Secular Trends of Reproductive Indices in Chuvashian Women

In the present cross-sectional study of the Chuvashian rural population, we examined the secular trends of age at menarche, the age at menopause, the reproductive period, and the age of the first marriage of Chuvashian women. The cohort included 745 women aged 18–90 years; age at menarche (N = 653) ranging from 10 to 24 years (mean 15.42 ± 2.11). Data regarding menopausal age was obtained from 316 women born between 1920 and 1950 (mean 48.5 ± 4.6). Statistical analyses included the maximum likelihood estimation and a Whiskers plot. Women born during the second through the fourth decade of the 20th century showed increasing mean values of age at menarche from 15.4 (second decade) up to 16.5 (fourth decade) and after that a decrease of the mean values to 14.0 (ninth decade). The mean values of menopausal age increased from 47.0 (women born from 1920 to 1925) to 49.3 (born from 1945 to 1950). Age at first marriage showed a trend of decreasing age. Our study demonstrated secular trends of age at menarche in Chuvashian women who had matured after World War II and also confirmed secular trends of increased age at menopause and the duration of the reproductive period. Women, whose maturation was during or immediately after World War II, showed a higher age at menarche and a higher dispersion of age at menopause.     

Age at menopause in Puebla,Mexico

Comparisons of age at menopause are made difficult by the different methodologies applied across populations. This study extended an opportunity to apply different methodologies to the same data to draw some preliminary conclusions about age at menopause in Puebla, Mexico. Among 755 women aged 28 to 70 interviewed in the capital city of Puebla, Mexico, 447 (59.6%) were naturally or surgically postmenopausal. Mean recalled age at natural menopause in Puebla (46.7 years) appears to be similar to mean recalled age at menopause in Mexico City (46.5 years), suggesting that age at menopause is similar in urban Mexican populations. However, median age at menopause computed by probit analysis was later in the city of Puebla (49.6 years) compared to the median age computed by the same method in the capital city of León, Guanajuato, Mexico (48.2 years). Median age at menopause computed by Kaplan-Meier survival analysis suggests that age at menopause in Puebla (50.0 years) is older still, and close to that of the United States (51.1 years). The differences in median ages at menopause in Puebla are solely due to methodological choices and highlight the difficulty inherent in making inferences across studies of age at menopause between biological and/or cultural groups. Factors associated with age at menopause offer another avenue for comparing and understanding variation in this basic biological process. In Puebla, smoking, low levels of education, and nulliparity are associated with an earlier age at menopause.     

Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia.

Some discrepancies exist about the relationship between serum albumin level and the pathogenesis of osteoporosis; moreover, most of the studies available have especially concerned patients with osteoporosis, often associated with fractures. Our study, therefore, aims to investigate the presence of a relationship between serum albumin level and bone mineral density in a group of healthy women (n=650; mean age 59.0 +/- 7.4 years) who voluntarily underwent screening for osteoporosis only because they were menopausal (11.2 +/- 7.4 years since menopause) and, for comparison, in a group of outpatients (n = 44; mean age 57.6 +/- 7.0 years; 9.1 +/- 6.7 years since menopause) with hypoalbuminemia associated with diseases. The results show a lack of any relationship in healthy women between serum albumin value and bone mineral density; the lack of correlation was also shown when the postmenopausal women were down into normal, osteopenic and osteoporotic (WHO criteria) or in hypo, normal and hyperalbuminemic. The only significant parameters associated with lower bone mineral density, in fact, were age and years since menopause (p<0.0001 and p<0.0001 respectively at lumbar spine and p<0.02 and p<0.001 at femoral neck level). In the group of patients with hypoalbuminemia associated with diseases, on the other hand, a relationship between reduced bone mineral density and hypoalbuminemia was found (p<0.01 and p<0.05 respectively at lumbar spine and femoral neck). In conclusion, in healthy postmenopausal women the serum albumin level does not play a significant role in the pathogenesis of bone density reduction, which is mainly due to the number of years since menopause and advancing age. The hypoalbuminemia may be related to the reduction of bone mass only in the subjects affected by diseases associated with a significant albumin reduction.     

Circadian Rhythms in Hot Flashes in Natural and Surgically-Induced Menopause

The aim of this study was to investigate arcadian and ultradian variations in menopausal hot flash. The number of hot flashes per 2-hr period was collected from 25 diurnally-active, perimenopausal women for 1 week in January or February of each year for 3 consecutive years. Fourteen women were experiencing natural menopause (NM) (mean age 51.9 years) and 11 were experiencing surgically-induced menopause (SIM) (mean age 52.0 years). The difference in the number of hot flashes between the two types of menopause at each clock time was not statistically significant; neither was the mean number of hot flashes per 24 hr different between the two groups (Student's f-test). Data when normalized for each woman and placed end-to-end revealed by cosinor analysis circadian rhythmicity in the SIM group (P =0.02) but not in the NM group. A 12-hr periodicity was detected in both groups (P< 0.001 for both). An 8-hr rhythm was detected only for the NM group (P = 0.04). Both groups combined exhibited statistically significant rhythmicities with periods of 24 hr (p= 0.003), 12 hr (P<0.001) and 8 hr (P= 0.005). Regardless of the type of menopause, the women could be separated into two groups based on the temporal pattern of hot flashes during the day. One group was defined by the occurrence of peak frequency of flashes during the morning (0400–0959), while the second group was defined by the occurrence of the peak in the evening (1600–2159). The difference between the two groups in the number of hot flashes during the morning wasstatistically significant (Student's r-test, P = 0.009) as was the number of hot flashes in the evening (Student's r-test, P= 0.03).     

Hip Fracture Incidence in Relation to Age,Menopausal Status,and Age at Menopause: Prospective Analysis

Background

Bone mineral density is known to decrease rapidly after the menopause. There is limited evidence about the separate contributions of a woman''s age, menopausal status and age at menopause to the incidence of hip fracture.

Methods and Findings

Over one million middle-aged women joined the UK Million Women Study in 1996–2001 providing information on their menopausal status, age at menopause, and other factors, which was updated, where possible, 3 y later. All women were registered with the UK National Health Service (NHS) and were routinely linked to information on cause-specific admissions to NHS hospitals. 561,609 women who had never used hormone replacement therapy and who provided complete information on menopausal variables (at baseline 25% were pre/perimenopausal and 75% postmenopausal) were followed up for a total of 3.4 million woman-years (an average 6.2 y per woman). During follow-up 1,676 (0.3%) were admitted to hospital with a first incident hip fracture. Among women aged 50–54 y the relative risk (RR) of hip fracture risk was significantly higher in postmenopausal than premenopausal women (adjusted RR 2.22, 95% confidence interval [CI] 1.22–4.04; p = 0.009); there were too few premenopausal women aged 55 y and over for valid comparisons. Among postmenopausal women, hip fracture incidence increased steeply with age (p<0.001), with rates being about seven times higher at age 70–74 y than at 50–54 y (incidence rates of 0.82 versus 0.11 per 100 women over 5 y). Among postmenopausal women of a given age there was no significant difference in hip fracture incidence between women whose menopause was due to bilateral oophorectomy compared to a natural menopause (adjusted RR 1.20, 95% CI 0.94–1.55; p = 0.15), and age at menopause had little, if any, effect on hip fracture incidence.

Conclusions

At around the time of the menopause, hip fracture incidence is about twice as high in postmenopausal than in premenopausal women, but this effect is short lived. Among postmenopausal women, age is by far the main determinant of hip fracture incidence and, for women of a given age, their age at menopause has, at most, a weak additional effect. Please see later in the article for the Editors'' Summary     

Reproductive life of some Gujar women of Punjab

Data was collected on current age, age at menarche, marriage age, maternal age at 1st birth, age at the birth of last child, age at menopause, total number of conceptions, live births, stillbirths, abortions, dead children and living children for a sample of 150 Gunjar women of Punjab, India, during September and October 1977 to study their reproductive life. The women ranged in age from 45-55 years. The mean age at menarche was 14.90 years for the sample. The median age at menopause was 46.20 years. The mean age at marriage of the present sample was 12.56+-2.50 years; the mean age of the mother at the birth of her 1st child was 16.85 years; and the mean age at the birth of the last child was 38.68 years. The average number of conceptions was 7.2; the average number of live births of these 150 women was 6.90. The fertility of this population was natural as they were not using any family planning method.     

Why do women stop reproducing before menopause? A life-history approach to age at last birth

Evolutionary biologists have long considered menopause to be a fundamental puzzle in understanding human fertility behaviour, as post-menopausal women are no longer physiologically capable of direct reproduction. Menopause typically occurs between 45 and 55 years of age, but across cultures and history, women often stop reproducing many years before menopause. Unlike age at first reproduction or even birth spacing, a woman nearing the end of her reproductive cycle is able to reflect upon the offspring she already has—their numbers and phenotypic qualities, including sexes. This paper reviews demographic data on age at last birth both across and within societies, and also presents a case study of age at last birth in rural Bangladeshi women. In this Bangladeshi sample, age at last birth preceded age at menopause by an average of 11 years, with marked variation around that mean, even during a period of high fertility. Moreover, age at last birth was not strongly related to age at menopause. Our literature review and case study provide evidence that stopping behaviour needs to be more closely examined as an important part of human reproductive strategies and life-history theory. Menopause may be a final marker of permanent reproductive cessation, but it is only one piece of the evolutionary puzzle.     

Circadian rhythms in hot flashes in natural and surgically-induced menopause

The aim of this study was to investigate circadian and ultradian variations in menopausal hot flash. The number of hot flashes per 2-hr period was collected from 25 diurnally-active, perimenopausal women for 1 week in January or February of each year for 3 consecutive years. Fourteen women were experiencing natural menopause (NM) (mean age 51.9 years) and 11 were experiencing surgically-induced menopause (SIM) (mean age 52.0 years). The difference in the number of hot flashes between the two types of menopause at each clock time was not statistically significant; neither was the mean number of hot flashes per 24 hr different between the two groups (Student's t-test). Data when normalized for each woman and placed end-to-end revealed by cosinor analysis circadian rhythmicity in the SIM group (P = 0.02) but not in the NM group. A 12-hr periodicity was detected in both groups (P less than 0.001 for both). An 8-hr rhythm was detected only for the NM group (P = 0.04). Both groups combined exhibited statistically significant rhythmicities with periods of 24 hr (P = 0.003), 12 hr (P less than 0.001) and 8 hr (P = 0.005). Regardless of the type of menopause, the women could be separated into two groups based on the temporal pattern of hot flashes during the day. One group was defined by the occurrence of peak frequency of flashes during the morning (0400-0959), while the second group was defined by the occurrence of the peak in the evening (1600-2159).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral microcirculation in post-menopause: a possible correlation with periodontitis

doi: 10.1111/j.1741‐2358.2011.00608.x Oral microcirculation in post‐menopause: a possible correlation with periodontitis Objectives: The reduction in the level of oestrogen, typical in menopause, has some effect on the health of the oral cavity. In fact, post‐menopausal women present more severe periodontal disease than pre‐menopausal women. Numerous factors can be held to be responsible for this increase, among which are the effects of oestrogens on the oral epithelium, on the salivary glands, on bone tissue and on the endothelium. Our double blind study aims to evaluate the possible variations in oral microcirculation in post‐menopausal women. Methods: Twenty‐seven women in post‐menopause (age: Mean ± SD: 57.3 ± 8.73) and 27 women in pre‐menopause (age: Mean ± SD: 27.77 ± 3.56) were examined. Oral microcirculation was investigated using oral videocapillaroscopy. Results: The study showed significant differences between cases and controls for the following parameters: decrease in diameter of loops (mean ± SD: 0.038 ± 0.008; 0.045 ± 0.005), increase in tortuosity (mean ± SD: 3.83 ± 1.13; 1.83 ± 1.06) in labial mucosa and decrease in density in periodontal mucosa (Mean ± SD: 28.86 ± 10.92; 89.62 ± 17.83). Conclusion: The decrease in periodontal density may compromise the epithelium tropism, making it prone to inflammation. The tortuosity may indicate a greater permanence of inflammatory factors, increased in post‐menopausal women.     

Relationship of Leptin Concentration to Gender,Menopause, Age,Diabetes, and Fat Mass in African Americans

This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34. 2 ± 7. 4 years), 29 age-matched premenopausal women (mean age, 32. 6 ± 3. 7 years), and 36 postmenopausal women (mean age, 57. 8 ± 5. 9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (^P=0. 04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0. 001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7. 51 ± 8. 5, 33. 9 ± 17. 3, 31. 4 ± 22. 3 ng/mL. Leptin/FM x 100 in the three groups were: 28. 9 ± 16. 1, 98. 65 ± 44. 9, 77. 1 ± 44. 5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0. 001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0. 83,p<0. 001), in premenopausal women it was FM only (R=0. 57,P<0. 001), and in postmenopausal women it was weight only (R=0. 67, p<0. 001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.     

Nutritional status and age at secondary sterility in rural Bangladesh

In a prospective study of 2324 women in Matlab, Bangladesh, the occurrence of primary and 2ndary sterility by age groups was examined. The results were related to the nutritional status of the women, as assessed by measurements of height, weight, arm circumference and ponderal index. Approximately 98% of the women who were in the age group 15-19 were found to be fertile. This proportion decreases gradually up to the age group 30-34 years and thereafter declines sharply, reaching only 31% in the age group 45-49. The height data suggest no significant difference in the age pattern of sterility among the 3 groups of women, although there is a slight tendency that women who were less tall reached menopause earlier than the other 2 groups. Variations in weight are more conspicuous than in height. There is the suggestion that thinner women may experience an earlier menopause. Women having an arm circumference less than 21 cm, between 21-22 cm, and 23 cm and above, and currently aged 17 years, have an expected fertile life estimated at 25.0, 25.8, and 26.6 years respectively. The median ages at sterility were 42.8, 44.0, and 44.3 years respectively with a difference of about 1 year between the 1st 2 groups. This suggests that sterility occurs earlier among the thinner women. Since detailed investigation of nutritional status was not possible, it was assessed by anthropometry. There was strong evidence that nutritional status is an important factor in the estimated age at sterility, with thinner women experiencing an earlier menopause. Although it is impossible to measure the onset of sterility, one can obtain a minimum estimate of it from the age-specific distribution of the proportion of women who have not produced a child for 5 years of being at risk.     

Menopause in Blackfeet women--a life span perspective

A lifespan perspective, combining quantitative and qualitative approaches, is used to examine factors related to the timing of menopause in Blackfeet women of northern Montana (USA). Cross-sectional survey data demonstrate a median age at menopause using a status quo method of 51.6 years, and a mean age of 47.0 +/- 5.0 years among those women who had already experienced menopause. Age at menopause is inversely associated with age at menarche and having been breastfed, and positively associated with use of contraceptives, household income, and current or recent employment. Household income and age at menarche influence menopause age jointly in multivariate models. These and other patterns are examined in the lives of two women with very divergent ages at menopause. Although these data support an effect of early life influences on shaping reproductive trajectories that culminate in menopause, environmental factors and human agency during adult life may play a modifying role.     

Trisomy 21 and maternal age of menopause: does reproductive age rather than chronological age influence risk of nondisjunction?

The biological basis underlying the increased risk of nondisjunction in offspring of women of advanced maternal age is not understood. We sought to test the hypothesis that maternal reproductive age (distance in time from approaching menopause) rather than chronological age is pivotal in the etiology of nondisjunction. Our results found no difference in age of menopause between women 30 years old at delivery of a child with trisomy 21 (i.e., age-related nondisjunction) compared to controls. Among women <30 years of age at delivery of a child with trisomy 21, none underwent premature menopause. Therefore, our findings fail to support the theory that reproductive age plays a major role in the etiology of nondisjunction.     

Edad de menopausia en pacientes tratadas con I131 por cáncer diferenciado de tiroides

IntroductionDifferentiated thyroid cancer (DTC) is an increasingly frequent endocrinological disease. Radioiodine is a key component of treatment.ObjectiveTo analyze the effects of I¹³¹ therapy on ovarian and reproductive function.Material and methodsWe retrospectively analyzed data from 202 women treated with radioiodine for DTC in our service from 1985–2008. Data on age at menopause in patients and their mothers and sisters, menstrual history, fertility and neonatal abnormalities were collected.ResultsMenopause occurred in 34 patients at follow-up. The mean age at menopause in patients was 49.94±3.45 while that in their mothers and sisters was 49.20±5.37 and 48.73±3.74 years, respectively. Three patients had transient amenorrhea. No infertility or neonatal alterations were found.ConclusionsIn our series, menopause did not occur earlier in patients than in their first degree relatives. No significant alterations in neonatal health, fertility or menstruation were found.     

The effects of high altitude on age at menarche and menopause

The age at menarche and menopause of three groups of Bhotia females living at high altitude, Himalayan region — Uttar Pradesh, North India, were studied. The Johari Bhotia women had earliest menarche (¯X=15.1±1.1 years) as compared to Rang Bhotias, settled (¯X=15.6±0.9 years) and Rang Bhotias, migratory (¯X=16.0±1.0 years). The differences between all these three groups for age at menarche were significant. A trend towards increase in age at menarche with an increase in altitude has been observed, but the total fertility period in the three groups remained similar as early menarche has been found to be associated with early onset of menopause and late menarche with late menopause.     

Evaluation of the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing

To evaluate the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing, three groups of women were studied by computerized bone densitometry at the radius mid-point and at the distal point, modified according to the Abwrey technique. All women were in apparent good health and never had estrogen therapy. In the first group there were 64 women aged between 30 and 50 who were ovariectomized between 25 and 35 years of age. The second group was made up of 309 women between 50 and 55 years. In the third group there were 136 women aged 30-50 with normal ovaric function. The ordinary functions of linear polynomial regression were used to describe the variations in density with age. The percentage of postmenopausal bone loss was determined by calculating the BMC value at the start of the menopause and again twenty years later, according to the linear regression equation of postmenopausal period of each group of women in the study. The women who had natural menopause showed an average bone loss per year of 1.63% at the mid radius and 1.0% at the distal point. The ovariectomized women had an average loss of 0.85% at the mid point and 0.66% at the distal point. No significant decrease of bone mass was found before menopause. From a comparison between the two groups of women with analogous periods of menopause, it comes out that, during the first 20 years of natural menopause, estrogen deficiency is responsible for 52.5%-66.4% of the bone mineral loss, the remaining amount being attributable to other causes, connected with ageing. Estrogen deficiency is therefore, the principal factor causing bone mineral loss in natural menopause.     

Effects of radiation on the longitudinal trends of total serum cholesterol levels in the atomic bomb survivors.

The effects of radiation on the long-term trends of the total serum cholesterol levels of the Hiroshima and Nagasaki atomic bomb survivors were examined using data collected in the Adult Health Study over a 28-year period (1958-1986). The growth-curve method was used to model the longitudinal age-dependent changes in cholesterol levels. For each sex, temporal trends of cholesterol levels were characterized with respect to age, body mass index, city and birth year. We then examined whether the temporal trends differed by radiation dose. We showed that the mean growth curve of cholesterol levels for the irradiated subjects were significantly higher than that for the unirradiated subjects, and that the increase was greater for women than for men. No difference in dose response was detected between Hiroshima and Nagasaki. An increased mean level of cholesterol was evident for irradiated women in general, but a notable increase was apparent in males only for the youngest birth cohort of 1935-1945. The difference in the mean cholesterol levels between the irradiated and unirradiated subjects diminished past 70 years of age. It is not known whether this is due to natural progression or is an artifact of nonrandom variation in the rate of participation in the examinations. The maximum predicted increase at 1 Gy for women occurred at age 52 years for the 1930 cohort: 2.5 mg/dl (95% CI 1.6-3.3 mg/dl) for Hiroshima and 2.3 mg/dl (95% CI 1.5-3.1 mg/dl) for Nagasaki. The corresponding increase for men occurred at age 29 years for the 1940 cohort: 1.6 mg/dl (95% CI 0.4-2.8) for Hiroshima and 1.4 mg/dl (95% CI 0.3-2.6) for Nagasaki. Controlling for cigarette smoking did not alter the dose-response relationship. Although the difference in the mean growth curves of the irradiated and unirradiated groups was statistically significant, there was a considerable overlap in the individual growth curves of the two groups. The significant sex difference and the greater magnitude of radiation effects in women suggest that hormonal changes resulting from radiation exposure, such as accelerated menopause, is an area worth investigating to delineate the mechanisms underlying the increased cholesterol levels of the irradiated female subjects. This increase may also partially explain the increased rate of coronary heart disease seen in the atomic bomb survivors.     

Race,Menopause, Health-Related Quality of Life,and Psychological Well-Being in Obese Women

Objective: To investigate the health-related quality of life (HR-QOL) in African-American (AA) and white (W) obese women. Research Methods and Procedures: Participants were 145 obese women (80 AA and 65 W; 87 premenopausal and 58 postmenopausal) who completed the Medical Outcomes Study short form, the Brief Symptom Inventory, the Life Distress Inventory, the Satisfaction With Life Scale, and the Rosenberg Self-Esteem Scale before entering a weight-loss study. The mean age of the subjects was 46.3 ± 11.1 years and the mean body mass index was 35.2 ± 4.2 kg/m². Results: Although AA women were slightly heavier (95.3 ± 10.3 kg vs. 91.5 ± 11.6 kg, p < 0.05) and less educated (14.2 ± 3.7 years vs. 15.7 ± 3.7 years, p < 0.05) than the W women in the sample, there was no difference between the two ethnic groups in any of the reported HR-QOL variables. Menopausal status had a significant effect on HR-QOL, with premenopausal women being more distressed (p = 0.002), having more limitations in social activity (p = 0.007), and having less vitality (p < 0.001) than the postmenopausal women. This was especially true in the AA women. Discussion: These data show no difference in HR-QOL between AA and W obese women and suggest that menopausal status may have an impact on HR-QOL, especially in AA women.     

Fragile X Premutations Are Not a Major Cause of Early Menopause

Fragile X syndrome is an X-linked mental retardation condition that usually is due to a trinucleotide-repeat expansion in the FMR1 gene. Whereas full-mutation alleles (> 230 repeats) lead to fragile X syndrome, premutation alleles (approximately 60-200 repeats) are apparently non-penetrant. However, previous studies have suggested that female premutation carriers may have an increased incidence of premature menopause. To test this possible association, we screened for premutation alleles among 216 women with early menopause (at age < 47 years), 33 of whom had premature menopause (at age < 40 years), as well as among 107 control women, all of whom were ascertained solely on the basis of age at menopause. No full-mutation alleles were found; and only one premutation allele was found, but, it was in a member of the control group. These results are consistent with what would be expected on the basis of chance only. Our sample size was sufficient to rule out a > or = 3-fold increased risk of early menopause and a > or = 9-fold increased risk of premature menopause due to an FMR1 premutation, under a model considering the risk of both sporadic and familial early menopause. Likewise, our results rule out a > or = 4-fold increased risk of familial early menopause and a > or = 26-fold increased risk of familial premature menopause, under a less probable model in which only familial early menopause is considered. These results indicate that the fragile X premutation is not a major risk factor for early menopause and suggest that the risk of premature menopause to fragile X-premutation carriers may not be as great as that reported elsewhere.