Menopause is the end of menstruation. The work comes from the Greek mens, meaning monthly and pausis, meaning cessation. Menopause is part of a woman’s natural ageing process when her natural aging process when her ovaries  produce lower levels of the hormones estrogen and progesterone and when she is no longer able to become pregnant. (Blumel et al, 200)

Unlike a woman’s first menstruation, which starts on a single day, the changes leading up to menopause happen over several years. The average age for menopause is 52. But menopause commonly happens anytime between the ages of 42 and 56.

A woman can say she has begun her menopause when she has not had a period for a full year.

Uric acid is a chemical created when the body breaks down substances called purines. Purines are found in some foods and drinks, such as liver, anchovies, mackerel, dried beans and peas, beer and wine.

Most uric acid dissolves in blood and travels to the kidneys where it passes out in wine. If your body produces too much uric acid or doesn’t remove enough of it, you can get sick; a high level of uric acid in the body is called hyperuricemia (Puig et al, 1991). The level of serum urate is generally elevated in menopausal women. In addition to estrogen, other menopausal related factors that may affect uric acid metabolism include; menopause-related insulin resistance, obesity and ethanol ingestion (Ortiz et al, 1993)

Serum calcium is the name given to the level of calcium found in our blood which is determined by performing a special blood test. Serum calcium indicates whether we are calcium deficient or have abnormal high level of calcium in our blood stream. These conditions are termed as; hypocalcaemia and hypercalcaemia respectively. Serum calcium definition tells us that both these conditions are dangerous for long-term health (Hegsted 1994).

The serum phosphorus test measures the amount of phosphate in the blood. The alternative names are phosphorus-serum, HPO4-2, HPO4-3, inorganic phosphate.

Most of the body’s phosphorus is combined with calcium in the bones, but about 15% exists as phosphate (PO4) ions in the blood and other soft tissues and body fluids (Keating et al 1969)

1.1      Aim And Objectives

The study is aimed at determining the levels of serum uric acid, calcium and inorganic phosphate in menopausal women and their effects.

 


CHAPTER TWO

2.1      MENOPAUSE

Menopause is the time in a woman’s life when her period stops it is a normal change in a woman’s body. A woman has reached menopause when she has not had a period for 12 months in a row (and there are no other causes, such as pregnancy or illness, for this change). Menopause is sometimes called, “the change of life”. The average age for menopause is 52. But menopause commonly happens anytime between the ages of 42 and 56 (McKinley S.M et al, 1992)

Around this age, many changes begin to occur in a woman’s body, unwanted symptoms of hormone imbalance associated include: Hot flushes, usually presented as flushing of the face neck, chest and back insomnia, mild to moderate depression joint pain and muscle pain, water retention (edema), heart palpitations, headaches, vaginal dryness and increased sweating. Hot flushes, nigh sweats, insomnia and palpitations, are usually referred to vasomotor symptoms (Losif et al, 1984).

 

 

2.2      The Effect of Menopause on Serum Uric Acid Levels.

Epidemiological evidence suggests that pre-menopausal women are at lower risk of coronary heart disease (CHD) than men of comparable age, and the relative cardiovascular protection is lost following the menopause (Cheang et al, 1994). This loss of protection can be linked to a loss of endogenous sex hormone production, both in women who have been Oophorectomized (Freedom DS, et al, 1995) and in women undergoing natural menopause (Leyva F, et al 1997). The cessation of sex, hormone production has been shown to affect known markers of CHD risk, and atherogenic changes in lipid profiles have been reported between pre-menopausal and post menopausal (Cummings 1991), (Meade et al, 1992). Elevations in serum uric acid have also been linked with a number of risks for CHD. Relative hyperuricemia has been associated with hypertension, hyperlipidema and obesity. Most recently, hyperuricemia has been incorporated into the into the insulin resistance syndrome (Law et a1, 1993).

Positive correlations between age and serum uric acid have only been found in women. Because serum urate increases with age, postmenopausal women tend to have higher serum uric acid levels than pre-menopausal women. It is therefore been attractive to hypothesizes that changes occurring at the menopause are the cause of this relative hyperuricemia. However, menopause statues were either undefined or determined by chronological age in these studies, so they can not be regarded as conclusive in implicating the menopause per se.

In addition, since the menopause is an age-dependent phenomenon, it is difficult to separate its effects from those of the chronological age, and this is true even of longitudinal studies.

Indeed, the Framingham study concluded that uric acid values increased with age in women, but it was unable to discus this effect in terms of menopause (Cigolini et al, 1995).

2.3 Uric acid: A Surrogate of Insulin Resistance in Menopausal women.

The association between hyper uricemia, hyper cholesterolemia and coronary heart disease has been reported for many years (Dobson 1999)

Serum uric acid (UA) was significantly higher in patients with cardiovascular disease (CVD) than other healthy controls (Torun et al 1998).

Physiologically, insulin acts and renal tubules to reduce and sodium and UA clearness and remains effective as insulin resistance deteriorated. The Framingham Heart study concluded that serum UA was not decisive in the development of coronary heart disease, death from CVD or all-cause mortality.

However, the longitudinal observation of the Framingham heart study vividly showed a sex-difference phenomenon in serum UA.

The main purpose of this study was to explore the sex-different relationship of insulin resistance and serum UA level in community living pre-menopausal and postmenopasual Chinese women in Taiwan (Muscelli et al, 1996)

2.4.    Gout: A common disorder of elevated serum uric acid (UA) in menopausal women.

Despite the doubling of the incidence of gout among women over the past 20 years (Arromdee et al, 2002) and the substantial prevalence particularly in the ageing female population (Kramer et al, 1994), little is known about and risk factors for gout and hyperuricaemia specifically among women. Given the important gender differences in the frequency of gout and serum uric acid levels the risk factors for gout may very between genders. A central factor behind these differences is thought to be female hormonal influences, but magnitude has not been comprehensively examined and quantified. Thus, it is unknown if menopause is associated with serum uric acid levels independent of age and other covariates and if so, by what magnitude. Conversely, postmenopausal hormone use may be independently associated with lower serum uric acid (UA) levels, but no nationally representative information is available.

Furthermore, previous studies reported an age dependent increase in serum UA level among women (Sturge et al, 1977), (Ak1zuki 1982), but it is unknown if this increase is independent of menopausal effect or other age related factor. To study these issue, we examined a nationally representative sample of women (The US third National Health and Nutritional Examination Survey (NHANES III) (NHANES III 1994), (National centre for Health Statistics 1996).

2.5 Treatment/Management of Elevated Serum Uric Acid Level in Menopausal Women Using Hormone Replacement Therapy (HRT).

Elevated uric acid levels and incidence of clinical gout are exceedingly rare in women before menopause but rise after cessation of menses, potentially explained by an effect of estrogen on the renal handling of uric acid (Manson et al, 2001). Despite this well established association, little is known about the effect of postmenopausal estrogen replacement on uric acid levels in women. Here Hak et al (Arthritis Research and Therapy, 2008) explore the association of menopause and postmenopausal hormone replacement therapy (HRT) on serum uric acid levels in women participating in the third National Health and Nutrition Survey (NHANES III, 1994).

2.6 Serum Calcium and Inorganic Phosphate Levels in Menopausal Women.

Reliable data concerning values for total, corrected total, ultra filtrated and ionized serum calcium levels in normal elderly women are essential for the evaluation of biochemical findings in patients with postmenopausal and senile osteoporosis and other disorders of calcium metabolism (Avioli et al, 1980). A significant decline in total serum calcium levels with age was noted in a report study dealing with the effect of age on uncorrected total serum calcium levels in women (Roberts, 1967). In another report a significant decrease in serum ionized calcium was seen with advancing age (Lingarde, 1972).

In a published data concerning age related changes in serum inorganic phosphate levels in women, four studies reported a trend to higher serum phosphate levels after the menopause (Greenber et al 1960), (Keating et al, 1969), (Morgan  1973) and (Young et al, 1967).

In ovarian failure estrogen declines by 80% and rapid bone loss occurs over period of about three years (Riggs et al, 2002). Renal calcium loss in post menopausal women correlates with increases in conjugate bases of inorganic and organic acids in the serum. Both calcium and phosphate are produced by bone degradation and this probably reflects independent regulation of calcium by the parathyroid calcium sensor (Austin et al 2003). Menopause is associated with numerous physiological and biochemical changes affecting bone mineral metabolism (Ashuma et al 2005). Hyperphosphatemia as seen in menopause is considered significant when levels are greater than 5mg/dl. Hyperphosphatemia occurs when the phosphorus load (from G.I absorption, exogenous administration, or cellular release) exceeds renal excretion and tissue uptake (Sutherland et al, 2008). Serum phosphorus levels rise after a large meal. Antacids decrease absorption because calcium, aluminum and magnesium bind phosphorus into insoluble complexes.

Hyperphosphatemia cause hypocalcemia by precipitating calcium, decreasing vitamin D production, and interfering with parathyroid hormone – mediated bone resorption. Signs and symptoms of acute hyper phosphatemia are due to the effects of hypocalcaemia which leads to osteoporosis and bone fracture in menopausal and post menopausal women (verdonck et al, 2009).


2.7 Calcium Metabolism in Health and In Disease

Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling (U.S National Academy Press, 1997). Bone calcium balance can be positive, neutral, or negative depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1, 25- dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone (Mc Cabe et al 2004). In some individuals, particularly the elderly, calcium supplements may be needed to achieve the recommended dietary calcium intake.  Calcium requirement is dependent on the state of calcium metabolism, which is regulated by three main mechanisms: intestinal absorption, renal reabsorption and bone turnover. These in turn are regulated by a set of interacting hormones (PTH), 1, 25 – dihydroxyvitamin D (1, 25 (OH)2 D), ionized  calcium itself, and their corresponding receptors in the gut, kidney, and bone (Moe et al, 2007).

2.8 Calcium and Osteoporosis in Menopausal and Postmenopausal Women.

Calcium is an essential nutrient that is involved in most metabolic processes and the phosphate salts of which provides mechanical rigidity to the bones and teeth, where 99% of the body’s calcium resides. The calcium in the skeleton has the additional role of calcium to meet the body’s metabolic needs in states of calcium deficiency (Baghurst et al, 1996).

The evidence linking calcium deficiency to osteoporosis in experimental animals is unequivocal. Unless there is a corresponding link in human’s calcium will remain a nutrient in search of a disease and osteoporosis a disease of obscure origin. In humans, osteoporosis is a common feature of aging. Loss of bone starts in women at the time of the menopause and in men at about age 55 and leads to an increase in fracture rates in both sexes (Elders et al, 1994). There is a rise in obligatory calcium excretion at menopause which increases the theoretical calcium requirement in post menopausal women to about 25 mmol (1000mg) and implies an allowance of perhaps 30 mmol (1200mg) or even more if calcium absorption declines at the same time (Soroko et al 1994).

2.9 Diagnosis and Treatment of Osteoporosis in Menopausal women

Osteoporotic bone fractures are a significant public health problem resulting in substantial morbidity and for those who suffer a hip fracture, a significant one – year mortality. Bone densitometry provides an important measure of fracture risk and the newer techniques are useful in the management of individuals with osteoporosis (Cummings et al 2008).

Treatment includes the use of calcium and vitamin D supplements and estrogen therapy in postmenopausal women. Newer therapies such as calcitonin and bisphosphonates are being evaluated for their ability to reduce the occurrence of fracture (Cooper et al 1991). This review focuses on bone densitometry as a diagnostic tool and on the use of therapeutic agents for osteoporosis (Consensus Development Conference Panel (C.D.C.P), 1991).