The Effect of Postmenopausal Ovarian Volume on Lipid and Hormonal Levels

Med. J. Cairo Univ., Vol. 8, No. 2, September: 31-35, 212 www.medicaljournalofcairouniversity.com The Effect of Postmenopausal Ovarian Volume on Lipid and Hormonal Levels AHMED SALEH, M.D.*; AHMED SOLIMAN, M.D.*; KHALED EL SHEIKHA, M.D.*; OSAMA AZMY, M.D.**; HEBATALLAH FAROUK, M.D.*** and OMAR AHMED, M.Sc.** The Departments of Obstetrics & Gynecology*, Reproductive Health** and Clinical Pathology***, National Research Centre, Al-Azhar University Abstract Introduction : Menopause is associated with a proatherogenic lipid profile characterized principally by lower high-density lipoprotein-cholesterol (HDL-cholesterol), higher low-density lipoprotein cholesterol (LDL-cholesterol) and triglyceride (TG) levels central adiposity and increased diastolic pressure. Sex steroid deficiency, is considered a crucial factor responsible for the menopause-associated changes in the cardiovascular disease (CVD) risk factor profile, and consequently for the increase in CVD risk. Aim : To find out whether menopausal ovarian volume can influence the serum levels of estrone (E 1 ), estradiol (E2) and free testosterone (FT) and the main serum lipid levels, high and low density lipoproteins (HDLs and LDLs), total cholesterol (TC) and total triglyceride (TG). Patients and Methods: One hundred postmenopausal women were included in this study. They were recruited from Al-Azhar University Hospital Out-patient Clinic. For each woman 5mL venous blood sample was withdrawn, transvaginal ultrasound was carried out and body mass index (BMI) was calculated. Results : Serum cholesterol level showed statistically significant values in relation to LDL, serum TG and E 2 levels (p-value <.1) while HDL, testosterone, E1, BMI, Rt. and Lt. Ovarian volume shows statistically insignificant values (p-value >.5). The BMI shows statistically significant values in relation to HDL and TG (p-value <.1, <.5 respectively). All the parameters showed statistically insignificant values (p-value >.5) in relation to LDL. Correlation between right and left ovarian volumes and body mass index showed a p- value >.5 which is insignificant. Conclusion : Although bigger ovarian size may be associated with higher hormonal levels, this is not true in postmenopausal women. Lipid derangement that is associated with lower estrogen levels that is associated with postmenstrual state is not related to ovarian volume. Key Words: Lipid profile postmenopausal Ovarian volume Hormones Correspondence to: Dr. Hebatallah Farouk, The Department of Clinical Pathology, National Research Centre Introduction MENOPAUSAL transition is a natural part of a woman s life, describing the change from the reproductive to the non-reproductive phase. This period starts between age of 4 and 5 and is characterized by low estrogen and progesterone and high gonadotrophin [follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels] [1]. While, androgen production in the adrenal cortex and to some extent from ovarian stromal cells remains fairly steady [2]. The hormonal conversion, especially the lack of estrogens, leads to moderate or severe menopausal symptoms in two thirds of women. These menopausal symptoms are not life-threatening, but may reduce quality of life considerably. The chief complaints are vasomotor and vaginal symptoms, accompanied by heart complaints, depressive episodes and sleep problems [3]. Other menopause-associated morbidities include increased cardiovascular risk, osteoporosis and body weight gain [4]. It is estimated that postmenopausal women had 2-6 times greater incidence of cardiovascular disease compared with premenopausal women [5]. The abdominal accumulation of adipose tissue and associated dyslipidemia are important components of a group of metabolic irregularities strongly related with increased cardiovascular risk in the menopausal woman [4]. Estrogen modulates lipid concentration in plasma by regulating lipidogenesis in adipocytes and hepatocytes. It regulates the expression of lipoprotein lipase and hormonesensitive lipase in abdominal adipocytes. Moreover, estrogen controls the synthesis of structural apolipoproteins to very low-density lipoproteins (VLDLs) and HDLs in hepatocytes and decreases the synthesis of hepatic lipases [6]. Furthermore, 31

32 The Effect of Postmenopausal Ovarian Volume on Lipid there is increased total serum cholesterol, triglycerides, and fibrinogen during the menopause [7]. The aim of this study was to find out whether postmenopausal ovarian volume can influence the serum levels of E 1, E2, FT, and the main serum lipid levels HDLs, LDLs, TC and TG. Patient and Methods This cross sectional study included one hundred postmenopausal women (at least 5 years of menopause) from Out-patient Clinic of University Hospital. Women on hormonal replacement therapy, history of oophorectomy, diabetes mellitus and morbid obesity (BMI >35kg/m 2 ) were excluded from the study. In addition, women with postmenopausal bleeding were also excluded from the study. Women had transvaginal ultrasound (Sonoace R7, Medison, Korea) to measure ovarian volume and BMI was calculated according to the following equation: BMI = Weight/Height Kg/m 2. Five ml of venous blood was withdrawn by a sterile plastic syringe and immediately centrifuged. The serum was distributed into three Eppendorfs for each sample then analyzed within the same day. The E 1, E2 and FT were analyzed by Abbott Architect i1sr device (USA). This is a fully automated, random access immunoassay analyzer that employs the Chemiluminescent Microparticle Immuno Assay technology. The i1sr utilizes a 1-test reagent kits and reagents. It can be loaded and unloaded without interrupting the instrument during assay processing. The HDLs, LDLs, TC and TG were measured by Olympus Auto analyzer that uses an enzymatic color test for their quantitative determination in human serum and specific ready to use reagents are utilized. The collected data were statistically analyzed using SPSS program version 17. Descriptive statistics were used for numerical Table (2): Lipid profile values among women studied. parametric data as mean ±SD (standard deviation) and minimum and maximum of the range. Inferential analyses were done in correlations using Pearson Correlation. The level of significance was taken at p-value of <.5. Results The women mean age was 57.3 ±4.5 years and BMI was 24.61 ±3.22 kg/m 2 (18.5-3). Their mean serum cholesterol, HDL, LDL and TG are shown in table two. The mean free testosterone index was 4.53±2.36 (.5-9.1), the mean E 1 was 173.58 ± 9.24pg/ml (25-35), the mean E 2 was 26.83 ± 1.9pg/ml (1-62), the mean right ovarian volume was 2.15 ±.71cm 3 (1-4), the mean left ovarian volume was 2.12±.67cm 3 (1-3.8) and the mean ovarian volume was 2.14±.65cm 3 (1.1-3.9). Table three shows the correlation between the different studied parameters. It was evident from these correlations that only the serum TC level is significantly related to LDL, TG and E 2, Where, the more TC the more LDL and TG levels. Whereas, the more TC the less the E 2 level (p<.1). Whereas BMI showed highly significant relation to HDL and serum TG levels, where the higher BMI the higher HDL and TG levels. There was no correlation between the ovarian volume and the lipid profile or the female steriodogenic hormone levels during the menopausal age. Table (1): Clinical characteristics of women recruited. Mean±SD Range Age (years) 57.3±4.5 51-63 Menopausal age (years) 49.6±2.1 46-52 Period of Menopause (years) 6.5± 1.4 5-7 BMI (kg/m 2 ) 24.61±3.22 18.5-3 Serum cholesterol HDL LDL Serum Triglycerides Mean±SD 174.51 ±64.75 63.75± 16.36 116.74±29.11 12.41 ±4.56 Range 56-299 31-89 64-2 37-25 Table (3): Correlation between various parameters. TC (mg/dl) HDL LDL TG FT (Index) E1 (pg/m1) E2 (pg/m1) BMI (Kg/m 2 ) (cm 3 ) TC -.83.28.363.31.59 -.266.15 -.47 HDL.68.78 -.13 -.3 -.56.276.4 LDL.89 -.29.78 -.58.72.86 TG FT (Index).21.85 -.82.245 -.23 -.71 -.56 -.62 -.88 E1 (pg/m1).47 -.162.54 If r>.195 it means p<.5 (significant) while, if r>.254 it means that p<.1 (highly significant). E2 (pg/m1) -.12.78 BMI Mean Ovarian (Kg/m 2 ) volume (cm 3 ).33

Ahmed Saleh, et al. 33 35 Correlation between serum cholesterol and mean ovarian volume Fig. (1): Scatter dispersion graph showing the correlation between serum cholesterol and mean ovarian volume. S cholesterol 3 25 2 15 1 5.5 1 1.5 2 2.5 3 3.5 4 4.5 1 Correlation between HDL and mean ovarian volume 8 Fig. (2): Scatter dispersion graph showing ovarian volume and HDL. HDL 6 4 2.5 1 1.5 2 2.5 3 3.5 4 4.5 25 Correlation between LDL and mean ovarian volume 2 Fig. (3): Scatter dispersion graph showing ovarian volume and LDL. LDL 15 1 5.5 1 1.5 2 2.5 3 3.5 4 4.5 3 Correlation between TG and mean ovarian volume Fig. (4): Scatter dispersion graph showing ovarian volume and TG. TG 25 2 15 1 5.5 1 1.5 2 2.5 3 3.5 4 4.5

34 The Effect of Postmenopausal Ovarian Volume on Lipid Discussion Menopause has been diagnosed retrospectively based on the lack of menstrual periods. With the advent of modern laboratory testing, menopause may now be more precisely defined as amenorrhea with signs of hypoestrogenemia, and an elevated serum FSH level of greater than 4IU/L. In addition to age increased cardiovascular disease maybe partially related to the endogenous sex hormone level and lipid derangement changes, initiated by menopause [2]. Several studies have looked at the ovarian volume in relation to hormonal profile and lipid profile in postmenopausal women, Berg et al. [8] showed that the increase in total-cholesterol and LDL-cholesterol to be linearly associated to menopausal status and estradiol concentration. Similarly, Derby et al. [9] found that the highest estradiol quartile had the lowest levels of total cholesterol, low density lipoprotein cholesterol, and triglycerides, although the association with triglycerides was only marginally statistically significant, contrary to findings for menopausal status, high density lipoprotein cholesterol was highest on average in the highest estradiol quartile. In contrast, Yasui et al. [1] established that serum levels of estradiol were not correlated with lipid profiles in menopausal women. Female hormones are secreted primarily from the ovary besides the peripheral conversion at the subcutaneous fat. Increased ovarian volume during the menopausal state may be a sensible logic for such association, where women with higher estrogen i.e. estrone and estradiol, would have bigger ovaries in contrast to those with lower estrogen and smaller ovaries. Furthermore the same would be true for women with higher BMI. Our results did not support both notions. Where there was no significant correlation between ovarian volume or size and either estrogen levels nor the lipid profile. Furthermore, BMI was not associated with any changes in the estrogen levels, even though there was a negative relation between BMI and the estrogen levels however, this association was statistically insignificant. On the contrary, BMI showed a positive correlation with higher HDL and total serum triglycerides. This was a highly significant correlation. In addition, BMI showed direct relationship with the dire lipids i.e. LDL, however this relation was statistically insignificant. Our findings do not sustain the world wide belief that the lack of estrogen is strongly associated with changes of lipid profile in a manner that increased the CVS risk i.e. increased LDL and TG with lower HDL. In contrast with our study Blümel et al. [11] found that higher BMI is not associated with significant changes in lipid profiles of postmenopausal women, consequently being overweight or obese during the menopausal period is not necessarily associated with deterioration in coronary risk factors. This seems to imply the existence of different metabolic pathways within this group of women. In a previous study performed by Bastos et al. [12], who performed a cross sectional study with 273 women aged 36-62 years, representative of the urban population of southern Brazil, they stated that the mean ovarian volume decreased with menopausal status adjusted for age. In addition there was a positive association between ovarian volume and BMI >_3 in every woman adjusted for menopausal status and age, our findings do not support these results as BMI in this study showed negative correlations regarding both E 1 and E2, however it were not significant, also BMI did not show significant relation regarding ovarian volume. This may be due to different sample characteristics upon which we included women, in addition, different race and genetic background which could reflect a variety in serum level of hormones and lipid profile. Factors that could affect lipid profile such as diet habits, smoking and physical activity may also explain this difference. In spite of the inverse relation between the lipid parameters measured and E 1 and E2, this connection did not hold statistical significance, These results are supported by previous results carried out on community-based women in China where Zhou et al., in a cohort study including 593 women in pre, peri and postmenopausal state [13] found that TG, HDL and total cholesterol have no relationship to menopausal status after adjusting the values to BMI, physical activity, age and antihypertensive medication. On the other hand, Murano and his colleagues while studying Japanese women [14] found that TC increased in approximately 1% within 2 years after menopause with increased LDLC, approximately 2%, and decreased HDLC and atherogenic indices were both elevated. Japanese women may represent different group of patients with special genetic background, eating habits and life style that may explain this difference with our results. In conclusion, although bigger ovarian size may be associated with higher hormonal levels, this is not true in postmenopausal women. Lipid derangement that is associated with lower estrogen levels that is associated with postmenstrual state is not related to ovarian volume.

Ahmed Saleh, et al. 35 References 1- APPLING S., PAEZ K. and ALLEN J.: "Ethnicity and vasomotor symptoms in postmenopausal women. " Journal of Women's Health, 16 (8): 113-38, 27. 2- GUTHRIE J.R., DENNERSTIEN I., TAFF J.R., LEHERT P. and BURGER H.G.: The-menopausal transition; a 9 years prospective population based study. The Melbourne Women Middle Health Project. Climacteric, 7: 375-389, 24. 3- AIDELSBURGER P., SCHAUER S., GRABEIN K. and WASEM J.: Alternative methods for the treatment of postmenopausal troubles. GMS Health Technol. Assess., 8: Doc 3, 212. 4- OLIVEIRA P., CARVALHO R., PORTINCASA P., BON- FRATE L. and SARDAO V.: Fatty Acid Oxidation and Cardiovascular Risk during Menopause: A Mitochondrial Connection? J. Lipids, 365-798, 212. 5- LAMBRINOUDAKI I., CHRISTODOULAKOS G., RIZOS D., ECONOMOU E., ARGEITIS J., VLACHOU S., CREASTA M., KOUSKOUNI E. and BOTSIS D.: Endogenous sex hormones and risks factors for atherosclerosis in health Greek postmenopausal women. European Journal of Endocrinology, 154: 97-16, 26. 6- YOSHIDA T., TAKAHASHI K., YAMATANI H., TAKA- TA K. and KURACHI H.: Impact of surgical menopause on lipid and bone metabolism. Climacteric, 14 (4): 445-52, 211. 7- HADDOCK B.L., HOPP MARSHAK H.P., MASON J.J., BLIX G.: The effect of hormone replacement therapy and exercise on cardiovascular disease risk factors in postmenopausal women. Sports Medicine, 29 (1): 39-49, 2. 8- BERG G., MESCH V., BOERO L., SAYEGH F., PRADA M., ROYER M., MUZZIO M.L., SCHREIER L., SISELES N. and BENENCIA H.: Lipid and lipoprotein profile in menopausal transition. Effects of hormones, age and fat distribution. Horm. Metab. Res., 36 (4): 215-2, 24. 9- DERBY C., CRAWFORD S., PASTERNAK R., SOW- ERS M., STERNFELD B., and MATTHEWS K.: Lipid Changes During the Menopause Transition in Relation to Age and Weight. The Study of Women s Health across the Nation. Am. J. Epidemiology, 169: 1352-1361, 29. 1- YASUI T., UEMURA H., IRAHARA M., ARAI M., KOJIMAHARA N., OKABE R., ISHII Y., TASHIRO S. and SATO H.: Associations of endogenous sex hormones and sex hormone-binding globulin with lipid profiles in aged Japanese men and women. Clin. Chim. Acta., 398 (1-2): 43-7, 28. 11- BLÜMEL J., CASTELO-BRANCO C., MARIA E., ROCANGLIOLO, BIFA R., TACLA X. and MAMANI L.: Changes in body mass index around menopause: A population study of Chilean woman. J. North American Menopause Society, 8 (4): 239-44, 21. 12- BASTOS C., OPPERMANN K., FUCHS S., DONATO G. and SPRITZER P.: Determinants of ovarian volume in pre-, menopausal transition, and post-menopausal women: A population-based study the European Menopause. J. Maturitas, 53: 45-12, 26. 13- ZHOU J., LIN S., SHEN Y., CHEN Y., ZHANG Y. and CHEN F.: Serum lipid profile changes during the menopausal transition in Chinese women: A community-based cohort study Menopause: The Journal of The North American Menopause Society, 17 (5): 997-13, 21. 14- MURANO T., IZUMI S., GOH KIKA G., HAQUE S., OKUWAKI S., MORI A., SUZOKI T., et al.: Impact of Menopause on Lipid and Bone Metabolism and Effect of Hormone Replacement Therapy. Tokai J. Exp. Clin. Med., 28 (3): 19-19, 23.