Urban Communities Of Women In Menopausal Transition Stage Study

[Background] The genesis, development and aging of the ovary are the foundation of women stages throughout their lifetime. The ovary aging involves several decades in women's life and has become an essential domain in reproductive endocrinology. It's a continuous process but with phasic specificity, and each phase has different characteristics and specific health problems. Menopausal transition (MT) is one of the important phases during which a series of health problems emerge, such as insulin resistance and abnormal serum lipoid profile in early MT, accelerated loss of bone mass in late MT. So it's considered as a key phase for women health care and prophylaxis of geratic chronic diseases. Staging the menopausal transition will help predict the initiation and endpoint (menopause) of the MT, discriminate the influence of health between ovary retrogression and aging, treat properly according to characters of different phases, and improve the comparability of correlative studies in ovary aging. There are several staging systems raised from studies on MT staging since 1980s, which mainly aimed towards Caucasian with multiple nations in individual study. The staging systems are incompatibility and there are some defects in practicability and availability. STRAW and ReSTAGE contribute to the staging system more widely while there is few research on MT in China. Lin SQ etc. looked into relationship between peri-/postmenopausal ovary, uterine and serum FSH and E2 levels with regard to ovary aging, but with no staging system raised from it. He Z. had analyzed menstrual calendar documented in 1 year, which showed menstrual cycle length and its variation as indictor of ovary aging, meanwhile, she debated on the increase of FSH level. The current research continues He's work, while focus on the menstrual cycle length and its variation to staging MT of the women from the community with more detailed data by comparing the MT staging criteria proposed by STRAW and ReSTAGE.This dissertation contains two sections:Section I Staging MT in the women who come from a community inBeijingSection II To assess the application of late MT criteria in clinical practicein gynecologic endocrinology Section I Staging MT in the women who come froma community in Beijing[Objective]To define a feasible MT staging criteria for women in our community by comparing the MT staging criteria proposed by STRAW and ReSTAGE, based on the menstrual cycle length recorded in menstrual calendar.[Specific Aims]1. To describe the changes of menstrual cycle length with age increasing.2. To describe the annual serum FSH, E2 level and hot flash in different baseline menstrual status.3. To compare 3 proposed menstrual criteria (marker events) for the onset of late MT: (1) cycle≥60d, (2) cycle≥90d, (3) skipped cycle. We determined the age at occurrence of each marker, the proportion of women in whom each menstrual criteria was observed, and the time from occurrence of each marker to FMP. We also assessed the relationship between annual serum FSH, E2 level and hot flash with each marker, and then defined a feasible menstrual criteria for the onset of late MT.4. To compare 3 proposed menstrual criteria (marker events) for the onset of early MT: (1) 1 cycle different from normal >6d, (2) 1 cycle different from the previous cycle >6d, (3) persisternt >6d difference. We determined the age at occurrence of each marker, the proportion of women in whom each menstrual criteria was observed, and the time from occurrence of each marker to late MT. We assessed the relationship between of annual serum FSH, E2 level and hot flash with each marker, and then defined a feasible menstrual criteria for the onset of early MT.[Materials and methods]Perspective longitudinal study design was used in the present study. From 2005-2007, 392 women lived Beijing community, aged 30-54 years, with regular menstrual cycle between the ages 20-30, at least one menstrual cycle in the prior 12 months, at least one intact ovary, and not using hormones in the prior 6 months attended our study. The last follow-up was in Jul 2009. Main measures included cycle length (by menstrual calendar) ; serum FSH and E₂ level measured in baseline and every 1 year (blood samples for hormone assays were taken between days 3-6 of the menstrual cycle for those still cycling, or after 60 days of amenorrhea), hot flash (in 2 weeks before baseline and follow-up interview), demographic information, menstrual history, disease history.[Statistics]All data were entered into database Epidata 3.02 and were analyzed by SPSS 13.0 (Statistics Software Package for Social Science). Qualitative data were analyzed by frequency, proportion; quantitative data were analyzed by mean and standard deviation. The age distribution of each marker event was calculated using K-M survival analysis. The within-individual differences of normal quantitative variables were calculated using a paired t test. By using logistic regression analysis, we assess the relationship between annual serum FSH, E2 level and hot flash with each marker. By using Cox model we assess the association between observation of a marker and time to FMP.[Results 1]1. 392 women participated in the baseline data collection, among which 361 women had recorded at least 10 menstrual cycles or were observed FMP during the follow-up. After 30.2±10.1 months follow-up, among 361 women, there were 37 women were observed FMP, 2 women began HT, 2 women had hysterectomy, 293 still menstruating, 25 women lost. The lost rate was 13.3% during the whole follow-up. Totally, 8596 cycles were provided (23.8±10.5 cycles per woman) and there were 12 intermittent missing cycles.2. Mean age of participants at baseline was 43.28±4.59 yr (30-54 yr). The mean length of their normal cycles was 29.09±1.60d. At baseline (the first 3 cycles during the follow), there were 257 women without 1 cycle different from normal >6d (a), 66 women with at least 1 cycle different from normal >6d (b), 38 women with at least 1 cycle≥60d (c). Serum FSH levels were highest in group (c) and lowest in group (a) (P=0.000). While serum E2 levels had no significant difference among groups. As regard with baseline age, serum FSH levels and the prevalence of hot flash were higher in older women than in younger women, while serum E2 levels did not show that trend.3. Mean age of FMP (n=37) was 51.3±1.90 yr. Determined by K-M survival analysis, the mean (median) age of FMP was 52.83 (52.67) yr.4. Calculating mean length of cycles (MLC) in different age groups by person-year, it was found that MLC shortened with age gradually after 30 yr, and reduced to the minimum at about 46 yr (with median of MLC 28.6d). Since then MLC extended gradually, when beyond 50 yr, the median of MLC was 39d.5. Evaluation of 3 proposed menstrual criteria for the onset of late MT: (1) Among the women with observed FMP, 96.9% had experienced cycle≥60d, 90.6% had experienced skipped cycle, and 71.9% had experienced cycle≥90d。(2) K-M estimates showed that the mean age at occurrence of cycle≥60d, skipped cycle and cycle>90d were 50.0 yr, 48.8 yr and 50.5yr, respectively, and the time to FMP were 2.51, 2.34 and 2.04 years, respectively.(3) The mean of annual serum FSH level before the occurrence of cycle≥60d, skipped cycle and cycle≥90d was 22.8, 20.6 and 31.4IU/L respectively, and the mean of annual serum FSH level increased to 25.1, 23.6 and 35.4 IU/L respectively (P<0.05) ; The mean of annual serum E2 level before the occurrence of cycle≥60d, skipped cycle and cycle≥90d was 91.2,83.0 and 71.7pg/ml, and after the occurrence of each marker the mean of annual serum E2 level decreased to 83.4, 77.8 and 65.3 pg/ml respectively(P<0.05) . There were no significant changes in the prevalence of hot flash between before and after the occurrence of markers.(4) All of 3 markers were positive associated with serum FSH level and hot flash (P<0.01). After adjusting age and BMI, compared with the women with annual serum FSH<10IU/L, the hazard of the occurrence of all of 3 markers were higher in the women with 40>FSH≥20IU/L (OR=1.96-6.62) and in the women with FSH≥40 IU/L (OR=4.14-26.87). The hazard of the occurrence of all of 3 markers in the women with hot flash were higher than in the women without hot flash (OR=2.11-3.24).(5) For all markers, the older the age at the occurrence of markers were, the shorter the time to FMP were(OR=1,24～1.40). Among the women in whom the age at the occurrence of markers < 45yr, nobody was observed FMP during the follow up。(6) Among the women in whom the age at the occurrence of markers>45yr, the mean time from the age at markers to FMP were 1.93～2.33 years。The hazards of FMP were significantly associated with serum FSH level. The women with FSH≥20IU/L were more close to FMP (OR=2.29～2.81).[Conclusion 1]1. These finds support the menstrual criteria for the onset of late MT proposed by STRAW and ReSTAGE, and consider cycle≥60d as acceptable criteria for the onset of late MT in women come from the community.2. Among the women in whom the age at the marker≥45yr, the women with FSH≥20IU/L are more close to FMP. Annual serum FSH≥20 IU/L is not the essential criteria for the onset of late MT.[Results2]Evaluation of 3 proposed menstrual criteria for the onset of early MT: (1) Excluding the women who were observed cycle≥60d (the criteria for the onset of late MT) in the first 10 cycles recorded in the study, there were 289 women included in the analysis. Until the last follow up, there were 58 women observed cycle≥60d among whom 6 women observed FMP, and another one women observed FMP who had not experienced cycle≥60d.(2) Among 58 women with observed cycle≥60d, 94.9% had experienced 1 cycle different from normal >6d, 91.5% had experienced 1 cycle different from the previous cycle >6d and persistent >6d difference. All of 7 women with observed FMP had experienced all 3 criteria.(3) K-M estimates showed that the mean age at the occurrence of 1 cycle different from normal >6d, 1 cycle different from the previous cycle >6d and persistent >6d difference were 44.1yr, 44.0yr, 45.1yr, respectively, and the time to cyc/e≥60d were 2.51, 2.55 and 2.39 year, respectively.(4) The within-individual difference in age at 3 markers were less than 0,2 year.(5) The mean of annual serum FSH level before the occurrence of 1 cycle different from normal >6d, 1 cycle different from the previous cycle >6d and persistent >6d difference was 9.31, 9.36 and 10.43 IU/L respectively, and the mean of annual serum FSH level increased to 11.97～14.69 IU/L (P<0.05) ; The means of annual serum E2 level before the occurrence of 3 markers were 92.65-99.83 pg/ml, and after the occurrence of each marker the mean of annual serum E2 level decreased to 85.15-90.78 pg/ml. Among 3 markers, the occurrence of 1 cycle different from normal >6d and persistent >6d difference brought significant change in serum E2 level (P=0.02-0.04). There were no significant changes in the prevalence of hot flash between before and after the occurrence of markers。(4) Among 3 markers, only persistent >6d difference were positive associated with serum FSH , E2 level (P<0.05). There was no significant association between hot flash with any marker. After adjusting age and BMI, compared with the women with annual serum FSH < 10IU/L, the hazard of the occurrence of persistent >6d difference were higher in the women with 20> FSH≥10IU/L (OR=1.87) and women with FSH≥20 IU/L (OR=3.58). Compared with the women with annual serum E2<80pg/ml, the hazard of the occurrence of persistent >6d difference in the women with E₂≥80pg/ml (OR=2.15).[Conclusion 2]1. These finds support the menstrual criteria for the onset of early MT proposed by ReSTAGE, and consider persistent >6d as acceptable criteria for the onset of early MT in women come from the community, but further study is needed.2. Among the women in whom the age at the marker≥45yr, the women with FSH≥20IU/L are more close to FMP. Annual serum FSH≥20 IU/L is not the essential criteria for the onset of late MT.3. For prevention, it is better to give concern to the women who has experience 1 cycle different from the previous cycle >6d.3.Annual serum FSH>10IU/L or E2≥80pg/ml in early follicular phase can be a auxiliary criteria, but not the essential criteria for the onset of early MT.Section II To assess the application of late MT criteria in clinicalpractice in gynecologic endocrinology[Objective]To evaluate of the application of cycle≥60d (the late MT criteria validated by Section I) in clinical practice of gynecologic endocrinology. [Specific Aims]1.Describe the age, serum FSH, E2 level, hot flash at the occurrence of cycle≥60d in the outpatient from the department of gynecologic endocrinology.2.Describe the age at FMP, the time from cycle≥60d to FMP in the outpatient from the department of gynecologic endocrinology. [Materials and methods]Retrospective cohort design was used in the present study. The out-patients who visited the department of gynecologic endocrinology in PUMC for cycle≥60d from Jan 2005 to Jan 2007 and had finished Menopause symptoms Scale and finished serum FSH, E₂ examination at least one time, were chosen for this study. The exclude criterions included pregnancy, with premature ovarian failure and in HT. 119 women were chosen from the medical records and were followed by telephone. Main measures included the age at amenorrhea≥60d, serum FSH and E₂ level, hot flash (in 2 weeks before visiting hospital), demographic information, menstrual history, disease history.[Statistics]All data were entered into database Epidata 3.02 and were analyzed by SPSS 13.0. Qualitative data were analyzed by frequency, proportion; quantitative data were analyzed by mean and standard deviation. The age at cycle≥60d and FMPwas calculated using K-M survival analysis. By using Cox model we assess the association between serum FSH, E₂ level, hot flash and the time to FMP.[Results 1]1. There were 74 women included in the analysis and 45 women lost (40 women were lost for the change of the telephone number and 5 women rejected to be followed). There was no significant difference between the women who were followed and who were lost.2. The mean age at cycle≥60d was 48.35±3.88 yr (42.17-57.83 yr). The mean of serum FSH level was 45.68±32.66 IU/L The mean of serum FSH level was 82.02±106.06 pg/ml. There were 62 (81.6%)women with hot flash.3. Until Jul 2009, there were 47 women with observed FMP, 24 women still menstruating and 3 women began HT. The mean age of FMP was 50.66±3.38yr.4. K-M estimates showed that the mean (median) age at FMP was 51.33 (52.22) yr and the mean time from cycle≥60d to FMP were 2.18 years. For the women in whom the age at cycle≥60d < 45yr the median time from cycle≥60d to FMP were 2.90 years, and for the women in whom the age at cycle>60d≥45yr the median time from cycle≥60d to FMP were 1.67 years. Among the women in whom the age at cycle≥60d≥45yr, the median time from cycle≥60d to FMP were 1.49 years in the women with serum FSH≥20 IU/L and 2.14 years in the women with serum FSH < 20 IU/L (P=0.15). Among the women in whom the age at cycle≥60d <45yr, the median time from cycle≥60d to FMP were 2.40 years in the women with serum FSH≥20 IU/L, while nobody was observed FMP in the women with serum FSH<20 IU/L the follow-up (the mean time were 2.9 years).5. The older the age at cycle≥60d were, the shorter the time to FMP were (OR=1.10). There was no significant association between serum FSH, E2 level, hot flash and the hazard of FMP.[Conclusion]1. In the clinical practice of gynecologic endocrinology, cycle≥60d is also feasible criteria for late MT, and the mean time from it to FMP are 2 years.2. Age and serum FSH level are influencing factors on the time from cycle≥60d to FMP.3. Serum FSH≥20 IU/L may be more informative for FMP in younger women in whom the age at cycle≥60d <45yr.