Khaw Shen Chuen, Martins da Silva Sarah
S Khaw, Reproductive Medicine Research Group, University of Dundee, Dundee, United Kingdom of Great Britain and Northern Ireland.
S Martins da Silva, Reproductive Medicine Research Group, University of Dundee, Dundee, DD1 9SY, United Kingdom of Great Britain and Northern Ireland.
Reprod Fertil. 2024 Sep 1;5(4). doi: 10.1530/RAF-24-0022.
Infertility is estimated to affect more than 50 million couples around the world, with male factor accounting for half of these cases, yet there is a notable absence of effective treatment options for men, other than in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). This review considers unlicensed and empirical treatments used for male subfertility, including hormonal therapy, phosphodiesterase inhibitors, and antioxidants. Compounds generally demonstrate variable improvements in sperm function but benefits for fertility are less clear. There is a pressing need for effective treatment options for subfertile men, however, our knowledge of sperm function is limited, restricting the identification of precise treatment targets. The traditional drug discovery pathway is also notorious for its extensive resource and time requirements, often extending over decades and demanding significant financial investment. Unfortunately, a substantial number of potential therapies fail before reaching the marketplace. Furthermore, reliance on mammalian models is not possible in the drug development process for male subfertility, due to significant variability between animals and man. We review recent breakthroughs and highlight novel methods aimed at improving the effectiveness and efficiency of drug discovery for male subfertility. High-throughput screening, combinatorial chemistry, and the repurposing of established medications have great potential. These strategies offer the promise of accelerating the pace of drug development, curbing the extensive demand for resources, and, in the case of drug repurposing, diminish the demand for comprehensive pharmacokinetic and pharmacodynamic studies. As these innovative approaches are adopted, the feasibility of addressing male subfertility through scientific advancements appears to be increasingly attainable.
据估计，全球有超过5000万对夫妇受到不孕症的影响，其中男性因素导致的病例占一半，但除了体外受精（IVF）或胞浆内单精子注射（ICSI）外，男性缺乏有效的治疗选择。本综述探讨了用于男性生育力低下的未经许可的经验性治疗方法，包括激素疗法、磷酸二酯酶抑制剂和抗氧化剂。这些化合物通常能在一定程度上改善精子功能，但对生育能力的益处尚不明确。对于生育力低下的男性，迫切需要有效的治疗方案，然而，我们对精子功能的了解有限，这限制了精确治疗靶点的确定。传统的药物研发途径因其对资源和时间的大量需求而声名狼藉，通常需要数十年时间，且需要大量资金投入。不幸的是，大量潜在疗法在进入市场之前就失败了。此外，由于动物和人类之间存在显著差异，在男性生育力低下的药物开发过程中无法依赖哺乳动物模型。我们回顾了近期的突破，并强调了旨在提高男性生育力低下药物研发有效性和效率的新方法。高通量筛选、组合化学和现有药物的重新利用具有巨大潜力。这些策略有望加快药物开发的步伐，抑制对资源的大量需求，并且在药物重新利用的情况下，减少对全面药代动力学和药效学研究的需求。随着这些创新方法的采用，通过科学进步解决男性生育力低下问题的可行性似乎越来越高。
