1.Introduction
Menopause is generally defined as the ”cessation” of menstruation for 12 consecutive months and is considered as the end of a woman’s reproductive life1. During this period, women always experience many metals distresses, such as poor concentration, agitation, anxiety, depression, and difficulty controlling themselves2,3. Depression was one of the most common and specific symptoms of menopause4-6, which may cause some serious problems such as disability and death7,8, leading to significant individual, family, and society burdens9.
Estrogen is the most used to treat depression and for relieving other symptoms among postmenopausal women in clinical10,11. However, several side effects and risks have been reported after estrogen treatment, including stroke, thromboembolism events, breast cancer, and vascular diseases12. Furthermore, Morrison et al . reported that hormone replacement therapy (HRT) does not treat post-menopause including relieving depressive symptoms in them13.
Nowadays, women are preferring to choose treatments with herbal medicine rather than exposing themselves to the risks associated with HRT3,14. Researchers have proposed that phytoestrogens, which are compounds extracted from plants15 can be used as an alternative approach to treating post-menopausal depression, without the risks associated with taking estrogens16. There are two main types of phytoestrogens: isoflavones and lignans. Isoflavones are found mainly in beans, fruits, and vegetables, especially soybeans; Lignans are found in lentils, cereals, wheat, and black rice, as well as fennel, sunflower seeds, and onions17.
The efficacy of phytoestrogens remains controversial. Some research findings have indicated a significant improvement in relieving depression among post-menopausal18,19, while other studies have argued that the treatment of soy isoflavones does not reduce depression20. There has been a meta-analysis published in 2018, which included 3 studies and 316 participants (149 in the phytoestrogen group and 167 in the placebo group) that showed phytoestrogen consumption is associated with a significant reduction in depressive symptoms among postmenopausal women21. However, as only three articles included all published in 2009 and 2010, more than twice as many eligible studies ranging from 2002 to 2017 were ignored. There are no convincing conclusions regarding the effects of phytoestrogens on postmenopausal depression until now.
The present systematic review and meta-analysis of randomized controlled trials (RCTs) aim to investigate the efficacy and safety, as well as the influencing factor of phytoestrogens in alleviating depression among postmenopausal women.
2.Method
The protocol for this systematic review has been registered on the International prospective register of systematic reviews (PROSPERO No. CRD4201804493). The Cochrane Handbook for Systematic Reviews of Interventions and PRISMA Statement helped guide the conduct and reporting of this review22.