Review
Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown

https://doi.org/10.1016/j.jsbmb.2014.01.016Get rights and content

Highlights

  • Menopause is characterized by several disquieting symptoms.

  • Hormone replacement therapy is administered in order to minimize these symptoms.

  • Phytoestrogens are a popular alternative to avoid the side effects of HRT.

  • The indiscriminate use of PEs needs to be re-assessed due to their toxicity.

Abstract

Menopause is characterized by an altered hormonal status and by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, with increasing life span, women spend one-third of their lifetime under menopause. Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important topic in the clinic. This review describes physiological and hormone alterations observed during menopause and therapeutic strategies used during this period. We critically address the benefits and doubts associated with estrogen/progesterone-based hormone replacement therapy (HRT) and discuss the use of phytoestrogens (PEs) as a possible alternative. These relevant plant-derived compounds have structural similarities to estradiol, interacting with cell proteins and organelles, presenting several advantages and disadvantages versus traditional HRT in the context of menopause. However, a better assessment of PEs safety/efficacy would warrant a possible widespread clinical use.

Introduction

The women's reproductive stage is controlled by autocrine, paracrine and endocrine factors, which regulate female development, especially the maturation of the ovarian follicle, ovulation, luteinisation and endometrium remodeling. Healthy women are expected to spend in average 36 years in a reproductive life span. However, with increasing life expectancy, women spend one-third of their lifetime under menopause. The hormonal alterations that occur during menopause, such as the decrease in 17-β-estradiol (E2) and the increase in follicle-stimulating hormone (FSH) trigger several alterations in the body, increasing the risk for the development of several pathologies. The transition to menopause is challenging for the majority of women, with an estradiol-based therapy (hormone replacement therapy, HRT) being in general used to minimize physiological alterations associated with menopause. However, several problems are associated with HRT, justifying the need for therapeutic alternatives. In this scenario, phytoestrogens (PEs) gain importance due to their chemical resemblance to E2 (Fig. 1). Here, we discuss the pros and cons associated with PEs-based therapy during menopause, a relevant topic in the clinic since the use of those compounds is increasing.

Section snippets

The role of estrogens in women

Estrogens are steroid hormones, which generate and regulate the menstrual cycle. Estrogens are mainly produced in the theca interna cells of ovaries resulting from the conversion of cholesterol to androstenedione or testosterone, being subsequently aromatized to estrone and estradiol in granulosa cells [1]. Estrogens can also be produced in the corpus luteum and placenta [2] or in non-traditional sources including adrenal glands, adipose tissue, brain and breast [3]. Estrogens promote the

Menopause

The symptoms associated with menopause are uncomfortable for women and affect their emotional and social life. Most of the symptoms result from hormonal changes, especially from the decline in estrogens [17]. The menopausal transition is initiated by fluctuations in the menstrual cycle, comprising a rise in follicle stimulating hormone (FSH) following a decrease in both estrogen and progesterone. The final menstrual period, medically confirmed after twelve months of amenorrhea [18], [19] sets

Hormone replacement therapy

It is estimated that by 2030, 47 million women will be undergoing menopause each year [45], [46]. Bearing in mind the burden of menopause-associated symptoms, a combination of estrogens with synthetic progesterone has been used as the classic hormone replacement therapy (HRT), available and administered since the 1940s [47].

Phytoestrogens

Phytoestrogens, a group of plant-derived chemicals, are a popular alternative to estrogens/progesterone therapy [65]. Due to their similar chemical structure to E2, it is thought that PEs can replace estrogens during HRT. Several studies have focused on their potential clinical use and influence on the regulation of cellular pathways [66]. The interest in the use of PEs stems from epidemiologic studies that suggested a decreased risk of breast cancer, lower incidences of menopausal symptoms and

Conclusions

The menopausal transition is a gradual endocrinologic continuum that leads to the ending of regular ovulatory cycles due to ovarian senescence and to lower levels of circulating estrogens. Several symptoms that clearly compromise women's quality of life are associated with the period. To decrease the incidence of these symptoms, HRT has been used by menopausal women, with undesired side effects raising some concerns on the use of this therapy. Thus, the search for safer and equally effective

Acknowledgments

The work in the authors’ laboratory is supported by the Portuguese Foundation for Science and Technology (FCT) PTDC/AGR-ALI/108326/2008 grant to MSS and PEst-C/SAU/LA0001/2013–2014 to CNC. ACM, AMS and VAS are funded by FCT fellowships SFRH/BD/33892/2009, SFRH/BD/76086/2011 and SFRH/BPD/31549/2006, respectively. The authors acknowledge Dr. Paulo J. Oliveira for critically reviewing the manuscript and Filipa S. Carvalho for helping with the figures. We are very thankful to Alexandra Holy for

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