Analysis of safety concerns regarding the use of phytoestrogen-containing products

• Published in: Drug safety 2023-04, Vol.46 (4), p.423-424
• Main Authors: Tjeerdsma, A M, van Hunsel, F P A M, van de Koppel, S, Ekhart, C, Vitalone, A, Woerdenbag, H J
• Format: Article
• Language: English
• Subjects: Actaea racemosa; Breast; Cardiovascular diseases; Disorders; Endocrine disruptors; Estrogen receptors; Estrogens; Flowers & plants; Gene expression; Glycine max; Heart diseases; Herbs; Literature reviews; Menopause; Osteoporosis; Pharmacology; Pharmacovigilance; Phytoestrogens; Plant species; Product safety; Reproductive system; Risk assessment; Safety; Statistical analysis
• ISSN: 0114-5916; 1179-1942

Introduction: Phytoestrogens (PEs) are able to interact with estrogen receptors and can therefore modulate gene expression. Plant products containing PEs are used for various conditions including cancer prevention, osteoporosis, heart disease, and menopausal complaints [1, 2], but are not without risks. Safety assessment including a critical analysis of adverse reaction (AR) reports is essential to come to responsible use of PE-containing products. Aim: To identify plant species containing PEs; to review the literature concerning the use and pharmacology of PEs; to evaluate Individual Case Safety Report (ICSR) on PE-containing products submitted to the databases of the World Health Organization (WHO) and the Netherlands Pharmacovigilance Centre Lareb. Methods: We performed a scoping review by systematically searching three electronic literature databases (PubMed, Scopus, Cochrane Library) over the period 2000-2022. The safety of PEcontaining products was assessed by investigating cases submitted to the WHO (Vigibase®) and Lareb. All reported AR were coded using MedDRA® (the Medical Dictionary for Regulatory Activities). For descriptive statistics, Microsoft Excel 2019 was used. Results: From the scoping review (n = 80 articles included) it appeared that amongst reported ARs (n = 1160), 958 (82.6%) occurred in single-herb products and 202 (17.4%) in multi-herb products with the System Organ Class (SOC) 'reproductive system and breast disorders' (n = 321) being most frequently reported, most common plant species found were Actaea racemosa L. (n = 17), Glycine max (L.) Merr. (n = 16), and Trifolium pratense L. (n = 7). Analysis of cases submitted to Lareb showed that amongst reported ARs (n = 67), 29 (43.3%) occurred in single-herb products and 38 (56.7%) in multi-herb products with SOC 'reproductive system and breast disorders' (n = 31) being most frequently reported, most common plant species found were Actaea racemosa L. (n = 32), Humulus lupulus L. (n = 22), and Glycine max (L.) Merr (n = 15). Analysis of cases in Vigibase® showed that amongst reported AR (n = 21,944), 4446 (20.3%) occurred in single-herb products, 4655 (21.2%) in multi-herb products and 12,843 (58.5%) in multiple-mixed products with SOC 'general disorders and administration site conditions' (n = 8999) being most frequently reported, and most common plant species found were Glycine max (L.) Merr. (n = 15,669), Actaea racemosa L. (n = 2549), and Vitex agnus-castus L. (n = 1401). Conclusion