Hypoandrogen-Metabolic Syndrome in Men

Gould DC, Kirby RS, Amoroso P. Hypoandrogen-metabolic syndrome: a potentially common and underdiagnosed condition in men. Int J Clin Pract. 2007 Feb;61(2):341-4.

Researchers writing in the International Journal of Clinical Practice say Men with (Hypoandrogen-metabolic syndrome) and symptoms of androgen deficiency may be managed by, in the absence of contraindications, testosterone replacement therapy along with weight reduction and other measures to normalize glucose, lipid and blood pressure control.

The researchers noted that symptoms of androgen deficiency (hypoandrogenaemia (hypogonadism, hypotestosteronaemia) may be a common accompanying factor in men with the metabolic syndrome and when androgen deficiency and metabolic syndrome are present together “they may be considered as a specific entity, the hypoandrogen-metabolic (HAM) syndrome.”

The researchers concluded: “The prevalence of both hypoandrogenaemia and the metabolic syndrome increases with age and the clinician will frequently attend to men in their middle to advanced years with obesity, low androgen levels and metabolic syndrome.

These conditions place men at an increased risk of cardiovascular and coronary heart disease and type 2 diabetes and can be simply investigated with weight, waist and blood pressure measurement and blood sample analyses.

Men with HAM and symptoms of androgen deficiency may be managed by, in the absence of contraindications, testosterone replacement therapy along with weight reduction and other measures to normalise glucose, lipid and blood pressure control.”

Insulin Sensitivity and Men with Heart Failure

Researchers writing in the European Journal of Heart Failure say “Testosterone improves fasting insulin sensitivity in men with chronic heart failure and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of chronic heart failure”

Malkin CJ, Jones TH, Channer KS. The effect of testosterone on insulin sensitivity in men with heart failure.European Journal of Heart Failure 2007 Jan;9(1):44-50.
Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis.

Studies of testosterone in non-(CHF) males suggest that physiological testosterone therapy improves insulin sensitivity.

This was a single-blind placebo controlled crossover trial to determine the effect of testosterone replacement on insulin sensitivity in 13 men with moderate to severe CHF (ejection fraction 30.5+/-1.3). The primary outcome was the homeostatic model index (HOMA-IR) of fasting insulin sensitivity and secondary outcomes were body composition as measured by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis was performed on the delta values with the treatment effect of placebo compared with that of testosterone. At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP=0.84, p=0.0001) and body mass index (rP=0.79, p=0.01)] but not with CHF severity.

Testosterone reduced HOMA-IR (-1.9+/-0.8, p=0.03) indicating improved fasting insulin sensitivity. Testosterone also increased total mass (+1.5+/-0.5 kg, p=0.008) and decreased body fat (-0.8+/-0.3%, p=0.02).

Testosterone improves fasting insulin sensitivity in men with CHF and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of CHF.

Testosterone and the Aging Male

A published report in the medical journal Aging Male says “The wide-ranging benefits of testosterone therapy in young and old men are clear and it appears that the route of administration (intramuscular, oral, or transdermal) does not alter this fact, but future work could illustrate even more profound effects of testosterone (e.g., in reducing cardiovascular risk) that could result in its recommended use in a wider range of patients.”

Abstratct:

Kohn FM. Testosterone and body functions. Aging Male. 2006 Dec;9(4):183-8

Testosterone supplementation can help reduce many of the symptoms associated with androgen deficiency in the aging male by its effects on various parts of the body.

Bone mineral density can decrease in the hypogonadal man and this may contribute to the increased fracture rate in the elderly. Testosterone therapy can improve bone mineral density and bone architecture by increasing bone formation and decreasing bone resorption – the possible benefits on fracture rate are unknown.

Testosterone also improves body composition by reducing body fat mass and increasing lean body mass, and by increasing epidermal thickness, but its effects on muscle strength are still debated.

In patients with diabetes and androgen deficiency, testosterone supplementation appears to reduce blood glucose and this could have important implications for cardiovascular risk reduction in patients with diabetes or the metabolic syndrome.

The wide-ranging benefits of testosterone therapy in young and old men are clear and it appears that the route of administration (intramuscular, oral, or transdermal) does not alter this fact, but future work could illustrate even more profound effects of testosterone (e.g., in reducing cardiovascular risk) that could result in its recommended use in a wider range of patients.

Testosterone and Prostate

Research published in the Journal of Steroid Biochemistry and Molecular Biology says “Data from all published prospective studies on circulating level of total and free testosterone do not support the hypothesis that high levels of circulating androgens are associated with an increased risk of prostate cancer.”

Raynaud JP. Prostate cancer risk in testosterone-treated men.
J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):261-6.

Men with classical androgen deficiency have reduced prostate volume and blood prostate-specific antigen (PSA) levels compared with their age peers. As it is plausible that androgen deficiency partially protects against prostate disease, and that restoring androgen exposure increases risk to that of eugonadal men of the same age, men using ART should have age-appropriate surveillance for prostate disease. This should comprise rectal examination and blood PSA measurement at regular intervals (determined by age and family history) according to the recommendations, permanently revisited, published by ISSAM, EAU, Endocrine Society….

Testosterone replacement therapy is now being prescribed more often for aging men, the same population in which prostate cancer incidence increases; it has been suggested that administration in men with unrecognised prostate cancer might promote the development of clinically significant disease.

In hypogonadal men who were candidates for testosterone therapy, a 14% incidence of occult cancer was found. A percentage (15.2%) of prostate cancer has been found in the placebo group (with normal DRE and PSA) in the prostate cancer prevention study investigating the chemoprevention potential of finasteride.

The hypothesis that high levels of circulating androgens is a risk factor for prostate cancer is supported by the dramatic regression, after castration, of tumour symptoms in men with advanced prostate cancer. However these effects, seen at a very late stage of cancer development, may not be relevant to reflect the effects of variations within a physiological range at an earlier stage. Data from all published prospective studies on circulating level of total and free testosterone do not support the hypothesis that high levels of circulating androgens are associated with an increased risk of prostate cancer.

A study on a large prospective cohort of 10,049 men, contributes to the gathering evidence that the long standing “androgen hypothesis” of increasing risk with increasing androgen levels can be rejected, suggesting instead that high levels within the reference range of androgens, estrogens and adrenal androgens decrease aggressive prostate cancer risk.

Indeed, high-grade prostate cancer has been associated with low plasma level of testosterone.

Furthermore, pre-treatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer; as testosterone decreases, patients have an increased likelihood of non-organ confined disease and low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy. A clinical implication of these results concerns androgen supplementation which has become easier to administer with the advent of transdermal preparations (patch or gel) that achieve physiological testosterone serum levels without supra physiological escape levels.

During the clinical development of a new testosterone patch in more than 200 primary or secondary hypogonadal patients, no prostate cancer was diagnosed.

Testosterone and Prostate Cancer: An Historical Perspective on a Modern Myth

Morgentaler A.

Eur Urol. 2006 Jul 26

CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding.

Read More
Testosterone replacement therapy and the risk of prostate cancer
The article says “The belief that testosterone increases the risk of prostate cancer is so widely accepted that study after study that tries to show it and can’t keeps getting repeated over and over,” says Dr. Abraham Morgentaler, a Boston urologist and author of the 2004 review. “People don’t believe it.”