dutasteride and Dyslipidemias

Benign prostatic hyperplasia (BPH), benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) belong to the most frequent diseases in ageing men. Beyond the 6th decade of life, more than 30% of men suffer from moderate to severe LUTS requiring intervention. The pathophysiology of BPH/BPE is still incompletely understood. The dominant role of the androgen system and the androgen receptor is well defined. Androgen receptors are expressed in BPH tissue in which they are activated by the potent androgen dihydrotestosterone. Synthesis of dihydrotestosterone is under control of the 5α-reductase enzyme, activity of which is antagonized by finasteride and dutasteride. More recently, the impact of prostatic inflammation and metabolic parameters particularly for the development of BPE and LUTS has increasingly been recognized. A better understanding of the pathophysiology is a prerequisite for the development of novel, more effective medical treatment options.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; 5-alpha Reductase Inhibitors; Aging; Diabetes Mellitus; Dihydrotestosterone; Dutasteride; Dyslipidemias; Finasteride; Humans; Inflammation; Lower Urinary Tract Symptoms; Male; Metabolic Syndrome; Prostatic Hyperplasia; Receptors, Androgen

To determine if cholesterol is a risk factor for the development of lower urinary tract symptoms in asymptomatic men.. A post-hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was carried out in 2323 men with baseline International Prostate Symptom Score <8 and not taking benign prostatic hyperplasia or cholesterol medications. Cox proportion models were used to test the association between cholesterol, high-density lipoprotein, low-density lipoprotein and the cholesterol : high-density lipoprotein ratio with incident lower urinary tract symptoms, defined as first report of medical treatment, surgery or two reports of an International Prostate Symptom Score >14.. A total of 253 men (10.9%) developed incident lower urinary tract symptoms. On crude analysis, higher high-density lipoprotein was associated with a decreased lower urinary tract symptoms risk (hazard ratio 0.89, P = 0.024), whereas total cholesterol and low-density lipoprotein showed no association. After multivariable adjustment, the association between high-density lipoprotein and incident lower urinary tract symptoms remained significant (hazard ratio 0.89, P = 0.044), whereas no association was observed for low-density lipoprotein (P = 0.611). There was a trend for higher cholesterol to be linked with higher lower urinary tract symptoms risk, though this was not statistically significant (hazard ratio 1.04, P = 0.054). A higher cholesterol : high-density lipoprotein ratio was associated with increased lower urinary tract symptoms risk on crude (hazard ratio 1.11, P = 0.016) and adjusted models (hazard ratio 1.12, P = 0.012).. Among asymptomatic men participating in the REDUCE study, higher cholesterol was associated with increased incident lower urinary tract symptoms risk, though the association was not significant. A higher cholesterol : high-density lipoprotein ratio was associated with increased incident lower urinary tract symptoms, whereas higher high-density lipoprotein was protective. These findings suggest dyslipidemia might play a role in lower urinary tract symptoms progression.

Topics: 5-alpha Reductase Inhibitors; Age Factors; Aged; Asymptomatic Diseases; Cholesterol; Datasets as Topic; Disease Progression; Dutasteride; Dyslipidemias; Humans; Incidence; Longitudinal Studies; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors