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Research Article

LOWER ELASTIN EXPRESSION OF SACROUTERINE LIGAMENT IN

POSTMENOPAUSAL WOMEN COMPARED TO PREMENOPAUSAL WOMEN

Wahyudi Wirawan, Ketut Suwiyoga, I Wayan Megadhana

Obstetrics and Gynecology Department


Medical Faculty of Udayana University /Sanglah General Hospital Denpasar Bali

Abstract

Background: Menopause is a natural process for every woman characterized by an


anatomical and physiological changes associated with changes in estradiol hormone. A
decreased in estradiol levels during menopause affects many things, one of which influences
the elastin expression of the sacrouterine ligament. This condition became important because
menopausal conditions affect the elastin expression of the sacrouterine ligament, which is
useful in preserving and maintaining the female pelvic organs to remain in a normal position.
Post menopausal describes the time after menopause occured. Elastin is an extracellular
matrix protein that converts biochemical materials to extensibility, flexibility and recoil in the
tissues. Elastin proteins undergo changes during menopausal to postmenopausal transition
period. The elastin expression decreases along with the aging of a woman entering post
menopausal period.

Objectives: To prove the difference in elastin expression of the sacrouterine ligament in


premenopausal and postmenopausal women.

Method: Observational analytic with cross sectional design was done for this study. It is
conducted in Obstetrics and Gynecology Sanglah Denpasar Hospital starting from January
2016 until November 2016. This study was done to prove the difference in elastin expression
of utetusacral ligament in premenopausal and postmenopausal women. The study samples
were all 40 to 75 year old menopausal women patients, who performed a total hysterectomy
at Sanglah Hospital Denpasar. They were selected with consecutive sampling of the
affordable population who fulfilled the inclusion and exclusion criteria. After signing the
informed consent, a total hysterectomy surgery was performed to them. The tissue sample
was taken from the premenopausal and postmenopausal uterosacral ligaments along 1.5 cm
from the cervix. This sample was kept in paraffin blocks and made for immunohistochemical
preparations. Immunohistochemical examination was performed to assess the elastin
expression then analyzed and reported. Investigation of elastin expression in the Laboratory
of Veterinary Medicine of Udayana University. Test with SPSS 17 for windows version.

Result: There were 60 women under this study, 30 postmenopausal women and 30
premenopausal women. Based on the results of the analysis with t-independent test it was
found that there was a significant difference of elastin expression in premenopausal women
compared with postmenopausal women (p <0.05).

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Conclusion: Based on the results of this study, it is known that there are differences in elastin
expression in premenopausal and postmenopausal women. The difference is that elastin
expresion in postmenopausal women is lower than elastin expression in premonopausal
women. Examination of elastin expression was done at the Laboratory Pathobiology of
Veterinary Medicine of Udayana University.

Keyword: Premenopausal, postmenopausal, elastin expression

Correspondent : Wahyudi Wirawan, Batu Bidak Residence-Kerobokan Kaja, Badung.


Email: wahyudi_wirawan83@yahoo.com, Hp: 081339455268.

INTRODUCTION

Menopause is characeterized by series of cycles with shorter follicular phases,

irregular cycles and anovulatory cycles. Estrogen deficiency has traditionally been an

important part of menopause1. WHO (2003), the number of women experiencing menopause

worldwide is estimated to reach 1.2 billion people. Based on population cencus in 2010,

Indonesian was in the top five countries with the most abundant elderly population as many

as 18.1 million people or 9.6% of the population. Based on the projection of Bappenas, the

elderly population age of 60 years or more is expected to increase from 18.1 million (2010)

to 29.1 million (2020) and 36 million (2025). The increasing number of elderly, will be

followed by increasing problems mainly in the health sector, one of which is the menopause.

At the age of 40 years the function of the ovaries undergoes a change in the progressive

fatigue of the ovarian follicles leading to a hypergonadotropic primary ovarian insufficiency.

This causes a decrease in estrogen formation in the ovaries2. For long-term disorders can be

osteoporosis, cardiovascular disease, Alzheimer's disease, stroke and pelvic organ prolapse

(POP) women. Most menopausal status characteristics are found in decreasing estradiol

levels in the uterosacral ligaments as in pelvic organ prolapse cases. This hypothesis is a

secondary cause of various factors involved, such as decreased estradiol during the

postmenopausal period. Proteins that play a role in strengthening the uterosacral ligament,

collagen and elastin. Elastin is an extracellular matrix protein that converts biochemical

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materials to lengthening and recoil of a tissue. Elastin plays a role in elastic extensibility and

recoil3. Elastin proteins alter during the menopausal to postmenopausal transition period.

Elastin proteins in the female reproductive organ go along with reproductive period in

woman life cycle. Hypoestrogen is a factor that increase postmenopausal incidence. Elastin

plays an important role in supporting pelvic organs in the genetic disorders of elastin

metabolism (cutis laxa) indicating the risk of prolapse of pelvic organs4.

METHOD

Observational analytic with cross sectional design was done for this study. It is

conducted in Obstetrics and Gynecology Sanglah Denpasar Hospital starting from January

2016 until November 2016. This study was done to prove the difference in elastin expression

of utetusacral ligament in premenopausal and postmenopausal women. The study samples

were all 40 to 75 year old menopausal women patients, who performed a total hysterectomy

at Sanglah Hospital Denpasar. They were selected with consecutive sampling of the

affordable population who fulfilled the inclusion and exclusion criteria. After signing the

informed consent, a total hysterectomy surgery was performed to them. The tissue sample

was taken from the premenopausal and postmenopausal uterosacral ligaments along 1.5 cm

from the cervix. This sample was kept in paraffin blocks and made for immunohistochemical

preparations. Immunohistochemical examination was performed to assess the elastin

expression then analyzed and reported. Investigation of elastin expression in the Laboratory

of Veterinary Medicine of Udayana University. Test with SPSS 17 for windows version.

RESULT

In this cross-sectional study, t-independent test was done to age, parity, and BMI

variable. As shown in Table 1.1, value for parity and BMI, variable was > 0.05, respectively

suggested no difference between the two groups. While the p value for age variable was

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<0.05, suggested the significantly difference between the age of pre menopausal and

postmenopausal women.

Table 1.1
Characteristic Distibution of age parity and BMI in both group

Pre Menopausal
Postmenopausal Group
Group
Risk Factor (n=30) P
(n=30)
Mean SD Mean SD
Age (year) 55,07 9,55 42,77 6,37 0,001
Parity 2,20 1,54 2,00 1,26 0,584
BMI 23,90 3,53 24,16 2,86 0,752

T-independent test was done to determine differences in elastin expression in pre menopausal

women compared with postmenopausal. The results are presented in Table 1.2.

Tabel 1.2
Differences in Elastin Expression in Pre Menopausal Women Compared to Post
Menopausal Women

Elastin
Subject Group n Expression SB t p
Mean

Pre Menopausal Women 30 9,13 3,63


8,07 0,001
Post Menopausal Women 30 3,65 0,85

Table 1.2 above showed the elastin expression in pre menopausal women compared

with postmenopausal women was significantly different (p <0.05).

DISCUSSION

The study result showed mean age of postmenopausal women was 55,07 9,55 year

and mean age pre menopausal women was 42,77 6,37 year, p value = 0,001. The mean age

of postmenopausal woman was significantly different with the pre menopausal women. The

mean postmenopausal parity was 2.20 1.54 and the mean pre menopausal parity was 2.00

1.26, p = 0.584. There was no difference in parity between postmenopausal and pre

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menopausal women. The mean BMI postmenopausal women was 23.90 3.53 and mean

BMI pre menopausal woman was 24.16 2.86, p = 0.752. There was no difference in BMI

between postmenopausal and pre menopausal women. By t-independent test it was found that

there was a significantly difference of elastin expression in pre-menopausal women compared

with postmenopausal women (p <0.05). The elastin expression of the sacrouterinal ligament

in postmenopausal women is lower than in premenopausal women.

This result could be explained that the uterosacral ligament consists of cells

(fibroblasts or fibrous connective tissue, chondrocytes or cartilages, osteoblasts and

osteocytes or bones), extracellular matrix consisting of fibers (collagen and elastin),

proteoglycans (Aggrekan, Versikan, Biglykan, Dekorin, (Fibronectin, Tenascin, Link

proteins, Fibromodulin, Osteopontin) where fibroblasts are the most dominant connective

tissue in uterosacral ligament and play an important role in extracellular matrix synthesis

including collagen5. A progressive decreasing of ovarian function in menopause associated

with specific changes in organs and tissues including atrophy of the labia, vagina and uterus6.

After menopause, the major secretions of the ovaries are androstenedione and testosterone.10

The circulating levels of androstenedione are about one and a half more during post-

menopausal than at menopause. Androstenedione derived from adrenal gland and only

slightly produced by the ovaries. Dehydroepiandrosterone (DHA) and sulfate (DHEAS),

derived from the adrenal glands, decrease with age. With loss of follicles and estrogens,

increased gonadotropin hormone triggers the ovaries secreting testosterone. Ovarian cells can

no longer produce steroid hormones when it is shrink and steroid capability decreases7.

Elastin plays a role in extensibility, tissue flexibility and elastic recoil, whereas

microfibrils composed by different proteins are stable structures and not extensible. Several

studies have shown a decrease in elastin levels in the uterosacral ligaments in pelvic organ

prolapse8. The molecular mechanism of the human elastin gene under most conditions was

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widely unknown. Elastin fibers consist of elastin rubber-like proteins formed over the

microfibril ladders. A number of elastin are required for the incorporation of elastic fibers in

order to attain a particularly stretching and circular ability. The mechanical properties of

tissue also depend on the proportion of elastin, a soluble polymer formed by a tropo-elastin

monomer followed by catalysis of a cross-linked formation by lysyl oxidases (LOX)9.

Elastin allows the tissue to stretch and return to its original form without energy input.

It is considered important in the reproductive tissues as it can accommodate the great

expansion in pregnancy and involution after childbirth. Elastin production is very unique

among buffer tissue proteins. In most organs, elastin biosynthesis is limited to a brief period

of growth. The maturation elastin fibers occurred when tropo-elastin synthesis has ceased. It

was found that LOX is very important for elastic fibers hemostasis in the tissues, including

female pelvic organs. Elastin allows the tissue to stretch and return to its original form

without energy input. It is considered important in the reproductive tissues as it can

accommodate the great expansion in pregnancy and involution after childbirth9.

CONCLUSIONS AND RECOMMENDATIONS

This study found that elastin expression in postmenopausal women uterosacral

ligaments was decreased compared with premenopausal women. Further study is suggested to

determine the severity of elastin expression decreased in postmenopausal women.

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