Division of Urology, Federal University of São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil.
Eur Urol. 2013 Oct;64(4):610-21. doi: 10.1016/j.eururo.2013.04.042. Epub 2013 May 7.
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.
To review pathophysiologic mechanisms and clinical and experimental data related to the development of new pharmacologic treatments for male LUTS.
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.
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).
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.
男性下尿路症状（LUTS）的病理生理学非常复杂且多因素。尽管人们已经认识到 LUTS 并非特定于性别或器官，但这一观念的转变并未带来可供选择的药物类别的显著创新。
综述与男性 LUTS 新药物治疗开发相关的病理生理机制以及临床和实验数据。
利用 PubMed 数据库，检索描述促成男性 LUTS 的病理生理机制的实验和临床研究的文章，并以此为基础，综述该领域具有临床或实验证据的新的药物治疗方法。
几种病理过程（如雄激素信号、炎症和代谢因素）和靶点（如尿路上皮、前列腺、间质细胞、逼尿肌、神经递质、神经调质和受体）与男性 LUTS 有关。一些新引入的药物，如磷酸二酯酶 5 抑制剂和β3-肾上腺素能激动剂，刚刚开始在临床实践中广泛应用。具有潜在益处的药物，如维生素 D3 受体类似物、促性腺激素释放激素拮抗剂、大麻素和注入前列腺的药物，已在实验研究中进行了评估，并已进入临床试验。然而，这些药物的安全性和疗效数据仍然有限。一些具有有趣特征的化合物仅在实验环境中进行了测试（如瞬时受体电位通道阻滞剂、Rho 激酶抑制剂、嘌呤能受体阻滞剂和内皮素转换酶抑制剂）。
描述了男性 LUTS 的新病理生理机制，这些机制导致了新药物治疗方法的不断发展。迄今为止，仅有少数药物被添加到现有的治疗方案中，还有一些药物正处于临床或实验研究的不同阶段。
