Factors affecting bone loss around menopause in women without HRT: a prospective study

OBJECTIVES: The present study evaluated the effects of menopause and other putative bone loss modifying factors on bone mineral density (BMD) change. METHODS: The study population, 396 healthy women aged 48-59 years with no history of hormone replacement therapy (HRT) use or any bone affecting disease or medications, was selected from a random sample (n=2025) of the OSTPRE-study cohort (n=13100) in Kuopio, Finland. BMD at lumbar spine (LS) and three areas of proximal femur (femoral neck (FN), Ward's triangle (W), trochanter (T)) was measured with dual X-ray absorptiometry at baseline in 1989-1991 and at 5 years in 1994-1997. RESULTS: 116 women who reported the beginning of menopause during the follow-up (perimenopausal) had the greatest mean annual bone loss (-1.22%/year (LS), -0.87% year (FN), -1.14%/year (W), -0.36%/year (T)). In women under 5 years postmenopausal at baseline (early postmenopausal, n=172) bone loss rate was significantly lower than in perimenopausal women. In women over 5 years postmenopausal at baseline (late postmenopausal, n=108) bone loss rate was significantly further decreased only at lumbar spine. In peri- and postmenopausal women the annual BMD change was best described as a trinomial function of the duration of menopause at all sites (P<0.03). Of the life-style factors studied protective effects were found in weight increase in both spinal and femoral bone (P=0.010/P<0.001), high baseline weight in spine (P<0.001) and high grip strength in femoral neck (P=0.002). CONCLUSION: The beginning of menopause is accompanied by significant bone loss, which decreases in later menopause. Few other physiological and life-style factors were found to significantly contribute to this phenomenon.     

Quantitative peripheral computed tomodensitometric study of cortical and trabecular bone mass in relation with menopause

Changes in total, cortical and trabecular bone mass were studied using quantitative peripheral computed tomodensitometry on the forearm of 58 normal eugonadal premenopausal women and 116 normal postmenopausal women to evaluate the evolution of bone components with age. In premenopausal women, no changes were seen in any bone component. In postmenopausal women, only trabecular bone mass diminished in the first 5 years after menopause (P < 0.05). It continued to decrease in the next 5 years (P < 0.05), but not later. Cortical bone mass experienced a significant loss 6–10 years after menopause (P < 0.001), and more than 15 years after menopause (P < 0.0005). These results are similar to those obtained with other techniques, and document the differing behavior of the cortical and trabecular bone components with years of menopause.     

Relative contribution of aging and menopause to changes in lean and fat mass in segmental regions

Objective: The aim of the study was to investigate the relative contribution of aging and menopause to the changes in lean and fat mass in segmental regions. Materials and methods: Subjects were 365 pre- and 201 postmenopausal Japanese women aged between 20 and 70 years old. Age, height, weight, body mass index (BMI, Wt/Ht²), age at menopause, years since menopause (YSM), and menopausal status were recorded. Lean and fat mass of the arms, trunk, legs, total body, and the ratio of trunk fat mass to leg fat mass amount (trunk–leg fat ratio) were measured by dual-energy X-ray absorptiometry (DEXA). Regional (arms, lumbar spine, pelvis, legs, and total body) bone mineral density (BMD) were measured by DEXA. Results: Total body lean mass and regional BMD decreased (P<0.001), while percentage of body fat, trunk fat mass, and trunk–leg fat ratio increased (P<0.001) with aging and after menopause. On multiple regression analyses, trunk and total body lean mass were inversely correlated with menopausal status (P<0.001 and 0.05, respectively) but not with age. Trunk fat mass, trunk–leg fat ratio, and percentage of body fat were positively correlated with age (P<0.01) but not with menopausal status. Regional BMD were more inversely correlated with menopausal status (P<0.001) than age. Conclusion: Decrease in lean mass and BMD are more menopause-related, while the shift toward upper body fat distribution and overall adiposity are more age-related. Lean tissue is similar to bone tissue from the viewpoint of more undergoing menopausal effect.     

Relationship between BMD, dental panoramic radiographic findings and biochemical markers of bone turnover in diagnosis of osteoporosis

OBJECTIVE: Mandibular indices, measured on panoramic radiographs, may be useful screening implements for low skeletal bone mass density (BMD). Recent studies suggest that radiographic examination of mandible may constitute an effective process for the early diagnosis of osteoporosis. Biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women. In contrast to the vast information available on dental radiographic findings and BMD only scarce data exist on the relationship between panoramic mandibular indices and biochemical markers. The aim of this study was to examine the diagnostic performance of dental panoramic radiography and biochemical markers of bone turnover in relation to BMD at the spine in a group of postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, mandibular cortical width (MCW) at the mental region and morphologic classification of mandibular inferior cortex (MIC grade) was performed on dental panoramic radiographs in a group of 141 postmenopausal women 38-81 years of age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. Serum bone alkaline phosphatase (BAP) was measured with an enzyme immunoassay. Cross-linked N-telopeptides of type I collagen (NTx) corrected for creatinine secretion, was measured with a competitive-inhibition enzyme-linked immunosorbent assay ELISA. RESULTS: In our study, a decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 47% (p-value<0.05), having taken into consideration the effect of the years elapsed since menopause. The increase of alkaline phosphatase (ALP) per unit increase the likelihood of osteopenia or osteoporosis to 14% (p-value<0.05), having checked the effect of the years since menopause. A decrease in MCW by 1mm increases the likelihood of moderately or severely eroded cortex to 97% (p-value<0.001). The increase in ALP per 1 unit increases the likelihood of moderate or severe erosion per 10% (p-value<0.05), taking into account the years since menopause. CONCLUSIONS: Our results suggest that dentists have sufficient clinical and radiographic information that enables them to play a significant role in early diagnosis of osteoporosis in postmenopausal women. Panoramic radiographs and biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women.     

Bone metabolism during the perimenopausal transition: a prospective study.

OBJECTIVE: Changes in biochemical markers of bone formation and resorption were followed over the course of 1 year in premenopausal, perimenopausal and early postmenopausal women. METHODS: Sixty-four subjects were analyzed, grouped according to their menstrual pattern, menopausal complaints and endocrinological parameters to be premenopausal (n=20), perimenopausal (n=24) or early postmenopausal (n=20). The parameters studied at four visits during the 12-month study period were the urinary pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD), and N-terminal telopeptide (NTX) as bone resorption markers, as well as osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) in serum, representing bone formation. The longitudinal changes over time as well as intergroup differences were analyzed using generalized estimating equations (GEE) in connection with Wald statistics. RESULTS: Over the course of 1 year BAP levels decreased in the late premenopausal group (P<0.05). The perimenopausal group exhibited significant changes of PYD, DPD and OC (P<0.01), NTX levels were higher than in premenopause. Postmenopausal subjects had elevated NTX values, while PYD and DPD levels remained close to the perimenopausal range. Only for OC a time effect was seen during postmenopause. CONCLUSIONS: Changes in bone turnover already begin in late premenopause, when decreased bone formation may precede increased bone resorption. The rise of NTX from late premenopause through early postmenopause indicates diagnostic sensitivity of this parameter to changes in bone metabolism induced by estrogen withdrawal. PYD and DPD do not follow this pattern, but change significantly with time during perimenopause to then remain largely unchanged in early postmenopause.     

Osteoporosis and bone metabolism in postmenopausal women with osteoarthritis of the hand

OBJECTIVE: Osteoarthritis and osteoporosis are two major health problems affecting postmenopausal women. Epidemiological observations seem to demonstrate a possible inverse relationship between osteoarthritis and osteoporosis. Erosive osteoarthritis (EOA) of the hand is a destructive form of primary osteoarthritis. This study evaluated bone mineral density and bone metabolism changes in erosive and nonerosive hand osteoarthritis women. DESIGN: Fifty-five women (mean age, 59 years; body mass index, 23 +/- 1.4 kg/m) who had been postmenopausal for an average of 9 years and who presented with hand osteoarthritis according to American College of Rheumatology criteria were enrolled in the study; 15 women showed clinical and radiological evidence of hand EOA. Twenty women matched for age, age at menopause, and body mass index formed the control group. Bone mineral density (g/cm) was measured at the hip and lumbar spine using dual-energy x-ray absorptiometry. Serum and urinary calcium and phosphate, serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and urinary breakdown products of bone matrix (CrossLaps) were analyzed. RESULTS: Women with hand EOA had a statistically significant lower T- and Z-score L2-L4 value than non-hand EOA women and controls (P < 0.01). Moreover, postmenopausal women with hand EOA had higher significant percentage of osteoporosis at lumbar spine when compared with non-hand EOA postmenopausal women and controls. Any statistically significant difference in osteocalcin and CrossLaps serum levels was noted among women with hand EOA, hand osteoarthritis, and controls. CONCLUSIONS: Our data suggest that postmenopausal women with clinical and radiological EOA are at risk for development of osteoporosis.     

Precedence of bone loss over changes in body composition and body fat distribution within a few years after menopause

OBJECTIVE: The present study investigated the sequence of certain phenomena with a few years after menopause: bone mineral loss, decrease in lean body mass, increase in body fat mass, or the shift toward upper body fat distribution. METHODS: Subjects were 64 postmenopausal women aged 50-53 years with right side dominance (mean age+/-S.D., 51.4+/-1.1 years), and 59 age-matched regularly menstruating premenopausal women (51.7+/-1.2 years) serving as controls. Height, weight, body mass index (BMI, wt./ht.(2)), age at menopause (in postmenopausal women), and years since menopause (YSM) were recorded. Anthropometries, bone mineral density (BMD), and body fat distribution were assessed by dual-energy X-ray absorptiometry. RESULTS: Age at menopause and YSM in postmenopausal women were 51.7+/-1.2 and 2.3+/-1.7 years, respectively. Age, height, weight, BMI did not differ between the two groups. BMD of the bilateral arm, lumbar spine (L2-4), pelvis, and total body were significantly lower in postmenopausal women. However, leg BMD, trunk-leg fat ratio, body fat mass, and the lean body mass did not differ between the two groups. CONCLUSION: Within a few years after menopause, bone mineral loss precedes lean mass loss, increase in body fat mass, and a shift toward upper body fat distribution. We can say that bone tissue is more sensitive to hypogonadism than lean and fat tissues are.     

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones,SHBG and bone mineral density

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2–3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E₁) and 17-β-estradiol (E₂) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E₂. During the next 3 years, the levels of E₂ and E₁ showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), Δ⁴-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E₁, E₂ and T. BMI correlated positively with E₁ and E₂. The concentrations of the free fraction of E₂ and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.     

Soy isoflavones for osteoporosis: an evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.     

Comparison of VO2max and disease risk factors between perimenopausal and postmenopausal women

OBJECTIVE: This study determines whether maximal oxygen consumption (VO2 max) is higher in perimenopausal women compared with similarly aged postmenopausal women and whether the lower VO2 max in postmenopausal women is associated with a higher total and visceral fat mass, less favorable lipid and glucose metabolism, and lower bone mineral density (BMD). DESIGN: Participants were 18 perimenopausal women (mean +/- SD; irregular menstrual cycle in the past 6 months) aged 49 +/- 4 years and 18 postmenopausal women (no menstrual cycle in the past year) aged 52 +/- 2 years who were matched for body mass index and race. Women were sedentary, and none were on hormone replacement therapy. Body composition (dual-energy x-ray absorptiometry and CT), VO2 max, fasting concentrations of sex steroid hormones, lipoproteins, insulin, and glucose were determined. RESULTS: VO2 max was 17% lower (22 +/- 3 v 27 +/- 7 mL.kg.min; P 相似文献   

Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study

OBJECTIVE: To determine the relationships among bone mineral density changes, bone marker changes, and plasma estrogens in postmenopausal women receiving estrogen replacement therapy. DESIGN: A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo daily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a subset after 12, 18, and 24 months. RESULTS: Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip) compared with baseline and placebo at 6, 12, 18, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral density changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. CONCLUSIONS: Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, unopposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12, 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.     

Bone mass and bone diminution of the axial and peripheral skeleton in normal and osteoporotic Austrian females.

Measurements of bone mass were performed in 133 healthy Austrian women using the quantitative computed tomography technique of the lumbar spine and single photon absorptiometry of the distal forearm. The data were compared with those of 110 Austrian females with osteoporotic spine fractures. A significant difference in mean bone density of the lumbar spine was observed between normal and osteoporotic patients in every decade, whereas forearm measurements showed statistical differences in the seventh and eighth decade but not in the sixth decade. Compared to age matched controls, bone mass of osteoporotic women showed the following diminution: sixth decade: distal forearm: -12.7%, spine: -46.8%; seventh decade: distal forearm: -19.0%, spine: -36.7%, eighth decade: distal forearm: -15.4%, spine: -33.7%. It appears that postmenopausal osteoporosis involves greater loss of bone in the spine in the first decade after menopause and slows down after this period, whereas loss of forearm bone mineral density (BMD) increases with advancing age.     

Peripheral QCT: a low-risk procedure to identify women predisposed to osteoporosis

A low-risk procedure is described for the precise quantitation of changes of trabecular and cortical bone density at peripheral measuring sites. The method is based on quantitative computed tomography (QCT). Bone parameters are calculated for a sample volume common to all examinations of a patient. This is achieved by matching stacks of tomograms according to the cross sectional area of the bone measured. With the help of a special-purpose CT system the described procedure enables a reproducibility for trabecular and cortical bone parameters of 0.3% (1 SD) at a local radiation dose of 0.1 mSv (10 mrem). The method was used to assess the individual changes in bone density of 39 perimenopausal women during an observation period of 2 to 3 years. The results are grouped according to their menstrual state. Regularly menstruating women experience minute or no changes in bone density. After menopause the interindividual differences are considerable: some women lose bone excessively, others remain relatively stable. The frequency distribution of the rate of bone loss appears to be bimodal. Hence women can be classified in fast losers and slow losers. We conclude that the rate of bone loss may be most helpful in the identification of those women predisposed to osteoporosis.     

The association between postmenopausal vertebral bone mineral density and estrogen receptor gene alleles in ethnic Japanese living in western Japan.

Bone mass and its mineral content has been shown to be under genetic control. Our purpose in this study was to assess whether estrogen receptor genotypes influence changes in bone mass in post menopausal Japanese women and clarify the regional differences in Japanese women. Pvu II and Xba I restriction enzyme fragment length polymorphism of the estrogen receptor gene and its relationship with vertebral bone mineral density were examined in 300 unrelated post menopausal women, aged 42-69 years, from the Kinki region in Japan. Vertebral bone mineral density was evaluated at the lumbar spine (L2-4) by dual energy X-ray absorptiometry. We found no relationship between any single restriction site polymorphism and the Z-score of bone mineral density. However, the allelic haplotype PPXx was found to be associated with a significantly low bone mineral density (Z-score for the lumbar spine -1.118+/-1.270 vs. PPxx 0.04+/-1.150; p<0.01, vs. ppxx 0.387+/-1.226; p<0.05, respectively). We suggest that ER gene polymorphism is associated with low bone mineral density and that this partly explains the cause of post menopausal bone loss in Japanese women. The contradictory conclusions compared with previous studies in the Japanese population regarding the association of BMD with ER RFLPs demands further investigation.     

Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer

BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.     

Effect of natural early menopause on bone mineral density

OBJECTIVES: Early menopause (EM) is included among the risk factors for osteoporosis. Several studies have shown that women with early menopause have lower bone mineral density (BMD) than those with normal expected age of menopause. The aim of our cross-sectional study was to investigate the effects of time of menopause on vertebral bone mass in healthy postmenopausal women and to evaluate if early menopause is a risk factor for lower vertebral BMD. METHOD: We studied 782 who had never received drugs acting on bone mass. The study population was divided into three groups: women with early, normal (NM), and late (LM) menopause. Our study population was further categorized in 5-year age segments between 45 and >75. RESULTS: The three groups examined did not differ for age, age at menarche, body mass index (BMI), and vertebral BMD, while there were significant differences in age at menopause and years since menopause. Our study showed that women with EM presented significantly lower vertebral BMD than NM and LM in 50-54 age segments. Beyond 55 years, EM, NM, and LM women had no differences in lumbar BMD values. CONCLUSIONS: In conclusion, controversial data demonstrated that the absolute amount of bone loss is greater after early menopause than after normal or late menopause, even if a slight effect of early menopause on bone mass cannot be excluded.     

Changes in the cortical and trabecular bone compartments with different types of menopause measured by peripheral quantitative computed tomography

Our objective was to study the changes in the bone mineral density of the cortical and trabecular compartments with different types of menopause. A total of 153 normal postmenopausal women (mean age 48 ± 5 years) were studied. The women were divided into three groups based on mean age at menopause: early menopause (menopause before 43 years), normal menopause (menopause at 44–52 years), and late menopause (menopause after 52 years). The number of years since menopause was similar in all three groups (±5 years). Cortical and trabecular bone mineral density was determined in all the women using peripheral quantitative computed tomography. Our results show that only the trabecular bone mineral density differed significantly among the groups (Kruskal-Wallis: P = 0.0029). The women with early menopause bad a lower trabecular bone density than the women with normal and late menopause (P = 0.0019 and P < 0.0001, respectively). Among the women with early menopause, 22 had experienced menopause before the age of 40 and 25 after the age of 40; there were significant differences in trabecular bone mineral density between these two subgroups (P < 0.05). Trabecular bone mineral density, the only variable studied that varied among the groups, correlated significantly with the duration of reproductive life (simple linear regression: r = 0.340, P < 0.0001). In conclusion, these findings emphasize the importance of the duration of reproductive life as a determinant of bone mass in women.     

Relationship between soft tissue body composition and bone mass in perimenopausal women

OBJECTIVES: Perimenopause, the transition into menopause, marks the beginning of accelerated bone loss, contributing to the development of osteoporosis, a major public health problem. This perimenopausal transition has also been associated with a decrease in body lean mass, an increase in fat mass, and an increase in body weight. How these changes in fat mass and lean mass may influence bone mineral density (BMD) is currently unknown. The purpose of this study is to determine the independent effect and relative contribution of lean mass and fat mass to BMD in perimenopausal women. MATERIAL AND METHODS: The sample consisted of 43 sedentary perimenopausal women (age: mean = 49.6; S.D. = 3.2) with an intact uterus and ovaries, participating in a study of exercise and perimenopausal symptoms. Total body BMD, regional BMD, and soft tissue body composition were measured by dual-energy X-ray absorptiometry. Other measures including age, height, weight, and serum FSH and E2 were also obtained. RESULTS: Findings revealed that 14% of these perimenopausal women had low bone mass (osteopenia) in the lumbar spine and/or the femoral neck. Overall body fat mass and lean mass had positive relationships with BMD of lumber spine and the femur. However, using multiple regression analyses, only lean mass and ethnicity remained significant predictors for BMD of the femoral neck (r2 = 45%) with lean mass explaining more variance than ethnicity. Lean mass was the sole predictor of total proximal femur BMD explaining 38% of the variance. Fat mass was not a significant predictor of BMD at any skeleton site. CONCLUSIONS: These findings suggest that body lean mass, not fat mass, is a significant contributor to femoral BMD in perimenopausal women.     

Influence of the menopausal transition on polysomnographic sleep characteristics: a longitudinal analysis

Study ObjectivesTo evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics.MethodsThe Study of Women’s Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for two to three nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep.ResultsThe women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power.ConclusionsSleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.     

Reproductive aging and risk for chronic disease: Insights from studies of nonhuman primates

Reproductive aging and ovarian senescence have considerable public health relevance because they are associated with increased risk for coronary heart disease (CHD), osteoporosis and other degenerative conditions including cognitive decline and potentially the metabolic syndrome. It has been suggested that the hormonal dysregulation that occurs during the perimenopausal transition may play a role in the initiation of pathobiological changes (e.g., adverse lipid profiles, atherosclerotic plaques) that will increase risk for chronic disease (e.g., CHD) during the postmenopausal years. Moreover, these early changes are suspected to establish a trajectory of disease progression that may be difficult to alter if interventions are not begun until after menopause. Even a slight increase in the rate of disease progression during the pre- or perimenopausal years could have substantial consequences for health and quality of life over the postmenopausal lifespan. Thus, the years leading up to menopause may offer a “critical window” for interventions aimed at reducing the postmenopausal disease burden. The relationship between perimenopausal hormonal dysregulation and the risk for chronic disease is poorly understood due, in large part, to the lack of appropriate animal models of the perimenopausal transition and natural menopause. In this review we assesses studies of nonhuman primates (NHPs) evaluated in various reproductive stages (naturally pre-, peri- and postmenopausal, surgically menopausal) and their contribution to our understanding about risk factors for chronic disease. Finally, because large numbers of naturally perimenopausal and menopausal NHPs are not available for research at present, experimental approaches that have the potential to hasten the onset of the perimenopausal transition will be described.