Popular Diabetes Drug Decreases Testosterone in Men with Diabetes

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2012.04510.x/abstract

Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: A randomized double blind placebo-controlled study

Abstract

Objectives

Pioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied.

Research design and methods

A randomized, double blind, placebo-controlled trial with six months follow-up. Fifty (25 in each group) eugonadal men (well virilized and total testosterone ≥ 12 nmol/L) with T2DM, aged 30-55 yr, and HbA1c of ≤ 7.5%, were randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy.

Results

As compared to placebo, six months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16.1 to 14.9 vs 17.1 to 17.0 nmol/L; p = 0.031), calculated free testosterone (p = 0.001) and bioavailable testosterone (p = 0.000) despite significant increase in sex hormone binding globulin (p = 0.000). Plasma androstenedione (∆⁴) level increased (1.5 to 1.9 ng/ml; p = 0.051) following pioglitazone therapy. The decrease in testosterone was independent of change in body weight, body fat, and HbA1c.

Conclusion

Pioglitazone therapy significantly decreases total, free and bioavailable testosterone in eugonadal men with T2DM. The effects of these alterations need to be determined by further long term studies.

Testosterone Research Studies Currently Looking for Patients

Those of you who want to help advance the understanding of testosterone use for different conditions can join research studies that are currently enrolling. I was amazed to see how many studies are out there! However, none are looking at long term management of side effects like polycythemia with therapeutic phlebotomy, testicular atrophy with long term or cycled HCG therapy, HPGA normalization protocols using HCG+Clomid+estrogen blockers, and other important modalities that are being used by many physicians but with little controlled data.

Remember that some studies have placebo arms. Every study requires for you to read and sign a consent form that should clearly describe the risks and implications in joining the study. Make sure that the private investigator or research nurse overseeing the study explains things to you clearly.

Testosterone Research Studies Currently Looking for Patients

What Should Be the Cut-Off Total Testosterone Blood Level for Men with Diabetes?

Diabetes mellitus is a common chronic disease, affecting 0.5–2% worldwide. The Massachusetts Male Aging Study reported that up to 75% of men with diabetes have a lifetime risk of developing ED. Type 2 diabetes is associated with low total serum testosterone (TT) identified in several cross-sectional studies and systemic analyses. There is a lack of consensus regarding what constitutes the lowest level of testosterone within the boundaries of normality.

This study proposes a cut-off value of 403.5 ng/dl of TT blood levels as an indicator for initiation of testosterone replacement therapy in diabetic men with ED.

What Should Be the Cut-Off Total Testosterone Blood Level for Men with Diabetes?

Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes

Endocrine Abstracts (2011) 25 P163

Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes

Vakkat Muraleedharan^1,2, Hazel Marsh¹ & Hugh Jones^1,2

¹Barnsley Hospital NHS Foundation Trust, Barnley, UK; ²University of Sheffield, Sheffield, UK.

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Background: Low testosterone in men is associated with increase in all-cause and cardiovascular mortality. There is a high prevalence of hypogonadism in men with type 2 diabetes and testosterone replacement therapy (TRT) improves cardiovascular risk. However there is no published data regarding mortality in these patients in relation to testosterone levels, and the long term effect of TRT on mortality.

Aim: We report a 6 year follow-up study examining the effect of baseline testosterone and TRT in hypogonadal men with type 2 diabetes on all-cause mortality.

Methods: Five hundred eighty-seven patients with type 2 diabetes had total testosterone (TT) performed between 2002 and 2005 and were followed up for 5.8±1.3 years.

Deaths during the first 6 months were excluded. Patients were then analysed in three groups. i) normal TT (>10.4 nmol/l) ii) low TT (≤10.4 nmol/l) without TRT. iii) low TT receiving TRT for 2 years or more.

Results: Of 580 patients analysed, 338 had normal TT (58%) and 240 low TT (42%). In the low TT group 58 patients received TRT. Mean age 61±11 S.D. and similarly matched in all three groups. Total deaths 72 (12.4%). Mortality rates – low TT without treatment (36/182-20%), normal TT (31/338-9%) and low TT with TRT (5/58-8.6%). Survival was significantly decreased in patients with low TT without TRT (P=0.001 log rank) compared to normal. The treated group had improved survival (P=0.049 log rank). In the Cox Regression model multi-variate (age, weight, HbA1c, pre existing cardiovascular disease, smoking, statin and ACEi/ARB use) adjusted hazard ratio for all-cause mortality was 2.2 (95% CI 1.3–3.7 P=0.001) for low TT.

Conclusions: This study shows that men with type 2 diabetes and low testosterone have a significant increased mortality. TRT improved survival compared to those untreated, recording a similar mortality rate to the normal TT group.

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Endocrine Abstracts (2011) 25 P163

Men with lower plasma concentrations of total testosterone have an increased risk of glucose intolerance or diabetes

Endocrinol Nutr. 2011 Jan 5. [Epub ahead of print]

Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study.

[Article in English, Spanish]

Menéndez E, Valdés S, Botas P, Delgado E, Abello N.

Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Oviedo, España.

Abstract

BACKGROUND AND OBJECTIVE: Studies in men have demonstrated a correlation between serum concentrations of androgens and sex hormone binding globulin (SHBG) with the presence of impaired glucose tolerance, diabetes and metabolic syndrome. The aim of this study was to evaluate circulating levels of total testosterone, SHBG, and bioavailable testosterone in the cohort of the Asturias Study and their association with the degree of glucose tolerance and metabolic syndrome.

PATIENTS AND METHODS: The study population consisted of 282 men aged 36 to 85 years old with normal concentrations of total testosterone. The degree of glucose tolerance and the presence of metabolic syndrome were evaluated.

RESULTS: Serum concentrations of testosterone and bioavailable testosterone were negatively correlated with age, body mass index, waist circumference, blood glucose, glycated hemoglobin levels and insulin. Serum concentrations of total testosterone, bioavailable testosterone and SHBG were lower in men with glucose intolerance or diabetes than in those with normal glucose tolerance. After multivariate analysis, age and total testosterone levels were independent predictors of the presence of diabetes or glucose intolerance. The risk of glucose intolerance or diabetes mellitus was over 2.5 times higher in men with total testosterone levels in the lowest quartile than in those with total testosterone in the top quartile.

CONCLUSIONS: In this general population sample from Asturias, men with lower plasma concentrations of total testosterone - even when within the normal range - have an increased risk of glucose intolerance or diabetes, regardless of age and body mass index.

The Dark Side of Testosterone Review Deficiency: Type 2 Diabetes and Insulin Resistance

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