Middle Aged Women Demographics Menopausal Transition Biology Essay
Worldwide, ageing is a phenomenon that grips every state as the productive population will bit by bit age into geriatric population, a greater proportion of which will be adult females given that 55 % of aged in the universe are adult females ( UN 1988, WHO 2002 ) . In India, middle-age population is increasing quickly and forms the productive population. The latest 2011 nose count ( Chandramouli 2011 ) estimates approximately half of the adult females ( 47.6 % ) in India are in the age group of 15-65 old ages. Demographic surveies estimate that, in 1990, there were 467 million postmenopausal adult females in the universe. Population projections based on these demographic surveies predict that, by the twelvemonth 2030, the figure of postmenopausal adult females will increase to 1.2 billion. At this clip, approx 47 million adult females will be come ining menopause each twelvemonth. Furthermore, it is estimated that adult females in developed states will pass about 30 years of their life in the postmenopausal province. This translates into increased public wellness disbursement on chronic diseases and finally a retarding force on the Indian economic system.
The wellness disbursement is highest, owing chiefly to chronic diseases in middle-age and aged population. This is obviously reflected in India ‘s increasing disbursement on the wellness, the major portion of which is in the private sector ( 4.5 % of GDP as compared to 1.2 % by the province in India ‘s entire public wellness disbursement of 5.2 % ) . One-half of this contributed by adult females, who unlike work forces, do n’t bask a smooth passage into the middle-age wellness hazards, chiefly on history of climacteric. Furthermore, there is grounds that Indian adult females may be relatively worse off than work forces with respect to many of the hazard factors for CHD, peculiarly post-menopausal adult females ( Vlassof 2007, Silander et al 2008, Njelekela 2009, Ghosh et al 2010, Abbasi et al 2012 ) .
Menopause signifies the surcease of ovarian map in adult females which marks the terminal of the generative life span in them. Clinically climacteric is defined as absence of catamenial periods for atleast 12 back-to-back months or more ( Soules et al 2001 ) . Although climacteric is a distinct event in the generative lifetime, the arrest of catamenial periods is non sudden ; the event itself represents the apogee of an altered endocrinological state of affairs, the beginnings of which normally precede the climacteric by more than a decennary. Based on this biological phenomenon of climacteric, the generative categorization of adult females is done into
Pre-Menopausal: Before the menopausal passage starts
Peri-Menopausal: the stage of passage from pre-menopause to menopause
Post-Menopausal: the period after climacteric has occurred
Contrary to the popular belief, where the full stage of passage into climacteric is referred to as climacteric ; clinically climacteric is considered as a individual event that marks terminal of catamenial periods.
The average age of happening of climacteric is 51-52 old ages ( Copeland 1993 ) . But recent tendencies indicate a displacement of this average age a small earlier in life, and the factors disputed to be causative here are unhealthy dietetic forms and sedentary life style and exposure to higher degrees of environmental pollutants. But non merely does any certification exist on this displacement in average menopausal age in the Indian context, but besides the function of diet and life style has non been studied. Hence mapping demands to be done in Indian adult females and influence of diet and lifestyle demands to be reviewed.
It is worthwhile to observe that while climacteric is a natural phenomenon, it is listed as a ‘disease ‘ in International Classification of Diseases – 9 & A ; 10, Disease Data Base, e-Medicine, and Medical Subject Headings. Menopause obviously alters the map of human organic structure ensuing in menopausal symptoms jointly called as ‘menopausal syndrome ‘ ( Govil 2010 ) .
Table 1 Clinical Reproductive Aging In Women
Reproductive Old ages
First Time period:
Concluding Time period: 51
Lengths of rhythms
2 or more
Signs and Symptoms
For a few
adult females, hot flashes
go on into their
60s and 70s
Beginning: American Society for Reproductive Medicine 2007
The biological effects of estrogen lack in females when the ovarian follicular shops decline, consequences in the a assortment of symptoms with changing grades of badness and uncomfortableness. This syndrome is called menopausal syndrome. The chief four categories of menopausal syndrome, harmonizing to the organ system being affected are classified into following four categories:
Ojljo ; jo’jo ‘
Large Numberss of estrogen receptors are found in the vagina, vulva, urethra, and trigone of the vesica. Therefore, wasting of the GU piece of land can happen as estrogen degrees diminish.
After climacteric, the vaginal walls thin and lose their snap. They besides produce fewer secernments and lose much of their lubricating ability in response to sexual stimulation. The vulva becomes flattened and thin as a consequence of the loss of collagen, adipose tissue and the ability to retain water8. The urethra besides becomes thinner and less efficient, with detrusor force per unit area at the urethral gap decreasing, both during and after invalidating. Estrogen lack besides leads to an addition in fibrosis of the vesica cervix, reduced collagen in environing tissues, and a lessening in the figure and diameter of the musculus fibres in the pelvic floor.
These alterations increase a adult female ‘s hazard of vaginal and urinary piece of land infection. Atrophic GU tissues are besides at increased hazard of hurt by injury. Estrogen replacing therapy can significantly decrease these jobs.
All of the alterations to the GU piece of land can ensue in dyspareunia, taking to a reduced involvement in sexual intercourse. Fatigue and depression brought on by the vasomotor symptoms and sleep perturbations of climacteric can worsen this deficiency of involvement in sexual intercourse.
Decreased degrees of endogenous testosterone, both in adult females who have undergone surgical climacteric, every bit good as in those who experience natural climacteric, may do reduced libido9. Womans who complain of deficiency of sex thrust may be campaigners for androgen replacing, every bit good as estrogen. In general, androgen degrees do non diminish suddenly at climacteric but lessening bit by bit as adult females age so that decreased libido may be a job of older postmenopausal adult females ( Dominiguez 2004 ) .
Normal Female Reproductive Endocrinology: Sexual activity Steroid Feedback Control Loop
Normal female generative endocrinology: sex steroid secretory feedback control cringle
Fig Sex Steroid Secretory Feedback Control Loop
Endocrinology of Menopause
The oncoming of climacteric is marked by abnormality in catamenial rhythms and eventually climaxing in complete expiration of menses. The endocrinologic alterations of climacteric consequence from interplay between worsening ovarian map and mutual alterations in go arounding gonadotrophins. For five to seven old ages before the oncoming of the last catamenial period, ovarian map begins to decrease. Thus one of the chief ovarian endocrines, Estrogen begins to decrease. This affects the pituitary feedback mechanisms and manifests as increased degrees of Follicle Stimulating Hormone ( FSH ) , secreted by the anterior hypophysis for exciting the ovaries to increase the production of estrogen.
Both steroids and protein endocrines from the ovary control pituitary production and secernment of LH and FSH. The chief ovarian steroid endocrines are estradiol ( prevailing in the follicular stage ) and Lipo-Lutin ( predominant in the luteal stage ) . These steroids regulate gona dotropin production and release via feedback cringles of the hypothalamic-pituitary-ovarian axis. In add-on, several peptide endocrines ( inhibin, activin, and follistatin ) produced by granulosa cells influence FSH synthesis and secernment.
Concurrently, the production Inhibin B, which is a endocrine secreted by the little antral follicles and is a major regulator of FSH, diminutions due to age-related diminution in the figure of follicles in the ovary, which in bend, leads to farther addition in FSH ( Warren and Dominguez, 2004 ) . Women older than the age of 45 exhibited catamenial abnormality when the mean figure of aboriginal follicles per ovary decreased to about 100 ( Burger et al 2008 ) .
The A function of inhibin in the ordinance of FSH secernment has received considerable attending given the dynamic alterations in serum concentrations that occur over the catamenial rhythm. There are two types of inhibin, each consisting of the sameA aa-subunit combined with a eitherA bA- orA bB-subunit to organize inhibin-A and inhibin-B, severally. These dimeric inhibins show different forms of secernment during the catamenial rhythm. Degrees of inhibin-A are low during the follicular stage, rise with ovulation, and extremum during the luteal stage ( 76 ) .A In contrast, inhibin-B degrees are highest during the midfollicular stage, diminution at midcycle, and expose a transeunt rise shortly after the LH rush ( 77 )
OneA of the most consistent endocrinologic alterations associated with oncoming of the perimenopause is the monotropic rise in FSH ( 7882 ) .A It has been hypothesized that this alteration in FSH may ensue from lessened map of the granulosa cell compartment of the ovary, manifested by reduced production of estradiol, inhibin, and/or insulin-like growing factors ( IGFs )
Early surveies showed that lifts in FSH are frequently accompanied by lessenings in go arounding degrees of estradiol ( 79,83,84 ) A and inhibin ( 8386 ) .A Other surveies of the perimenopausal passage have shown no important alteration in estradiol degrees ( 80,81 ) A or elevated estrogen degrees ( 8789 ) .A These evident struggles in the literature may reflect differences in the timing of the sample aggregations over the perimenopausal passage. Possibly, ab initio, the addition in FSH compensates for diminishing ovarian map and consequences in increased estradiol degrees. Then, as the ovary continues to age in the latter portion of the perimenopausal passage, a diminution in estradiol occurs. Worsening inhibin instead than estradiol production by the granulosa cells during the early stage of the perimenopause may be of import in originating the monotropic rise in FSH ( 9091 ) .A Whereas some surveies utilizing a polyclonal antibody to theA a-subunit have failed to demo a alteration in serum inhibin concentrations associated with the monotropic rise in FSH ( 87,92,93 ) , A decreased secernment of inhibin-B has been shown to be associated with this lift in FSH ( 94 ) .A Thus, decreased inhibin-B may reflect lessened map of the granulosa cells of older adult females and play a function in the ordinance of FSH during the perimenopause ( 95 ) .
These alterations disrupt the feedback control cringle of estrogen release and throw the whole hypothalamo-pituitary-ovarian axis into pandemonium. As a consequence a typical form of plasma hormonal degrees ( shown in Fig ) consequences in the stages environing climacteric. In this form, there are two estrogen degree extremums following FSH extremums and a Lipo-Lutin extremum following an LH extremum in premenopausal stage. In the peri menopausal stage, the sex endocrine production starts worsening ensuing in extremely fickle additions in let go ofing endocrines. Finally after the menopausal passage is complete, the ovarian sex endocrine production beads to the lower limit with let go ofing endocrine degrees staying elevated throughout.
In drumhead, the earliest endocrinologic grounds of lessened ovarian modesty may be diminished inhibin-B secernment and the monotropic rise in FSH. This may happen in the presence of elevated circulating degrees of estradiol.
DIMINISHED OVARIAN RESERVE
The venue of generative ripening is the ovary. It is here that the seeds of climacteric are sown, because the ovary contains a finite figure of unreplaceable aboriginal follicles. The perimenopausal old ages are marked by their accelerated abrasion. As the figure of ollicles dwindles, amplification of ovarian endocrines appears to alter slightly erratically. The catamenial regularity a adult female experiences during the perimenopausal old ages appears to be more related to her staying aboriginal follicle figure than to her age ( 40 ) . As the figure diminishes, irregular hemorrhage can happen after an estradiol extremum without subsequent ovulation or principal luteum formation. Both normal ( 36,41 ) and unequal ( 38,42 ) principal luteum secernment of Lipo-Lutin have been described in perimenopausal adult females.
Coordinately, early follicular stage estradiol concentrations are elevated in perimenopausal adult females compared with midreproductive-aged adult females ( 27,32,38,45,46 ) . In two little surveies of adult females aged 43 and older who were still cycling, ovulatory rhythms with high estrogen production were observed ( 38,46 ) , proposing that this accelerated folliculogenesis could be ebullient throughout. In other words, the ovary, less antiphonal to FSH, requires greater go arounding measures of FSH to originate folliculogenesis. Once started, FSH induces an ”overshoot ” of estradiol and accordingly, hyperestrogenemia occurs. These lifts in estrogen may be a characteristic of the early perimenopause, with reduced estrogen accounting for the catamenial rhythms instantly predating climacteric. It is clinically of import to understand how normally diminished Lipo-Lutin secernment might be coupled with hyperestrogenic rhythms, since this combination predisposes adult females to menorrhagia, endometrial hyperplasia, dysfunctional uterine hemorrhage, and even endometrial malignant neoplastic disease.
Glycoprotein endocrines elaborated by the granulosa cell include inhibin, a disulfide linked heterodimer, which has been shown to diminish over the perimenopausal passage ( 34,39 ) . A lessening in inhibin secernment by the granulosa cells begins at about age 35, but accelerates dramatically after age 40. The diminution in inhibin, which likely reflects both lesser follicular competency and a smaller ovarian follicular pool, is believed to ease the early follicular stage rise in FSH. Activin, a homodimer of the inhibin b-subunit, may be increased locally in the perimenopausal ovary, since inhibin a-subunit is worsening at this clip of life ( 34 ) . This addition in activin may foster increase go arounding FSH, and, at least in an carnal theoretical account, has been shown to take to hyperestrogenic superovulation ( 50 ) .
Therefore, the early perimenopause is heralded by the visual aspect of elevated FSH, possible lifts in estrogen, and decreased Lipo-Lutin secernment. The hormonal surroundings is one of comparatively unopposed estrogen, and this may advance the growing of uterine leiomyomata and a assortment of confusing shed blooding jobs. The perimenopausal generative hormonal environment should non be regarded as a simple waning of ovarian map over clip. It is a waxing and declining procedure, at times more like a “ roller coaster ” in its hormonal kineticss.
At the clip of climacteric, the ovary is about barren of aboriginal follicles ( 51 ) . Granulosa cell estrogen production is basically nonexistent. The go arounding degree of estrogen in adult females shows a really steep diminution over the first 12 minute after the climacteric, with merely a really little farther diminution in the old ages thenceforth ( 52,53 ) . The day-to-day production rate of estrogen falls about eightfold to a degree of approx 48 milligram per 24 h. Essentially, all estrogen in the postmenopausal adult female is derived from the peripheral transition of androstenedione. Indeed, postmenopausal adult females who have undergone bilateral ovariectomies for endometrial malignant neoplastic disease show no important decrease in their circulating degrees or urinary elimination rates of estrogen ( 5456 ) .
Glucocorticoid suppression, nevertheless, dramatically reduces the go arounding degree of estrogen ( 54,57 ) , whereas suprarenalectomy efficaciously eliminates mensurable estrogens from the piss ( 55 ) . The go arounding degree of theelin in postmenopausal adult females is approx 3070 pg/mL. The go arounding degree of estradiol is even lower, approx 1020 pg/mL, as most is derived from the peripheral transition of theelin ( 53,58,59 ) . Estrone sulphate is an inactive metabolite of both estradiol and theelin, which diminishes in a similar mode postmenopausally. However, it still is present in higher concentrations than its precursors in both plasma and chest tumour tissue. It may hold important biological effects as civilization surveies with rat mammary tumour cell lines show about complete desulfation of the endocrine and tumour settlement proliferation ( 60 ) . Sporadic and transeunt additions in estradiol concentrations, neither accompanied nor followed by lifts in Lipo-Lutin, have been noted in some postmenopausal adult females ( 61 ) . Such cases may stand for residuary follicular activity without subsequent ovulation, or possibly are associated with stromal hyperplasia.
Ovarian stromas possess a limited capacity to perfume androgens and hence to more straight lend to the go arounding pool of estrogen. Immunohistochemical scrutiny of ovarian stromal cells has besides late demonstrated the presence of aromatase cytochrome P-450 in both pre and postmenopausal ovaries ( 68 ) . Whatever ability to perfume androgens the postmenopausal ovary may possess in vivo, it is by and large agreed to be at most rather limited. This may be because of a disproportionately lower concentration of FSH as compared to LH receptors in the ovarian stromal cells.
As adult females traverse the climacteric, ovarian androgen secernment diminutions ( 52,69 ) . Midcycle testosterone and androstenedione have been reported to be decreased at midcycle in adult females in their mid-40s who are still holding regular catamenial periods, when compared to younger, midreproductive-aged adult females ( 70 ) . This aside, a solid foundation of grounds exists that demonstrates the postmenopausal ovary to stay a extremely functional androgen-secreting organ. Histologic scrutiny reveals the stromal cell of the ovarian cerebral mantle and the hilar cell of the ovarian myelin to be responsible for this production
Effects OF MENOPAUSAL ENDOCRINOLOGICAL CHANGES ON BODY COMPOSITION, CHRONIC DISEASE PHYSIOLOGY AND METABOLISM
Estrogen receptors are present in assorted organ systems in the organic structure, hence depletion in estrogen, exerts an consequence of lack on these organ systems, one among these being the cardiovascular system.
Effectss on Body Composition
A figure of surveies have been reported the association of menopausal passage and alterations in organic structure composing, particularly increase in the splanchnic fat terminal in adult females ( Ley et al 1992, Hunter et al 1996, Tremollieres et Al 1996, Reubinoff et al 1995, Lovejoy et al 2008 ) . Franklin et Al ( 2009 ) followed up 8 pre menopausal adult females for 8 old ages till they were one complete twelvemonth into their climacteric and studied the alterations in entire organic structure fat and distribution
Effectss of Estrogen and Estrogen Withdrawal on the Physiology of the Heart and Vasculature
The add-on of estrogen has been shown to increase cardiac end product, arterial conformity, and myocardial perfusion, and to diminish vascular opposition and systolic and diastolic blood force per unit area both in animate beings and worlds. The consequence of the physiologic remotion of estrogen with climacteric on cardiovascular map is less clear.
Changes in Blood Flow
The endothelium plays a critical function in the control of blood flow in the interaction between the blood and the vas wall. Endothelial map has been assessed in patients by mensurating coronary hemodynamic response to intracoronary disposal of an endothelium dependant vasodilative, acetylcholine. Coronary thrombosiss with usually working endothelium exhibit acetylcholine-induced dilation, manifested by an increased epicardial cross-sectional country and coronary flow augmentation. In patients with coronary artery disease or dysfunctional endothelium, self-contradictory acetylcholine-induced bottleneck is manifested by lessenings both in country and blood flow. Of note, acetylcholine-induced alterations in coronary tone mimic those to common vasomotor stimulation, such as exercising and mental emphasis and, therefore, are utile in experimental scenes. Endothelial disfunction is progressively recognized as an of import factor in the patterned advance of cardiovascular disease. Numerous surveies suggest that estrogen has a good consequence on endothelial disfunction and, therefore, worsening estrogen degrees with climacteric and the subsequent negative consequence on vascular tone, could be an of import mechanism by which coronary artery disease occurs in postmenopausal adult females. The clinical grounds and proposed mechanisms are summarized below.
Effectss on Vasculature
Most of the recent literature has focused on the effects ( ague and chronic ) of estrogen disposal to postmenopausal adult females with coronary artery disease and impaired vascular tone. A few cross-sectional surveies have looked at the direct consequence of climacteric ( and, therefore, estrogen backdown ) on vascular tone. A group of research workers used high declaration ultrasound to measure endothelial reactivity in the brachial arteria ( which has been shown to be an effectual placeholder for coronary endothelial map ( 13 ) . in a big series of males and females ) ( 11 ) . Flow-mediated dilation was preserved in immature male topics and so declined after 40 year of age. In adult females, nevertheless, flow mediated dilation was maintained until the early 50s, and so declined significantly more than it did in work forces. Another recent survey looked at both normotensive and hypertensive males and females and found that age-related endothelial disfunction is attenuated in premenopausal adult females both with and without high blood pressure as compared to males. This gender difference was non seen postmenopausally ( 14 ) . The same writers who studied alterations in forearm blood flow
used brachial arteria strain gage plethysmography to mensurate the consequence of surgical climacteric on vascular tone in a little series of adult females who were scheduled to hold TAH/BSO for uterine leiomyoma. In association with dramatic beads in estrogen degrees these adult females had a important decrease in acetylcholine-induced vasodilation compared to their presurgical baseline. These alterations were significantly attenuated in a little subset of the adult females who received estrogen replacing over the following three months ( 15 ) .
There are informations that both short- and long-run estrogen disposal improves endothelial cell-mediated vasodilation in ovariectomized monkeys fed an atherogenic diet ( 15,16,18 ) . Recent surveies looking at the effects of estrogen disposal on vascular tone in postmenopausal adult females are summarized in Table 2. Most of these surveies have looked at the acute consequence of estrogen on vascular responsiveness. As seen in Table 2, earlier surveies used cardiac catheterisation to mensurate coronary flow opposition in cross-sectional countries before and after endovenous estrogen. Later surveies used brachial strain gage plethysmography and brachial arteria high-resolution ultrasound. There is limited informations on the effects of long-run estrogen disposal and coronary endothelial cell map. One survey, in ovariectomized monkeys treated with hormonal replacing for 26 minute, has shown a good consequence ( 17 ) . A survey by Lieberman ( 22 ) , treated 13 postmenopausal adult females with hormone replacing therapy in a double-blind placebo controlled crossover test. Measurements of flow-mediated vasodilation of the brachial arteria taken at the terminal of each 9-wk intervention suggested statistically important alterations in flow-mediated vasodilation in postmenopausal adult females on short-run endocrine replacing therapy. In contrast, Gilligan ( 24 ) found no betterment after 3 wk of endocrine replacing therapy in contrast to the consequence of ague estrogen disposal on flow mediated dilation utilizing the same method. The recent survey by McCrohon, which was a cross-sectional survey comparing postmenopausal adult females who had taken HRT with age-matched controls ( who had ne’er taken HRT ) , demonstrated statistically significantly greater flow mediated dilation in adult females taking HRT, as measured by brachial arteria high-resolution ultrasound ( 26 ) .
In drumhead, clinical surveies suggest a function for acute estrogen in the betterment of endothelial-dependent flow-mediated vasodilation. The information for short-run or chronic endocrine replacing therapy is less clear. There are a figure of possible grounds for these differences. First, the plasma degree of estradiol achieved by acute extract, when measured in surveies, was 34 times higher than what would be achieved by usual doses of endocrine replacing therapy. It is besides possible that chronic estrogen disposal acts through different cellular mechanisms in modulating vascular tone. Finally, surveies to day of the month hold been limited to little sample sizes, proposing the possibility of a beta mistake ( i.e. , inability to observe a little benefit in vasomotor reactivity in patients on chronic endocrine replacing therapy ) .
Endothelium Dependent Vasodilation
The endothelium consists of a monolayer of cells that lines the intimal surface of the full cardiovascular system. It plays a major function in modulating vascular tone through the release of dilator and constrictor substances that act upon vascular smooth musculus. There is roll uping grounds that damage of endothelium-mediated vasodilation is an of import early characteristic in the development of vascular disease non merely in patients with known coronary artery disease but besides with patients with high blood pressure, hypercholesteremia, smoke, and diabetes ( 3237 ) .
Endothelium dependent vasodilatives, such as acetylcholine stimulate the endothelium to bring forth endothelial-derived loosen uping factor ( EDRF ) , which is azotic oxide ( NO ) . Nitric oxide is released by normal vascular endothelium in response to many types of clinical and physical stimulations, including neurotransmitters ( acetylcholine ) , catecholamines, thrombocyte merchandises ( 5-hydroxytryptamine ) , shear emphasis and alterations in O tenseness. NO causes vasodilation in endothelium integral coronary arterias and is a merchandise of the transition of L-arginine by azotic oxide synthetase ( NOS ) to NO and citrulline. NO is released in response to many factors, including acetylcholine, doing a subsequent relaxation of the blood vas. In arterias damaged by coronary artery disease, nevertheless, acetylcholine causes bottleneck proposing that atheroma impairs endothelium mediated dilation of the coronary arterias. Patients with cardinal high blood pressure besides have impaired endothelium dependent vasodilation. At least one survey has demonstrated that unnatural endothelial map of patients with cardinal high blood pressure is related to a defect in the endothelium-derived azotic oxide system, because of decreased synthesis, release, or diffusion of azotic oxide to vascular smooth musculus ( 38 ) .
NO has several actions that are cardioprotective including vasodilation, suppression of thrombocyte adhesion and collection, and suppression of smooth musculus cell proliferation and the sum of available NOS in a cell. NO has besides been observed to decelerate the development of atheroma by suppressing smooth cell proliferation or exciting proliferation of endothelial cells. Estrogen is besides a powerful antioxidant of lipoids and oxidised lipoids inhibit NO. Estrogen may, hence, protect the vascular tone by heightening and/or protracting the half life of released NO. The clip class for this consequence is unknown and effects may merely be seen with long-run estrogen therapy. In one survey of HRT in postmenopausal adult females, research workers measured NO2 and NO3 degrees as markers for NOS synthase activity and found an addition in adult females who were on estrogen entirely ( 40 ) . One survey in guinea hogs has suggested that long-run disposal of estrogen up-regulates the written text of azotic oxide synthase. A recent survey in worlds has demonstrated fluctuations in expired NO production with cyclical endocrine alterations in premenopausal adult females. No degrees peak at the center of the catamenial rhythm proposing an influence of endocrines on the synthesis and release of NO in worlds ( 41 ) .
Vascular smooth musculus ( VSM ) contraction is enhanced by intravascular Ca. Substances that block the flow of Ca into cells cause VSM relaxation and decreased vascular tone. It has been hypothesized, based on animate being theoretical accounts, that some of the cardiovascular benefit of estrogen replacing therapy may be because of a Ca counter consequence of estrogen ( 43 ) . These belongingss have been demonstrated in several carnal theoretical accounts. 17-b Estradiol was shown to hold a negative inotropic consequence on single-isolated guinea hog ventricular myocytes by suppressing inward Ca currents and so cut downing intracellular free Ca ( 42 ) .
Prostacyclin is a prostaglandin produced by endothelial cells. Its synthesis is thought to be coupled to NO release. It has been shown to bring on vasodilation and suppression of thrombocyte activation in carnal theoretical accounts. Evidence in worlds is light, but there is an indicant that estrogen may consequence curdling and vasodilatation by its effects on prostacyclin ( 39 ) .
Inhibition of Constrictor Factors
Animal surveies suggest that estrogen inhibits the release of or response to vascular constrictor factors. Vasoconstrictors include endothelin and fibronectin. There is a correlativity between high endothelin degrees and the development of coronary artery disease in worlds ( 44 ) . One survey demonstrated that plasma endothelin degrees tend to be higher in work forces than adult females and lower still in pregnant adult females ( 45 ) . As a corollary, the same writers demonstrated in transexuals that sex endocrines may modulate endothelin degrees, with male endocrines increasing and female endocrines diminishing the degree. The consequence of worsening degrees of estrogen with climacteric on vascular constrictor factors is still ill-defined.
Estrogen besides inhibits angiotensin II-induced constrictor effects in carnal surveies proposing an repressive consequence on the renin-angiotensin system ( 39 ) . In males elevated activity of serum angiotensin-converting-enzyme ( ACE ) may be associated with an increased hazard of developing CAD. To day of the month, there are no surveies looking at ACE degrees in adult females pre- and postmenopausally and correlating them with increased hazard of developing CAD. In one of postmenopausal adult females treated with 6 minutes of endocrine replacing therapy, ACE-activity was reduced by 20 % in 28 treated adult females as compared with 16 untreated controls ( 46 ) .
Effectss on Vasoactive Neurotransmitters
Epinephrine and noradrenaline are released from sympathetic and parasympathetic nervus terminations in the arterial wall and, therefore, can do vasoconstriction and vasodilation, playing an of import function in the care of vascular tone. Estrogens and progestogens are thought to act upon the release of these neurotransmitters by several mechanisms ( 47 ) . Of note, vasomotor instability ( VMI ) the trademark of estrogen lack, occurs with rapid fluctuations in serum adrenaline and norepinephrine concentrations. Medicines that decrease cardinal noradrenergic activity, such as Catapres, have been shown to successfully handle hot flashes. The diminution of estrogen degrees that is seen with climacteric is besides associated with a comparative addition in catecholamine release associated with physical and mental emphasis ( 48 ) .
Effectss on Vascular Wall Composition
Animal surveies have shown that vascular smooth musculus hyperplasia and collagen biogenesis are reduced by estrogen disposal ( 49 ) . In one clinical survey, postmenopausal estrogen usage was associated with important boundary line decreases in mensural common carotid arteria wall intimal median thickness even after commanding for other hazard factors such age, smoke, lipoids, etc. ( 50 ) .
In a subanalysis of the Asymptomatic Carotid Atherosclerosis Progression Study ( ACAPS ) , adult females who used ERT ( readying and dose non specified ) were assessed for carotid arteria wall intimal-medial thickness ( IMT ) by carotid echography. IMT, which is a marker for coronary artery disease, appeared to be retarded and to perchance change by reversal in adult females who took estrogen without having lipid-lowering therapy ( 51 ) .
Changes in Vascular Compliance and Blood Pressure
A freshly recognized marker for high blood pressure and coronary artery disease is reduced vascular conformity. The latter describes the status of the arterial wall that influences the relation between volume and force per unit area. In stiffer vass, a smaller volume alteration will do a greater force per unit area rise as compared to a usually compliant system. Vascular conformity is known to diminish with climacteric.
One direct step of vascular stiffness is the pulsatility index ( PI ) . This represents the electric resistance to blood flow downstream from the point of measuring. An addition in PI is closely correlated with the clip elapsed after the climacteric. Decreases in arterial wave form pulsatility index in the uterine and carotid arterias have been demonstrated in postmenopausal adult females after chronic estrogen replacing proposing an betterment in arterial conformity ( 52 ) . In another recent survey, patients were treated with estrogen and Lipo-Lutin for 1 years and a important lessening in PI was observed at 48 wk ( 53 ) . Arterial conformity is increased with gestation but returns to normal within 8 wk postpartum proposing that these alterations were non secondary to a alteration in vascular construction, but to a decrease in smooth musculus tone ( 56 ) .
Premenopausal adult females have lower systolic blood force per unit area than work forces of a similar age. After climacteric, nevertheless, systolic blood force per unit area tends to be higher than in age-matched males. One survey has besides shown that an addition in pulsatile constituents of blood force per unit area is associated with higher cardiovascular hazard in postmenopausal adult females ( 55 ) . The alterations in blood force per unit area with climacteric were explored in a survey of both premenopausal and postmenopausal adult females who were compared with age-matched work forces ( 56 ) . Using ultrasound/Doppler to mensurate vascular flow, the writers found that premenopausal adult females had lower systolic blood force per unit area in their peripheral arterias, but non in their cardinal ( i.e. , carotid ) arteria. Males had greater peripheral blood force per unit area that was attributed to elaboration of blood force per unit area from cardinal to peripheral arterias, which increased with organic structure tallness and decreased with arterial distensibility. In contrast, in postmenopausal adult females, arterial distensibility was similar to that of age-matched work forces and no longer compensated for smaller organic structure size, ensuing in a persistent increased defect of moving ridge contemplations in cardinal arterias, and greater peripheral blood force per unit area ( 56 ) .
In a related survey, 18 adult females with indispensable high blood pressure were followed for 3 year, during which clip they went through climacteric, to look into whether a natural lessening in sex endocrines in hypertensive adult females caused an addition in the stiffness of the aortal root ( 57 ) . The writers found that aortal root distensibility decreased significantly in adult females who had gone through menopause as compared with age-matched controls, proposing an of import function for worsening estrogen degrees in this procedure.
Changes in Cardiac Function
Estrogens consequence hemodynamic parametric quantities through several different mechanisms. There is less grounds about the effects of worsening estrogen degrees with climacteric on hemodynamic map. In one survey, which followed adult females through the climacteric passage, no important alteration in echocardiographic measurings of end-diastolic and end-systolic dimensions were found after climacteric. However, important lessenings in remainder Doppler measurings of left ventricular contractility appeared increasingly over the old ages after climacteric in adult females non treated with endocrine replacing therapy ( 58 ) . These factors appeared to be modified with endocrine replacing therapy proposing a positive inotropic consequence of estrogen ( 59,60 ) .
METABOLIC CHANGES WITH MENOPAUSE
Changes in Lipid Metabolism
Several epidemiologic surveies have suggested additions in degrees of entire cholesterin, low-density lipoproteins and triglyceride rich lipoproteins associated with climacteric. In general, HDL degrees are stable in the old ages after climacteric, although there may be a little decrease in HDL2 subfraction. Presumably, these alterations with climacteric are secondary to redcution in endogenous endocrines. This is surely supported by the good consequence of postmenopausal endocrine therapy on lipoprotein metamorphosis in postmenopasusal adult females. Surveies suggest that estrogen usage is associated with lifts in high-density lipoprotein ( HDL ) cholesterin, particularly ( HDL ) cholesterin, particularly HDL2 ny every bit much as 20 % and decrease in low-density lipoprotein ( LDL ) cholesterin by every bit much as 19 %
An elevated Lp ( a ) degree is independently associated with the development of CAD in adult females ( 64 ) every bit good as work forces. Lp ( a ) is a modified signifier of LDL to which an apolipoprotein is attached. Its familial construction is similar to plasminogen and, therefore it interferes with the binding of plasminogen to sites of cells and molecules. Degrees of Lp ( a ) are chiefly determined by gentic and, as such, there are no disconnected alterations in Lp ( a ) with climacteric. However, estrogen theraphy appears to cut down Lp ( a ) degrees. An elevated plasmahomocysteine degree is an independent hazard factor for CAD particularly premature coronary artery disease. Degrees are known to increase in both genders with age. After climacteric, fasting homocysteine degrees may increase or remain the same ( 65 ) . Therefore, the impact of worsening estrogen degrees on homocysteine degrees is ill-defined.
In carnal surveies, estrogen appears to interfere with cholesterin deposition in the arterial wall ( 66 ) and in laboratory surveies to cut down arterial smooth musculus cells proliferation ( 29 ) . Oxidative alteration of LDL cholesterin may be an of import measure in atherogenesis. In carnal surveies, the oxidised signifier of LDL appears to be more effectual than inactive LDL in impairing endothelium-dependent vasodilation. One recent survey suggests that endothelium mediated vasodilation is improved with lipid take downing drugs in patients with elevated cholesterin peculiarly if the lipid lowering therapy lowers rates of LDL oxidization ( 67 ) . In vitro surveies suggest that 17-i?? estradiol appears to suppress LDL oxidization and cut down cholesterin ester formation ( 68 ) . In one survey, 17-i?? estradiol disposal significantly reduced the oxidization of LDL cholesterin from postmenopausal adult females ( 69 ) .
Changes in Cloting
Certain styptic variables change with climacteric with a possible impact on both thrombosis and fibrinolysis. After climacteric, factor I degrees addition as do degrees of factor VII and antithrombin III. Higher degrees of PAI-1 an adversary of fibrinolysis in worlds, have been noted in postmenopausal adult females in the Framingham Offspring Study ( 71 ) . Surveies of HRT in postmenopausal adult females suggest a lessening in factor I ( 72 ) , and a lessening in PAI-1 ( 73 ) . Animal surveies besides suggest that estrogen inhibits platelet collection.
Symptoms of Vasomotor Instability
Symptoms of vasomotor instability include palpitations and, in a little per centum of adult females, symptoms of chest force per unit area. Although they occur most frequently in concurrence with hot flashes, an addition in palpitations can be seen in the absence of other symptoms. The badness of these cardiac symptoms appears to be related to the badness of the hot flashes ( 74 ) . Vasomotor symptoms and associated cardiac symptoms are more terrible in patients who experience a sudden bead in their estrogen degree ( e.g. , surgical climacteric ) . In one longitudinal survey of 200 perimenopausal adult females from Scandinavia, palpitations figured conspicuously in the symptomatology in association with other vasomotor ailments ( 75 ) . In another study of 501 adult females, 1220 % of those who were postmenopausal celebrated force per unit area in thorax and 3647 % noted a alteration in bosom rate in association with their hot flashes ( 76 ) .
Fig Changes in Hormone Level Patterns Over Six Months
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Beginning: Harvard Women ‘s Health Watch 1999
Fig Estrogen Levels From Puberty to Menopause
The above discussed alterations in endocrine degrees during menopausal passage consequence in a assortment of symptoms which cause changing grades of uncomfortableness and is jointly known as the Menopausal Syndrome. Menopausal symptoms affect the countries where the deficiency of estrogen consequence is felt due to menopausal passage. These countries are the
temperature modulating centre of the hypothalamus which causes hot flashes and dark workout suits
vascular endothelium, which increases hazard of CVD
bone which undergoes more reabsorption
vaginal musculuss, which wasting and go thin
urinary vesica musculuss, which lose a small spot of tone ensuing in incontinency
adipose tissue beneath the tegument which atrophies ensuing in rougher and looser tegument
The symptoms ( rapid effects ) which are normally seen in adult females sing climacteric and which have been established to be consequences of menopausal passage are vasomotor symptoms. These include hot flashes and dark workout suits. The prevalence of vasomotor symptoms runs every bit high as 45.6 % in African American adult females, 35.4 % in Latino adult females, 31.2 % in white adult females, 20.5 % in Chinese adult females and 17.8 % in Nipponese women6. In a survey done in underprivileged centers aged adult females ( Chauhan and Nair 2006 ) in Vadodara territory, the prevalence of vasomotor symptoms was reported to be 38 % moderate hot flashes and 19 % hot flashes of terrible nature. Other symptoms reported by them were backache ( 71 % ) , swelling in hands/legs ( 27 % moderate, 26 % terrible )
MENOPAUSAL TRANSITION AND CHRONIC DISEASE PHYSIOLOGY
The effects estrogen has on cardiovascular system can be viewed as rapid consequence which follows the non-genetic path and includes estrogen mediated vasodilatation. Then there are slow effects which are familial in nature and include production of vasodilative substances, good effects in lipid profile and opposition to atherosclerosis. Therefore low estrogen degrees during climacteric, has damaging effects on the vasculature, lipid profile, curdling and fibrinolytic systems ( Wood and Cox 2000 ) .
Figure: Cascade of Metabolic Events due to Estrogen Deficiency
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WHEATGRASS – THE WONDER HERB OF AYURVEDA
The antiprolifrative and anti tumour consequence of wheat leaf ribonucleinase was tested in vitro on human ML-2 cell line and in vivo on athymic bare mice bearing human melanoma tumours. The antiproliferative activity of this works ribinuclease was negligible in comperision with bovid seminal ribonucleinase. In the experiments in vivo, a important lessening of tumour size nevertheless was observed in the mice treated with wheat foliage ribonucleinase compared with the control Rnase and polyethyleneglycol [ 45 ( Adom KK, Sorrells ME, Liu RH. Phytochemical profiles and antioxidant activity of wheat varities. J Agric Food Chem 2003 ; 51 ( 26 ) : 7225-34. ) Vol 1:4 ( 2011 ) IJPI ‘S Journal of Pharmacognosy and Herbal Formulations Shankul Kumar et Al Page 101 ]
The antioxidant activity of wheat-grass was estimated at different degrees. The methods employed include FRAP, ABTS, and DPPH checks. Aqueous and ethanol infusions of wheat-grass grown under different conditions over a period of 6, 7, 8, 10 and 15 yearss were used. Lipid peroxidation and O extremist optical density capacity ( ORAC ) were determined and utilized to look into the authority of a few selected infusions. . Different conditions used for growing were ( 1 ) pat H2O, ( 2 ) pat H2O with foods, ( 3 ) dirt and tap H2O, and ( 4 ) dirt with foods. The ethanol infusions were found to hold a higher phenoplast and flavonoid content than the aqueous infusions. The highest FRAP values occurred on twenty-four hours 15 of growing under status 4, the values being 0.463 and 0.573 mmol of ascorbic acid and Trolox equivalents/100 g fresh wheat-grass for aqueous and ethanol infusions, severally [ 52 ( Siener R, Honow R, Voss S, Seidler A, Hesse A. Oxalate content of cereals and cereal merchandises. J Agric Food Chem. 2006 Apr 19 ; 54 ( 8 ) : 3008-11. ) ]
Julian EA, Jhonson G, Jhonson DK, Donnelly BJ. The glycoflavonoid swineherds of wheat, Triticum aestivum, leaves. Phytochemistry 1971 ; 10 ( 12 ) : 3185-93.
Kulkarni SD, Tilak JC, Acharya R, Rajurkar NS, Devasagayam TP, Reddy AV. Evaluation of the antioxidant activity of wheat grass ( Triticum aestivum L. ) as a map of growing under different conditions. Phytother Res. 2006 ; 20 ( 3 ) : 218-27.
Skvor J, Lipovova P, Pouckova P, Soucek J, Slavik K, Matousek J. consequence of wheat leaf ribonucleinase on tumour cells and tissue. Anticancer drugs 2006 ; 17 ( 7 ) : 815-23.
Falcioni G, Fedeli D, Tiano L, Mancinelli L, Marsili V, Gianfranceschi G. Antioxidant activity of wheat sprouts extracts invitro: suppression of DNA oxidative harm. Journal of Food Science2002 ; 67 ( 8 ) : 2918-22.
Kulkarni SD, Tilak JC, Acharya R, Rajurkar NS, Devasagayam TP, Reddy AV. Evaluation of the antioxidant activity of wheat grass ( Triticum aestivum L. ) as a map of growing under different conditions.Phytother Res. 2006 ; 20 ( 3 ) : 218-27.
Kyrychenko OV, Tyshchenko OM. Effect of exogenic specific lectin on lectin activity in the wheat seedlings and foliages. Ukr Biokhim Zh. 2005 ; 77 ( 4 ) : 133-7.
The different degree of impregnation of hazard factors in adult females, together with their interaction with female endocrines, plays an of import function in the development of cardiovascular disease ; and given that in-between adult females form a ample portion of the Indian human ecology, the wellness disbursals incurred towards chronic disease relief by this immense section of the population would be a cause of grave concern for the interest holders. However, to chalk out conclusive determinations on the intercessions and the extent of coverage, comprehensive surveies crossing the complete image of the metabolic and cardio-vascular hazard factors across a important portion of the Indian population is a pre-requisite.
But in this respect, most of the surveies are on the western population and informations in the regional context is missing. Furthermore, the reappraisal suggests that Indian surveies even though documented, are scattered and do non supply an across-the-board portrayal of the state of affairs.
In this context, a broad scope of nutraceuticals and functional nutrients have been tried as has been reviewed, but discreetly designed tests on the Indian cultural population groups are scarce and fail to supply any conclusive grounds. On the other manus, the benefits of the admiration herb of Ayurveda- Wheatgrass has been scientifically shown to possess a assortment of vitamins, indispensable minerals, phytochemicals, antioxidants and other bioactive molecules which render wheat-grass to be a promising natural substance to be considered for cut downing serum cholesterin and lipid peroxidation due to oxidative emphasis. Therefore, a scientifically designed test in this respect is justified to divide myths from facts and to measure whether wheat-grass can be promoted as a functional nutrient for the direction of lipemia.
Therefore a demand was felt to set about a set of surveies which would turn to all these questions and the inside informations of the research inquiries addressed therein are described in the subsequent subdivision.