Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes

Wang, Christina; Jackson, Graham; Jones, T. Hugh; Matsumoto, Alvin M.; Nehra, Ajay; Perelman, Michael A.; Swerdloff, Ronald S.; Traish, Abdul; Zitzmann, Michael; Cunningham, Glenn R.

doi:10.2337/dc10-2339

Cited by 306 publications

(267 citation statements)

References 59 publications

Supporting

Mentioning

236

Contrasting

Unclassified

Order By: Relevance

“…identified in this study, and were very similar to those reported in the literature. 3,5,9,12 When statistical measures were considered, the prediction model created from the significant multivariate associations did not perform well. Only 66% of the participants were correctly classified as having low total testosterone levels.…”

Section: Notementioning

confidence: 99%

“…11 A low testosterone level could also just be a biomarker that coexists with diabetes because of mutual risk factors, such as obesity and advancing age. 3,5 It was found in a previous study that at least 25% of men with type 2 diabetes had subnormal testosterone levels, with inappropriately low luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations, indicative of hypogonadotropic hypogonadism. 11 A small percentage had subnormal testosterone levels with elevated LH and FSH concentrations, implying primary hypogonadism.…”

Section: Introductionmentioning

confidence: 99%

“…11,14 Obesity is a proinflammatory state. 3 Visceral fat produces inflammatory cytokines, adipokines and other proinflammatory factors, such as interleukin (IL)-6, IL-1β, tumour necrosis factor-alpha, plasminogen activator inhibitor-1, angiotensinogen, vascular endothelial growth factor and serum amyloid A. Obesity also leads to an increased release of oestrogen and free fatty acid. These factors can all potentially contribute to the suppression of the hypothalamus-pituitary-gonadal axis, and can lead to androgen deficiency.…”

Section: Introductionmentioning

confidence: 99%

“…1,9,16 Interactions between visceral adiposity and low testosterone levels through proinflammatory factors can result in insulin resistance and vascular endothelial dysfunction. 3 These can be potential causal factors for increased erectile dysfunction and cardiovascular disease. Leptin resistance at the hypothalamicpituitary and testicular levels can also contribute to lowered testosterone levels.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The prevalence and association of low testosterone levels in a South African male, diabetic, urban population

Kemp

Rheeder

2015

Journal of Endocrinology, Metabolism and Diabetes of South Afri

View full text Add to dashboard Cite

Background: According to the literature, low serum testosterone levels are associated with diabetes mellitus. No or minimal data exist for its prevalence or predictors in South Africa. Design: This was a cross-sectional study. Setting: The setting was an academic centre, i.e. the University of Pretoria and Steve Biko Academic Hospital Diabetes Clinic. Subjects: A total of 150 consecutive male patients aged 50 years and older with diabetes mellitus were selected using convenience sampling. Outcome measures: The patients were evaluated for diabetes control and complications, and for hypogonadism symptoms. Early-morning serum testosterone levels were determined. Results: The prevalence of androgen deficiency symptoms was 94.7%. Some 50% of the men had low total testosterone levels. Using multivariate logistic regression, the significant factors associated with low total testosterone were waist circumference and known cardiovascular disease. The prevalence of symptoms of androgen deficiency was very high; 94.7% of the patients reported a significant number of symptoms listed on the Androgen Deficiency in the Aging Male questionnaire. Conclusion: This study confirms the high prevalence of low testosterone levels in diabetic male patients in a tertiary setting. Universal screening remains controversial owing to uncertainty regarding the risks and benefits of testosterone therapy in this population group. Predictors of low testosterone levels were identified.

show abstract

Section: Notementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The prevalence and association of low testosterone levels in a South African male, diabetic, urban population

Kemp

Rheeder

2015

Journal of Endocrinology, Metabolism and Diabetes of South Afri

View full text Add to dashboard Cite

show abstract

“…Low concentrations of testosterone can occur for a variety of reasons. Men with low testosterone experience fatigue, depression, diminished libido, loss of muscle strength,2 osteoporosis,3 visceral obesity, and insulin resistance 4. Testosterone replacement therapy (TRT) is the first‐line treatment for testosterone deficiency and has been shown to improve bone density, alleviate depression, and maintain sexual function 5.…”

mentioning

confidence: 99%

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Basit

Amory

Prasad

2018

Clinical Translational Sci

View full text Add to dashboard Cite

Development of an oral testosterone therapy has proven extremely challenging because of extensive and variable first‐pass metabolism. We investigated the in vivo metabolism of testosterone with increasing oral doses of testosterone, both alone and with the co‐administration of dutasteride (5α‐reductase inhibitor) by liquid‐chromatography tandem mass spectrometry (LC‐MS/MS). In eugonadal men prior to dosing, the circulating concentration of testosterone, androstenedione, etiocholanolone‐glucuronide, and androsterone‐glucuronide was 8.6, 20.9, 9.1, and 55.3%, respectively, of the total testosterone‐related species, whereas testosterone‐glucuronide was ∼1%. When testosterone was dosed orally to men with experimental hypogonadism, a proportion of testosterone‐glucuronide increased to 13%. Dutasteride treatment significantly decreased levels of androsterone and its metabolites. This work reveals extensive metabolism of orally dosed testosterone to androsterone glucuronide via androstenedione, with testosterone‐glucuronide appearing to be the second most important metabolite. This information is of importance in the development of an effective oral testosterone therapy and may have implications for testosterone doping research.

show abstract

Examining the associations between testosterone and biomarkers as men age

Smith

Bekele

Lopresti

et al. 2023

American J Hum Biol

View full text Add to dashboard Cite

ObjectivesTestosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone‐binding globulin (SHBG), using a large nationally‐representative data set (National Health and Nutrition Examination Survey; NHANES).MethodsNHANES is a cross‐sectional survey, physical examination, and laboratory evaluation of a nationally‐representative sample of a non‐institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013–2014 and NHANES 2015–2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA‐IR), insulin, glucose, and age.ResultsAn overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA‐IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA‐IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre‐diabetic HOMA‐IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables.ConclusionThe results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

show abstract

Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes

Cited by 306 publications

References 59 publications

The prevalence and association of low testosterone levels in a South African male, diabetic, urban population

The prevalence and association of low testosterone levels in a South African male, diabetic, urban population

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Examining the associations between testosterone and biomarkers as men age

Contact Info

Product

Resources

About