American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.

Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer

Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal–obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.

Testosterone and obesity.

Introduction: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events.Areas covered: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed.Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adver...

Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

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Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men

Testosterone Replacement Therapy with Long-Acting Testosterone Undecanoate Improves Sexual Function and Quality-of-Life Parameters vs. Placebo in a Population of Men with Type 2 Diabetes

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

BACKGROUND

The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established. Current Endocrine Society and European Association of Urology guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes and in men suffering from erectile dysfunction. It is recognised that a range of physical symptoms appear as the testosterone level falls but few studies have addressed the threshold at which symptoms improve with physiological replacement. We report the first double-blind placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess the metabolic changes with testosterone replacement.

METHODS

The type 2 diabetes registers of seven general practices were screened to establish the prevalence of low testosterone and the associations with diabetes control. Of 550 eligible patients approached, 488 men (mean age 62.6) consented to take part in screening with a morning testosterone level, assessed between 8 and 11 am. This identified 211 patients for a double-blind placebo-controlled study of long acting testosterone undecanoate (TU) 1000 mg lasting 30 weeks followed by 52 weeks of open label use. The population was divided into a SEVERE group with either total testosterone (TT) of 8 nmol/l or less or free testosterone (FT) 180 pmol/l or less or a MILD group with TT 8.1-12 nmol/l or FT 181-250 pmol/l.

RESULTS

Men in the SEVERE group increased mean through TT from 7.73 nmol/l at baseline to 9.93 at 30 weeks and the MILD group from 10.47 to 11.94. The SEVERE group showed marked improvement in sexual function, but no significant improvement in metabolic parameters. The MILD group showed no improvement in sexual function, but significant improvement in weight, body mass index, waist circumference and Hospital Anxiety and Depression Scale. Improvement was seen in all parameters during 52 weeks open label treatment where trough TT levels approached 15 nmol/l. Baseline prostate-specific antigen (PSA) was lower in the SEVERE group and increased with TU for 30 weeks and then stabilised. There was no increase in PSA with treatment in the MILD group.

CONCLUSIONS

Testosterone undecanoate significantly improves sexual parameters and Ageing Male Symptom Score, but not metabolic factors at 30 weeks in men with SEVERE testosterone deficiency syndrome (TDS). In men with MILD TDS, significant improvements in metabolic but not sexual parameters were seen, suggesting that there are threshold levels for response to testosterone replacement therapy and that trials of therapy need to achieve sustained therapeutic levels to be effective. PSA showed minor rises, but only for 30 weeks in the SEVERE group.

The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study).

Objective: This study explores the links between testosterone deficiency and Quality Outcomes Framework (QOF) parameters in three south Staffordshire practices prior to a major double-blind placebo-controlled intervention study. Research design and methods: Four hundred and eighty-eight consecutive type 2 diabetic patients, aged over 18, attending their general practitioner for routine diabetes visits were assessed for sex hormone binding globulin, total testosterone (TT), calculated free testosterone (FT) and bioavailable testosterone, glycated haemoglobin A1c (HbA1c), body mass index, waist circumference, blood pressure, lipid profile, Sexual Health Inventory for Men, and current and past prescriptions for erectile dysfunction (ED). Results: TT and FT were significantly inversely associated with raised body mass index, waist circumference and HbA1C. The prevalence of ED was 77%, which was associated with low levels of TT, FT and raised HbA1C. Only 10% were receiving treatment for ED. Conclusions: Patients with low testosterone were more likely to fall outside the QOF targets and new markers might be difficult to achieve unless low testosterone is addressed. There is a strong case for the inclusion of TT and FT estimation in routine diabetic care. Br J Diabetes Vasc Dis 2009;9:226-231

Peter Wilkinson

Papers

Testosterone Replacement Therapy with Long-Acting Testosterone Undecanoate Improves Sexual Function and Quality-of-Life Parameters vs. Placebo in a Population of Men with Type 2 Diabetes

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study).

Biochemical hypogonadism in men with type 2 diabetes in primary care practice