The possible role of NOS alterations effecting LUTS development is supported by the known increased autonomic hyperactivity occurring in systemic disorders which affect the bladder and prostate (e.g. diabetes, obesity), and the observed improvement in LUTS with phosphodiesterase type 5 inhibitor use without a change in flow rate [14,15,37–39]. Here, NOS2 is linked to obesity due to melanocortin 4 receptor deficiency.