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22 April 2013

Testosterone may be beneficial for metabolic syndrome-associated prostate inflammation

The Correlation Between Metabolic Syndrome and Prostatic Diseases. De Nunzio C, Aronson W, Freedland SJ, Giovannucci E. Eur Urology 2012;61:560-570.

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. Vignozzi L, Morelli A, Sarchielli S, et al. J Endocrinology 2012;212:71-84.



Key Points

  • There is evidence of a strong and independent association between obesity/metabolic syndrome and BPH/LUTS; one of their common denominators is hypogonadism
  • As the prevalence of this condition increases the management of metabolic syndrome is considered a major challenge to global public health. An effective way to combat metabolic syndrome and its related consequences is through primary prevention. However, examination of metabolic syndrome molecular pathways and prostatic diseases may offer new therapeutic perspectives for these conditions
  • In a rabbit model of metabolic syndrome overt hypogonadism was induced and characterized by low testosterone along with prostate, seminal vesicle, and testis hypotrophy when compared with controls. In this model, prostatic mRNA levels of several inflammatory markers (e.g., IL-8, IL-1β, TNF-α and IL-6) were upregulated as was the expression of fibrotic and myofibroblast activation markers (including TGFβ1, αSMA, RhoA, ROCK1 and ROCK2)
  • Testosterone prevented (and did not induce) prostatic diseases and normalized markers of metabolic syndrome in HFD-treated rabbits. In addition, oral treatment with INT-747 also significantly (p<0.05) normalized fasting glucose, glucose tolerance, and decreased visceral fat in HFD-treated rabbits
  • Whereas testosterone treatment normalized prostate fibrosis and levels of HFD-upregulated mRNA of all the prostatic inflammatory markers plus expression of fibrotic and myofibroblast activation markers, INT-747 treatment had no effect on these parameters suggesting that the positive effect of testosterone on the prostate gland is not via a metabolic syndrome component
  • It is evident that testosterone protects rabbit prostate from metabolic syndrome-induced prostatic hypoxia, fibrosis and inflammation, thus providing new insights and perspectives for prevention and intervention in BPH/LUTS

22 April 2013

Metabolic syndrome may influence the development of prostatic diseases, including benign prostatic hyperplasia and prostate cancer

Whilst metabolic syndrome is known to be directly associated with a number of cardiovascular diseases and type 2 diabetes there is now growing evidence of its influence on the initiation and clinical progression of prostatic diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A recent review of the scientific literature evaluated studies providing evidence of the role of metabolic syndrome in the development and progression of BPH and PCa. In this evaluation the authors considered relevant articles published between 1995 and September 2011 that were identified using one of the main scientific citation databases – PubMed.

25 April 2011

Testosterone deficiency – data available from RHYME study in 2013

The natural history of testosterone deficiency in men and outcomes associated with testosterone therapy: a multi-national patient registry. RC Rosen, AB Araujo, AB O'Donnell, JB McKinlay. New England Research Institutes, Watertown, MA, USA.

Despite testosterone (T) therapy being used to treat testosterone deficiency for approximately 70 years, no large scale, long term study has fully addressed the natural history of testosterone deficiency or the long term safety of testosterone treatment.

In May 2009 it was announced that a Registry of HYpogonadism in MEn (RHYME) would be established to maintain a multi-national (European) data-set of around 1,000 patients (aged 18 and over), drawn from some 20 clinical sites, diagnosed with late-onset hypogonadism (HG), hypogonadism secondary to medical illness, and classical hypogonadism (eg, Klinefelter's syndrome).1,2 Men registered on RHYME are not required to undergo T treatment for diagnosed HG.

The primary goal of RHYME is to examine the association between testosterone therapy and prostate health (eg, rate of positive prostate biopsies (primary endpoint), incidence of prostate cancer and Benign Prostatic Hyperplasia) of men with HG that some believe is put at risk by testosterone therapy. Other goals include the assessment of HG symptoms and general health outcomes in men with HG treated with T, as well as their clinical course compared to those men with HG who are not treated.

The Registry will draw on observational studies at baseline, three months, and then yearly intervals (for a minimum of two years). Data collected will include a full medical history, a physical examination, blood sampling, and patient questionnaires.

Last updated: 2018
L.ZA.MKT.GM.10.2016.1381