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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.
4
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
5
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.
6
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
7
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
8
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
10
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
11
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.
12
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
REFERENCES
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supplementation on bone mineral metabolism and serum lipid in postmenopausal
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hormone replacement therapy. A follow up study among 1689 women aged 45–60
years.
3. Glazier MG, Bowman MA: A review of the evidence for the use of
phytoestrogens as a replacement for traditional estrogen replacement therapy.
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4. Franke AA, Halm BM, Kakazu K, Li X, Custer LJ. Phytoestrogenic isoflavonoids in
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