Menopause and risk factors for coronary heart disease

Postmenopausal women are believed to have a higher risk of coronary artery disease than premenopausal women. In this study, we prospectively determined changes in coronary risk factors that were attributable to natural menopause in 541 healthy, initially premenopausal women 42 to 50 years of age. After approximately 2 1/2 years, 69 women had spontaneously stopped menstruating for at least 12 months, and 32 women had stopped natural menstruation and received hormone-replacement therapy for a period of at least 12 months. An equal number of age-matched premenopausal women in the study group served as controls. In women who had a natural menopause and did not receive hormone-replacement therapy, serum levels of high-density lipoprotein (HDL) cholesterol declined as compared with those of premenopausal controls (-0.09 vs. 0.00 mmol per liter; P = 0.01), and levels of low-density lipoprotein (LDL) cholesterol increased (+0.31 vs. +0.14 mmol per liter; P = 0.04). In menopausal women who received hormone-replacement therapy, HDL and LDL cholesterol levels did not change, but the levels of triglycerides (+0.42 vs. -0.04 mmol per liter; P less than 0.001), apolipoprotein A-I (+0.18 vs. +0.03 g per liter; P less than 0.01), and apolipoprotein A-II (+0.05 vs. -0.03 g per liter; P less than 0.05) increased as compared with premenopausal controls. Natural menopause did not affect blood pressure, plasma glucose or insulin levels, body weight, the total number of kilojoules consumed in the diet, or the total number of kilojoules expended in physical activity. These results suggest that a natural menopause has an unfavorable effect on lipid metabolism, which may contribute to an increase in the risk of coronary disease. Hormone-replacement therapy may prevent some of these changes.     

A longitudinal study of cognition change during early menopausal transition in a rural community

OBJECTIVE: To characterize changes in cognition that occur during the hormonal transitions of menopause. METHOD: We conducted a longitudinal population-based study in Kinmen, Taiwan, recruiting all women age 40-54 years who were premenopausal and without a history of hormone replacement therapy (HRT) or hysterectomy. The cognitive measures used to assess function included the Auditory-Verbal Learning Test, visual memory, verbal fluency, Trail Making Test and digit span. RESULTS: A total of 694 eligible women participated in the baseline study, and 573 women (83%) completed follow-up 18 months later. After excluding 78 women who received hysterectomy or HRT, the final sample was composed of 495 subjects, of whom 114 (23%) progressed to perimenopause during follow-up. Women who remained premenopausal were younger than those who became perimenopausal (44.7 +/- 2.3 years versus 47.1 +/- 3.0 years, p < 0.01). All follow-up cognitive scores in women who entered perimenopause were slightly better than baseline measures except for Rey Auditory-Verbal Learning Test, which decreased by 0.23 (S.D. = 2.9, p = 0.3). At follow-up, cognitive function except for verbal fluency did not differ significantly between women who stayed premenopausal and those became perimenopausal after controlling for age, education, and baseline cognitive scores. Women who entered perimenopause have an average of 1.3 items (S.D. = 0.4) less in verbal fluency measures as compared with their premenopausal peers at the follow-up period. CONCLUSIONS: The menopausal transition might not accompany significant cognitive decline except for verbal fluency.     

Menopause and the risk of coronary heart disease in women

To determine the relation of menopause to the risk of coronary heart disease, we analyzed data on a prospective cohort of 121,700 U.S. women 30 to 55 years old who were followed from 1976 to 1982. Information on menopausal status, the type of menopause, and other risk factors was obtained in 1976 and updated every two years by mailing questionnaires. Through 1982, the follow-up rate was 98.3 percent for mortality and 95.4 percent for nonfatal events. After we controlled for age and cigarette smoking, women who had had a natural menopause and who had never taken replacement estrogen had no appreciable increase in the risk of coronary heart disease, as compared with premenopausal women (adjusted rate ratio, 1.2; 95 percent confidence limits, 0.8 and 1.8). Again compared with premenopausal women, the occurrence of a natural menopause together with the use of estrogens did not affect the risk (rate ratio, 0.8, 95 percent confidence limits, 0.4 and 1.3). Women who had undergone bilateral oophorectomy and who had never taken estrogens after menopause had an increased risk (rate ratio, 2.2; 95 percent confidence limits, 1.2 and 4.2). However, the use of estrogens in the postmenopausal period appeared to eliminate this increased risk among these women as compared with premenopausal women (rate ratio, 0.9; 95 percent confidence limits, 0.6 and 1.6). These data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease. This increase appears to be prevented by estrogen-replacement therapy.     

A comparison of health-related quality of life (HRQOL) after natural and surgical menopause

Objective

To compare the health-related quality of life (HRQOL) of women at surgical menopause with that of women at natural menopause, utilizing the Menopause Rating Scale (MRS-II).

Study design

An institution-based cross-sectional study design was used, with 32 participants in each of two groups: women who had undergone surgical menopause of 9–12 months previously; and women who were more than 40 years of age and had had oligomenorrhoea for at least 1 year. The MRS-II was used to assess HRQOL. None of the women had received any hormonal therapy before assessment.

Main outcome measures

Total MRS-II scores along with the scores on the somato-vegetative, psychological and urogenital sub-scales were compared between the two groups.

Results

HRQOL was rated as worse by the surgical menopause group than by the natural menopause group: the total MRS-II scores were much higher for the surgical menopause group (mean = 29.4, SD = 6.7) than for natural menopause group (mean = 20.7, SD = 6.5), and this difference was significant (p < 0.0001). Similar results were obtained on the three sub-scales—somato-vegetative (p = 0.030), psychological (p < 0.0001) and urogenital (p < 0.0001).

Conclusion

HRQOL is worse after surgical than in natural menopause. Routine surgical castration at hysterectomy should be avoided because of adverse short-term effects and, potentially, long-term consequences.     

Association between menopause status and central adiposity measured at different cutoffs of waist circumference and waist-to-hip ratio

OBJECTIVE: To assess the association between menopause status and central adiposity measured using two different cutoffs of waist circumference and waist-to-hip ratio, while controlling for body mass index and other confounding factors. DESIGN: Cross-sectional study of a representative population-based sample of 358 women from Passo Fundo, Southern Brazil. Medical students performed standardized interviews and anthropometric measurements under supervision. Menopause status was categorized as premenopausal for those with no change in menstrual frequency or flow; menopause transition for those who had these changes; and postmenopausal after 12 months of amenorrhea or bilateral oophorectomy. Obesity was defined by body mass index (BMI) equal or greater than 30 kg/m, whereas central adiposity was defined as a waist circumference equal or greater than 80 or 88 cm and a waist-to-hip-ratio equal or greater than 0.80 or 0.86. RESULTS: The anthropometric assessment showed that compared with postmenopausal women, premenopausal women were taller, had a thinner waist circumference, and had a lower waist-to-hip ratio. Postmenopausal women had five times the chance of having central adiposity than premenopausal women, even after controlling for BMI and other confounding factors. Women in the menopause transition had an increased BMI, but there was no independent association with central obesity. CONCLUSION: Postmenopausal women are at greater risk of central adiposity as detected by both waist circumference and waist-to-hip ratio.     

The normal menopause transition.

This paper presents analyses from perhaps the largest and most comprehensive prospective cohort study of mid-aged women--the Massachusetts Women's Health Study (MWHS)--with numbers sufficient to provide, for the first time, stable estimates of parameters in the normal menopause transition. The three questions addressed in this analysis are (i) what are the natural menopause transitions and when do they occur, (ii) what factors affect these transitions and (iii) what signs and/or symptoms accompany these transitions? The data were obtained primarily from 5 years of follow-up of 2570 women in Massachusetts who were aged 45-55 years as of January 1, 1982. An initial baseline cross-sectional survey (T0) yielded a total of 8050 completed responses with an overall response rate of 77%. From this cross-sectional sample a cohort of approximately 2570 women was identified, consisting of women who had menstruated in the preceding 3 months and who had not undergone removal of the uterus and/or ovaries. Prospective study of the cohort consisted of six telephone contacts (T1-T6) at 9-month intervals with excellent retention of the respondents. A subset of the full cohort was defined that consisted of women who were premenopausal (rather than perimenopausal) at baseline (T0) (n = 1178). Confirming prior reports, the age at natural menopause occurred at 51.3 years with a highly significant median difference (1.8 years) between current smokers and non-smokers. The new analyses reported here on median age at inception of perimenopause (47.5 years) and factors affecting it are consistent with findings for age at last menstrual period, particularly the overwhelming effect of smoking. Smokers tend to have not only an earlier but also a shorter perimenopause. The length of the perimenopausal transition (estimated at nearly 4 years) has not been previously reported. Moreover, the highest rate of physician consultations is observed among those with longer perimenopause transitions. The relationship between menopause transitions and symptom reporting appears to be transitory, with reported rates showing an increase in the perimenopause and a compensatory decrease in the postmenopause. The implications of combined hormone replacement therapy for future research on menopause in industrial societies is discussed in relation to these findings.     

The menopause, urinary incontinence and other symptoms of the genito-urinary tract.

In a study on incontinence and other symptoms of the genito-urinary tract in postmenopausal women covering their prevalence, consequences and predisposing factors, the prevalence of incontinence was found to be 26.4%. Daily incontinence was present in postmenopausal women more than twice as often as before the menopause (P < 0.05). The frequency of medical consultation for such incontinence was low; only 26.1% of the postmenopausal women had ever seen their doctor about it. Urgency, nocturia and dyspareunia were more prevalent in postmenopausal women, while vaginal itching and discharge were more frequent in premenopausal women (P < 0.05). The prevalence of incontinence and the other genito-urinary symptoms was higher after surgical than after natural menopause. Multivariate analysis showed the menopause to be the only factor that contributed significantly to the onset of incontinence (P < 0.001).     

Menopausal transition and psychological development

OBJECTIVE: To study women's psychological development during menopause and to examine the relationship between women's appraisal of menopause and symptom reporting. DESIGN: A population-based sample of 130 healthy women was assessed annually for 5 consecutive years using semistructured interviews, a menopausal symptom rating scale, and the Symptom Checklist-90 rating scale. RESULTS: Qualitative analyses of the interviews showed that the majority of the women (57%) had neutral beliefs about menopause, whereas 31% were pessimistic and 12% were optimistic. Optimistic and neutral expectations were associated with low levels of symptom reporting, whereas the pessimistic appraisal was significantly related to elevated symptom scores. The majority of the neutral and pessimistic women reappraised menopause during the study period, and at the last follow-up, 67% appraised menopause positively. A positive reappraisal among the initially pessimistic women was associated with more frequent statements about personal growth compared with the other subgroups. CONCLUSIONS: Menopause has a developmental potential and is a positive period for most women.     

Risk factors for clinically diagnosed uterine fibroids in women around menopause

OBJECTIVE: We analysed the risk factors for clinically diagnosed uterine fibroids in women attending menopause clinics in Italy. METHODS: Between 1997 and 2003 we conducted a large cross-sectional study on the characteristics of women around menopause attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. A total of 85,967 non-hysterectomized women not reporting myomectomy entered the study; 2239 had a diagnosis of uterine fibroids. A woman was defined as having uterine fibroids if she had at gynecological examination an enlarged uterus (2 months of gestation or more) and a clinical diagnosis of fibroids. In 769 cases was performed in ultrasound examination which confirmed the diagnosis. RESULTS: In comparison with women with a body mass index (BMI) <22, the multivariate ORs for BMI 26 or more were 1.30 (95% CI, 1.09-1.55) for cases with clinical diagnosis, and 1.29 (95% CI, 1.01-1.45) for women with ultrasonographic diagnosis. In comparison with premenopausal women, the multivariate OR for clinically detected fibroids was 0.63 (95% CI, 0.55-0.72) for post-menopausal ones. The risk of fibroids was lower in parous women than in nulliparous ones, and the risk decreased with number of births regardless the type of diagnosis. CONCLUSION: This study confirms in a large sample that parity is the main protective factor for the development of fibroids. Overweight increases the risk.     

Increased risk of early menopausal transition and natural menopause after poor response at first IVF treatment

BACKGROUND: Our aim was to examine whether women who had a low number of retrieved oocytes at their first IVF attempt reach the menopausal transition and/or the natural menopause earlier than women of similar ages with a high number of retrieved oocytes. METHODS: We conducted a retrospective cohort study among women in The Netherlands who received IVF treatment between 1983 and 1995. For the present study, we selected all cohort members who had a regular menstrual cycle at the time of the first visit to the gynaecologist (n = 4601). After a median follow-up of 5.5 years, 3871 (84%) women still had a regular menstrual cycle pattern, 547 (12%) women had entered the menopausal transition (i.e. no menses for 3-11 months, use of HRT or irregular menstrual cycles) and 27 (1%) women had reached natural menopause. We examined whether the quantity and the quality of the retrieved oocytes were related to an early menopausal transition and early menopause. The live birth rate per embryo transfer was used as indicative of the quality of the oocytes. RESULTS: The age-adjusted odds ratio (OR) for having entered the menopausal transition/natural menopause for women with a poor response (0-3 oocytes) at their first IVF attempt was 3.1 [95% confidence interval (CI) 2.4-3.8] compared with women with a normal response (>3 oocytes). Women who were stimulated with gonadotrophins during IVF treatment but did not undergo an IVF puncture because of an anticipated poor response (cancelled IVF cycle) had an age-adjusted OR of 3.2 (95% CI 2.3-4.3). There was no significant difference in the odds of reaching the menopausal transition/natural menopause, after adjustment for age and the number or retrieved oocytes, between women who did and did not have a live birth following their first embryo transfer (OR = 1.3; 95% CI 0.95-1.7). CONCLUSIONS: These results indicate that a low remaining quantity of oocytes, as reflected by a low number of retrieved oocytes at first IVF treatment, is an important predictor of the risk of an early menopausal transition/natural menopause. The quality of the oocytes did not affect the risk of an early menopausal transition/natural menopause once the number of retrieved oocytes had been taken into account. Our findings support the concept that the number of remaining follicles in the ovaries is one of the main aspects of reproductive ageing.     

Associations with menopause and menopausal transition in a nationally representative US sample

OBJECTIVES: The purpose of this study was to assess sociodemographic and behavioral factors in relation to menopausal status in a representative sample of the United States population. METHODS: Data were taken from the 1999 National Health Interview Survey (NHIS), limited to women aged 40-54 years who had not undergone surgical menopause. Menopausal transition was defined as absence of menstrual cycles for at least 3 but no more than 11 months or cycles that had become irregular in the past 12 months. Postmenopause was defined as absence of a menstrual cycle for 12 or more months. We used age-adjusted three-level logistic regression to examine the association between menopausal status and smoking, race/ethnicity, education, body mass index, exercise, and alcohol use. RESULTS: Twenty percent of women in this sample had experienced natural menopause, 18% were in the menopausal transition and 61% were premenopausal. Using premenopause as the reference group, current cigarette smoking was strongly associated with being postmenopausal (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.7, 3.0) and weakly associated with being in the menopausal transition (OR 1.4, 95% CI 1.1, 1.8). Education level was associated with being postmenopausal (OR 0.4, 95% CI 0.3, 0.6 comparing women with a college degree to women who had not completed high school), and alcohol use was weakly associated with being postmenopausal, with no evidence of a dose-response. CONCLUSIONS: The associations with smoking were stronger for postmenopause than for the transition phase, suggesting that the effect of smoking may be to shorten the transition period. Education level may be a marker for other exposures that affect ovarian senescence.     

Cognitive function across the life course and the menopausal transition in a British birth cohort

OBJECTIVE: Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. RESULTS: There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. CONCLUSION: Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.     

The influence of a Vitamin D receptor gene polymorphism on the timing of female reproductive functions in humans

OBJECTIVE: To evaluate the association between a common polymorphism of the Vitamin D receptor gene (VDR) and the timing of female reproductive functions in humans. METHODS: One thousand fifty-eight consecutive women were included in this cross-sectional study. We analyzed the intron 8 Bsm I restriction fragment length polymorphism (RFLP) of VDR on chromosome 12q using a microarray-based system. RESULTS: The presence of the VDR polymorphism did not influence the timing of menarche and natural menopause and was not associated with the number of spontaneous abortions, full term pregnancies (FTP) as well as the total number of pregnancies. Of note, women with at least one mutant allele of VDR were at a significantly decreased risk for experiencing surgical menopause (odds ratio [OR] 0.65, 95% confidence interval [CI], 0.46-0.92, P = 0.02). Smoking and a body mass index (BMI) > 25 were associated with an earlier natural menopause and an increased risk for surgical menopause, respectively. CONCLUSIONS: While no association of a common polymorphism of VDR with the timing of menarche and menopause was ascertained, we found the presence of at least one mutant allele of VDR to be associated with a decreased risk of experiencing surgical menopause, i.e., premenopausal hysterectomy, in a large series of Caucasian women.     

Are cause of subfertility and in vitro fertilization treatment risk factors for an earlier start of menopause?

OBJECTIVE: To study whether women diagnosed with unexplained subfertility reach the menopause transition and natural menopause earlier than women with tubal subfertility, in an in vitro fertilization (IVF)-treated population, and to examine the influence of the number of IVF cycles on the occurrence of an early menopause transition and natural menopause. DESIGN: This retrospective cohort study included 12 IVF clinics in the Netherlands. A nationwide retrospective cohort study was conducted among women whose first IVF cycle was stimulated with gonadotrophins in the Netherlands between 1983 and 1995 (n = 7,842). Most of the women were in their late 30s at the end of the follow-up period (range 24-55 y). The main outcome measures were the relative risk (RR) of having reached natural menopause and the risks (RR) of having entered the menopause transition or natural menopause according to the cause of subfertility and the number of IVF cycles. RESULTS: Women with unexplained subfertility did not have an increased risk of entering the menopause transition or natural menopause (adjusted RR = 0.5; 95% CI, 0.2-1.5; and RR = 0.8; 95% CI, 0.6-1.1). After a 5-year follow-up period, we found no increased risk for entering the menopause transition or natural menopause among women who had undergone six or more IVF cycles when compared with women who had undergone only one IVF cycle (adjusted RR = 0.4; 95% CI, 0.1-1.7; and RR = 0.9; 95% CI, 0.6-1.6). CONCLUSIONS: Underlying causes of unexplained subfertility do not predispose women to an early start of menopause. Although the number of IVF cycles was not associated with early menopause, longer follow-up is needed.     

Early postmenopausal hormone therapy improves postural balance

OBJECTIVE: Postmenopausal hormone therapy (HT) results in more substantial reductions in the risk of hip fracture when initiated sooner rather than later after menopause. We studied the effects of postmenopausal HT on the postural balance of postmenopausal women, with further assessment according to the time since they achieved menopause. DESIGN: One hundred women with a mean age of 52.5 years (91 evaluable) were randomly and blindly assigned to either a sequential estradiol-norethisterone acetate regimen or placebo for 3 months, after which all participants received open HT for a further 3 months. Postural balance was assessed as sway velocity using a force platform. RESULTS: After 3 months of HT, sway velocity had improved (decreased) from baseline by 7.0% (P = 0.007 vs baseline and P = 0.038 vs placebo). Continued HT for 6 months further improved sway velocity by 12% from baseline (P < 0.0001) to reach values similar to those historically found in younger women or in postmenopausal women after long-term HT. Closer proximity to menopause and more pronounced increases in serum estradiol values were associated with stronger improvements in sway velocity (P = 0.018 for interaction). HT also improved dizziness (P = 0.016 vs baseline and 0.022 vs placebo). (Nonparametric statistics are used throughout, except for analyses of interaction and dizziness.) CONCLUSIONS: Initiation of HT soon after menopause rapidly improved postural balance to levels normally seen in young women. We suggest that improved postural balance can contribute to the protection against fractures associated with HT and explain the more substantial reduction in hip fracture risk after HT initiated sooner, compared with later, after menopause. Further study is required to confirm these results.     

Reporting endometrial cells in women 40 years and older: assessing the clinical usefulness of Bethesda 2001

We assessed the usefulness of revised Bethesda System reporting of exfoliated benign endometrial cells (EMs) in postmenopausal women. Cervicovaginal cytology specimens with benign EMs in postmenopausal women and "out-of-phase EMs" in premenopausal women 40 years and older were identified. Cases with histologic follow-up within 12 months were selected. There was tissue follow-up for 130 postmenopausal women: 10 (7.7%) had significant findings (endometrial adenocarcinoma, 6 [2 (33%) in asymptomatic women]; complex atypical endometrial hyperplasia [CAH], 3; leiomyosarcoma, 1); 20 were receiving hormone replacement therapy (HRT; n = 15) or tamoxifen (n = 5); 2 (10%) had significant pathology (endometrial adenocarcinoma, 1; CAH, 1). Eight not taking hormones (7.3%) had significant pathology (adenocarcinoma, 5; CAH, 2; leiomyosarcoma, 1). There were follow-up data for 96 premenopausal women; only 1 (who had vaginal bleeding) had significant pathology (CAH). The difference in incidence of preneoplastic and neoplastic conditions after a cytologic interpretation of "benign EM" between postmenopausal and premenopausal women was significant (P pound .025); There was no difference between postmenopausal women receiving or not receiving HRT (P > .05). Reporting benign EMs for premenopausal women 40 years and older has no clinical significance but does for postmenopausal women, regardless of HRT and symptoms.     

Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause

To assess the safety and efficacy of oestriol in relieving post-menopausal symptoms 53 post-menopausal Japanese women with climacteric symptoms, 27 with natural menopause (group I) and 26 with surgically induced menopause (group II), received oral oestriol, 2 mg daily for 12 months. Clinical parameters including Kupperman index (KI) and the degree of satisfaction with symptomatic relief; serum concentrations of oestradiol, FSH and LH; serum lipids; blood pressure; bone mineral density, serum calcium (Ca), alkaline phosphatase (ALP), and urinary Ca were compared between the two groups. Oestriol improved KI in groups I and II by 49 and 80% respectively. Satisfaction with treatment was 85% in group I and 93% in group II. For both parameters, values were significantly different between groups I and II (P < 0.05 for both). Serum concentrations of oestradiol, FSH and LH changed in group I versus group II 6 months after initiation. A significant decrease in serum ALP and Ca/Cr was observed in group I at 6 months. Except for serum triglycerides, oestriol had no significant effect on lipids. Systolic and diastolic blood pressures were significantly decreased in group I at 3 months versus baseline. Slight vaginal bleeding occurred in 14.3% of group I. Histological evaluation of the endometrium in all women of group I and ultrasound assessment of the breasts following 12 months of oestriol treatment found normal results in all women. Therefore, oestriol appeared to be safe and effective in relieving symptoms of menopausal women. The beneficial biochemical effects of oestriol were marked in the natural menopause. Overall, oestriol may serve as a good choice for hormone replacement therapy to protect against other climacteric symptoms in post-menopausal women who do not need medication for osteoporosis or coronary artery disease.     

The normal menopause transition

This paper presents analyses from a comprehensive prospective cohort study of mid-aged women [the Massachusetts Women's Health Study (MWHS)], with numbers sufficient to provide stable estimates of parameters in the normal menopause transition. Three questions are addressed: what are the natural menopause transitions and when do they occur; what factors affect the transitions; and what signs and/or symptoms accompany the transitions? The data were obtained primarily from 5 years of follow-up of 2,570 women in Massachusetts who were aged 44–55 years as of January 1, 1982. Prospective study of the cohort consisted of six telephone contacts (T₁–T₆) at 9 month intervals with excellent retention. A subset of the full cohort was defined that consisted of women who were premenopausal (rather than perimenopausal) at baseline (T_o) (n = 1,178). Confirming prior reports, the age at natural menopause occurred at 51.3 years with a highly significant median difference (1.8 years) between current smokers and non-smokers. The new analyses reported here on median age at inception of perimenopause (47.5 years) and factors affecting it are consistent with findings for age at last menstrual period. Smokers tend to have not only an earlier but also shorter perimenopause. The length of the perimenopausal transition, estimated at about 3.5 years, has not been previously reported. The relationship between menopause transitions and symptom reporting appears to be transitory, with reporting rates showing an increase in the perimenopause and a compensatory decrease in postmenopause. The implications of combined hormone replacement therapy for future research on menopause in industrial societies is discussed in relation to these findings.     

Premenopausal factors influencing premature ovarian failure and early menopause

OBJECTIVES: We conducted this study to examine premenopausal risk factors associated with premature ovarian failure (POF) and early menopause (EM) among Korean women. METHODS: A 73% of total women aged 30-69 at four districts in the KMCC (Korean Multi-center Cancer Cohort) was participated in this study during 2002-2003. We selected 137 POF and 281 EM cases who had menopause before age 40 and at age 40-44, respectively, and 1318 normal menopause (NM) controls that experienced menopause at age 45-60, and among them, selected idiopathic POF (n=84) and EM (n=261) after excluding surgical/medical menopause. We collected the information of premenopausal lifestyle and reproductive risk factors. Multivariate and polytomous logistic regression were used to estimate POF and EM risk and to differentiate POF and EM risk using ordinal and nominal scale. RESULTS: Cigarette smoking was associated with an increased risk of idiopathic POF (OR=1.82 [1.03-3.23]), whereas oral contraceptive use was associated with a reduced risk of natural EM (OR=0.62 [0.43-0.90]). Idiopathic POF risk by both factors differed from idiopathic EM risk (p-nominal<0.05). Factors related to ovulation, such as later menarche, irregular menstruation and longer breast feeding cumulatively reduced the risk of natural EM and POF (p-ordinal<0.05). In analysis including medical and surgical menopause, lung tuberculosis, hysterectomy, past cancers, and lower number of deliveries before menopause were associated with POF. CONCLUSIONS: Our findings indicate that etiology in POF development may partly differ from that in EM.     

Epidemiology of insomnia: a longitudinal study in a UK population

STUDY OBJECTIVES: To investigate the incidence, persistence, and consequences of insomnia and their associations with psychological health and pain. DESIGN: A population based, longitudinal, cohort study using postal questionnaires at baseline and 12-month follow-up. Sleep problems in the past month were assessed using 4 questions: insomnia was defined as having at least 1 of the sleep problems "on most nights." Questions about psychological health, presence of pain at different sites, and demographic details were included in the questionnaire. SETTING: Five general practices in Staffordshire, UK. PARTICIPANTS: The questionnaire was mailed to a random sample of 4885 adults aged 18 years and over registered with these practices. There were 2662 questionnaires returned. RESULTS: Of the responders, 2363 completed all 4 sleep questions at baseline: 870 (37%) had insomnia and 1493 (63%) did not have insomnia. Of those without insomnia at baseline, the incidence of insomnia at 12 months was 15%, and this was significantly associated with baseline anxiety, depression, and pain. Of those who did have insomnia at baseline, 69% had insomnia at 12-month follow-up; persistence of insomnia was significantly associated with older age. Insomnia at baseline was significantly associated with incidence of anxiety, depression, and widespread pain at 12-month follow-up. CONCLUSIONS: Insomnia is common and often persistent. Older people appear more vulnerable to persistent symptoms. Our results provide evidence that the common problems of insomnia, pain, and psychological distress are intertwined and suggest that combined approaches to treatment may be needed to reduce the onset and persistence of these problems in the community.