Abstract
The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.
Highlights
Endometriosis is a common benign chronic disease affecting reproductive-age women [1]
We assessed the risk of bias according to the following domains: (i) Can we be confident in the assessment of exposure?; (ii) Can we be confident that cases had developed the outcome of interest and controls had not?; (iii) Were the cases properly selected?; (iv) Were the controls properly selected?; (v) Were cases and controls matched according to important prognostic variables or was statistical adjustment carried out for those variables? We graded each potential source of bias as Definitely yes, Probably yes (Moderate risk of bias), Probably no (Serious risk of bias), or Definitely no (Critical, high risk of bias)
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Summary
Endometriosis is a common benign chronic disease affecting reproductive-age women [1]. High local concentrations of estradiol and alterations in estrogen receptor (ER) α and ERβ receptor expression may activate a network of genes regulating cell proliferation [7,8]. In line with these observations, medical treatment for endometriosis is still focused on pain and lesion size control with hormonal therapies able to establish either a hypo-estrogenic or a hyper-progestogenic milieu [9,10]. In other conditions in which hormones exert a specific role, such as breast and endometrial carcinogenesis, research has demonstrated that diet may strongly affect incidence [13]
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