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Year : 2011  |  Volume : 43  |  Issue : 4  |  Page : 369--370

The promise of phytoestrogens

Behram S Anklesaria 
 Chairman, Indian College of Obstetrics and Gynecology, Past President, Federation of Obstetrics and Gynecology Societies (FOGSI), India, Founder President, South Asian Federation of Menopause Societies

Correspondence Address:
Behram S Anklesaria
Chairman, Indian College of Obstetrics and Gynecology, Past President, Federation of Obstetrics and Gynecology Societies (FOGSI), India, Founder President, South Asian Federation of Menopause Societies




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Anklesaria BS. The promise of phytoestrogens.Indian J Pharmacol 2011;43:369-370


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Anklesaria BS. The promise of phytoestrogens. Indian J Pharmacol [serial online] 2011 [cited 2019 Sep 21 ];43:369-370
Available from: http://www.ijp-online.com/text.asp?2011/43/4/369/83102


Full Text

The last decade has seen a dramatic rise in the academic and clinical interest in phytoestrogens (PEs) as an alternative to conventional estrogen replacement therapy (ERT) for menopause. [1] Is the pharmacological action of these compounds really the same as that of conventional estrogen? If not, perhaps a change in nomenclature can help clear some of the misconceptions surrounding the exact role of phytoestrogens.

Menopause is classified in various stages [Table 1]. ERT has been widely used in the west by women in menopause. [2] It provides relief from acute menopausal symptoms and, in the later stage, it prevents complications like osteoporosis. [3] However, the reports of increased incidence of cardiac disease, cerebrovascular accidents and breast cancer in women taking conventional ERT has been a major turning point. These adverse effects diverted the attention from conventional estrogens and increased the interest in PEs, presuming them to be a safe alternative. An obvious question is, are PEs safe?{Table 1}

PEs are non-steroidal compounds of plant origin that are metabolized in the body to substances having estrogenic activity. They exist in plants as glycoside conjugates ("glycons") and get converted by the gut bacteria to active glycons. The three classes of PEs are isoflavones (e.g., soya), lignins (e.g., whole grain cereals) and coumestans (e.g., red clover). Of these, isoflavones have been the most widely studied. Earlier, it was believed that the effects of estrogen are mediated through a single estrogen receptor, ER-α, found in the uterus, vagina and female breast. The discovery of a second estrogen receptor, ER-β, in bones, brain, blood vessels and the heart improved the understanding of the role of estrogen in prevention of menopausal vasomotor symptoms (brain), cardiac disease (heart and blood vessels) and osteoporosis (bone). Conventional estrogens bind to both ER-α and ER-β with the same affinity, while the beneficial effects listed above are mainly due to ER-β activation. In fact, activation of the ER-α receptor results in adverse effects like breast carcinoma. PEs (isoflavones) exhibit a mechanism different from conventional estrogens. They bind more strongly to ER-β than to the ER-α receptor. [4] In addition, the concentration of PEs required for cellular growth is much higher than the concentration of conventional estrogens. The preferential binding of isoflavones to ER-β receptors and higher concentration required for cellular growth may explain fewer chances of adverse effects like breast cancer. [5] Because PEs act more like a selective estrogen receptor modulator, they can be termed as natural "Selective Estrogen Receptor Modulators (SERMs)," [6] and it seems that the term "Phytoestrogen" is misleading.

It has also been realized that the time of conventional estrogen and PE administration is crucial for menopause intervention. The results of the Women's Health Initiative demonstrated that many of the ill-effects of conventional estrogen therapy are due to the late age (mean, 63 years) of women taking this treatment. The standard now is to initiate estrogen therapy in stage II (1-5 years of menopause) and not later. The great promise of PE use is that because they are "Natural SERMs" and basically derived from food products, they can be successfully used in all stages of menopause, without any serious harmful effects reported so far. Additionally, PEs have been shown to have lipid-lowering effects, especially on low-density lipoprotein, total cholesterol and triglycerides. A study published in 2006 showed that isoflavones can decrease the arterial stiffness and reduce blood pressure in women as late as in stage III of menopause. [7] However, the efficacy of conventional estrogens in treating acute vasomotor and psychosomatic symptoms is much superior to that of the weaker PEs. The rule of the thumb is to use conventional estrogens for the alleviation of acute symptoms for a short time because of greater efficacy. Conversely, PEs should be used for long-term prevention, as they are slow-acting, but safer on extended use. The impairment of cognitive function in stage III of menopause is one such area where estrogen therapy has not been effective. However, a double-blind, randomized, placebo-controlled clinical trial in post-menopausal women (aged 55-74 years) suggests that isoflavone supplementation has a favorable effect on cognitive functions, particularly verbal memory. [8] Further, a recent study showed that a combined intervention of isoflavones and regular walk three-times a week had a significant favourable effect on bone mineral density at total hip and serum high-density lipoprotein than either treatment alone. In addition, 1-year treatment with isoflavones showed a significant reduction in trunk fat mass. [9] A correlation with dietary contents of PEs and carcinoma revealed interesting observations. Japanese and Chinese diets have the highest PE content, and they have much lower rates of breast, colon and prostate cancers compared with the western countries, where PE content in the diet is low. However, the incidence of the same cancers in oriental countries, including India, has rising due to a change in diet and life style. Surprisingly, PEs have also been evaluated in men for the prevention and treatment of prostate cancer. A significant decrease in the prostate-specific antigen levels was observed in men supplemented with isoflavone for 6 months. [10]

Pharmacologically, phytoestrogens are NOT estrogens, but are natural SERMs. However, due to our past experience with conventional ERT, they should not be used without a standard monitoring. Further studies should also be undertaken to elucidate several aspects of PE use, including the exact dose for different indications. If good-quality clinical evidence confirms the initial promise, PEs may become an important alternative to long-term ERT in the management of menopause.

References

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