EFFECTS OF PHYTOESTROGEN IN OLD WOMEN WITH

MENOPAUSE

SYLVIA ALVIODITA

030.09.249

Trisakti University Faculty of Medicine

JAKARTA

2013

Table of Contents

Abstract 2

Introduction 3

Discussion

Menopause 4

Phytoestrogen 5

Effects of phytoestrogens in old women with menopause 7

Conclusion 13

References 14

1

ABSTRACT

Estrogen deficiency is a major risk factor for osteoporosis in postmenopausal

women. Although hormone replacement therapy (HRT) has been rampantly used to

recompense for the bone loss, but the procedure is coupled with severe adverse

effects. Hence, there is a boost in the production of newer synthetic products to ward

off the effects of menopause-related osteoporosis. As of today, there are several

prescription products available for the treatment of postmenopause osteoporosis; most

of these are estrogenic agents and combination products. Nevertheless, in view of the

lack of effect and/or toxicity of these products, majority of the postmenopausal

women are now fascinated by highly publicized natural products. This is an offshoot

of the generalized consensus that these products are more effective and free from any

adverse effects. Recently, certain plant-derived natural products, mostly

phytoestrogens (isoflavones, lignans, coumestanes, stilbenes, flavonoids) and many

more novel estrogen-like compounds in plants have been immensely used to prevent

menopause-related depletion in bone mineral density (BMD), sexual dysfunction,

cardiovascular diseases, Alzheimer's disease, diabetes, colon, and breast

cancers.Menopause is a period normally occupying one-third of women's life.

Reduced bone density is one of the most prominent symptoms during menopause.

Osteoporosis is a serious problem for postmenopausal women which increases the

risk of bone fracture and worsens with age, increasing from 4% in 50–59 year age

bracket to 50% in 80 years old women. Bone fractures are also prevalent in these

women. Today estrogen therapy (ERT) and drugs like bisphosphonates, calcitonin and

raloxifene is employed to prevent and treat osteoporosis

2

INTRODUCTION

The cessation of ovarian function at the time of menopause and resulting

hormonal changes are associated with specific health conditions that are unrelated to

those typically attributed to aging. Estrogen deficiency plays a major role in

menopausal bone loss, hot flashes, and vaginal epithelium atrophy, thus until recently

menopausal symptoms and the prevention of bone loss had been primarily managed

with hormone replacement. The findings of increased risk of breast cancer and

cardiovascular complications. In response to these well publicized results many

menopausal women discontinued or did not start hormonal replacement therapy. The

belief that products containing “natural” estrogens would provide all of the benefits

but none of the risks of prescription hormones has resulted in a vast increase in the

use of herbal products containing phytoestrogens by women seeking to alleviate

menopausal symptoms and prevent osteoporosis.

Although results of randomized trials suggest that isoflavones, the

phytoestrogens found in soy, may prevent bone loss and help with menopausal

symptoms, these studies have had serious limitations. Most have enrolled a small

number of women, included women in a wide-range of ages and years from

menopause, Isoflavones are phyto-estrogens similar to women's estrogens and are

bound to cellular estrogen receptors in various organs, thus phytoestrogens affinity is

weak compared to human's estrogens. Recent studies have shown that cells have two

types estrogen receptors α and β. Human estrogens have more affinity to α-receptors,

whereas, isoflavones have high affinity to β-receptors. β-receptors exist in brain,

bone, bladder and vascular epithelium, being important in the function of non-steroid

estrogens.

3

DISCUSSION

Discussion 1: Menopause

The time in a woman's life when menstrual periods permanently stop; it is also

called the "change of life." Menopause is the opposite of the menarche. Menopause is

defined as the time when there has been no menstrual periods for 12 consecutive

months and no other biological or physiological cause can be identified. It is the end

of fertility, the end of the childbearing years. (A woman may still, however, be able to

become pregnant unless 12 consecutive months have passed without a period.)

A woman can usually tell if she is approaching menopause because her

menstrual periods starts changing. The medical terms used to describe this time are

"perimenopause" and the "menopause transition."Natural menopause occurs when the

ovaries naturally begin decreasing their production of the sex hormones estrogen and

progesterone.

Induced menopause occurs if the ovaries are surgically removed (by bilateral

oophorectomy) or damaged by radiation or drugs. Due to the abrupt cutoff of ovarian

hormones, induced menopause causes the sudden onset of hot flashes and other

menopause-related symptoms such as a dry vagina and a decline in sex drive. Early

menopause (before age 40), whether natural or induced, carries a greater risk for heart

disease and osteoporosis since there are more years spent beyond the protective cover

of estrogen.

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Discussion 2: Phytoestrogen

Compounds with estrogen-like biological activity similar to "Isoflavones" present in

plants especially soy, may reduce bone loss in postmenopausal women as they are

similar in structure to estrogens.

There are three main classes of phytoestrogens: isoflavones, coumestans, and

lignans, which occur in either plants or their seeds. Resorcylic acid lactones exhibit

estrogenic activity and are produced by molds that commonly contaminate cereal

crops and hence are better termed mycoestrogens. A single plant often contains more

than one class of phytoestrogen. For example, the soy bean is rich in isoflavones,

whereas the soy sprout is a potent source of coumestrol, the major coumestan. The

major isoflavones, genistein and daidzein, commonly exist as inactive glucosides.

They are also derived from precursors, biochanin A and formononetin, which are

converted to genistein and daidzein respectively, after breakdown by intestinal

glucosidases. Daidzein is further partially metabolized to equol and O

desmethylangiolensin (O-DMA).

The estrogenically active lignans, enterodiol and enterolactone, are derived

from the compounds secoisolariciresinol and matairesinol found in plants. These

lignan precursors occur in the aleuronic layer of the grain close to the fiber layer.

In humans, after consumption of plant lignans and isoflavones, complex enzymatic

metabolic conversions occur in the gastrointestinal tract, resulting in the formation of

heterocyclic phenols with a close similarity in structure to estrogens. Absorbed

phytoestrogen metabolites undergo enterohepatic circulation and may be excreted in

the bile deconjugated by intestinal flora, reabsorbed, reconjugated by the liver, and

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excreted in the urine. Lignans and isoflavones can be measured in urine, plasma,

faeces, semen, bile, saliva, and breast milk. Concentrations of the different

phytoestrogen metabolites vary widely between individuals even when a controlled

quantity of an isoflavone or lignan supplement is administered. As dietary

phytoestrogen metabolism is predominantly determined by the gastrointestinal flora,

antibiotic use, or bowel disease and gender will modify metabolism.

Concurrent dietary intake, in particular high dietary fiber, vegetable and fruit

intake and duration of exposure, exert a major influence on lignan and isoflavone

metabolism. There is need for caution in relating dietary components to disease states

due to the complex interactions between ingested foods, metabolism and absorption of

specific dietary constituents as, similarly dietary fat, fiber, protein, alcohol, and

micronutrients may all independently effect endogenous estrogen metabolism.

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Discussion 3: Effect of phytoestrogens in old women with menopause

Phytoestrogens are plant-derived polyphenol compounds that show a structural

similarity to steroid hormone (17-beta-estradiol). Although phytoestrogens are not as

potential as the endogenous estrogens, they are widely self-prescribed against the

treatment of menopause and postmenopausal osteoporosis and are considered safe and

beneficial throughout the world. Most of the flavonoids (isoflavones) are classified as

phytoestrogens, based on their ability to mimic estrogen. The classical phytoestrogens

constitute a group of compounds (isoflavones, lignans, coumestanes, stilbenes,

flavonoids quercetin and kaempherol) of plant origin.

Isoflavones are natural endocrine active phytoestrogens found in Leguminosae

and are generally considered to prevent osteoporosis by promoting bone health.

Exposure to these products is through soy foods and soy protein, in addition to

processed foods or through supplements. They may be useful as dietary alternative or

supplement to postmenopausal HRT, because of their beneficial effects on

atherosclerosis and cancer risk. Soy isoflavones are structurally and functionally

related to 17-beta-estradiol and are known to act on both osteoblasts and osteoclasts

through genomic and nongenomic pathways and have beneficial effects on BMD,

bone turnover markers, and bone mechanical strength in postmenopausal women.The

effect of isoflavones on bone formation is by binding on estrogen receptors on the

target cell surface; hence it is believed that isoflavones may help in the treatment of

patients by estrogen replacement therapy for osteoporosis.

Genistein and daidzein are the other isoflavones of soy that have been shown

to conserve bone in ovariectomized rodent models and probably have similar

conservatory effects in higher mammalian species. Hooshmand et al. reported

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genistin-rich isoflavones to prevent loss of BMD in the rat model of ovaridectomy.

Isoflavone-containing soy intake was found to physiologic fluctuations in bone

turnover, thereby preventing osteoporosis, in addition to protection against breast

cancer and cardiovascular diseases.

There are yet some other plants (black cohosh, licorice, red raspberry, red

clover, and kudzu) that contain phenolic compounds and are suggested to have

estrogenic potential for relieving menopausal symptoms. In a study to assess the

estrogen bioactivity of some herbs, Oerter Klein et al. found that soy, clover, licorice,

hops, and fo-ti to have high estrogen activity, while chaste tree berry, black cohosh

and dong quai did not have measurable estrogen activity. They further found that

removal of the glycone group from soy increases its estrogen bioactivity significantly.

Many more novel estrogen-like compounds in the plant kingdom are being

discovered, thus expanding the spectrum of phytoestrogens in nature.Danggui Buxue

Tang, a Chinese medicinal decoction containing Radix astragali and Radix angelicae

sinensis, was found to stimulate osteoblast proliferation, estrogen promoter activation,

in addition to increasing the anti-platelet aggregation activity. Red clover (Trifolium

pratense), a phytoestrogen is shown to improve deteriorating bone health during

menopause. It was also found to improve arterial compliance, a risk factor for

atherosclerosis.Whelan et al. showed natural health products to prevent and treat

osteoporosis in postmenopausal women. Das et al. found that the supplementation of

the phytoestrogen (Camellia sinensi) showed a significant improvement in the

markers of osteoporosis, such as bone resorption and osteoclastic activity, collagen

degradation, bone loss, and bone density

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Sources and classification of dietary estrogens

9

Disease Relationships

Cardiovascular disease

There is evidence to support the hypothesis that phytoestrogen consumption

contributes to the lower incidence of cardiovascular disease in Asian countries and in

vegetarians and that phytoestrogens may be cardioprotective.

Consumption of 25-g soy protein enriched bread resulted in a decreased total

serum cholesterol and increased HDL cholesterol in hypercholesterolemic men. A

soybean protein diet in subjects with Type II hyperlipoproteinemia may lower

cholesterol on average by 20%. A meta-analysis of 38 published controlled clinical

trials of soy protein consumption that averaged 47 g per day and serum lipid and

lipoprotein concentrations found that consumption of soy protein was associated

significantly with mean reductions in total cholesterol (9.3% decrease, 95% CI 0.35–

0.85 mmol/L), LDL cholesterol (12.9% decrease, 95% CI 0.30–0.82 mmol/L), and

triglycerides (10.5% decrease, 95% CI 0.003–0.29 mmol/L). The

hypocholesterolemic effect appears to be significantly related to pretreatment plasma

cholesterol. A recent study of normolipemic postmenopausal women supplemented

with a 40-mg phytoestrogen pill demonstrated a 22% increase in HDL cholesterol and

no significant change in other parameters. Dietary soy phytoestrogens may provide

cardioprotective benefits via a direct effect on lipids. Other reported properties, such

as inhibition of platelet aggregation and antioxidant effects, may also be important.

Osteoporosis

Osteoporosis is related to multiple factors including aging, hormone

deficiency, and diet. There is a paucity of data regarding the possible role of

phytoestrogens in bone metabolism and the incidence of osteoporosis. Dietary

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soybean prevents significant bone loss in ovarectomized rats (P < 0.001). Ipriflavone

(7 isopropoxy-isoflavone), a synthetic flavonoid, inhibits osteoclast recruitment and

function, and 600 mg/day has prevented bone loss at the distal radius in osteoporotic

postmenopausal women. Postmenopausal women randomized to receive casein, soy

protein with either 1.39 mg total isoflavones/g protein (ISP), or 2.25 mg total

isoflavones/g protein (ISP+) for six months demonstrated increased bone mineral

content and density with ISP+ compared with controls (P< 0.005). Postmenopausal

women increased bone mineral content when fed 45 g soy enriched bread compared

with controls fed wheat kibble bread (P < 0.03). At present there is little published

data to support a specific role for phytoestrogens in the prevention of osteoporosis,

and further studies of longer duration are needed.

Cancer

The incidence of hormone dependent tumors is lower in Asia and Eastern

Europe than western countries and amongst vegetarians. Breast, ovarian, prostate, and

colon cancer show a negative correlation with cereal and phytoestrogen intake when

comparing cancer mortality rates and food availability data between countries.

Breast cancer

Protective effects of isoflavones including soy, measured by tumor number,

incidence, metastases, and latency (85–7), are seen in animal models with

experimentally induced breast cancer. Prepubertal genistein-treated rats developed

fewer mammary gland terminal-end buds, with significantly less cells in the S-phase

of the cell cycle, and more lobules than controls at 50-days-old. Breast cell lines

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saturated with predominantly genistein exhibited receptor stimulation at low

concentrations, and dose dependent inhibition at increased concentrations.

The epidemiological, animal, and cell-line data suggest that phytoestrogens

may play a role in breast cancer. Prepubertal phytoestrogens may cause precocious

maturation of breast terminal end buds to more differentiated lobules and subsequent

breast cancer protection. In contrast, increased post-pubertal exposure, without breast

maturation from significant phytoestrogen ingestion in childhood, or another stimulus

for breast maturation such as full-term pregnancy, could potentially increase breast

cancer risks via an agonistic estrogenic action.

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CONCLUSION

Phytoestrogens appear to have physiological effects in humans, with the most

supportive data being related to the effects of soy protein supplements on lipids and

lipoproteins and on vascular function. Mild estrogenic effects have been seen in

postmenopausal women; however, larger and longer term studies are needed to more

thoroughly document clinical effects and to examine the target effects on estrogen

responsive tissue such as breast and endometrium. Phytoestrogens are now available

in tablet form, and this will enhance future study designs.

Generally considered to prevent osteoporosis by promoting bone health.

Exposure to these products is through soy foods and soy protein, in addition to

processed foods or through supplements. They may be useful as dietary alternative or

supplement to postmenopausal HRT, because of their beneficial effects on

atherosclerosis and cancer risk. Soy isoflavones are structurally and functionally

related to 17-beta-estradiol and are known to act on both osteoblasts and osteoclasts

through genomic and nongenomic pathways and have beneficial effects on BMD,

bone turnover markers, and bone mechanical strength in postmenopausal women.The

effect of isoflavones on bone formation is by binding on estrogen receptors on the

target cell surface; hence it is believed that isoflavones may help in the treatment of

patients by estrogen replacement therapy for osteoporosis. And decrease the riskof

vascular disease, breast cancer, etc

13

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