GKT School of Medical Education, King's College London, London, United Kingdom.
MRC Centre for Transplantation, Guy's Hospital Campus, King's College London, King's Health Partners, London, United Kingdom.
Phytomedicine. 2022 Nov;106:154398. doi: 10.1016/j.phymed.2022.154398. Epub 2022 Aug 19.
Male factor infertility often results from testicular disorders leading to inadequate sperm quantity and quality. Both beneficial and detrimental effects of botanical products, especially herbal medicines, on testicular functions and male fertility have been reported in the literature.
This scoping review aims to map the main clinical evidence on different impacts of botanical entities on the testis and to critically appraise relevant randomized controlled trials (RCTs) published in the recent 5 years, so as to inform the future.
Systematic reviews, meta-analyses and RCT reports on botanical impacts on testicular functions and male fertility were retrieved and synthesized from Pubmed, Web of Science, Scopus, Embase, ProQuest, Cochrane Library and Google Scholar up to 10th May 2022. RCTs published since 2018 were critically appraised against good practice guidelines for RCT and for reporting herbal studies.
We identified 24 systematic reviews and meta-analyses published since 2005, by authors from Iran (25%), China (21%), USA (12.5%) and 9 other countries. All but two were published in English. Only 3 systematic review protocols were identified, all published in English from China in the recent 3 years. We identified 125 RCTs published in six languages, mainly English (55%) and Chinese (42%). They were published since 1994 from 23 countries on all the six inhabitable continents, with China (46%), Australia (8%), USA (8%), India (7%) and Iran (5%) being the leading contributors. 72% and 28% RCTs published in English were on efficacy (botanicals vs placebo) and comparative effectiveness (a botanical vs other treatments), respectively. In contrast, 98% RCT reports in Chinese were on comparative effectiveness, with merely 2% on efficacy. Among all the 125 RCTs, 57% were studies in patients with semen abnormality and/or male infertility, 22% investigated herbal effects in healthy men, 14% were on patients with male sexual dysfunction and hypogonadism, and 7% were conducted in men with non-sexual disorders. Since 2018, 32 RCTs have been published, in English (69%) or Chinese (31%). Nineteen RCT reports from China, India, Japan and Korea all studied herbal formulae while the 13 RCT reports from Australia, Brazil, Czech and Italy, Iran, Malaysia, Spain, the UK and the USA all exclusively studied extracts of a single species. Putting geo-cultural differences aside, gossypol and extracts of Tripterygium wilfordii Hook. f. were found to be detrimental to the testis and male fertility, while the extracts of Withania somnifera (L.) Dunal and traditional Chinese medicine Qilin Pill, etc., might improve testosterone levels and semen parameters, thus could be therapeutic for male sexual dysfunction and infertility. However, all still require further evaluation in view of recurring weaknesses in quality control of herbal materials, RCT design and reporting. For example, only 9%-23% of the RCTs published since 2018 provided information on voucher samples, chemical profiling, herbal authentication and herbal extraction.
Research on botanicals and the testis has been reported worldwide, demonstrating clear geo-cultural differences in studied plant species, botanical types, study objectives and quality of research design, implementation and reporting. Due to a few recurring weaknesses in the literature, this study is unable to recommend the use of any specific botanicals, however, current evidence does indicate that botanicals can be double-edged swords to the testis and male fertility. To secure better clinical evidence, future studies must faithfully implement existing and emerging good practice guidelines.
男性因素不育症通常是由于睾丸疾病导致精子数量和质量不足引起的。植物产品，尤其是草药，对睾丸功能和男性生育能力既有有益的影响，也有有害的影响，这在文献中有报道。
本范围综述旨在绘制不同植物实体对睾丸的主要临床影响，并批判性地评价最近 5 年内发表的相关随机对照试验（RCT），以提供未来的信息。
从 Pubmed、Web of Science、Scopus、Embase、ProQuest、Cochrane Library 和 Google Scholar 中检索并综合了关于植物对睾丸功能和男性生育力影响的系统评价、荟萃分析和 RCT 报告，检索时间截至 2022 年 5 月 10 日。根据 RCT 和草药研究报告的良好实践指南，对 2018 年以后发表的 RCT 进行了批判性评价。
我们确定了自 2005 年以来发表的 24 篇系统评价和荟萃分析，作者来自伊朗（25%）、中国（21%）、美国（12.5%）和其他 9 个国家。除了两篇之外，其余的都是用英语发表的。只确定了 3 篇系统评价方案，都是来自中国，发表时间在最近 3 年，都是英语。我们确定了 125 篇发表在六种语言的 RCT，主要是英语（55%）和中文（42%）。它们自 1994 年以来在六个洲的 23 个国家发表，其中中国（46%）、澳大利亚（8%）、美国（8%）、印度（7%）和伊朗（5%）是主要贡献者。72%和 28%的英语 RCT 分别是关于功效（植物与安慰剂）和比较疗效（一种植物与其他治疗方法）的。相比之下，98%的中文 RCT 报告是关于比较疗效的，只有 2%是关于功效的。在所有 125 项 RCT 中，57%是针对精液异常和/或男性不育症患者的研究，22%是研究健康男性的草药作用，14%是针对男性性功能障碍和性腺功能减退症患者的研究，7%是针对非性疾病患者的研究。自 2018 年以来，已有 32 项 RCT 发表，其中包括英语（69%）和中文（31%）。来自中国、印度、日本和韩国的 19 项 RCT 报告都研究了草药配方，而来自澳大利亚、巴西、捷克和意大利、伊朗、马来西亚、西班牙、英国和美国的 13 项 RCT 报告则专门研究了单一物种的提取物。撇开 地缘文化差异，棉酚和雷公藤红素提取物被发现对睾丸和男性生育能力有害，而睡茄（Withania somnifera（L.）Dunal）和中药麒麟丸等提取物可能提高睾酮水平和精液参数，因此可能对男性性功能障碍和不育症有治疗作用。然而，由于草药材料的质量控制、RCT 设计和报告方面经常存在弱点，所有这些都需要进一步评估。例如，自 2018 年以来发表的 RCT 中，只有 9%-23%提供了关于凭证样本、化学特征、草药鉴定和草药提取的信息。
全球范围内都有关于植物和睾丸的研究，研究的植物种类、植物类型、研究目标以及研究设计、实施和报告的质量都有明显的地缘文化差异。由于文献中存在一些反复出现的弱点，本研究无法推荐任何特定的植物，但目前的证据确实表明植物对睾丸和男性生育能力可能是一把双刃剑。为了获得更好的临床证据，未来的研究必须忠实地实施现有的和新出现的良好实践指南。
