Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management

Fernandez, Cornelius James; Chacko, Elias C; Pappachan, Joseph M

doi:10.17925/ee.2019.15.2.83

Cited by 106 publications

(113 citation statements)

References 107 publications

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“…3,5 Obesity is considered to be the most frequent cause of FH. [6][7][8][9] Obesity and T2D are high risk factors for cardiovascular disease (CVD), 2,[10][11][12] and are also risk factors for benign prostatic hyperplasia (BPH); men with T2D are twice as likely to have an enlarged prostate as men without T2D. 13 Pathophysiological mechanisms explaining the correlation between obesity, T2D, risk of BPH, and prostate carcinoma (PCa) are hyperinsulinemic state, increased estrogen-toandrogen ratio, increased sympathetic nervous activity, promotion of inflammation processes, which in turn contribute to ischemia, oxidative stress, and an intraprostatic environment favorable to BPH and PCa.…”

Section: Introductionmentioning

confidence: 99%

“…22 Meta-analyses of testosterone trials did not show that testosterone increases the risk of PCa. 9,11,23 ''Saturation model'' hypothesis postulates that once testosterone concentrations have stabilized as a result of TTh, further effects of testosterone on prostate will diminish. 24 Evidence supports obesity as a risk factor for both BPH and PCa.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Testosterone Therapy on Erythrocytosis and Prostate Adverse Events in Obese Males with Functional Hypogonadism and Type 2 Diabetes in a 2-Year Clinical Trial

Antonič

Antonič²,

Pfeifer

2020

Androgens: Clinical Research and Therapeutics

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Aims: Testosterone therapy (TTh) has been postulated to increase the risk of prostate adverse events (PAEs) and erythrocytosis, risk further exacerbated in high-risk obese patients with type 2 diabetes (T2D) and functional hypogonadism (FH). We investigated safety aspects of TTh in obese males with FH and T2D by observing the incidence of PAEs and erythrocytosis and determining when statistically significant difference from the baseline manifests in hematocrit (Hct) and prostate-specific antigen (PSA) levels. Materials and Methods: Fifty-five obese Caucasian men with FH and T2D participated in a two-part prospective observational clinical study (first year: double-blind randomized placebo-controlled trial employing testosterone undecanoate; second year: open-label follow-up with all participants receiving TTh). Outcomes were assessments of Hct and PSA levels at the baseline, and 3, 6, and 12 months into each of 2 years of the study. Results: No adverse cardiovascular events or PAEs were observed. Hct first increased at statistically significant level from the baseline after 3 months of TTh in group T and after 6 months of TTh in group P. Individual Hct values for all participants remained <0.52 throughout 2-year course of the study. PSA increased from the baseline in both groups within 3-6 months of trial start regardless of intervention applied (placebo or TTh). Fifty-two patients never exceeded PSA level of 4.0 lg/L nor experienced year-on-year PSA increase >1.4 lg/L. No subject ever reached supraphysiological concentration of total testosterone. Conclusions: Our results show that TTh may be safe in obese males with FH and T2D. ClinicalTrials.gov ID: NCT0379232.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Testosterone Therapy on Erythrocytosis and Prostate Adverse Events in Obese Males with Functional Hypogonadism and Type 2 Diabetes in a 2-Year Clinical Trial

Antonič

Antonič²,

Pfeifer

2020

Androgens: Clinical Research and Therapeutics

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“…The demographic determinants of TRT blood donors in the tested blood centers revealed that these donors are likely to be middle‐aged white and Hispanic males, with average BMI over 30 kg/m 2 (defined as obese) and MAP that was significantly higher than that of their matched controls. As noted, obesity is a risk factor for late‐onset hypogonadism or testosterone deficiency, which may explain the observed differences in BMI values between TRT donors and controls. A previous study, which determined the rates of obesity and BMI in over 1 million blood donors between 2007‐2008, has suggested that about 29% of male donors were obese .…”

Section: Discussionmentioning

confidence: 46%

The prevalence and demographic determinants of blood donors receiving testosterone replacement therapy at a large USA blood service organization

et al. 2020

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BACKGROUND: Blood donors receiving testosterone replacement therapy (TRT) often require therapeutic phlebotomy due to erythrocytosis. Red blood cells (RBCs) donated by eligible TRT donors are approved for collection and transfusion. This study was aimed at defining the prevalence and demographic determinants of TRT donors at a large USA blood service organization.STUDY DESIGN: Donation data from TRT donors and matched controls was collected from a de-identified electronic donor database across 16 blood centers in 2017-2018. Demographic determinants included race, sex, age, hemoglobin (Hb), body mass index (BMI), mean arterial pressure (MAP), and the frequency of donations in the 2-year period.RESULTS: TRT donors comprised 1.6% of the donor population and produced 2.2% of RBC units during 2018. TRT donors were likely to be middle-aged white or Hispanic men, with high prevalence of obesity (50.8% of TRT donors had BMI ≥30 kg/m 2 compared with 36.2% in controls) and intensive donation frequency (1 to 29 donations in 2 years vs. 1 to 12 in controls). TRT donors had significantly (p < 0.0001) higher MAP and Hb compared with controls (MAP 99.9 AE 9.81 vs. 96.5 AE 10.1 mmHg; Hb 17.8 AE 1.44 vs. 15.6 AE 1.37 g/dL). One year of donations was associated with significant decreases in MAP and Hb for TRT donors.CONCLUSIONS: TRT is associated with high prevalence of erythrocytosis and obesity that may explain the intensive donation frequency, high MAP, and Hb. Frequent phlebotomies had a moderately positive effect on blood pressure and Hb levels. Potential implications of TRT on the quality of the RBC products require further evaluation.From the

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“…This could again predispose an obese individual to an exaggerated cytokine response in the presence of SARS-CoV-2, manifesting as severe disease and ARDS. In addition, obesity is associated with subclinical hypothyroidism and functional hypogonadism that, at least in part, is mediated by cytokines [16,17]. These could be aggravated amid a pro-inflammatory milieu induced by COVID-19.…”

Section: Covid-19 and Endocrine Pancreasmentioning

confidence: 99%

COVID-19 and the endocrine system: exploring the unexplored

Pal

Banerjee

2020

J Endocrinol Invest

237

235

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Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management

Cited by 106 publications

References 107 publications

Effects of Testosterone Therapy on Erythrocytosis and Prostate Adverse Events in Obese Males with Functional Hypogonadism and Type 2 Diabetes in a 2-Year Clinical Trial

Effects of Testosterone Therapy on Erythrocytosis and Prostate Adverse Events in Obese Males with Functional Hypogonadism and Type 2 Diabetes in a 2-Year Clinical Trial

The prevalence and demographic determinants of blood donors receiving testosterone replacement therapy at a large USA blood service organization

COVID-19 and the endocrine system: exploring the unexplored

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