Font Size: a A A

Establishing Age-specific Normal Reference Range For Ovarian Aging Markers And Determining Relationships Between The Markers And Cardiovascular Disease

Posted on:2017-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:X F DuFull Text:PDF
GTID:1314330482994325Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Backgroud:The increasing use of anti-Mullerian hormone (AMH) and Inhibin B in clinic has raised concerns regarding the reliable reference range for this test. However, the reference range for AMH and Inhibin B in normal Chinese female population has not been established. Furthermore, relationship between AMH and Inhibin B with other clinical markers such as body-mass index (BMI) and antral follicle counts (AFCs) and other sex-related hormones have not been examined in normal population-based women.Objective:We aimed to determine the age-specific reference range for serum AMH and Inhibin B in healthy Chinese women throughout reproductive age to menopause and to estimate relationship between AMH and Inhibin B and other clinical markers in healthy women.Study Design:In this multi-center and nationwide study, advertisements were used to recruit 2055 women, aged 20 to 55 years, from six different regions in China; and 1590 (77.37%) women met the inclusion criteria for the reference-range population. We measured the baseline serum AMH levels using the Beckman Coulter Gen II assay and the Anhs Labs ultrasensitive AMH ELISA assay, respectively. The levels of Inhibin B were measured by Inhibin B ELISA kits from Beckman Coulter Inc. Serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), progesterone (PRG) and AFCs were also determined in the follicular phase.Main Outcome Measures:The AMH-Age nomogram and AMH levels of different age groups and the relationship between AMH and other clinical markers; The Inhibin B levels of different age groups and the relationship between Inhibin B and other clinical markers..Results:Serum AMH concentrations declined progressively with age. When measured by the Beckman Coulter Gen ? assay,we found a quadratic model defined as log (AMH)= (-1.970+0.296* Age-0.006* Age2) fitted best the decline of AMH with age. The median AMH levels were 6.23,5.65,4.55,3.74,2.78 and 1.09 ng/ml for the 20<age<25,25<age<30,30<age<33,33<age<37,37<age<40 and 40<age <55 groups, respectively. The 5th-95th percentiles of the AMH levels, as the reference range, were 2.06-12.66,1.77-13.83,1.48-11.45,0.87-9.76,0.56-9.49, and 0.08-5.70 ng/ml for each age group. The AMH levels were positively correlated with AFCs and T, LH, PRL and PRG levels, negatively correlated with body mass index (BMI) and FSH levels and were not significantly correlated with E2 levels. The relationship between AMH and other variables remain unchanged except for PRL, which was not significantly correlated with AMH levels after controlling for both age and BMI. While for the new Ansh Labs Ultra-Sensitive AMH ELISA assays, a quadratic model defined as log (AMH)= (-0.707+0.116* Age-0.002? Age2) fitted best the decline of AMH with age. The median AMH levels were 5.55,4.80,3.76, 3.42,2.44 and 0.77 ng/ml for the 20<age<25,25<age<30,30<age<33,33<age< 37,37<age<40 and 40<age<55 groups, respectively. The 5th-95th percentiles of the AMH levels were 1.43-13.14,1.31-13.55,1.06-10.97,0.69-9.52,0.38-8.03, and 0.04-4.79 ng/ml for each age group. Serum Inhibin B concentrations declined rapidly after the age of 40 years. The value between the two age groups of 20-40 years and 40-55 years was significantly different according to both the t-test and Wilcoxon's test, so the reference range was determined for these two groups. The median Inhibin B levels for each age group were 83.13 and 56.32 pg/ml, and the reference range(5th-95th percentiles) were 34.38-143.75,2.6-142.33 pg/ml. The Inhibin B levels were positively correlated with AMH, AFC and T levels, negatively correlated with age, BMI and FSH, LH levels and were not significantly correlated with PRG, PRL levels.Conclusions:This study determined the normal reference ranges for serum AMH and Inhibin B levels in a large population-based sample of healthy Chinese women.Background:Antral follicle count (AFC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and total testosterone (T) are the important reproductive markers for which some researchers suggested that age-specific levels be used for diagnostic purposes in clinical practice rather than universal ranges. However age-specific levels of these markers have not been determined in healthy Chinese women. In addition, relationships between AFC and other clinic markers such as BMI and sex-related hormones (FSH, LH, E2, T) have not been examined in normal population-based women with regular menstrual cycles.Objective:To establish age-specific reference ranges for AFC, FSH, LH, E2 and total T. In addition, determine the relationships between AFC and other clinic markers in normal population-based women.Patient(s):2055 women (aged 20-55 years) were recruited by advertisements, from six different regions of China; and 1590 (77.37%) women met the inclusion criteria for the reference-range population.Study Design:We measured AFC by transvaginal ultrasound examination, and serum concentration of FSH, LH, E2 and total T were also determined during the follicular phase.Main Outcome Measure(s):Establishing the optimal models fitted the changes in AFC, FSH, LH, E2, T with age and reference ranges of these markers in different age groups, and estimating the relationships between AFC and other clinical markers.Results:AFC declined progressively with age and a quadratic model defined as AFC =9.0998+0.6128*Age-0.0159* Age2 fitted best the decline of AMH with age. FSH consistently increased with age, and its age-related changes were best fitted by a quadratic model defined as FSH=12.7885-0.5031* Age+0.0101* Age2. The age-related changes of other reproductive hormones can also be best fitted by quadratic models defined as LH=11.5678-0.4101* Age+0.0059* Age2, E2=85.6229-3.002* Age+0.0546* Age2, T=33.1488+0.4427* Age-0.0176* Age2, respectively. The reference ranges for AFC, FSH, LH, E2 and T levels were estimated by three age groups:20-30,30-40,40-55 years. The AFC were negatively correlated with Age, BMI and FSH levels, positively correlated with LH and T levels; FSH were positively correlated with Age and LH levels, negatively correlated with AFC, BMI and T levels; LH were negatively correlated with Age and BMI, positively correlated with AFC, FSH and E2 levels; The levels of E2 were not significantly correlated with Age, positively correlated with LH and T levels, and negatively correlated with BMI.Conclusions:This study determined the normal reference ranges for the serum AFC, FSH, LH, E2 and total T in a large population-based sample of healthy Chinese women.Objective:The relationships between ovarian function related markers and cardiovarscular diseases have not been determined. So this study aimed at determining the markers which related to the cardiovarscular diseases.Study Design:We recruited female volunteers in physical examination center of tongji hospital using advertisement, a total of 536 people who met the inclusion criteria took part in the study. We measured the baseline serum AMH levels using the Beckman Coulter Gen ? assay. Serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL) and AFCs were also determined in the follicular phase. Detecting risk indexs of cardiovascular disease including:total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hypersensitive c-reactive protein levels (h-CRP). Then, analyzing the correlation between all the markers of ovarian function and cardiovascular disease risk indexs.Main Outcome Measures:The relationship between ovarian function related markers and cardiovarscular diseases risk indexs.Results:The results of Pearson correlation showed that the level of AMH was negatively correlated with TC, TG and LDL-C levels, the level of FSH was positively correlated with TC, TG and LDL-C levels, E2 level was negatively correlated with TC, TG and LDL-C levels, LH level was positively correlated with TC, TG and LDL-C levels, AFCs was negatively correlated with TC, TG and LDL-C levels, the level of T was positively correlated with LDL-C level, the level of PRL was positively correlated with HDL-C, and negatively correlated with h-CRP. The results of Logistic regression analysis shows that AMH and FSH can enter to the regression equation which the Y value was the overall risk of cardiovascular disease.Conclusions:Ovarian function is closely associated with the risk of cardiovascular disease, of all ovarian function related markers, AMH and AFC may have more advantages in early warning on cardiovascular disease than FSH, LH, E2 and other indicators; AMH can serve as a predictor of cardiovascular disease risk.Objective:Determining whether there is a correlation between AMH, menstruation and cardiovascular diseases (including coronary heart disease and other cardiovascular disease).Study Design:From October 2013 to December 2015, a total of 229 hospitalized patients aged 20 to 55 years were enrolled in cardiovascular internal medicine of tongji hospital, they were divided into two groups:128 patients with coronary heart disease diagnosed by coronary angiography as the case group 2, the other 101 patients who cann't been confirmed as CHD by coronary angiography, as the case group 1. At the same period, we recruited volunteers at several communities surrounding in tongji hospital by advertising, match according to age stratification, enrolled 243 healthy women as control group (group 0). We used questionnaire to survey the general information including menstrual and maternal history, measured the baseline serum AMH levels using the Beckman Coulter Gen ? assay, detecting risk indexs of cardiovascular disease including:total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hypersensitive c-reactive protein levels (h-CRP). Then using analysis of variance to determine whether there was any difference of AMH and other markers between this 3 groups (group 2, group 1 and group 0).Results:As to age, analysis of variance showed that there was no significant difference between the 3 groups. In other words, the baseline ages of 3 groups were similar, so indexs were comparable between this 3 groups. Variance analysis showed that these indexs were significant different between 3 groups:the level of AMH, menstrul situation (i.e., menopause or not), gravidity and systolic pressure. Variance analysis showed no difference between 3 groups as to these indexs:parity, BMI, TC, LDL-C and HDL-C. There were significant differences between group 0 and group 2 as to diastolic pressure, while no difference between group 0 and group 1, group 1 and group 2. As to TG, there were significant differences between group 0 and group 1, while no difference between group 0 and group 2, group 1 and group 2. As to blood glucose, there were significant differences between group 0 and group 1, group 0 and group 2, while no difference between group 1 and group 2.Conclusions:The level of AMH and menstrul situation is closely associated with the cardiovascular disease. Moreover, the AMH level and menstrual situation change before the index of TC, HDL-C and LDL-C, so the AMH level and the menstrual situation may have more advantages in early warning on cardiovascular disease.
Keywords/Search Tags:AMH, Inhibin B, reference range, Chinese women, nationwide population-based study, AFC, reproductive hormone, ovarian function related markers, the risk of cardiovascular disease, early warning, menstrual situation, cardiovascular disease
PDF Full Text Request
Related items