KnE Medicine | The 6th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2016) | pages: 89-98


1. Introduction

The increasing of life expectancy is proportional with the increasing number of women in the menopausal age 2030 [1-3]. At menopause, there will be a variety of physical and psychological complaints due to declination of estrogen levels [4,5]. Vasomotor syndrome (50-75%) is most common symptoms suffered by menopause women [6-8].

Vasomotor syndrome is different in each persons based on the declination velocity of estrogen level [9-10], depends on the population, geographic area, and personal biological characteristic [11]. Vasomotor syndrome can be uncomfortable even cause disruption in the daily activities and reduce the quality of life [12,13]. We need early marker to predict the presence and severity of vasomotor syndromes, to prepare women facing menopause syndromes, especially vasomotor syndromes [14].

As it is known that reduction of ovary function will reduce estrogen levels to only 5-20 mcg/24 hr in menopause period [15,16]. Estrogen has three derviates, estrone (E1), estradiol (E2), and estriol (E3). Estradiol (E2) is the most abundant and most potent derivates with the greatest number of receptors in variety of organs [17,18]. Estradiol serum level in young woman is more thatn 1000 pg/mL, which will decrease to only

Wahdi (2003) showed that estradiol serum levels wass lower in women with than those without vasomotor syndromes. However, in this study does not explain the difference of estradiol serum levels between the severity of vasomotor symptom [17].

Therefore, author is interested in determining the difference of estradiol serum level between women with and without vasomotor syndrome, also the difference among mild, moderate, and severe degree of syndromes.

2. Materials and Methods

2.1. Study Design

This study was an analytical cross sectional study that conducted in Departemen of Obstetrics and Gynecology H. Adam Malik Hospital and its satellite hospital, Univeristy of Sumatera Utara, Medan, Indonesia. The study has been approved by the local institutional review board.

2.2. Subjects

From February to April 2015, we screened 50 consecutive menopausal women aged 45-65 years old who were working in our institutions. Written informed consents were previously obtained. The inclusion criteria were as follow: not taking hormone replacement therapy; no history of hysterectomy or bilateral oophorectomy; had any malignancy, cardiovascular, diabetes mellitus, osteoporosis, hypertension, or psychiatrics disorder; not smoking or taking alcohol. Subjects who withdrew before the end of the study or if their blood samples were broken, were excluded from this study.

2.3. Study Protocols

Baseline characteristics such as, age, menopause age, body mass index, duration of menopause, and parity were recorded. All eligible subjects were interviewed by a blinded investigators to assess vasomotor symptoms. If the woman denied any symptom of hot flushes, she was said to have no vasomotor syndrome. Conversely, if symptom of hot flushes was presence, the woman was said to have vasomotor syndrome. The syndrome was categorized mild if no sweating occurred, moderate if there was sweating but no limitation of daliy activity, severe if there was sweating with disturbance in daily activity. Estradiol serum was analyezed in Prodia Laboratory using chemiluminescent principle.

2.4. Estradiol Serum Analysis

We took 5 cc of blood sample from median cubital vein. The sample was then We took 5 cc blood sample from mediana cubiti vein. The sample was then centrifuged. About 80 uL sample and 75 uL reagen Ancillary pack was being put inside cuvetteI and incubated at 370C for 4.5 minutes. 75 uL Reagent Lite was taken and incubated at 370C for 2.75 minutes. 25 uL Ancillary well was added to 100 uL solid phase reagent and incubated at 370C for 5.5 minutes. Cuvette was then separated, aspirated, and washed by Wash 1 liquid. Then, 300 uL each acid and base reagents were added to initiate chemiluminescent reaction. The estradiol was counted inversely to relative light units detected by system.

2.5. Data Analysis

Data were analyzed descriptively to see the frequency distribution of the characteristics. All data was tested for the normality of distribution to determine the choice of statistical analysis. To analyze the difference between serum estradio level between both study groups, we used Mann-Whitney test. Meanwhile, the correlation characteristics of postmenopausal women with estradiol serum level were determined using Spearman correlation. The degress of confidence was 95%.

3. Results

In this study, about 26 of 50 menopausal women (52%) had vasomotor syndromes. Subjects who experience vasomotor syndrome mostly aged 45-50 years old (84.6%), had parity ≥ 4 (85.3%), normoweight (100%), menopausal age 45-50 years old (96.1%), and duration of menopause 1-2 years (100%).

Table 1

Baseline characteristics of subjects.


Characteristics Vasomotor syndrome No vasomotor syndrome Total
Age (years old)
45-50 0 (0%) 22 (84.6%) 22 (36.7%)
51-55 11 (32.4%) 4 (15.4%) 15 (25%)
56-60 14 (41.2%) 0 (0%) 13 (23.3%)
61-65 9 (26.4%) 0 (0%) 9 (15.0%)
Parity
0 0 (0%) 1 (4%) 1 (1.7%)
1-3 5 (14.7%) 25 (96%) 30 (50%)
≥4 29 (85.3%) 0 (0%) 29 (48.3%)
IMT
Normoweight 34 (100%) 0 (0%) 34 (56.7%)
Obese 0 (0%) 22 (84.6%) 22 (36.7%)
Overweight 0 (0%) 4 (15.4%) 4 (6.7%)
Menopause age (years old)
45-50 0 (0%) 25 (96.1%) 25 (41.7%)
51-55 24 (70.6%) 1 (3.9%) 25 (41.7%)
56-60 10 (29.4%) 0 (0%) 10 (16.7%)
Duration of menopause
1-2 5 (14.7%) 26 (100%) 31 (51.7%)
3-4 9 (26.5%) 0 (0%) 9 (15.0%)
≥5 20 (58.8%) 0 (0%) 20 (33.3%)

Age, parity, menopause, age, and duration of menopause were strong negatively correlated with estradiol serum levels. Body mass index was proportionally correlated with estradiol serum levels.

Table 2

Correlation between menopausal women characteristics and estradiol serum level.


Characteristics Estradiol serum level
r p value
Age -0.859 <0.001
Body mass index 0.699 0.316
Parity -0.907 0.002
Menopausal age -0.830 <0.001
Duration of menopause -0.880 <0.001

As shown in Table 3, women with mild vasomotor syndromes had higher estradiol serum level (23.9-29 pg/ml) than those with moderate (12-19.7 pg/ml) and severe (11.8 pg/ml) degree. There was significant difference of mean estradiol serum level between women with and without vasomotor syndromes (17.5 pg/ml and 47.5 pg/ml, respectively; p = 0.0001).

Table 3

Estradiol serum level based on vasomotor syndrome severity degres.


Vasomotor syndrome severity degree Estadiol serum level (pg/ml) Total
Mild 23.9-29.0 4 (11,8%)
Moderate 12.0-19.7 15 (44,1%)
Severe 11.8 15 (44,1%)
Total 34 (100,0%)
Table 4

Difference of estradiol serum level between women with and without vasomotor syndrome.


Group N Estadiol serum level P value*
Vasomotor syndrome 34 17.50 pg/ml
No vasomotor syndrome 26 47.50 pg/ml 0,0001
Total 60
* Mann-Whitney test

4. Discussion

Menopause is the cessation of menstruation for at least 12 months due to loss of ovarium function [7,8]. The declination of ovaries cause deficiency of estrogen production, which will bring many menopausal symptoms. The menopase syndrome consists of vasomotor syndrome (hot flushed, sweating, palpitation, headache, insomnia), psychologic disorders (moody, fatigue, low libido), urogenital symptoms (dryness of vagina, dyspareunia), osteoporosis, dryness of skin, and increases incidence of cardiovascular disorders [13].

Vasomotor syndrome is the most common syndrome suffered by menopause women [4,20-22]. There are three severity degress of vasomotor syndrome such as mild if there was presence of hot flushes without sweating, moderate if both symptoms were presence, and severe if both symptoms have caused limitations of daily activities.

This syndrome was found since climacteric until post menopause. Some studies reported that 75%-80% women have complained of vasomotor syndromes since several years before menopause [17,23]. In Bandung, Indonesia, study showed that higher proportion of menopause women (88.3%) complained of vasomotor syndrome during her life. About 85% women that suffering from vasomotor syndrome will continue to have it in entire year and 25-50% will continue untul 5 years later [24]

However, characteristics of vasomotor complaints differ depending on the geography area [7,9,25]. Blumel showed that in poulation with severe vasomotor symptoms, they mostly had low education level, nulliparity, surgical menopause, and had also severe both psychological and urogenital disorders [26]. In this study, subjects who experience vasomotor syndrome mostly aged 45-50 years old (84.6%), had parity ≥ 4 (85.3%), normoweight (100%), menopausal age 45-50 years old (96.1%), and duration of menopause 1-2 years (100%).

High parity is associated with menopause which previously described by Kuzmarek [27] but there is no theory that can explain the association. In the other hand, Kriplani in India showed controversial results about this [28].

In obesity, fat causes greater peripheral conversion of adrenal androgen to estrogen. Besides that, lower sex hormone binding globulin increase protection against hot flushes [29]. The decline of estrogen in menopause does not occur suddenly. Estrogen is still presence in blood from peripheral conversion. The adrenal gland is the main source of estrone. Most estrone generated from peripheral aromatization of androstenendion. Aromatization of androstenendion can occur in fat, muscle, liver, bone marrow. But only 30-40% of this conversion are derived from fat cells and muscles. Therefore, obese women have a higher number of estrogen levels than lean women [16,19,28].

This results was similar to that of Study of Women's Health Across the Nation (SWAN) study. In 3.302 menopause women with vasomotor syndrome, women with BMI 28 kg/m2 had more severe vasomotor syndrome than women with BMI 31 kg/m2 [30]. This association was remained significant after controlled of other risk factors. However, Amabebe showed positive correlation between the high BMI and severity of syndrome [31].

Early menopause age is associated with more significant morbidity and mortality of symptoms. However, mostly women menopause at 45-50 years old [32]. Stanford reported that median menopause age in developing countries was 50-51 years old [33]. Kwawukume showed that in developing countries, natural age of menopause is 4 years earlier thatn that of developing countries [34]. In a large study by Oloran, they showed mean menopause age was 48.5 +/- 4.6 years old [35].

Age, parity, menopause, age, and duration of menopause were strong negatively correlated with serum estradiol levels. Body mass index was proportionally correlated with serum estradiol levels. These results were similar to theories, as ovaries follicles decreased by aging while estradiol increased by the increasing fats [17].

Before a woman experiences menopause, there have been anatomical changes in the ovary as a result of the aging process that cause sclerosis and reduction in the number of primordial follicles, as well as a decrease in the activity of steroid hormone synthesis. The decline of estrogen levels will mark the beginning of climacteric and continue decreasing during menopause, reaching lowest level during the post menopause period. This cause negative feedback on the hypothalamus, which in turn causes increased production of gonadotropins, resulting in hipergonadotropin-hypogonadism condition. With declining estrogen levels in the body, then all physiological functions of sex hormones will be disturbed, causing neurovegetative disorders, psychological disorders, somatic disorders and menstruation disorder [4,17].

The age of menopause is determined by the number of follicles present in the ovaries. When the fetus was 20 weeks, the follicles were estimated to contain 7 million of ovaries. In puberty, follicles will reach its peak level and then decrease linearly until the age of 40 years old. At the age of 40-45 years old, the average number of primordial follicles decreases to 8.300 [15]. These processes occur continuously during a woman's life, until ovaries become very tired at the age of 49-51 years old. Furthermore, the number of follicles decline of the sharply. After menopause, there were no more follicles [17]. This condition resulted in disorder of ovaries metabolism and growth, leading to ovarian atrophy and thickening of albuginea. All these processes are genetically aroused. So it is clear that the process of aging and decreased ovarian function dimish the pituitary to produce steroid, which cuase related symptoms [16].

Estrogen is composed three derivates, estrone (E1), estradiol (E2), estriol (E3). Estrone (E1) is an estrogen compound with C18H22O2 chemical groups, found on the body as a metabolite of estradiol, secreted primarily in the ovaries. Estradiol (E2) is a natural hormone estrogen with phenolic alcohol C18H24O2 chemical groups that are generally secreted by the ovaries, with the greatest number, and the most potent activity [5].

Estrogen deficiency leads to loss of estrogen-catecholamines precusors, resulting in decreased sympatho-hypothalamic control. Core body temperature will raised. Initially, thereis a compensatory increase in the secretion of adrenaline to synchronize the central temperature to the high peripheral temparature. Along with this, there will also an increase in the activity of parasympathetic nervous system. This is in accordance with the pathophysiology in which hot flashes and headaches occured and followed by vasodilation due to subsequent increase followed by decrease in serum adrenaline. Vasodilation limited to the face, arm and hand. The other issued raised hypothesis that decreased of ovarium funnction caused decrease of opioid tonus at ypothalamus and instablity of temperature regulation [8,17,23].

Hot flushes is the classic sign of vasomotor syndrome. Its mechanisms remained controversial. It was presumed that hormonal, metabolic, and psychologic factors induce vasodilatation and increase body core temperature. Some women reported that hot flushes begin with headache that extend to entire body, especially around face and uppert trunk, then their skin will redden, hot, begin sweating, and palpitations. At this time, skin temperature increases 5-9C and core temperature decreases 0.6C. Therefore, this was like a compensation to reduce core temperature. The frequency of each hot flush varies 1-2 times per hours to 1-2 times per week. In some situations, severe symtpoms can last for 54 minutes [23].

There was significant difference of mean estradiol serum level between women with and without vasomotor syndromes (17.5 pg/ml and 47.5 pg/ml, respectively; p = 0.0001). Wahdi (2003) also showed significant difference of serum estradiol level between both groups (p < 0.01) with 9.557 pg/ml in women with vasomotor symptoms compared to 14,160 pg/mL in women without vasomotor symptoms [17]. In this study, it was shown that there was a tendency of low serum estradiol level in lower severity of syndrome.

Wahdi (2003) showed that estradiol serum levels wass lower in women with than those without vasomotor syndromes. However, in this study does not explain the difference of estradiol serum levels between the severity of vasomotor symptom. He also showed that 63% subjects in his study overcomed vasomotor symptoms 1-2 years after menstrual cessation, 30% had symptoms after 1-2 years before menstrual cessation, and 7% had symptoms immediate after menstrual cessation [17].

To manage vasomotor symptoms, first, one's should change her lifestyle to be more healthy and avoid of psychoogic stress. Evaluation was done 3 months later. If symptoms were decreased, follow up was done annually. If symptoms were persist, clinicians should decide of prescribing drugs. Phytoestrogen is the first line therapy for mild vasomotor syndrome but being the second line in moderate to severe syndrome. Estrogen and hormon replacement therapy are the first line drugs for moderate to severe vasomotor syndrome. The other alternative drugs are clonidine or gabapentin [45].

5. Conclusion

This study showed significant difference of serum estradiol level between women with and without vasomotor syndrome. There was a tendency of lower serum estradiol level in lower severity of syndrome. Further research is needed to make this marker applicable in all clinical settings.

References

1 

Affandi B., Masalah kesehatan pada menopause. Panduan menopause, Balai Penerbit FK UI, Year: 2000, Page: 57

2 

Marosa L., Siregar F. G., Munthe I. G., Perbandingan Kadar Saliva 17ß Estradiol Pada Wanita Menopause Dengan Keluhan Dan Tanpa Keluhan Di, RSUP H Adam Malik Dan RS Jejaring FK USU Medan, Fakultas Kedokteran USU, Year: 2014, MedanIG Munthe Page: 78

3 

Siregar FG., Perimenopausal and Postmenopausal Complaints in Paramedics Asseds by Menopause rating, IQSR-JDMS, Year: 2014, Page: 13-12.

4 

Darmasetiawan MS., Seputar Masalah Wanita Menopause di Indonesia. Departemen Obstetri dan Ginekologi RSPAD Gatot Subroto, Departemen Obstetri dan Ginekologi RSPAD Gatot Subroto, Year: 2006, Page: 12

5 

Klein NA., MR Soules. Endocrine changes of the menopause, Clin Obstet Gynecol, Year: 2004, Volume: 41, Page: 912-20.

6 

Greendale G. A., Lee N. P., Arriola E. R., The menopause, Lancet, Year: 1999, Volume: 353, Issue: 9152, Page: 571-580. DOI: 10.1016/S0140-6736(98)05352-5

7 

Hammond C. B., Menopause and hormone replacement therapy: An overview, Obstetrics and Gynecology, Year: 1996, Volume: 87, Issue: 2, DOI: 10.1016/0029-7844(95)00429-7

8 

Pramono N., Upaya Meningkatkan Kualitas Hidup Manusia, Disampaikan pada Pidato Guru Besar Bagian Obstetri dan Ginekologi FK Undip, Year: 1998, Page: 18

9 

Jappe R. B., The Menopause and Perimenopausal Period, Reproductive Endocrinology, Year: 2005, 3rdPhiladelphiaW.B. Sounders Company Page: 389-404.

10 

Speroff L., Glass RH., Kase N. G., Neuroendocrinology, Clinical Gynecologic Endocrinology and Infertility, Year: 2010, Volume: 5, 5thBaltimore: WilliamWilkins

11 

Birkhauser M., Life after The Menopause: A Demographic, Medical and Social Challenge, Medicographia, Year: 2010, Volume: 21, Page: 262

12 

Affandi B., Masalah Kesehatan Pada Menopause, Dalam, Baziad A, Affani B.(ed), Panduan Menopause dan Terapi Hormon Pengganti, Edisi Pertama, Year: 2004, POGI-PERMIJakarta Page: 11-20.

13 

Baziad A., Lazuardi S., Darmawan S., Seputar Masalah Menopause, Dalam KSERI, Year: 2002, JakartaProseding Page: 11-23.

14 

Widya J., Analisis Karakteristik Wanita Premenopause dalam Kesiapan Menghadapi Sindrom Menopause Di Kelurahan Pendrikan Lor Kecamatan Semarang Tengah Tahun 2011, Universitas Diponogoro, Year: 2011, Page: 1-35.

15 

Pernoll M. I., The Non Reproductive Years, Handbook of Obstetrics and Gynaecology, Year: 2001, 10thPhiladelphiaMcGraw Hill Inc Page: 743-54.

16 

Rachman IA., Perubahan tubuh menjelang menopause dan gejala serta tanda yang menyertainya, Dalam, Menopause Masalah dan Penanggulangannya, FK UI, Year: 2006, Page: 19

17 

Wahdi Pramono N., Hidayat S. T., Kadar Estradiol Serum Pada Wanita Menopause Dengan Dan Tanpa Sindroma Vasomotor, Fakultas Kedokteran Universitas Diponogoro, Year: 2003, Page: 1-38.

18 

Jacob T. Z., Baziad A., Endokrinologi Reproduksi. Edisi ke-1, Year: 2000, JakartaKSERI Page: 43-51.

19 

Hurt W. W., Berek J. S., Menopause, Novak’s Gynecology, Year: 2008, Volume: 29, 12thBaltimoreWilliam and Wilkins Page: 981-1011.

20 

Speroff L., Glass R. H., Kase N. G., Menopause and Postmenopausal Hormon Therapy, Clnical Gynecologic Endocrinology and Infertility, Year: 2006, Volume: 5, 5thBaltimore: WilliamWilkins Page: 583-650.

21 

Smith E. K., Judd H. L., Menopause and Postmenopause, Current Obstetric and Gynecologic Diagnosis and Treatment, Year: 2007, Volume: 57, 8thPhiladelphiaPrentice-Heinemann Page: 1030-1049.

22 

Bachman G. A., Vasomotor Flushes in Menopausal Women, Am J Obstet Gynaecol, Year: 2009, Page: 312-6.

23 

Dusitsin N., Symptoms of The Menopause and Their Treatments, The Proceedings of the first Consensus Meeting on Menopause in the East Asian Region; Geneva: Medical Forum International, Page: 37

24 

Panay N., Versi E., Savvas M., A comparison of 25 mg and 50 mg oestradiol implants in the control of climacteric symptoms following hysterectomy and bilateral salpingo-oophorectomy, British Journal of Obstetrics and Gynaecology, Year: 2000, Volume: 107, Issue: 8, Page: 1012-1016. DOI: 10.1111/j.1471-0528.2000.tb10405.x

25 

Burger H. G., The Menopause: Clinical Features and Associated Disoders, Medicographia, Year: 2012, Volume: 21, Page: 219-22.

26 

Blümel J. E., Chedraui P., Baron G., Belzares E., Bencosme A., Calle A., Danckers L., Espinoza M. T., Flores D., Gomez G., Hernandez-Bueno J. A., Izaguirre H., Leon-Leon P., Lima S., Mezones-Holguin E., Monterrosa A., Mostajo D., Navarro D., Ojeda E., Onatra W., Royer M., Soto E., Tserotas K., Vallejo S., A large multinational study of vasomotor symptom prevalence, duration, and impact on quality of life in middle-aged women, Menopause, Year: 2011, Volume: 18, Issue: 7, Page: 778-785. DOI: 10.1097/gme.0b013e318207851d

27 

Kaczmarek M., The timing of natural menopause in Poland and associated factors, Maturitas, Year: 2007, Volume: 57, Issue: 2, Page: 139-153. DOI: 10.1016/j.maturitas.2006.12.001

28 

Kriplani A., Banerjee K., An overview of age of onset of menopause in northern India, Maturitas, Year: 2005, Volume: 52, Issue: 3-4, Page: 199-204. DOI: 10.1016/j.maturitas.2005.02.001

29 

Pakarinen M., Raitanen J., Kaaja R., Luoto R., Secular trend in the menopausal age in Finland 1997-2007 and correlation with socioeconomic, reproductive and lifestyle factors, Maturitas, Year: 2010, Volume: 66, Issue: 4, Page: 417-422. DOI: 10.1016/j.maturitas.2010.04.005

30 

Gold E. B., Colvin A., Avis N., Bromberger J., Greendale G. A., Powell L., Sternfeld B., Matthews K., Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: Study of women's health across the nation, American Journal of Public Health, Year: 2006, Volume: 96, Issue: 7, Page: 1226-1235. DOI: 10.2105/AJPH.2005.066936

31 

Amabebe E., Relationship between Menopausal Sweating and Body Mass Index, Open Journal of Endocrine and Metabolic Diseases, Year: 2007, Volume: 4, Page: 137-146.

32 

Rizvanovic M., Balic D., Begic Z., Babovic A., Bogadanovic G., Kameric L., Parity and menarche as risk factors of time of menopause occurrence., Medicinski arhiv, Year: 2013, Volume: 67, Issue: 5, Page: 336-338. DOI: 10.5455/medarh.2013.67.336-338

33 

Stanford J. L., Hartge P., Brinton L. A., Hoover R. N., Brookmeyer R., Factors influencing the age at natural menopause, Journal of Chronic Diseases, Year: 1987, Volume: 40, Issue: 11, Page: 995-1002. DOI: 10.1016/0021-9681(87)90113-5

34 

Kwawukume E. Y., Ghosh T. S., Wilson J. B., Menopausal age of Ghanaian women, International Journal of Gynecology and Obstetrics, Year: 1993, Volume: 40, Issue: 2, Page: 151-155. DOI: 10.1016/0020-7292(93)90376-8

35 

Olaolorun F., Lawoyin T., Age at menopause and factors associated with attainment of menopause in an urban community in Ibadan, Nigeria, Climacteric, Year: 2009, Volume: 12, Issue: 4, Page: 352-363. DOI: 10.1080/13697130802521282

36 

Smith EK., Judd H. L., DeCherney A. H., Menopause and Postmenopause, DeCherney AH Pernoll LM Current Obstetric and Gynecologic Diagnosis and Treatment. Eigth Edition, 2007 Page: 1030-49. vol. 57

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