Future direction in pharmacotherapy for non-neurogenic male lower urinary tract symptoms

Abstract

Background: The pathophysiology of male lower urinary tract symptoms (LUTS) is highly complex and multifactorial. The shift in perception that LUTS are not sex or organ specific has not been followed by significant innovations regarding the available drug classes.

Objective: To review pathophysiologic mechanisms and clinical and experimental data related to the development of new pharmacologic treatments for male LUTS.

Evidence acquisition: The PubMed database was used to identify articles describing experimental and clinical studies of pathophysiologic mechanisms contributing to male LUTS and, supported by them, new pharmacotherapies with clinical or experimental evidence in the field.

Evidence synthesis: Several pathologic processes (eg, androgen signaling, inflammation, and metabolic factors) and targets (eg, the urothelium, prostate, interstitial cells, detrusor, neurotransmitters, neuromodulators, and receptors) have been implicated in male LUTS. Some newly introduced drugs, such as phosphodiesterase type 5 inhibitors and β3-adrenergic agonists, have just started broad use in clinical practice. Drugs with potential benefit, such as vitamin D3 receptor analogs, gonadotropin-releasing hormone antagonists, cannabinoids, and drugs injected into the prostate, have been evaluated in experimental studies and have progressed to clinical trials. However, safety and efficacy data for these drugs are still scarce. Some compounds with interesting profiles have only been tested in experimental settings (eg, transient receptor potential channel blockers, Rho-kinase inhibitors, purinergic receptor blockers, and endothelin-converting enzyme inhibitors).

Conclusions: New pathophysiologic mechanisms of male LUTS are described that lead to the continuous development of new pharmacotherapies. To date, few drugs have been added to the current armamentarium, and several are in various phases of clinical or experimental investigation.

Keywords: Benign prostatic hyperplasia; Bladder; Lower urinary tract symptoms; Male; Pathophysiology; Pharmacotherapy; Prostate.