[Effect of shift work on menopausal age and menstruation span of professional women].

Objective: To explore the relationship between shift work and menopausal age and menstruation span of retired women. Methods: During July 2017 and October 2018, the research was performed by using cluster sampling in nine districts of Shenzhen City to select all permanent residents (3518 people) with Shenzhen household registration in which was equal to or over 60 years old from the Community Health Service Centers. The data of age, marital status, menopausal age, smoking, drinking, shift experience and shift years were collected. The relationship between shift work and menopausal age as well as menstruation span of professional women were analyzed by multivariate linear regression model. Results: There were 359 people (10.2%) in the shift experience group, the menopausal age was (49.71±3.63) years, and the menstrual period was (34.27±3.92) years. The non-shift experience group were 3159 people (89.8%) , the menopausal age was (50.20±3.60) years, and the menstrual period was (34.86±4.13) years. The differences of menopausal age and menstrual years between the two groups were statistically significant (P<0.05) . After adjusting for factors such as passive smoking and drinking, the results of the multiple linear regression model showed that menopausal age, menstrual years were negatively correlated with shift work (ß=-0.493, -0.575, P<0.05) . Conclusion: Shifts are related to women's menopausal age and menstrual years, and attention should be paid to the impact of work intensity and circadian rhythm on the occupational health of female employees.

[Influence of complex rehabilitation programs on the uterine blood flow in patients of different age after plastic surgery for rectocele]. / Vliyanie reabilitatsionnykh kompleksnykh programm na pokazateli matochnogo krovotoka po dannym 3D-ekhodopplerografii u patsientok raznykh vozrastnykh grupp posle plasticheskoi operatsii po povodu rektotsele.

OBJECTIVE: To develop the optimized complex programs, including general magnetotherapy, fractional microablative therapy with a CO2 laser, electromyostimulation with biofeedback of the pelvic floor muscles, and a special exercise therapy complex in late rehabilitation programs for women of different age after reconstructive plastic surgery for rectocele. MATERIAL AND METHODS: There were 200 women of childbearing, peri- and menopausal age with rectocele grade II-III and 20 healthy women of comparable age. All patients were divided into 4 groups by 50 womes: main group, two comparison groups and control group. Surgical treatment of rectocele was followed by long-term postoperative rehabilitation including symptomatic therapy, general magnetotherapy, and electromyostimulation with biofeedback of the pelvic floor muscles, intra-vaginal fractional microablative therapy with a CO2 laser and special complex of therapeutic physical education. RESULTS: General magnetotherapy in early (1 day) postoperative period and complex rehabilitation in long-term postoperative period (within a month after surgery) including 2 procedures of intra-vaginal microablative fractional therapy with carbon dioxide laser, electromyostimulation with biological connection of the pelvic floor muscles and special complex of therapeutic physical education ensured more significant improvement of uterine blood flow regardless age and baseline disorders in the uterine arteries in patients with rectocele. In our opinion, this is primarily due to vasoactive effects of general magnetotherapy, recovery of circulation via relief of spasm in the arteries and arterioles, improved vein contractility and venous outflow. These processes combined with electrical stimulation and therapeutic exercises of pelvic floor muscle followed by their reinforcement, as well as fractional microablative therapy ensured significant vascular effect.

Chinese women with 29-30 FMR1 CGG repeats have an earlier menopause.

Purpose: A strong, well-established non-linear relationship exists between fragile X mental retardation (FMR1) premutation and menopausal age. The aim of this study is to evaluate whether this relationship continues into the normal CGG repeat range.Methods:FMR1 CGG repeats of 111 Chinese postmenopausal women from a prospective cohort and the relationship with age at menopause were analyzed. Associations of FMR1 genotypes with annually measured estradiol and follicle stimulating hormone (FSH) levels were also assessed.Results: One premutation and two intermediate carriers were identified, with a prevalence of 0.90% and 1.80%, respectively. The age at menopause differed with statistical significance (p = 0.007) between women carrying bi-allelic 29-30 repeats (49.66 ± 3.26 years) and those carrying a different number of repeats (51.26 ± 2.74 years). Age at menopause among subgroups (≤28, 29-30, and ≥31 repeats) of alleles 1 and 2 were also different (p = 0.014, p = 0.044). FSH trajectories to final menstrual period differed between women with the bi-allelic 29-30 repeats and others (p = 0.019).Conclusions: Women with 29-30 FMR1 CGG repeats may experience menopause approximately 2 years earlier than those carrying ≤28 or ≥31 CGG repeats, and have a longer FSH fluctuant period.

A new corrective model to evaluate TBS in obese post-menopausal women: a cross-sectional study.

INTRODUCTION: The relationship between post-menopausal osteoporosis and obesity has been mainly investigated using bone mineral density (BMD) as marker of bone health. Since BMD does not reflect bone microarchitecture, another analytical tool, the Trabecular Bone Score (TBS), has been recently developed for this purpose. In this study, we intended to investigate the validity of TBS as marker of bone quality in obese post-menopausal women. METHODS AND MATERIALS: Three hundred fifty-two post-menopausal women were consecutively enrolled in the study and underwent anthropometric and dual-energy X-ray absorptiometry (DXA) examination. DXA-based BMD was used to classify subjects into osteoporotic (9%), osteopenic (58%), and controls (33%) categories. As TBS is sometimes sensitive to the effects of increased image noise with higher BMI, a corrected version of the TBS (TBS*) was also used to assess bone microarchitecture quality in this cohort. RESULTS: As expected, BMI was positively and negatively related to total BMD (r = 0.22, p < 0.0001) and TBS (r = - 0.12, p < 0.05), respectively. TBS* was found positively and significantly correlated with femoral neck BMD (r = 0.40, p < 0.001), total hip (r = 0.33, p < 0.001) and lumbar spine BMD (r = 0.50, p < 0.001). CONCLUSION: TBS, once removed the effect of BMI, can serve as a good surrogate maker of bone microarchitecture in obese post-menopausal women in addition to BMD.

[Myostimulating effect of comprehensive application of general magnetotherapy, fractional CO2 laser, electro-myostimulation and special complex of exercise in patients with rectoceleal after open-peconstructure]. / Miostimuliruyushchii effekt kompleksnogo primeneniya obshchei magnitoterapii, fraktsionnogo CO2-lazera, elektromiostimulyatsii i spetsial'nogo kompleksa LFK u patsientok s rektotsele posle rekonstruktivno-plasticheskikh operatsii.

The article presents data on the treatment of 200 women of childbearing, peri - and menopausal age with rectocele of II-III degree, which were divided into 4 groups comparable in clinical and functional characteristics: 1-50 patients who, after surgical treatment of rectocele, underwent a complex consisting of a course of General magnetic therapy, 2 intra-vascular procedures of fractional microablative CO2 laser therapy, electromyostimulation with the pelvic floor muscles and a special complex of therapeutic physical education; comparison 1, which included 50 patients who underwent the above-mentioned complex of rehabilitation measures without General magnetotherapy; comparison of 2-50 patients after surgical treatment of rectocele, who in the late postoperative period (one month after the operation) underwent a set of rehabilitation measures, including a course of electromyostimulation with the biological connection of the pelvic floor muscles, consisting of 10 daily procedures and a special complex of physical therapy and a control group - 50 patients after surgical treatment of rectocele, who in the late postoperative period were treated with symptomatic therapy, including painkillers and antispasmodics, which served as a background for all other groups. As a result of the research, it was found that the developed rehabilitation complexes have a pronounced myostimulating effect, and can be recommended for wide use in rehabilitation programs for postoperative management of patients with rectocele.

[Influence of various rehabilitation complexes on sexual function in fertile females and women of perimenopausal and menopausal age after surgery for rectocele]. / Otsenka vliyaniya razlichnykh reabilitatsionnykh kompleksov na seksual'nuyu funktsiyu u patsientok detorodnogo i perimenopauzal'nogo i menopauzal'nogo vozrasta posle operatsii po povodu rektotsele.

OBJECTIVE: To study the effect of general magnetotherapy, muscle stimulation with biofeedback of pelvic floor muscles, and a special complex of physiotherapy exercises with and without fractional microablative CO2-laser therapy on sexual status in females after plastic surgery for rectocele. MATERIAL AND METHODS: There were 200 fertile females and women of perimenopausal and menopausal age with rectocele grade II-III. Various rehabilitation programs were used in delayed postoperative period in order to improve sexual function. Rehabilitation included various combinations general magnetotherapy, electrical muscle stimulation with biofeedback of pelvic floor muscles, intravaginal fractional microablative CO2-laser therapy and a special complex of exercise therapy. RESULTS AND CONCLUSION: Postoperative rehabilitation including general magnetotherapy, fractional microablative CO2-laser therapy, muscle stimulation with biofeedback of pelvic floor muscles and a special exercise therapy significantly improves sexual function in patients with rectocele. This is true for fertile females and women of perimenopausal and menopausal age. Significant data on PISQ-12 questionnaire (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire) and Female Sexual Function Index of (FSFI) confirmed these results.

SCD1 methylation in subcutaneous adipose tissue associated with menopausal age.

Objective: This study was designed to investigate associations between menopausal age and the DNA methylation levels of stearoyl-coenzyme A desaturase 1 (SCD1, selected by the Illumina Human Methylation 450 K Bead Chip) and explore the changes in mRNA levels of SCD1 and DNA methyltransferases (DNMTs) in response to estrogen replacement therapy (ERT). Methods: In the human experiment, we performed subcutaneous adipose tissue DNA extraction on 85 menopausal women. Methylation of SCD1 was measured by MethyLight polymerase chain reaction. In the rat experiment, we established models of menopause (ovariectomy group) and ERT (ovariectomy + 17ß-estradiol group). The mRNA levels of SCD1, DNMT1, DNMT3A, and DNMT3B were determined. Results: The results showed that DNA methylation of SCD1 was inversely correlated with menopausal age (r = 0.370, P < 0.001). In the rat study, the mRNA levels of SCD1 decreased (P < 0.001) and those of DNMT3A (P < 0.001) and DNMT3B increased (P < 0.001) after ERT. Conclusion: Methylation levels of SCD1 were significantly associated with menopausal age. DNMT3A and DNMT3B may be involved in the methylation of SCD1.

Higher menopausal age but no differences in parity in women with polycystic ovary syndrome compared with controls.

INTRODUCTION: To address the question of whether women with polycystic ovary syndrome (PCOS) reach menopause later than age-matched controls, we conducted a follow-up cohort study of women with well-characterized PCOS that was diagnosed 24 years ago. The hypothesis was that women with PCOS would reach menopause later than non-PCOS women. Parity during these 24 years was also studied. MATERIAL AND METHODS: Twenty-seven women diagnosed with PCOS in 1992 (mean age 29.5 years) were re-examined in 2016 (mean age 52.4 years). Randomly selected women, n = 94 (mean age 52.4 years), from the same geographic area included in the World Health Organization MONICA study, Gothenburg, Sweden, served as controls. RESULTS: The mean menopausal age in women with PCOS was higher than in controls (53.3 ± 2.2 years vs 49.3 ± 3.5 years, P < 0.01). Serum-follicle stimulating hormone levels were lower in the PCOS women than in controls (31.0 ± 28.1 IU/L vs 52.3 ± 37.7 IU/L, P = 0.01). There was no difference in parity between women with PCOS (1.9 ± 1.3 children, range 0-4) and controls (1.7 ± 1.0, range 0-4 children). CONCLUSIONS: Women with PCOS reached menopause 4 years later and had lower serum-follicle stimulating hormone compared with age-matched controls. Neither parity nor nulliparity differed between women with PCOS and controls.

Influence of the frequency of consumption of foodstuffs on the risk of overweight and obesity in a group of post-menopausal women.

INTRODUCTION: A noticeable change during the post-menopausal period is a modification of nutritional behaviors. The aim was to study the frequency of consumption of specific foodstuffs by post-menopausal women. Additionally, the influence of nutritional behaviors on the risk of overweight and obesity among post-menopausal women was assessed. MATERIAL AND METHODS: The study was conducted among 103 post-menopausal women in Poland in January to July 2016. It was a nationally recruited sample. To determine the frequency of consumption of foodstuffs the validated Food Frequency Questionnaire (FFQ-D10) was used. Additionally, socio-economic data were gathered and anthropometric examinations were carried out. Finally, multivariate logistic regression was performed and odds ratios (ORs) and 95% confidence intervals (CIs) were computed. RESULTS: The results showed that the most frequently consumed products included: vegetables, fresh and dried fruits, sausages and cold meats, refined and unrefined cereal products, milk and milk drinks, sweets, potatoes, cheeses and meat, butter, creams, and oil. The studied women reported no change in nutritional preferences and nutritional behavior during the post-menopausal period but 75% of surveyed women noticed a body weight change. The analysis of products' consumption frequency did not reveal any actual impact on increased risk of becoming overweight or obese in the studied group of women (OR [95% CI], p > 0.05). CONCLUSIONS: The development of overweight and obesity probably did not depend on the frequency of consumption of foodstuffs; however, the place of residence and professional activity could be significant.

Standards for thyroid laboratory testing, and cognitive functions after menopause.

INTRODUCTION: The aim of the study is to analyze the relationship between normative and non-normative thyroid tests (TSH, TT4, TT3, FT3, FT4, anti-TPO, anti-Tg, AB-TSHR) and the level of cognitive functions in postmenopausal women. MATERIAL AND METHODS: The study group consisted of 383 women from south-eastern Poland, aged 50-65 years. The cognitive functions were evaluated using a diagnostic instrument - Central Nervous System - Vital Signs (CNS-VS). Blood was collected for determination of the following parameters: TSH, TT4, TT3, FT3, FT4, anti-TPO, anti-Tg, AB-TSHR. RESULTS: There were significant differences in NCI, executive functions, psychomotor speed, reaction time, complex attention and cognitive flexibility, depending on the normative and non-normative level of TSH. Women whose level of FT3 was at the lower limit of the normal range obtained poorer results in psychomotor speed, while subjects with levels of FT4 below the standard achieved significantly lower scores for this function. The relationship between NCI and cognitive functions, and the normative and non-normative anti-TPO results, showed significant differences in verbal memory, visual memory, processing speed and reaction time. The level of AB-TSHR reported as normal or above the norm significantly differentiated from the results of NCI, processing speed, executive functions, psychomotor speed, complex attention and cognitive flexibility. CONCLUSIONS: Concentrations of laboratory parameters assessing the thyroid function located within the upper limits of the normal range showed a different relationship with the cognitive performance than concentrations located within the lower limits of the standard.

The menopausal age and associated factors in Gorgan, Iran.

BACKGROUND: Considering the physical, emotional and psychological complications of early or delayed menopause on women's life, it is necessary to determine associated factors of menopause age. This study designed to determine menopausal age and associated factors in women of Gorgan, i.e. the capital of Golestan province in the north-east of Iran. METHODS: In this cross-sectional study, 804 menopausal women in Gorgan were selected via two-stage sampling method in 2009. The study included only women who had undergone natural menopause and had their last menstrual bleeding at least one year before. Data were gathered through structured questionnaire that included individual characteristics, socioeconomic characteristics, menstrual and fertility characteristics and climacteric complaints. Socioeconomic status was defined using principal component analysis. Data were analyzed with T-student's and ANOVA tests using SPSS version 16 (SPSS Inc, Chicago, IL, USA) for Windows. RESULTS: The mean menopause age was 47.6±4.45 years with the median age of 48 years. The mean menopause age in women with first pregnancy before 30 years (47.58±4.47years), without pregnancy (46.26±4.90years) and without delivery (46.30±4.47 years) was significantly lower than others (p<0.01). The mean menopause age was lower in single women (46.6±2.80 years), with low income level (47.7±4.39 years) and smokers (47.6±4.45 years) compared to others; but these differences were not statistically significant (p>0.05). Socioeconomic status was not associated significantly with menopause age (p>0.05). CONCLUSION: This study illustrated that menstrual and fertility factors have influence on menopausal age while socioeconomic factors were not effective.

Factors predicting age at menopause among Iranian women in the Bandare-Kong cohort study (a cross-sectional survey of PERSIAN cohort study).

BACKGROUND: Menopause is a natural period in women's life and can be affected by several factors. The aim of this study was to identify the associated factors for age of natural menopause and among women with early and premature menopause based on a cohort study in Iran. METHODS: This population-based study was conducted on 894 post menopause women between 35 and 70 years old who participated in the Bandare-Kong Non-Communicable Diseases (BKNCD) Cohort Study, a part of Prospective Epidemiological Research Studies in Iran (PERSIAN) from March 2016 to February 2019. All women completed a standard self-reported questionnaire. Data were analyzed using chi-square test, independent t test, and ANOVA as well as a multivariable linear regression model. RESULTS: The mean age at natural menopause was 48.31 ± 6.34 years. After adjusting other variables, gravida, history of cardiac disease, socioeconomic status and residence status were predictive of age at menopause (P < 0.001). Among the premature menopause group, the mean age at menopause was significantly higher among women with diabetes compared to women without diabetes group (35.68 ± 2.92 vs. 33.82 ± 3.06; P = 0.043), while the mean age at menopause was significantly lower in women with infertility compared to women without infertility (29.13 ± 5.22 vs. 34.84 ± 2.826; P = 0.048). CONCLUSIONS: This study suggests that the predictors of menopausal age differed in women with premature menopause compared to overall menopause age. Prospective studies are needed to evaluation the effects of these factors on menopausal age.

STop OVarian CAncer (STOPOVCA) young: Protocol for a multicenter follow-up study to determine the long-term effects of opportunistic salpingectomy on age at menopause.

BACKGROUND: Opportunistic salpingectomy comprises additional bilateral salpingectomy during abdominal surgery as a prophylactic method to reduce the risk of ovarian cancer. However, opportunistic salpingectomy may potentially damage (micro)blood circulation to the ovaries, resulting in earlier onset of menopause. PRIMARY OBJECTIVE: To evaluate the long-term effects of opportunistic salpingectomy on the onset of menopause in women who underwent sterilization through salpingectomy compared with a control group who underwent sterilization by tubal ligation or no surgery at all. STUDY HYPOTHESIS: Opportunistic salpingectomy does not lower the mean age at onset of menopause. TRIAL DESIGN: In a multicenter observational noninferiority study, we will prospectively compare the age at menopause of women initially aged 35-45 who underwent sterilization through opportunistic salpingectomy with a similarly aged control group who underwent sterilization by tubal ligation or no sterilization. Participants will be asked to complete an annual questionnaire on onset of menopause to eventually determine whether there is more than a one-year decrease in mean age at onset of menopause in the opportunistic salpingectomy group. Follow-up will last until determination of menopause, with a maximum of 15 years. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: pre-menopausal; age between 35 and 45; intact ovaries. EXCLUSION CRITERIA: post-menopausal; previous bilateral salpingectomy or oophorectomy; previous hysterectomy; abnormal karyotype; previous or current chemotherapy or pelvic radiation. PRIMARY ENDPOINT(S): Determination of age of menopause measured by annual questionnaire. SAMPLE SIZE: 1200 (400 intervention group; 800 control group). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated that recruitment will be completed by 2023 and results will be published by 2039. GOV IDENTIFIER: NCT04757922 PROTOCOL VERSION: : Version 1, February 2021.

The effect of opportunistic salpingectomy for primary prevention of ovarian cancer on ovarian reserve: a systematic review and meta-analysis.

BACKGROUND: Opportunistic salpingectomy (OS) is an attractive method for primary prevention of ovarian cancer. Although OS has not been associated with a higher complication rate, it may be associated with earlier onset of menopause. OBJECTIVE: To provide a systematic review and meta-analysis of the effect of OS on both age at menopause and ovarian reserve. METHODS: A search was conducted in the Cochrane Library, Embase and MEDLINE databases from inception until March 2022. We included randomized clinical trials and cohort studies investigating the effect of OS on onset of menopause and/or ovarian reserve through change in anti-Müllerian hormone (AMH), antral follicle count (AFC), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Data was extracted independently by two researchers. Random-effects meta-analyses were conducted to estimate the pooled effect of OS on ovarian reserve. RESULTS: The initial search yielded 1047 studies. No studies were found investigating the effect of OS on age of menopause. Fifteen studies were included in the meta-analysis on ovarian reserve. Meta-analyses did not result in statistically significant differences in mean change in AMH (MD -0.07 ng/ml, 95%CI -0.18;0.05), AFC (MD 0.20 n, 95 % CI -4.91;5.30), E2 (MD 3.97 pg/ml, 95%CI -0.92;8.86), FSH (MD 0.33mIU/ml, 95%CI -0.15;0.81) and LH (MD 0.03mIU/ml; 95%CI -0.47;0.53). CONCLUSION: Our study shows that OS does not result in a significant reduction of ovarian reserve in the short term. Further research is essential to confirm the absence of major effects of OS on menopausal onset since clear evidence on this subject is lacking. Registration number PROSPERO CRD42021260966.

The epidemiology of atrial fibrillation in Chinese postmenopausal women and its association with age of menopause.

OBJECTIVES: To investigate the epidemiology of atrial fibrillation (AF) in postmenopausal women and to evaluate the association between age of menopause and AF. STUDY DESIGN: A total of 9117 postmenopausal women were selected from a cross-sectional study conducted among the general population of north-east China from September 2017 and March 2019. MAIN OUTCOME MEASURES: AF was diagnosed according to self-reported medical history of AF and/or current ECG findings. The epidemiology of AF including prevalence, awareness, use of anticoagulants and cardiovascular risk factors in postmenopausal women were carefully assessed. The association between age of menopause and AF was evaluated by stepwise logistic regression. RESULTS: The prevalence of AF was up to 1.1 % (95 % CI, 0.9 %-1.3 %) in postmenopausal women, but the awareness of it was 61.2 %. The proportion of AF patients requiring treatment with an oral anticoagulant (OAC) was as high as 87.8 % according to CHA2DS2-VASc score, while only 5.8 % of them received it. The prevalence of cardiovascular risks factors was high among postmenopausal women with AF, but awareness, treatment and control of these comorbidities were unacceptably low. Compared with the women with premature menopause (< 45 years), participants reporting onset of menopause at 50-54 years had a significantly lower risk of AF (OR 0.49, 95 % CI 0.27-0.91). CONCLUSIONS: The widespread use of OAC and the control of cardiovascular risk factors in postmenopausal women with AF was of great significance in preventing AF-related stroke. The history of premature menopause provided a reliable opportunity for primary prevention of AF.

Menarche age exceed 17 years and menopausal age smaller than 48 years may affect prevalence of osteoporosis for Chinese women.

In this work, we used a cross-sectional study to evaluate influence of menarche age, menstrual cycle, menstrual period, menopausal age, and menopause years for osteoporosis in women from China. We found that different menarche age, menstrual cycle, menopausal years, and menopausal age are related with the prevalence of osteoporosis. However, menarche age exceeds 17 years and menopausal age smaller than 48 years are risk factors for osteoporosis in women. STUDY DESIGN: A cross-sectional, population-based study. PURPOSE: The purpose of this study was to explore relationship between prevalence of osteoporosis and menarche age, menstrual cycle, menstrual period, menopausal age, and menopause years for women. METHODS: From March to October 2016, the cluster sampling method was used to conduct an osteoporosis-related questionnaire survey on women aged 40-80 in two communities in Lanzhou City, Gansu, China, and bone mineral density(BMD)was carried out using the DTX-200 dual-energy X-ray absorptiometer produced by the US OSTEOMETER company. The relationship between prevalence of osteoporosis and menarche age, menstrual cycle, menstrual period, menopausal age, and menopause years were analyzed using logistic regression analysis. RESULTS: There were 2224 female participates enrolled in this study and average age was 61.60 ± 8.05 years and total rate of prevalence was 32.73%; among them, different menarche age, menstrual cycle, menopausal years, and menopausal age have statistical differences with the prevalence of osteoporosis, but there is no statistical difference between different menstruation and the prevalence of osteoporosis. Single logistic regression analysis found that older menarche age, earlier menopausal age, and longer menopausal years were related factors for the prevalence of osteoporosis, while menarche age exceed 17 years and menopausal age smaller than 48 years are risk factors for osteoporosis for women in multivariate regression analysis. CONCLUSIONS: In China, ages at menarche and menopause are associated with prevalence of osteoporosis. Later, menarche and earlier menopause are associated with higher osteoporosis risk. Menarche and menopause history may help identify women with increased risk of developing osteoporosis.

Comparison between Different Diagnostic Strategies in Low-Risk Reproductive Age and Pre-Menopausal Women Presenting Abnormal Uterine Bleeding.

Abnormal uterine bleeding (AUB) is a common symptom in the female population, with an estimated prevalence of 10 to 30% in fertile age and up to 90% in perimenopausal women. In most cases, AUB is due to a benign cause. However, it can also be a symptom of atypical endometrial hyperplasia or endometrial cancer, a more common disease during menopause which can also affect women in their reproductive age. Considering the high prevalence of this symptom an appropriate diagnostic algorithm is needed. Concerns about the risks, pain, and stress associated with an endometrial biopsy and its impact on the healthcare system make the choice of AUB diagnostic strategy extremely relevant. Even if the scientific community agrees on the definition of AUB, International Guidelines show some differences in the management of women of reproductive age with AUB, especially regarding the age cut-off as an independent indication for endometrial biopsy. This study compared different diagnostic strategies to identify a diagnostic pathway with high sensitivity and specificity but low impact on the health system's resources. The analysis was based on three diagnostic algorithms defined as part of the guidelines of leading scientific societies. Women of reproductive age with AUB (n = 625) and without risk of endometrial cancer were included in the study. Results showed that the best criterion to investigate AUB in women at low risk of endometrial cancer is not age cut-off but the presence or absence of focal endometrial pathology at the ultrasound and the response to the progestin therapy. This approach makes it possible to perform fewer outpatient hysteroscopic biopsies without excluding positive cases from the examination.

The association between diabetes and age at the onset of menopause: a systematic review protocol.

BACKGROUND: Age at the onset of menopause is the most important determinant of women's future health outcomes. While the basic mechanisms contributing to the onset of menopause are still not fully understood, age at menopause depends on a complex set of various factors. In this regard, the effects of diabetes (DM I/II) on the age at the onset of menopause have received little attention. METHODS AND ANALYSIS: Electronic databases including PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and Google Scholar will be searched for articles published during January 2000 to August 2018 and containing combinations of related MeSH terms, i.e., "age at menopause" and "diabetes." Additional studies will also be extracted from the reference lists of the selected papers, gray literature, and key journals in the field. A set of inclusion criteria will be defined, and all eligible observational studies will be included. Two reviewers will independently conduct the study selection, data extraction, and quality assessment of the selected studies. All cases of disagreement will be resolved through consensus. The methodological assessment of the primary studies will be performed based on the Newcastle-Ottawa Scale (NOS). In case of the availability of sufficient data, fixed or random effects models will be used to combine all data. Heterogeneity will be assessed by I 2 statistic and chi-square test. Stata V.11.1 will be used for data analysis (CRD42017080789). ETHICS AND DISSEMINATION: This systematic review will not raise any ethical issues. Journal publication and conference presentations will facilitate the wide dissemination of the findings to relevant clinicians and researchers.

Repetitive Element DNA Methylation is Associated with Menopausal Age.

To investigate associations between the age of menopause and the DNA methylation levels of two repetitive elements, Alu and LINE-1, we performed plasma DNA extraction on 161 subjects and serum cell-free DNA extraction on 120 subjects. We grouped women by menopausal age as follows: ≤ 48 years (earlier menopause), ≥ 52 years (later menopause), and 48-52 years (control). The DNA methylation levels of Alu and LINE-1 were measured by MethyLight PCR. The results showed that the DNA methylation levels of both Alu and LINE-1 were inversely correlated with menopausal age in the plasma DNA cohort (r = 0.079, P < 0.001 for Alu; r = 0.045, P = 0.007 for LINE-1) as well as in the serum DNA cohort (r = 0.087, P = 0.001 for Alu; r = 0.041, P = 0.026 for LINE-1). Alu methylation levels in both the plasma and serum DNA cohorts and LINE-1 methylation levels in the plasma cohort were remarkably higher in the earlier menopause group than in the later menopause and control groups (P < 0.01 and P < 0.05, respectively). In the serum DNA cohort, the LINE-1 methylation levels in the later menopause group were significantly lower than that in the earlier menopause group and control group (P < 0.05). Therefore, methylation levels of Alu and LINE-1 were significantly associated with menopausal age. Women with earlier menopause showed hypermethylation in both repetitive elements, while women with later menopause showed hypomethylation. These findings suggest that altered DNA methylation in leukocytes and serum cell-free DNA may represent a biomarker of menopausal age.