Botanicals in health and disease of the testis and male fertility: A scoping review.

BACKGROUND: 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.

PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.