Endocrine Abstracts

Objectives: BPH is characterised by prostate inflammation, which frequently occurs in men with metabolic syndrome (MetS). MetS is often associated with low testosterone (T). Recent evidence shows that low, rather than high, T is associated with BPH/lower urinary tract symptoms (LUTS). To evaluate if T replacement therapy (TRT) for 6 months in BPH men with MetS and low T, is able to improve LUTS and prostate inflammation.

Methods: 120 men in waiting list for BPH surgery and diagnosed with MetS were enrolled in the trial. According to total T (TT) and calculated free T (cFT), they were categorized into eugonadal (TT≥12 nmol/L and cFT≥225 pmol/L; n=48) and hypogonadal men (TT<12 nmol/L and/or cFT<225 pmol/L; n=72). Hypogonadal men randomly received T gel 2% (5 g/daily) or placebo for 6 months. At baseline and follow-up visit (after 6 months), all men filled-out the IPSS and NIH-CSPI questionnaires and underwent a transrectal prostatic ultrasound. After surgery, prostate tissue was collected for the assessment of gene expression, by RT-PCR, and of the histopathologic inflammatory score.

Results: After adjusting for the baseline value, age, TT and waist circumference, NIH-CSPI total score significantly decreased in both the groups (P<0.001 vs. baseline), whereas IPSS total score did not change in any of the groups. IPSS bother score significantly decreased only in T-treated (P=0.042 vs. baseline). Although a significant increase in total prostate and adenoma volume occurred in T-treated (both P<0.05 vs. baseline), TRT arm was characterised by a significant decrease in ultrasound markers of prostate inflammation, including arterial velocity and acceleration (both P<0.01 vs. baseline value). The assessment of the gene expression showed that several markers of inflammation (COX2, MCP1, RORγt and IP10) and metabolic-induced inflammation (LDLoxR, RAGE and IRS1), were significantly down-regulated in T-treated men as compared with placebo arm (all P<0.05) and, in some cases, TRT was even able to decrease the gene expression below the values of eugonadal men (MCP1, IP10 and IL12) (all P<0.05). In a subset of men (23 eugonadal, 8 placebo-treated and 9 TRT), TRT showed a trend towards a lower histopathological inflammatory score as compared with eugonadal and placebo-treated men (analyses ongoing).

Conclusions: Six-month treatment with T gel 2% in hypogonadal men with BPH and MetS is able to improve several clinical, ultrasound and molecular proxies of prostate inflammation. This results into a moderate improvement in symptoms, particularly bother for LUTS.