Abstract in ovarian hormone production. Oestrogen deficiency and

Abstract

 Background: Menopause is the permanent cessation of menstruation seen in women
between 40-61 years of age. Menopause is characterised by reduction in ovarian
hormone production. Oestrogen deficiency and age related processes cause
decrease in calcium levels in post menopausal women.

 Aims and Objectives: To study serum calcium levels in premenopausal
and post menopausal women.

Materials
and Methods: Cross
sectional study was conducted. 35 pre menopausal and 30 post menopausal women
were selected according to inclusion and exclusion criteria . Patients with medical
history of major systemic diseases, women on hormone replacement therapy, and
women who had surgical menopause were not included in the study .Serum calcium levels were estimated in
both groups.
For statistical analysis the value of laboratory parameters were presented as
the Mean±SD (standard deviation). A Student’s  t-test was used for cross-sectional
comparisons of continuous variables between the groups.

Results: Serum calcium levels were
significantly lower in post menopausal women than in pre menopausal women.

Conclusion: Post menopausal women are calcium
deficient.

 

 Keywords:  Premenopausal
women  , postmenopausal women ,Menopause
, serum calcium .

 

 

Introduction:

Menopause
is permanent cessation of menstruation , seen in women between 40-61 years of
age .It is characterised by the menstrual changes that reflect oocyte depletion
and subsequent reduction in ovarian hormone production. Menopause typically
occurs in middle age , 40-61 years of age, signalling the end of the fertile
phases of life1 . Menopause is characterised by hot flushes, night
sweats and various other psychological and biochemical changes . It also leads
to metabolic bone disorders .With the onset of menopause , rapid bone loss
occurs which is believed to average 2 to 3 % over the following 5 to 10 years
,being greatest in the early post menopausal years 2,3 .Calcium ion
is an essential structural component of skeleton .Body cannot synthesize it
.Nutrition imbalance  with endocrine
abnormalities may be involved in osteoporosis 4. Extracellular
calcium ion concentration is determined by the interaction of calcium   absorption from intestine , renal excretion of
calcium and bone uptake and release of calcium , each of which is regulated by  parathormone , vitamin D and calcitonin 5
. Estrogen deficiency is present in post menopausal women. Estrogen deficiency
results in longer life span of osteoclasts 6.This estrogen
deficiency is reason for osteoporosis seen after menopause .The female sex hormone
diminish to almost none after menopause .Bone turnover increases to high levels
in women soon after menopause . The 2 main causes of bone loss are estrogen
deficiency after menopause and age related process 7 . Intestinal
calcium absorption decreases in post menopausal women 8 .Osteoporosis
is a late complication of menopause.It is a degenerative bone disorder where
there is thinning and weakening of the bone and a general decrease in bone mass
and density .So susceptible to fractures .Fractures related to osteoporosis are
estimated to affect around 30% of women in developed countries and are a major
health problem.Normally bone will go through a process where old bone is
replaced by new bone cells .Our body’s ability to handle this process changes
with age. Estrogen is involved in the process of calcium absorption into the
bones .During menopause there is a drop in estrogen levels .All women will
experience acceleration in bone density reduction as their estrogen levels
drop. Menopause in elderly women is associated with accelerated loss of
cortical bone .Rapid bone loss occurs when the balance between formation and
resorption is upset resulting in a negative remodelling balance and leads to
osteoporosis. It is mainly due to imbalance in hormonal factors like estrogen,
prolactin and changes in bone formation markers like calcium, phosphorus .
The decrease in the level of sex steroid
hormones during menopause in women causes various somatic, vasomotor, sexual
and psychological symptom. The risk of osteoporosis, cardiovascular disease,
arterial hypertension, impairment of glucose metabolism, and degenerative
cognition disease incidence rises. The impact of deficiency of female sex
hormones after menopause on the trace minerals has not been widely studied but
expected menopause related changes in their status may have an impact on the
above pathologies. There are very
few reports on the changes in serum calcium and magnesium levels in various
phases of the menstrual cycle in otherwise healthy women. Estrogen induces
hypercalcemia through the action of the parathyroid gland. Withdrawal of
estrogen is reported to cause a significant loss of bone calcium. Increase in
serum calcium levels during the follicular and ovulatory phases could be due to
the effect of estrogen on the parathyroid glands. In addition to bone calcium
content the level of serum calcium appears to be associated with blood pressure,
and could be a metabolic risk factor for cardiovascular disease.
The study was carried out to evaluate calcium status in pre and post menopausal
women.

Materials and Methods: 

Cross
sectional study was conducted in 35 pre menopausal women ( 25-45 years of age)
and 30 post menopausal women(46-65 years of age) in department of Physiology.
Subjects were selected from general population according to the inclusion
criteria  . Consent was taken from
subjects and procedure was explained to subjects.

Inclusion
criteria   : Post menopausal women between
age 46-65 years.

Exclusion
criteria  : 1) Surgical menopause due to
hysterectomy

                               2) Post
menopausal women on estrogen therapy

                               3) Women
having  Diabetes / Hypertension.

Collection
of blood sample 5 ml of venous blood was drawn aseptically from each subject .
It was centrifuged at 3000rpm for 10 minutes and serum was separated .Serum
calcium levels were estimated by photocolorimetry
method.

Statistics

Student
 t test was applied to see the
significance of difference of  parameters
between 2 groups .Mean and standard deviation of variables was determined  Correlation was done by using Pearson s
correlation coefficient. The interpretation of P value are as follow

P
>0.05 – not significant

P
<0.05 - significant P <0.01 - highly significant. Findings : The table shows that age of pre menopausal women was 36.73± 3.8 years (Mean± SD). Age of post menopausal women was 53.64±6.30 years (Mean± SD). Serum calcium levels in post menopausal women were less as compared to premenopausal women and this was statistically significant(P=0.037). Bar diagram shows mean serum calcium levels in pre and post menopausal women. It is observed that serum calcium levels are low in post menopausal as compared to pre menopausal women. Table : Serum calcium levels in pre-menopausal and postmenopausal women Parameter Pre menopausal women n = 35 Post menopausal women n = 30 P value Age(years) 36.73 ± 3.8  years 53.64 ± 6.30 years ---- Serum Calcium(mg/dl) 10..07 ± 0.66  (mg/dl/) 8.4 ± 0.076 (mg/dl) 0.037   Bar diagram: Comparison of serum calcium in pre-menopausal and postmenopausal women   Discussion Calcium ion is an essential structural component of the skeleton. Estrogen deficiency after menopause induces calcium loss by indirect effects on extra skeletal calcium homeostasis as well as decreased intestinal calcium absorption. When estrogen is deficient, there is an increase in the activation of new bone remodeling units. Both formation and resorption are altered with the result that resorption exceeds formation, producing a negative balance. Estrogen deficiency may induce calcium loss due to decreased intestinal calcium absorption and decreased renal calcium conservation. The results of the present study indicated that the level of serum calcium declined significantly in post menopausal women. In this study serum calcium was evaluated in premenopausal and postmenopausal women. Serum calcium was significantly lower in postmenopausal women as compared to premenopausal women. Lower calcium levels after menopause lead to osteoporosis. Osteoporosis is late complication of menopause. Osteoporosis causes thinning and weakening of bone and general decrease in bone mass and density. So  menopausal women are susceptible to fractures. Fractures related to osteoporosis are estimated to affect around 30% of women both in developing and developed countries and are major health problem  9 . During menopause there is drop in estrogen levels which caused decreased calcium levels in postmenopausal women. All women will experience acceleration in bone density reduction as their estrogen levels drop. Thus serum calcium could be used as indicator of increased bone turnover , to enable early intervention so as to minimize fractures due to osteoporotic changes 10. The variation of serum calcium with age is proposed to be explained by alterations in levels of serum albumin to which approximately 40% of circulating calcium is bound and which was not adjusted for the study along with the modification of the resorption, excretion and reabsorption of calcium. Studies have demonstrated that in addition to low estrogen levels, osteoporotic postmenopausal women had kidneys that did not reabsorb as much calcium as the kidneys of women without osteoporosis. Comparable to few other study series our study also had significantly reduced serum calcium in the postmenopausal group when compared to the premenopausal group Conclusion Serum calcium levels are decreased in postmenopausal women. The similar results have been found in many other studies11-15. We have used cross-sectional analyses to compare postmenopausal women with premenopausal women. Although cross-sectional investigations may provide clues regarding the effects of the menopause on the physiological and biochemical changes, confounding factors such as age, ethnicity, average energy intake, physical activity, serum albumin levels etc., have to be adjusted for statistical procedures to find out the changes in the variables independent of these factors. The present study revealed that the differences between the mean values and standard deviations of the variables in the premenopausal and postmenopausal groups were small; thus making large samples necessary to detect these differences. Our premenopausal group included few perimenopausal subjects also. Thus in order to establish standard reference values and formulate predictive equations, a representation of the whole population needs to be studied. Further large scale multicentric and longitudinal studies are required to further determine the actual changes in BMI, serum levels of magnesium and calcium, and correlation or independent association between them for their clinical implications in various disorders with transition of age, and passage of menopause which is inevitable in every woman's life. It can be recommended that calcium supplementation can be given as prophylaxis to prevent the long term bone loss and to decrease the risk of fracture and osteoporosis in postmenopausal women . Acknowledgement We are thankfull to subjects who participated in this study ,and also to lab technicians who gave full cooperation in this study . Conflicts of Interest   :There are no conflicts of interest. Source of funding       :Self funded. Ethical clearance        : Done References 1) Howkins and Bourne. Shaws textbook of gynecology 13th ed, Elsevier ,chapter 5, p 57-61. 2) Susan A calcium supplementation in postmenopausal women.From Medscape Ob/Gy and women health,2003:8(2). 3) Gupta A.Osteoporosis in India –the nutritional hypothesis.Natl med J Ind 1996:9(6):268-74. 4) Sheweita S, Khosal K .Calcium metabolismand oxidative stress in bone fractures: role of antioxidants .Curr Drug metab 2007;8:519-25. 5) Guyton AC ,Hall JE. Parathroid hormone , calcitonin and phosphate metabolism, Vitamin D, bone and teeth. Textbook of physiology 11th ed Philadelphia: Elsevier Saunders; 2006.pp.901,940,978-95. 6) Garneo P, Delmas PD. Bhone turnover markers. In: Encyclopedia of endocrine Diseases .Eds Martin L .California : Elsevier Inc; 2004.pp 401-13. 7) Riggs BL, melton LJ .Medical progress series  in voluntary osteoporosis N Engl J Med 1986 ;314:1676-86.