reverses these processes. We must, in other words, shift the argument from epidemiological to interventional studies.
The history of this treatment is that it began with a number of persuasive trials of full dose testosterone treatment of both young and older men with hypogonadism. For example, for three years Snyder and his colleagues treated a group of almost healthy men over the age of 65 years with testosterone patches in doses sufficient to raise their serum testosterone concentrations into the range appropriate for men in their 20s. The overall effects on bone mineral density were no different from those obtained with placebo.
So far as sexual activity is concerned the role of testosterone in elderly men is still not well defined. Indeed some have suggested that the development of erectile dysfunction should be regarded as sentinel of disease and constitute an indication for careful medical assessment. Recent work, reviewed elsewhere, has shown that what ultimately determines potency is the ability of muscles in the walls of the artery supplying the penis to relax and so permit engorgement to occur.
Nitric oxide released from parasympathetic nerve endings in response to sexual stimulation causes guanylate cyclase to produce cyclic guanosine monophosphate cyclic GMP , which relaxes arterial smooth muscle. Cyclic GMP is metabolised by a specific phosphodiesterase. Sildenafil citrate Viagra inhibits this enzyme, prolongs arterial relaxation, and so enhances erection. As far as impotence in the older man is concerned, unless hypogonadism can be clearly shown, treatment with sildenafil citrate with appropriate warnings about cardiovascular risks and drug interactions with nitrites is likely to be safer and more efficacious than injections of testosterone esters.
To conclude, I really do not find the analogy of the female menopause helpful in understanding or trying to manage the problems of senescence in men. Moreover, the endocrinology of ageing is much broader than that the term suggests. As Lamberts, van den Beld, and van der Lely have pointed out, while the fragility of elderly people might be related to a gonadopause, an adrenopause the age related fall of dehydroepiandrosterone sulphate concentrations , or a somatopause the decline in secretion of growth hormone and insulin like growth factor , actually in old people the commonest endocrine disorders are diabetes mellitus and hypothyroidism.
These conditions are definitely treatable. National Center for Biotechnology Information , U. Journal List BMJ v. This article has been cited by other articles in PMC. Duncan C Gould , consultant and Richard Petty , medical director. Investigations and treatment Whatever the nomenclature, be it male menopause or climacteric or age related hypotestosteronaemia, men presenting with symptoms outlined in the box should be investigated.
Endocrinology In the ageing man reduction in testosterone concentration is due mainly to a decline in Leydig cell mass in the testicles or a dysfunction in hypothalamic-pituitary homeostatic control, or both, leading to abnormally low secretion of luteinising hormone with resultant low testosterone production.
Symptoms encountered in the male climacteric syndrome Depression, nervousness Flushes and sweats Decreased libido Erectile dysfunction Easily fatigued Poor concentration and memory. Acknowledgments We thank Dr Pierre Bouloux, reader in endocrinology, centre for neuroendocrinology, Royal Free Hospital School of Medicine, London, for reviewing this manuscript and assisting in its preparation. The endocrine function of the human testis in regard to sexuality.
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Representativeness of a single point plasma testosterone level for the long term hormonal milieu in men. Possible age-dependent influence of oestrogens on the binding of testosterone in plasma of adult men. Nahoul K, Roger M. Age related decline of plasma bioavailable testosterone in adult men. Bioavailable testosterone and depressed mood in older men: Secondary hypogonadism in older men: Testosterone and the ageing male. Kaufman JM, Vermeulen A. Androgens in male senescence.
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Effects of acute and repeated alcohol ingestion on hypothalamic-pituitary gonadal and hypothalamic-pituitary-adrenal functioning in normal males. Adverse effects of psychological stress on gonadal function and insulin levels in middle-aged males. Job strain variation in relation to plasma testosterone in working men—a longitudinal study. Hormonal changes and sexual function in ageing men. A long-term, prospective study of the physiologic and behavioural effects of hormone replacement in untreated hypogonadal men.
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The role of hypogonadism in Klinefelter Syndrome
() Association between Serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care – Gagnon. 20 Jan Apart from the association between low testosterone, body .. Low serum testosterone level as a predictor of increased visceral fat in. Febr. Meta-analysis reported varied associations between serum testosterone levels and prostate cancer (PCa) survival outcomes both in different.