Opening the floodgates: benign prostatic hyperplasia may represent another disease in the compendium of ailments caused by the global sympathetic bias that emerges with aging.

We have previously posited that the global sympathetic bias that emerges with aging may constitute the common etiologic thread that links a myriad of ailments associated with aging. Recent data suggests that benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) may also be caused by sympathetic bias as an independent etiology from androgen dysfunction. The association of BPH with heart disease, independent of other variables, supports the view that both entities represent downstream manifestations of global sympathetic bias. The risk for development of BPH increases with caffeine intake and decreases with alcohol consumption, factors which wield opposing effects on autonomic balance. Heavy smoking, which induces chronic sympathetic bias, also increases the risk of BPH, a link also previously attributed to hormonal alterations. Sympathetic dysfunction appears to have a mitogenic effect on the prostate. The high prevalence of prostate cancer, a condition detected in the autopsy of many elderly men, may arise from this activity combined with a Th2 shift induced by sympathetic bias, leading to decreased cancer surveillance by the immune system. Exercise may improve BPH by restoring autonomic balance and normalizing the sympathovagal ratio. The benefits of alpha-adrenergic blockers on BPH, generally felt to achieve symptomatic relief afforded by bladder wall and sphincter remodeling, may independently exert a direct effect on prostate growth and enlargement. Sympathetic bias may play a role in adaptive enlargement of other organs such as the salivary glands, heart, liver, spleen, and skeletal muscles in response to stress. We envision novel pharmacologic and device-based neuromodulation therapies for BPH and related urologic dysfunctions based on these principles.