Polymorphisms of the CYP1B1 gene may be associated with the onset of natural menopause in Chinese women

The Cytochrome P450 1B1 (CYP1B1) is one of the major CYP450 enzymes catalyzing 4-hydroxylation, an important elimination step for estrogens. Relatively little is known, however, about the impact of this gene on the onset and cessation of menstruation, which are significant milestones in a woman's life and predictors of many hormone related diseases. In this report, we described the association of four SNPs in the CYP1B1 gene, Arg48Gly, Ala119Ser, Leu432Val, and Asp449Asp, with the ages of menarche and menopause, years of menstruation and total number of menstrual cycles. Included in the study were 1958 community controls from two recently completed population-based case-control studies of breast cancer and endometrial cancer. No association was observed between the CYP1B1 polymorphisms and the age of menarche among either pre- or post-menopausal women. Among the women who experienced natural menopause, the three non-synonymous SNPs were significantly associated with menopausal age, years of menstruation, and total number of menstrual cycles. The Gly and Ser alleles of Arg48Gly and Ala119Ser were associated with later menopause, more years of menstruation and more menstrual cycles, while women with allele Val at Leu432Val had a 0.9 year earlier menopause, 1.0 year shorter reproductive span, and 12.6 fewer menstrual cycles than those women without this allele. In conclusion, the results from this study suggested that CYP1B1 genetic polymorphisms may be associated with the natural onset of menopause.     

The timing of natural menopause in Poland and associated factors

OBJECTIVES: The outcome of interest was the assessment of age at natural menopause and the variables hypothesized as covariates of age at menopause were indicators of demographic and social status, characteristics of the reproductive history and lifestyle behaviour. METHODOLOGY: Seven thousand one hundred and eighty-three women from all social strata of non-clinical population, and aged between 35 and 65 years were investigated in cross-sectional survey across Poland in 2000-2004. The demographic, social, lifestyle behaviour and reproductive history aspects of the menopause-specific questionnaire were examined. The non-parametric Kaplan-Meier cumulative survivorship estimates were used to assess the timing of natural menopause. Univariate and multivariate Cox proportional hazards regression models were used to assess the association of age at natural menopause with factors of interest and to estimate relevant relative risk (the hazard ratio) for earlier age at menopause. RESULTS: The overall median age at natural menopause was 51.25 years; 25th percentile 49; 75th percentile 54 years. Temporal changes in age at menopause were not demonstrated in the sample (p=0.9 for differences among age cohorts). Univariate Cox models were first fitted to the age at natural menopause for all covariates singly. The findings revealed that marital status, living environment, employment, BMI, age at first live birth delivered by a woman, breastfeeding, physical activity, smoking amount, and consumption of alcohol were not associated with age at menopause (p>0.05). The multiple Cox model revealed that early menarche, short menstrual cycle length, smoking cigarettes, a low level of education, and a negative health perception were associated with younger age at menopause (p<0.01). Use of oral contraceptives and parity were associated with later menopause (p<0.01). CONCLUSION: The present study provides an estimate of median age at natural menopause in Poland that may be used as a measure of health for the growing number of Polish women whose survival is calculated at 30 years after menopause. This study has revealed that the pattern of relationship between age at menopause and the study factors reflects its population-specific character for its social and cultural backgrounds, socio-economic status, and social behaviours.     

Early menarche and premature natural menopause in Indonesia

Background: An association has been suggested between early menarche and premature natural menopause. However, existing studies in developed countries show mixed findings.

Aim: This study examined whether early menarche (first menstrual period ≤11 years old) is a factor for premature natural menopause (final menstrual period <40 years old) in the context of a developing country.

Subjects and methods: Data came from the Indonesia Family Life Survey (IFLS) 2014, which consists of 1608 post-menopausal women.

Results: Results of hierarchical logistic regression show that women who experienced early menarche (first menstrual period ≤11 years old) were found to be at higher risk of premature natural menopause (β?=?0.94, p?<?0.01, CI?=?0.24–1.63). The results are robust against potential confounding factors including individual reproductive history, lifestyle and sociodemographic characteristics, as well as unobserved factors at the household and community levels.

Conclusion: The findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with premature natural menopause.     

Factors associated with premature ovarian failure, early menopause and earlier onset of menopause in Japanese women

Objective

The purpose of this study is to clarify the median age at natural menopause and the proportions of women with premature ovarian failure (POF) and early menopause (EM) by using Kaplan–Meier cumulative estimates and differences in reproductive and lifestyle factors associated with POF, EM and median age at menopause in a large population of Japanese women.

Subjects and methods

This study is a cross-sectional analysis of the Japan Nurses’ Health Study (JNHS). We analyzed data for 24,152 pre- and postmenopausal women who were 40 years or older at the JNHS baseline survey.

Results

The overall estimated median age at natural menopause was 52.1 years, and the proportions of women with POF and EM were 0.28% and 1.67%, respectively. Older generation, cigarette smoking, low body mass index, regular menstruation cycles at 18–22 years of age, nulliparity and unilateral oophorectomy were associated with earlier onset of natural menopause.Only unilateral oophorectomy was associated with increased risk of POF, and nulliparity and unilateral oophorectomy were associated with increased risk of EM.

Conclusion

Unilateral oophorectomy is a common factor associated with earlier onset of menopause, EM and POF, although other reproductive and lifestyle factors are not associated with POF or EM.     

Factors associated with the age of natural menopause and menopausal symptoms in Chinese women

ObjectiveTo investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.Study designIn this cross-sectional study, a total of 20,275 women (40–65 years) attending health screening in Jiangsu Province of China were enrolled. A structured questionnaire was used to collect data of demographics, menopausal status, chronic diseases, reproductive history, etc. Also we evaluated the severity of menopausal symptoms by Kupperman menopause index (KMI).Main outcome measureMenopausal age and scorings of Kupperman menopause index.ResultsThe overall median age at natural menopause was 50 years. Lower educational level, poor economic status, lower body mass index (BMI), age at menarche less than 14 years, nulliparity and smoking were associated with earlier onset of natural menopause (P < 0.05). The most frequently symptoms in postmenopausal women were sexual problems (57.05%), muscle/joint pain (53.29%) and insomnia (51.02%), while fatigue, insomnia and muscle/joint pain were predominant symptoms in pre- and peri-menopausal women. After adjusting for confounding factors, logistic regression analysis revealed that women with poor educational background, low income, divorce, higher BMI, higher parity, smoking and chronic diseases presented higher KMI scores (P < 0.05).ConclusionThe study provided an estimate of median age at natural menopause in Chinese women. The main factors contributing to earlier onset of menopause and severity of menopausal symptoms were lower educational level, poor economic status, and smoking. Thus, this study provides important insights for physicians to prevent and treat menopause related symptoms.     

Factors associated with the age of natural menopause and menopausal symptoms in Chinese women

Objective

To investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.

Study design

In this cross-sectional study, a total of 20,275 women (40–65 years) attending health screening in Jiangsu Province of China were enrolled. A structured questionnaire was used to collect data of demographics, menopausal status, chronic diseases, reproductive history, etc. Also we evaluated the severity of menopausal symptoms by Kupperman menopause index (KMI).

Main outcome measure

Menopausal age and scorings of Kupperman menopause index.

Results

The overall median age at natural menopause was 50 years. Lower educational level, poor economic status, lower body mass index (BMI), age at menarche less than 14 years, nulliparity and smoking were associated with earlier onset of natural menopause (P < 0.05). The most frequently symptoms in postmenopausal women were sexual problems (57.05%), muscle/joint pain (53.29%) and insomnia (51.02%), while fatigue, insomnia and muscle/joint pain were predominant symptoms in pre- and peri-menopausal women. After adjusting for confounding factors, logistic regression analysis revealed that women with poor educational background, low income, divorce, higher BMI, higher parity, smoking and chronic diseases presented higher KMI scores (P < 0.05).

Conclusion

The study provided an estimate of median age at natural menopause in Chinese women. The main factors contributing to earlier onset of menopause and severity of menopausal symptoms were lower educational level, poor economic status, and smoking. Thus, this study provides important insights for physicians to prevent and treat menopause related symptoms.     

Replication of loci influencing ages at menarche and menopause in Hispanic women: the Women's Health Initiative SHARe Study

Several genome-wide studies have identified loci associated with reproductive traits, such as ages of menarche and menopause, in women of European ancestry. In this study, we investigated the relevance of these loci in minority US Hispanic women. We utilized data from 3468 women who were genotyped as a part of the Women's Health Initiative SNP Health Association Resource. We replicated associations of eight loci (LRP18, LIN28B, CENPW, INHBA, TMEM38B, ZNF483, NFAT5 and OLFM2) with age at menarche, and of two loci (MCM8 and BRSK1/TMEM150B) with age at menopause. The MCM8 locus was also associated with early menopause risk. Three loci (CENPW, MCM8 and BRSK1/TMEM150B) were associated with the length of reproductive lifespan. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in minority US Hispanic women.     

Ages at menopause and menarche in a high-altitude Himalayan population

Women in a Tibetan speaking population living at 3250-3560 m in Upper Chumik, Nepal, have median ages at menopause and menarche of 46.8 and 16.2 years, respectively, assessed by the status quo technique. Recalled ages at menopause and menarche yield similar results and suggest a long-term existence of a pattern of relatively accelerated age at menopause and delayed age at menarche. Variation in the length of the calculated biological reproductive span in this sample is more strongly associated with recalled age at menopause than recalled age at menarche. The age at menopause in Upper Chumik is accelerated relative to that reported for Western industrial populations; however, these data do not permit drawing conclusions about the reasons underlying the acceleration.     

Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population

Objectives

Timing of menopause affects postmenopausal health risks. The objective of this study was to evaluate the associations of the single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR)-related genes (PPARD, PPARG, and PPARGC1A) and environmental factors with timing of natural menopause among the general Japanese population.

Study design

We analyzed cross-sectional data from 1758 women aged 40–69 years who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.

Main outcome measures

Associations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models.

Results

Lower body mass index and later age at menarche were significantly associated with earlier natural menopause. Women with minor alleles at T-48444C in PPARD showed a significantly higher adjusted hazard ratio of 1.57 (95% confidence interval: 1.18–2.10) for earlier natural menopause. In contrast, women with minor alleles at Thr394Thr in PPARGC1A showed a significantly lower adjusted hazard ratio of 0.86 (0.76–0.97) for earlier natural menopause. These associations did not substantially alter when re-analyzed after excluding the subjects who self-reported a history of diabetes or the subjects whose age was more than 65 years.

Conclusions

Gene variants in PPARD and PPARGC1A might be associated with timing of natural menopause, probably through direct actions on the ovaries, among the general Japanese population.     

Factors associated with elective Norplant removal in black and white women.

Premature removal of contraceptive implants (Norplant [levonorgestrel implants], Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a cause of a sizable national medical expenditure in the United States. Understanding the factors that influence the decision to remove the implants and being able to predict which users are likely to elect discontinuation prematurely could provide useful information for counseling patients as they are considering contraceptive implants so that potentially enormous long-term savings could be achieved. This study surveyed 98 women who had Norplant inserted and removed between January 1991 and December 1994. Data were collected from chart review, and when necessary, a questionnaire was used to extract information not found in the chart. The chi-squared statistic and t-test were used to compare demographic variables. All but one subject received comprehensive pre-implant counseling. The main reason given for electively removing the Norplant prematurely was irregular menstrual bleeding (60%). Pre-implant counseling did not influence the decision for removal. These results indicate the importance of clarifying patients'' doubts regarding menstrual bleeding irregularities during follow-up visits rather than relying on the information patients received during preimplant counseling.     

Season of birth influences the timing of menopause

BACKGROUND: Seasons may influence prenatal growth and future fertility. This study investigated whether season and month of birth influenced the timing of menopause in a group of women attending three Italian menopause clinics. METHODS and RESULTS: Age at menopause of 2822 post-menopausal women (>12 months of amenorrhoea) was stratified by month and season of birth. Mean age at menopause was 49.42 years (SEM: 0.78 years). Menopause occurred earlier for women born in the spring (age 49.04+/-0.15 years) than in the autumn (49.97+/-0.14 years). The earliest menopause was found in women born in March (48.9+/-0.25 years) and the latest in women born in October (50.3+/-0.25 years). The effect of season of birth on age at menopause remained even when considering factors that in our analysis were capable of significantly interfering with the timing of menopause, such as age at menarche, body mass index, smoking habit, level of education and type of job. CONCLUSIONS: Taking into consideration the retrospective design of the study, and a possible recall bias, the present data seem to suggest that environmental factors linked to seasons are capable of interfering with the timing of a woman's ovarian exhaustion by an action exerted in the prenatal period.     

Adiposity and age of menarche in Hispanic women

Women with increased adiposity have been shown to have earlier menarche. However, the association between menarche and body fat distribution has been controversial. The present study examined relationships between several anthropometric data and age at menarche in 2,494 women aged 25 to 74 years from the Hispanic Health and Nutrition Examination Survey. Early menarche was similarly related to adiposity as measured by body mass index (BMI), skinfolds representative of central adiposity (subscapular and iliac), and skinfolds representative of peripheral adiposity (triceps and calf). These relationships persisted after controlling for a variety of influences such as socioeconomic status; they were consistent in all three ethnic groups studied, but were significant only in Puerto Rican women. Ratios of central/peripheral skinfold measures were not associated with menarche. These analyses describe the relationship between early maturation and overall adiposity in three distinct Hispanic groups and reject a specific association between menarche and central body fat distribution.     

Splenic white pulp and associated vascular channels in chicken spleen

We have studied the chicken spleen by light and transmission electron microscopy. Germinal centers are located at the beginning of the central artery which is surrounded by the periarterial lymphatic sheath (PALS). The central artery has no branch crossing the PALS, and there is no histologically identifiable marginal zone in the chicken spleen. The central artery continues as penicilliform capillaries. The mid-portion of the penicilliform capillary is surrounded by the ellipsoid or Schweigger-Seidel sheath. The endothelial lining of this part of the pencilliform capillary contains small channels, formed between neighboring endothelial cells, which enter the ellipsoid. These channels allow circulating substances to accumulate in the ellipsoid. The cells of the ellipsoid are reticular cells, round or ovoid in shape, exhibiting a limited number of cell junctions. At the surface of the ellipsoid are ellipsoid-associated cells (EAC) which have an affinity for toluidine blue. After perfusion fixation, the majority of the cells in the ellipsoid are lost; this suggests weak cellular connections between the ellipsoid cells. The ellipsoid-associated cells remain in loco. On the basis of their shape and cytological features, two stages of EACs can be distinguished. The round or ovoid EACs elaborate active Golgi zones surrounded by numerous small vesicles containing an electron-dense substance. Occasionally, mitotic figures can be seen among them which may suggest that they are immature forms. In the second or more mature stage, the EACs assume an elongated spindle shape. The spindle-shaped EACs reveal inactive Golgi cis-ternae and fewer but larger granules than the round or immature EACs. Unmyelinated nerve fibers and nerve ending were observed in the ellipsoid. Perfusion fixation reveals that the distal portions of the penicilliform capillaries extend into the red pulp and become the sinuses. Therefore, the circulation of the chicken spleen is anatomically closed except for the channels in the mid-portion of the penicilliform capillary. The periellipsoid white pulp (PWP) possesses a few small lymphocytes, macrophages, and plasma cells with the majority of cells being young blastlike cells which may replenish the EACs and ellipsoidal cells. Carbon, injected intravenously, appears on the EAC membrane by 30 minutes, while Brucella abortus is completely phagocytized at this time. Binding the carbon triggers the EAC to detach from the ellipsoid and migrate to the periellipsoidal white pulp (PWP). The EACs phagocytize carbon by 2 hours, and by 5 and 8 days are present in the red pulp and surround the germinal centers at the border of the periarterial lymphatic sheath, respectively. Secretory cells which have been identified in germinal centers might originate from EACs.     

Associations between mammographic density and body composition in Hispanic and non-Hispanic white women by menopause status

OBJECTIVE: To evaluate the associations of body composition, including percentage of lean and fat mass, with the percentage of mammographic density and mammographic dense area among pre- and postmenopausal Hispanic and non-Hispanic white women. DESIGN: In this cross-sectional study, a total of 238 women aged 41 to 50 or 56 to 70 years were recruited from local mammography clinics and community health centers. Postmenopausal status was defined as an absence of any menstrual cycle within the past 12 calendar months or having a follicle-stimulating hormone level between 22 and 138 mIU/mL. The participants' most recent mammograms were used for the mammographic density analysis. Body composition was measured by dual-energy x-ray absorptiometry. The associations between the percentage of mammographic density or mammographic dense area and body composition components were analyzed using logistic regression. RESULTS: Mammographic dense areas were similar in Hispanic and non-Hispanic white women. The percentage of mammographic density varied by ethnicity in premenopausal (P = 0.023), but not in postmenopausal women. Body composition, both higher lean mass and lower fat mass, was associated with a higher percentage of mammographic density (P < 0.05). Interestingly, a higher percentage of total body fat mass and a lower percentage of total body lean mass were correlated with larger breast dense areas in premenopausal women but with lower breast dense areas in postmenopausal women. These relationships between body composition and mammographic density measurements were not significantly affected by factors such as age, ethnicity, and body weight. CONCLUSIONS: Body composition is highly correlated with mammographic density and should be examined as a possible confounding factor in studies involving mammographic density measurements and breast cancer risk.