Phytoestrogens – A Boon For Aging Women
Abstract:Men and women reach old age with different prospects of aging. Aging is a real challenge for woman as she has to suffer from inevitable scars of menopause. Longer life expectancy of women has resulted in rise in their health needs. Postmenopausal women have an increased affinity towards cardiovascular diseases and osteoporosis.
...
During the past decade, menopausal and postmenopausal period are being considered as the phase of life needing substantial involvement of all medicalsciences to develop potential treatments for women to live a happy and healthy latter half of her life. The use of Hormone Replacement Therapy in managing menopausal and postmenopausal period is now questioned with increasing risks of cancer with long term HRT treatment. Less effectiveness and more side effects of other new therapeutics along with financial burden of management of osteoporosis related fractures, has led tremendous interest in herbal alternatives. The search
for natural alternative to estrogen has led to a tremendous interest in phytoestrogens. Phytoestrogens include a variety of plant products that exert estrogenic and / or antiestrogenic effects either inherently or after conversion by intestinal flora. More details regarding sources of phytoestrogens especially from Ayurvedic herbs and their efficacy in retarding the risks of postmenopausal related conditions will be dealt in full paper.
Key Words: Phytoestrogens, menopause, HRT, postmenopausal osteoporosis, SERM’s
Introduction: Old age is vulnerable time for both men and women - but for women it is even more
so. The aftermath of ageing strikes women twice, because in addition to process of senility, women suffer simultaneously from the inevitable scars of menopause. Life expectancy is increasing around the globe and the number of elderly individuals is rising in every geographic region. There are currently 323 million individuals aged 65 years or over, and this number is expected to reach 1555 million by the year 2050.
Women's lives are very closely related to female sex hormones i.e. estrogen and progesterone. Hormonal changes proceed gradually in men but women encounter fast hormonal change (menopause). Menopause, the permanent loss of menstruation after amenorrhea lasting more than one year due to the loss of estrogen production by the ovaries, is a major aging process of women and most women encounter this hormonal change between 40 and 55 years of age.1 Therefore, many women spend almost 1/3 of their lives in menopause. As women age, they are more likely to experience disease and disability.2After menopause, there are many effects of female sex hormones on other body functions. Changes that occur in pituitary, adrenal gland physiology, and thyroid function and subtle, but alterations in glucose homeostasis, reproductive function, and calcium metabolism are more apparent.3 There are significant alterations in metabolism of skin and hair, body composition, and subcutaneous fat distribution throughout life.4 Therefore, women have many diseases and disabilities requiring intervention and treatment after menopause.5 Significant diseases in older
women that are hormone-dependent include osteoporosis, Alzheimer’s disease, urinary incontinence, and coronary atherosclerosis.Consequences of aging in women:
Cardiovascular Changes
In the postmenopausal women, there is an increase in circulating androgens associated with the increased risk of cardiovascular disease after five years post menopause, usually after the age of sixty years. There are changes in the cardiac functions in the form of decreased myocardial contractility, decreased stroke volume, decreased peak flow, decreased peak flow velocity and decreased vascular resistance.
Metabolic changes (Lipid Profile)
At menopause, there is an increase in cholesterol and Low Density Lipoprotein with a decrease in High Density Lipoprotein. This is associated with increased central body mass and insulin resistance. Insulin resistance and dyslipidaemia are known to be especially high cardiovascular risk factors.
Bone Loss (Osteoporosis)
Bone mass starts declining between the age of 30 to 40. Bone loss is accelerated at 3% of bone mass at menopause for the first five years and thereafter it is 1 to 2% per year. By the age of seventy years there is 50% loss of bone mass. Statistics revealed that around 250 million women worldwide have osteoporosis now. Because of increase in ageing population, it is estimated that by the year 2020, the number of women affected will be double.
Alzheimer’s Disease
Women comprise 72% of the population over the age of 85 year, and roughly half of this group has Alzheimer’s disease.6 Not only do women constitute a grated population of this older population but Alzheimer’s disease is expressed earlier in women than men.This may be related to estrogen loss that occurs with menopause. The exact mechanism is not understood. The hypothesis is that a apolipoprotein E which is believed to damage neural function by interfering with the action of
chemical messengers or neurotransmitters, which convey messages to various parts of brain, is suppressed by estrogen during reproductive life.
Urinary Tract Dysfunction
The prevalence of Stress urinary incontinence has been reported to increase at menopause and at postmenopausal age, and is more common in women than men, implicating menopause.The female lower urinary tract is thought to be a target organ for the action of the sex steroid hormones estrogen and progesterone since estrogen receptors are found in the urethra and lower urinary tract.10, 11
Other Changes
Skin aging has been reported to be affected by the reduction of female hormones after menopause.12 Carbohydrate metabolism and adipose tissue distribution are also regulated by female sex hormones, and metabolic changes lead to obesity.
Hormone Replacement Therapy
Hormone Replacement Therapy (HRT) was considered as standard therapy for treatment of menopausal syndrome and postmenopausal diseases. But recent data suggests that it has more risks than benefits. The HERS (Heart Estrogen/Progestin Replacement Study) data showed that long term HRT increases the risk of cardio vascular diseases. In addition to this, latest research data indicates an excess risk from HRT regarding the incidence of breast and endometrial cancer as well as increased incidence of stroke, coronary artery disease and other thrombotic diseases.The risk of
cardiovascular event rather increased in women treated with HRT for many years after menopause.
Thus, it is the health provider’s obligation to participate in the risk assessment and assist each woman is designing plan for life long good health.
Phytoestrogens – An Alternative To Hrt ?
The word phytoestrogens comes from “phyto” which means plant and “estrogen” due to their ability to affect estrogenic activity in the body. Hence phytoestrogens are plant derived substances whose structure results in chemical nature similar to endogenous estrogens of humans. Although phytoestrogens have some similar actions to estrogens, they are not true estrogens that are produced in human body. Phytoestrogens can either act as weak estrogens, or provide precursors to substances that affect our estrogen activity. Phytoestrogens, while they displace the human
estrogens, support female hormone levels by exerting an estrogen like effect on the reproductive organs and are 100- 150 times less potent in their estrogenic effect than human estrogen.
Classification:
One gross classification of phytoestrogens is –
(a) Steroidal (b) Non steroidal
Most of the plants containing phytoestrogens are non-steroidal. They belong to the family of compound called phenolics. They are divided into three groups.Isoflavones (2) Coumestans (3) LignansIsoflavones are further classified intoDiadzein(ii)Genistein (iii )GlycetinIsoflavones are receiving a great deal of commercial interest at present; they are found almost exclusively in legumes, the soya bean the most abundant source. Steroidal saponins are also classified under steroidal group of phytoestrogens. The two main classes of interest to human health are lignans and isoflavones.
Isoflavones exist in at least 15 different chemical forms. Their effect on human health has been investigated to some extent. Lignans are much more widespread inplant foods but the work on lignans has been limited.
Sources Of Phytoestrogens
Sources of lignans: Linseed meal, Linseed flour, Linseed oil, Oat bran, Oat meal, Lentil, Asparagus
Sources of isoflavones: Textured soyabean, Soya flakes, Soya flour, Soya sauce, Pulses, Red clover, Beans.
Phytoestrogens are also found in cabbage, grains and hops.
METABOLISM OF PHYTOESTROGENS
Natural hormones do not accumulate in tissues, and stay in the blood stream only for minutes or hours. After that, enzymes in the liver break up the hormones that are either flushed out or reused to build other molecules. The same holds true for phytoestrogens. When eaten, these plant compounds are flushed, broken apart, or absorbed into the body. Health effects of phytoestrogens are influenced by individual’s age. In contrast to natural estrogens or phytoestrogens, synthetic
estrogens don’t easily break down, are long lived and accumulate in fatty tissue. After consumption, phytoestrogens gets metabolized into heterocyclic phenols, containing a diphenolic ring similar to human endogenous estrogens, accounting for their estrogenic effects.
Mechanism Of Action
The main action of phytoestrogens is due to their adaptogenic activity. They can be beneficial in both hyperestrogenic and hypoestrogenic state in the body. Thus they have mixed estrogenic and anti estrogenic actions, depending on target tissue. This variation in activity may be due to the fact that phytoestrogens have a greater affinity for the estrogen receptor (beta) β compared with estrogen receptor (alpha) α. When phytoestrogens are metabolized, they bind on the same cellular sites as do estrogens.
A second mechanism of action for phytoestrogens may be their ability to affect the endogenous production of estrogen. The pituitary gland releases gonadotropins that stimulate estrogen synthesis in the ovaries. Phytoestrogens appear to lower gonadotropin levels.27, 28 Phytoestrogens To Prevent Cardiovascular Disease. The beneficial effects of phytoestrogens on the cardiovascular systems is by inhibiting new intima formation, decrease in LDL, increase in HDL and thus providing protection from coronary artery disease. The cardiovascular benefits with isoflavones are by
the following mechanism of action whereby cholesterol is reduced, inhibition of cholesterol synthesis reduction in lipoprotein levels and up regulation of LDL receptors in liver. In addition to this there is increased bile acid synthesis, by enhanced removal of cholesterol from LDL, responsible for making cholesterol dissolve in bile. Isoflavones, genestein and daidzein inhibit platelet aggregation by preventing thrombozane A2 form binding with its receptor. Several mechanisms are involved in the prevention of atherosclerosis by isoflavones.
Phytoestrogens To prevent Bone Loss
Isoflavone rich soya protein has been found to attenuate bone loss in postmenopausal women. In addition, soya protein increased bone formation by stimulating insulin like growth factor and moderately increasing bone turnover with bone formation being greater than bone resorption. Isoflavones facilitate bone formation action of osteoclasts combining especially with ER beta. They also suppress recruitment and functioning of osteoclasts.
Phytoestrogens And Breast
The isoflavone genestein has shown anti proliferative effects against estrogen dependent and independent human breast carcinoma cell lines.Phytoestrogens can act as anti estrogens to compete with estradoil for cytoplasmic receptors in estrogen sensitive tissues studies show a correlation between high levels of urinary lignans and genistein and a low incidence of hormone dependent cancers such as breast and prostate cancer. In vitro studies show genistein and diadzen inhibiting
growth of both estrogen receptor positive and estrogen receptor negative human breast cancer cell lines.
Phytoestrogens To Improve Memory
Animal studies show that phytoestrogens up regulate cognition markers and improve memory in rats equally when compared with estrogen. Soy supplements have been reported to improve measurements of memory and attention in postmenopausal women.
Phytoestrogens Can Act As Serm’s
Recent reports indicate that phytoestrogens exert their effect in a SERM like manner. SERM’S – Selective Estrogen Receptor Modulators act by inhibiting the binding of estrogen to estrogen receptors. The SERM – estrogen receptor complex is a unique structure which in the presence of several co-regulatory proteins, exhibits estrogenic and anti estrogenic activities in different target organs. They act as anti estrogenic in breast and uterine tissue, but estrogenic in bone, brain and lipid metabolism.
Sources Of Phytoestrogens In Herbs
Elaborate research studies conducted in recent past had shown the medicinal values in about 300 herbs containing phytoestrogens and possessing estrogenic property. Ayurveda, the oldest system of medicine, has provided many herbs which can be used in prevention of geriatric problems in women. Some of the main identified herbs contains phytoestrogens are Asaparagus racemosus, Ipomea digitata, Trigonella foenum, Dioscorea villosa, Sida cordifolia, Glycyrrhiza glabra, Puereria tuberose, Foeniculum vulgare, other varieties ofDioscorea and Puereria. Out of these Shatavari- Asparagus racemosus contains active compounds Steroidal saponins, Shatavarin I – IV, Isoflavones including 8-methoxy-5,6,4'- trihydroxyisoflavone 7-O-beta-D-glucopyranoside which shows estrogenic activity. Shatavari is a well known female rejuvenative and is widely used by women for overall health and vitality, for conception and to promote lactation. Clinical Studies on Shatavari prove the efficacy of this drug in relieving menopausal symptoms.The specific effect of Shatavari on women in balancing homeostasis can be attributed to presence of phytoestrogens. Pharmacological action of Shatavari shows Antioxidant, Immunomodulatory, Antimicrobial, Cardiotonic, Digestive, Antiallergic, Anti-oxytocic and Estrogenic properties.36Effect of Shatavari in minimizing bone loss in menopausal and postmenopausal women was studied in which Shatavari has shown encouraging results in increasing serum calcium (Bone formation markers)levels and decreasing urine calcium
(Bone resorption markers) and also relieved Ashti kshaya lakshana at significant level. 37The total number of patients investigated were 45. All the patients were in menopausal and post menopausal conditions.The biochemical And clinical analysis is given in Table numbers 1 and 2 respectively.Table 1: effect of shatavari moola churna on Markers of bone formation & resorption
MarkersMean
ScoreSDSEtpB.TA.TSerum Calcium9.259.898.632.303.86< 0.01Urine Calcium 192.3187 84.18 22.503.33< 0.01
Table 2: effect of shatavari moola churna on asthi kshaya lakshana
Asthi Kshaya
Lakshana%
reliefPAsthivedana68.57%<0.001Katishoola70.37%<0.001Sandhishoola80.0%<0.001Shrama85.29% 0.001Keshapatan71.42%<0.001
Above observations determine highly significant decline in symptoms of Asthi Kshaya and significant increase and decrease in the levels of serum calcium and urine calcium respectively.ConclusionWomen’s aging problems have created attention during last 2- 3 decades because of increase in incidences of menopausal and postmenopausal disorders and risk of their management through Hormone replacement therapy. Need for a better, safe and efficacious drug has driven the attention of all medical sciences towards phytoestrogens.More than thousand articles are published in last 30 years about phytoestrogens. These studies provide evidences on the effect phytoestrogens in relieving menopausal symptoms, inhibition of growth cancer cell lines in vitro
and in animals, reduction of cholesterol levels and in prevention of osteoporosis. But very limited good quality research has been carried out on Ayurvedic herbs in general. Herbs containing phytoestrogens like Shatavari, Vidari, Yashtimadhu, Shatpushpa may be considered as alternatives to HRT but much more well- designed clinical trials are needed in present era.
References :1. Miquel J, A Ramírez-Boscá, JV Ramírez-Bosca, JD Alperi. Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants, Arch Gerontol Geriatr.42:289–306, 2006, [PubMed].2. Amin SH, CL Kuhle, LA Fitzpatrick, Comprehensive evaluation of the older
woman. Mayo Clin Proc.; 78:1157–1185, 2003, [PubMed].3. Mooradian AD, JE Morley, SG Korenman, Endocrinology in aging. Dis Mon. ; 34:393–461, 1988, [PubMed].4. Gruber CJ, F Wieser, IM Gruber, K Ferlitsch, DM Gruber, JC Huber, Current concepts in aesthetic endocrinology, Gynecol Endocrinol.;16:431–441, 2002 [PubMed].5. Applegate WB, JP Blass, TF Williams, Instruments for the functional assessment of older patients, N Engl J Med.;322:1207–1214, 1990, [PubMed].6. Jorm AF, AE Korten, AS Henderson, The prevalence of dementia: a quantitative integration of the literature,
Acta Psychiatr Scand.;76:465– 479, 1987, [PubMed].7. Kokmen E, CM Beard, PC O'Brien, LT Kurland, Epidemiology of dementia in Rochester, Minnesota. Mayo Clin Proc.;71:275–282, 1996,[PubMed].8. Hagnell O, L Ojesjö, B Rorsman, Incidence of dementia in the Lundby tudy.Neuroepidemiology.;11(suppl 1)(1):61–66, 1992, [PubMed].9. Iosif S, L Henriksson, U Ulmsten, The frequency of disorders of the lower urinary tract, urinary incontinence in particular, as evaluated by a questionnaire survey in a gynecological health control population, Acta Obstet
Gynecol Scand.;60:71–76, 1981.10. Iosif CS, S Batra, A Ek, B Astedt, Estrogen receptors in the human female lower urinary tract, Am J Obstet Gynecol.;141:817–820, 1981, [PubMed].11. Wilson PD, G Barker, RJ Barnard, NC Siddle, Steroid hormone receptors in the female lower urinary tract, Urol Int.;39:5–8, 1984, [PubMed].12. Raine-Fenning NJ, MP Brincat, Y Muscat-Baron, Skin aging and menopause: implications for treatment, Am J Clin Dermatol.;4:371–378, 2003
Author: Dr. Jasmine Gujarathi* and Dr. Ritesh Gujarathi**
G. J. Patel Ayurveda College & Research Center, New V.V. Nagar, Anand,Gujrat, India
Comment feed for this post
