Influence of menopause on high density lipoprotein-cholesterol and lipids

It has been generally accepted that high density lipoprotein cholesterol (HDL-C) level decreases with menopause in women. However, recent reports show different results. There is very little data concerning perimenopausal women. To verify these findings, lipids and lipoprotein(a) [Lp(a)] levels were compared among pre-, peri- and postmenopausal women of similar mean ages. Postmenopausal women had higher HDL-C levels than premenopausal women (p<0.001) and there was no difference between peri- and postmenopausal women. LDL-C level in perimenopausal women was lower than in postmenopausal women (p<0.001) and higher than in premenopausal women with borderline significance (p=.051). Total cholesterol levels showed stepwise elevation from premenopause to postmenopause. Perimenopausal women had lower Lp(a) levels than postmenopausal women (p<0.0005) and similar levels to premenopausal women. Lp(a) levels between 0.1 to 10.0 mg/dL were the most prevalent in pre- and perimenopausal women, and those between 10.1 to 20.0 mg/dL in postmenopausal women. In conclusion, menopause itself is associated with the elevation of HDL-C level, and the postmenopausal increase of coronary artery disease is not related to postmenopausal change of HDL-C level. Perimenopausal status, although transient, may favor Lp(a) and lipid profiles for delaying atherosclerosis.     

Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study

INTRODUCTION: Bone density is lower in postmenopausal than in premenopausal women. Recent findings have suggested that accelerated bone loss already begins before menopause. Despite numerous cross-sectional studies on menopause-related bone density, longitudinal data on perimenopausal bone density changes are scarce. This study sought to characterize the dynamics of changes leading to postmenopausal osteopenia and to possibly find the time point at which accelerated bone loss begins. METHODS: We prospectively followed 34 pre-, peri- and early postmenopausal women without prior external hormone use, measuring their lumbar spine trabecular bone density with quantitative computer tomography at 0, 2 and 6 years. The analysis of the changes over time was done in a tri-parted fashion, since menopausal status changed variably for individual subjects: we grouped the participants according to their currently valid menopausal classification for prospective (baseline classification), interim (2 years) and retrospective (6-year classification) analysis. RESULTS: Six different patterns of menopausal transition were identified in our sample. Bone loss in the groups not reaching postmenopause during 6 years of observation was >50% of the maximum bone loss observed during the study period. Invariably for all analyses, the perimenopausal phase with estrogen levels still adequate was associated with the greatest reduction of trabecular bone mineral density, reaching 6.3% loss annually in the lumbar spine. By comparison, the average rate of loss was slower in the early postmenopause; total bone loss differed by pattern of menopausal transition (one-way ANOVA p<0.05). CONCLUSION: The presented data for the first time show the perimenopausal course of trabecular bone loss (as measured by QCT of the lumbar spine). Acceleration of bone loss during perimenopause reached half-maximal values of the total bone loss measured around menopause, despite adequate serum estradiol levels.     

Climacteric symptoms in a representative Dutch population sample as measured with the Greene Climacteric Scale

OBJECTIVE: To measure climacteric symptoms in a population-based survey as assessed by the Greene Climacteric Scale and to obtain normative data for the total score and subscales (psychological, somatic, vasomotor, and sexual) of the Greene Climacteric Scale. METHODS: A sample representative of the Dutch female population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269 women aged 45-65 years) and from the NIPO-CAPI@HOME database (a sample of 235 women aged 45-65 years). They all filled in the 21 items of the Greene Climacteric Scale. The women were divided in four groups according their menopausal status: premenopausal, perimenopausal, postmenopausal and posthysterectomy. RESULTS: The total score of the Greene Climacteric Scale (mean; SD) was in premenopausal women 10.53 +/- 7.36). The score in perimenopausal women (15.78 +/- 9.09) and postmenopausal women (15.33 +/- 9.01) were significant higher than in the premenopause. The same significant difference between pre and peri/postmenopausal women was observed in the psychological, somatic and vasomotor subscales. The depression subscale did not change significantly during the menopausal transition. Hysterectomized women had the same score as postmenopausal women, reflecting the rather high mean age of the hysterectomized women (55.8 years). CONCLUSIONS: Prevalence and intensity of climacteric symptoms as expressed in the Greene Climacteric Scale do increase during the menopausal transition and stay high during the postmenopause. Data presented can be considered normative for the Greene Climacteric Scale in a mainly Caucasian population.     

Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a vasoactive, proinflammatory neuropeptide implicated in the pathogenesis of cardiovascular disease. Elevated CGRP levels during hot flushes and pregnancy suggest that reproductive hormones may influence CGRP secretion. CGRP and the related protein adrenomedullin (ADM) may function through adipose tissue-mediated effects, since adipose tissue is an important site of cytokine production and the main site for estrogen production after menopause. This study examined mRNA and protein expression of CGRP, ADM, and the receptor activity-modifying proteins and the effects of menopausal status in human adipose tissue. DESIGN: Protein/mRNA levels were determined in adipose tissue biopsy samples collected from premenopausal (n = 22: follicle-stimulating hormone, <20 IU/L; estradiol [mean +/- SEM], 434.5 +/- 87.81 pmol/L) and postmenopausal (n = 25: follicle-stimulating hormone, >20 IU/L; estradiol, 43.4 +/- 6.95 pmol/L) women. RESULTS: Our studies determined that CGRP, ADM, and receptor activity-modifying proteins were expressed in abdominal fat, adipocytes, and preadipocytes. CGRP and ADM mRNA levels were increased in abdominal subcutaneous fat in postmenopausal women compared with premenopausal women (betaCGRP: premenopause Delta cycle threshold [Ct], 31.07 +/- 0.28 vs postmenopause DeltaCt, 30.35 +/- 0.17, P = 0.035; ADM: premenopause subcutaneous fat DeltaCt, 12.41 +/- 0.2 vs postmenopause subcutaneous fat DeltaCt, 11.55 +/- 0.14, P < 0.001) with CGRP differentially expressed in subcutaneous and omental depots. CGRP protein expression was higher in postmenopausal women (P < 0.05) in both fat depots. CONCLUSIONS: Our findings suggest that adipose tissue represents an important site for CGRP and ADM production and that menopause status alters their expression in abdominal fat. This offers a potential mechanism to explain the role of CGRP in menopausal vasomotor symptoms and the increased risk of cardiovascular disease in postmenopausal women.     

Age-related changes in body composition of healthy and osteoporotic women

Objectives: The study was carried out to assess age-related changes of body composition and to evaluate the influence of lean and fat mass in bone mineral density of healthy and osteoporotic women. Methods: 166 healthy women in premenopause (43.2 ± 6.7 years), 591 healthy postmenopausal women (59.9 ± 8.1 years) and 373 women with established involutive osteoporosis (66.2 ± 7.8 years) were evaluated: bone mineral density (BMD) and soft tissue composition (fat mass, lean mass) were measured by a total body Lunar DPX device. Results: no difference in lean mass was appreciated between the groups. Fat mass was significantly lower in premenopausal women (19.5 ± 6.5 kg) and osteoporotic patients (18.8 ± 5.2 kg) than in postmenopausal healthy women (21.8 ± 5.7 kg). In premenopause weight, soft tissue mass and fat mass increased with age (P < 0.05). In postmenopause, lean mass decreased significantly in healthy women (P < 0.05). Fat mass was lower in the osteoporotics than in normals. Total BMD correlated significantly with fat and lean mass in all groups (P < 0.01). BMD/height ratio correlated significantly with fat mass (P < 0.01), not with lean mass. Conclusions: BMD is closely related to fat mass in healthy premenopausal and postmenopausal women, and in osteoporotic patients; osteoporotic patients and healthy premenopausal women are characterized by a lower fat mass than healthy postmenopausal women; fat mass may be considered one of the determinants of bone mass also in involutive osteoporosis.     

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.     

Differential associations for menopause and age in measures of vitamin K, osteocalcin, and bone density: a cross-sectional exploratory study in healthy volunteers

OBJECTIVE: To distinguish the effects of midlife aging from early postmenopause on vitamin K measures, bone formation biomarkers, and bone density. DESIGN: Cycling older volunteers (CO; 40-52 years, n = 19) were compared to cycling young (CY; 20-30 years, n = 21) and untreated, age-matched women in the early postmenopause years (EPM; 40-52 years, mean years PM = 2.8 +/- 0.5, n = 19). We assessed sex steroids, vitamin status (phylloquinone, 25-hydroxyvitamin D, retinol), osteocalcin (OC), percentage of undercarboxylated osteocalcin (%ucOC), and bone mineral density (BMD) at the spine and hip with dual-energy x-ray absorptiometry. RESULTS: CO women had similar estradiol and vitamin status as CY women, but lower OC (0.64 +/- 0.04 vs 0.97 +/- 0.08 nmol/L, P = 0.01) and BMD at the total hip (1.0038 +/- 0.032 vs 1.1126 +/- 0.030 g/cm2, P = 0.02). In the two older groups, BMD was similar at all sites, but OC was elevated in the EPM women (1.10 +/- 0.10 vs 0.64 +/- 0.04 nmol/L, EPM vs CO, P = 0.001). Although phylloquinone was highest in the EPM women, %ucOC was also higher when compared with all cycling women (21.9 +/- 1.7% vs 17.4 +/- 0.9%, n = 40; P = 0.02). CONCLUSIONS: Premenopausal women show reduced BMD despite normal estrogen profiles. %ucOC may be a specific bone marker of the early postmenopause in healthy women.     

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.     

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women

Objective

We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period.

Methods

The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured.

Results

Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p < 0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p < 0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different.

Conclusion

The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.     

Effects of postmenopausal hypoestrogenism on skin collagen

Objective: The aim of our study was to evaluate the effect of aging and postmenopausal hypoestrogenism on skin collagen content. Methods: Thirty-two women (mean age 48.78±9.86; year±S.D., range 28–68), 14 in premenopause and 18 in postmenopause, underwent skin biopsies performed during laparotomic operation. The amount of collagen type I, III and type III/type I ratio was evaluated by immunohistochemistry and computerised image analysis, and was related to age and years of postmenopause. Results: In the postmenopausal patients, a significant (P<0.01) decrease of percentage of skin collagen type I, type III and type III/type I ratio was observed in comparison to premenopausal women. The percentages of collagen type I, type III and type III/I ratio of all patients studied was significantly (P<0.01) correlated with chronological age (r=0.88, 0.89 and 0.61, respectively). Considering only postmenopausal subjects, the correlation with chronological age was significant (P<0.01) for collagen type I and type III of postmenopausal women (r=0.59, r=0.64, respectively), but not for the type III/I ratio (r=0.37, P=0.131). The percentages of collagen type I, type III and type III/I ratio of postmenopausal women showed a significant (P<0.01) inverse correlation with years of postmenopause (r=0.76, 0.73 and 0.73, respectively). Conclusions: Our data suggest that the decrease of skin collagen is an estrogen-related phenomenon.     

High Serum Osteopontin Levels Are Associated with Low Bone Mineral Density in Postmenopausal Women

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6±25.9 vs 26.3±18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.     

The effects of sulphasalazine on urinary excretion of the hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 +/- 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 +/- 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 +/- 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 +/- 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 +/- 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 +/- 3.16 nmol/mmol cr) than in the inactive (8.25 +/- 4.23 nmol/mmol cr) period in patients with premenopausal RA (p < 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 +/- 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 +/- 2.13 nmol/mmol cr) and inactive periods (5.08 +/- 0.87 nmol/mmol cr) (p > 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p < 0.01, r=0.5953 p < 0.01, r=0.6125 p < 0.01 and r=0.6232, p < 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.     

Bisphosphonates for prevention of postmenopausal osteoporosis

Our studies showed that 5 mg alendronate per day was the lowest, most effective dose that persistently prevented bone loss in recently postmenopausal women with normal bone mass. The effect on bone mass and biochemical markers was found comparable to that of commonly recommended regimens of postmenopausal HRT, and 5 mg alendronate per day is suggested as a new option for prevention of postmenopausal osteoporosis. HRT must, however, still be considered the first choice for this indication because of additional beneficial effects on other organ systems. The effect of alendronate was unaffected by bone or fat mass status, but increased with increasing postmenopausal age. The implications were that alendronate stabilized bone mass to a comparable extent in women at particular risk of osteoporosis because of thin body habitus or low bone mass and in healthy postmenopausal women with normal bone mass. Calcium supplementation was insufficient to prevent bone loss and did not add an effect on bone metabolism when combined with alendronate treatment in recently postmenopausal women. The gastrointestinal risk and adverse event profile of 5 mg alendronate per day was comparable to that of placebo, and this dose of alendronate appeared safe for long-term use. Bone loss resumed at a normal postmenopausal rate promptly after withdrawal of alendronate in early postmenopausal women consistent with a substantial underlying natural bone loss during early menopause. Oral ibandronate increased bone mass at all skeletal regions in elderly postmenopausal women with low bone mass, and 2.5 mg ibandronate per day was the lowest dose with this effect. The results are indicative of ibandronate as an option for secondary prevention of postmenopausal osteoporosis, but longer-term phase III trials should be performed before ibandronate can be recommended for this indication. The study showed that 2.5 mg ibandronate per day was efficient for prevention of bone loss and increment in bone mass in a population of women at particular risk of osteoporosis because of low bone mass. There were no differences between 2.5 mg ibandronate per day and placebo in terms of side effects, including complaints from the gastrointestinal tract, and ibandronate appeared safe for longer-term use in this dosing. Bone loss resumed at a normal postmenopausal rate when treatment was withdrawn. The response in bone mass and biochemical markers indicated that 2.5 mg ibandronate per day is equivalent to 10 mg alendronate per day in postmenopausal women. Our studies of two recently developed biochemical markers, urine CTX and serum total OC, showed that bone turnover was lowest in the premenopausal period, where these biochemical markers furthermore revealed a negative association with bone mass. It indicated that increased bone turnover contributes to a small premenopausal bone loss and resulting lowered bone mass. In consistence, a small premenopausal bone loss was observed in some regions of the hip. The biochemical markers increased at the time of menopause, consistent with initiation of the postmenopausal bone loss, and became gradually more negatively associated with bone mass as time past the menopause increased. The biochemical markers were furthermore higher in postmenopausal women with low bone mass, consistent with the characterization of postmenopausal osteoporosis as a condition with increased bone turnover. Our results consistently indicated a central role of increased bone turnover for development of low bone mass and osteoporosis. It is, however, also important to stress that the associations between biochemical markers and bone mass were too weak to allow for a valid individual estimation of bone mass based on biochemical markers. In contrast, the biochemical markers were shown as valid tools for monitoring and prediction of treatment effect of bisphosphonates. CTX, NTX, and total OC revealed the best performance characteristics in this respect. Six months after start of treatment, the level of suppression of these biochemical markers of bone resorption and formation accurately reflected the size of the 1-2 year response in bone mass in groups of women treated with bisphosphonate. This was a clear advance over bone densitometry, which has a precision error in the area of the anticipated yearly bone mass response during bisphosphonate therapy. The relationship was consistent during treatment with alendronate or ibandronate and in younger or elderly postmenopausal women. In individual patients, cut-off values of an about 40% decrease in urine CTX or NTX and an about 20% decrease in total OC validly predicted long-term prevention of bone loss. The sensitivity of prediction was high, but the specificity low. This implicated that the biochemical markers could be used as an exact method to detect "responders" to therapy, whereas "non-responders" to bisphosphonate treatment should be detected with bone densitometry in patients who do not reveal a decrease below the cut-off value in the biochemical marker during treatment. However, before such approach can be generally recommended the cut-off values of the biochemical markers should be validated in future clinical trials of bisphosphonate. Postmenopausal osteoporosis develops slowly over many years and mainly becomes a significant individual and socio-economic health problem 1-3 decades after the menopause. Prevention of postmenopausal osteoporosis by bisphosphonates is therefore likely to imply a treatment regimen of at least a decade, as presently recommended for HRT (Consensus Development Statement 1997). However, future cost-effectiveness studies should reveal when bisphosphonate treatment should ideally be initiated. Our studies showed that the bisphosphonates were effective over the range from general recommendation (recently postmenopausal women with normal bone mass) to a reservation for women at particular risk of osteoporosis (elderly women, thin women, or women with osteopenia). Presently available biochemical markers could be used for groupwise and individual monitoring and prediction of treatment response. Most presently available biochemical markers, however, have the drawback of a low specificity. Recent studies of CTX measured in serum are promising, and indicate that this new biochemical marker might have overcome these drawbacks due to a pronounced response to treatment and a low long-term biological variation (Christgau et al. 1998b, Rosen et al. 1998, and 2000).     

Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism

BACKGROUND: Although overt hyperthyroidism is a well known cause of bone loss, systemic effects of subclinical hyperthyroidism (SH) are still a matter of debate. Objective: The aim of this cross-sectional study was to evaluate the effect of endogenous SH on bone in relation to the menopausal status. METHODS: Bone mass and turnover were assessed in a group of 60 patients with endogenous SH due to multinodular goitre; 30 of them were premenopausal and 30 early postmenopausal (mean age, 40.9 +/- 7.3 and 57.7 +/- 6.75, respectively). Sixty healthy women matched for age-, BMI- and menopausal status served as controls. Three different skeletal sites were evaluated using two different techniques: lumbar spine and femoral neck were assessed by DEXA whereas the proximal phalanges were evaluated by quantitative ultrasonometry (QUS), measuring the amplitude-dependent speed of sound (Ad-SoS). Serum osteocalcin and urinary deoxypyridinoline (DPD) were also determined as markers of bone turnover. RESULTS: A significant decrease was found in femoral BMD (P < 0.05) and phalangeal Ad-SoS (P < 0.001) in pre- and postmenopausal patients compared to controls, being greater in those postmenopausal. Lumbar BMD was decreased only in postmenopausal patients (P < 0.05). Bone turnover markers were higher in patients than in controls and in post- than in the premenopausal ones. A significant negative correlation was found between femoral BMD, Ad-SoS and serum free T3 levels, the latter considered a marker of disease activity. CONCLUSIONS: A significant increase in bone turnover markers and a decrease in bone mass was found in women affected by endogenous SH, being greater in early postmenopausal patients. Cortical rich bone was mainly affected. Both QUS and the conventional DEXA technique were equally able to determine bone density decrease related to mild thyroid hormone excess and sexual hormone decrease.     

Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care

OBJECTIVE: To compare the relationship between vasomotor symptoms (hot flushes and night sweats) and depression in perimenopausal women with that in postmenopausal and older premenopausal women. DESIGN: Questionnaire data assessing current depressive symptoms (Center for Epidemiologic Studies Depression Scale), hot flushes, night sweats, menopausal status, depression history, hormonal therapy use, and demographic characteristics were collected from women aged 40 to 60 years seeking primary care. Multivariable logistic regression models were used to examine the relationship between vasomotor symptoms and depression. RESULTS: Depression (defined by a Center for Epidemiologic Studies Depression Scale score >/= 25) was observed in 14.9% of 141 perimenopausal women, 13.9% of 151 postmenopausal women, and 7.6% of 184 older premenopausal women. Recent vasomotor symptoms were reported by 53.9% of perimenopausal women, 43.7% of postmenopausal women, and 20.7% of older premenopausal women. Perimenopausal women with vasomotor symptoms were 4.39 times more likely to be depressed than those without vasomotor symptoms (95% CI, 1.40-13.83), an association that did not change after controlling for depression history. In contrast with perimenopausal women, postmenopausal and older premenopausal women with vasomotor symptoms did not have a significantly greater risk for depression than women of the same menopausal status without vasomotor symptoms (adjusted odds ratios, 1.28 and 1.77; 95% CI, 0.47-3.46 and 0.53-5.89, respectively). CONCLUSIONS: Hot flushes and night sweats are associated with depression in perimenopausal women. Further investigation is warranted to elucidate the mechanism by which hot flushes may be associated with depression in perimenopausal women and not in postmenopausal or older premenopausal women.     

Serum Cathepsin K levels are not suitable to differentiate women with chronic bone disorders such as osteopenia and osteoporosis from healthy pre- and postmenopausal women

Objectives

Cathepsin K (CatK) is expressed in high levels in osteoplasts and therefore plays an important role in bone resorption. Thus CatK serum levels may be useful in the diagnosis of chronic bone disorders such as osteopenia and osteoporosis. Therefore we aimed at studying CatK levels in women putatively free of known skeletal disorders.

Study design

In total, 121 voluntary women, 27 premenopausal women aged between 20 and 45 years, and 94 postmenopausal women aged 59–81 years, all free of known skeletal disorders were included. All women underwent bone density measurement, routine labor parameter and measurement of serum CatK levels.

Main outcome measures

Based on WHO criteria, women were stratified in four groups (premenopausal: healthy; postmenopausal: healthy, osteopenia, osteoporosis), and their CatK levels were statistically analyzed.

Results

Using WHO criteria 21 postmenopausal women had normal bone mineral density (BMD), 49 had osteopenia and 24 had osteoporosis. All 27 premenopausal women had normal BMD. There were no significant differences in CatK between these groups. ROC analysis resulted in poor diagnostic validity of CatK, where the area under curve was 0.544. There was no correlation neither between CatK and other biomarkers as C-telopeptide crosslaps (CTX) or bone-specific alkaline phosphatase (BAP) nor between CatK and age.

Conclusions

Serum levels of CatK are not suitable to differentiate women with osteoporosis from healthy subjects.     

去势大鼠5种骨转换生化指标的动态变化

目的： 对去势大鼠骨质疏松动物模型形成过程中5种骨转换指标的变化及其相关性进行研究。方法: 将3月龄SD雌性大鼠分为3组：切除卵巢组(OVX)，假手术组(sham)和对照组(control)，术前和术后分别于1、1.5、2、2.5、3和4月检测血清骨钙素(OC)、碱性磷酸酶(ALP)、 骨碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRAP)和羟脯氨酸(HYP)水平，并作大鼠胫骨病理切片检查。结果: OVX组血清OC、ALP、BALP、TRAP和HYP水平均明显高于sham组，其变化顺序依次为：TRAP/HYP→OC→ALP/BALP；5种指标之间呈显著正相关；术后3月OVX组大鼠胫骨小梁结构有病理改变。结论: 去势大鼠属于高转换型骨质疏松；在模型形成过程中，骨吸收指标的变化早于骨形成指标的改变；骨转换指标是反映绝经后早期骨量丢失的灵敏指标。     

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.     

Bone resorption versus estrogen loss following oophorectomy and menopause

OBJECTIVES: To investigate if menopause and oophorectomy may represent different risk factors for bone resorption/loss. METHODS: The urinary levels of pyridinoline (Pyr) and deoxypyridinoline (D-pyr), the serum levels of type I carboxy-terminal pyridinoline cross-linked telopeptide (ICTP), and lumbar bone mineral density (BMD), were compared in 80 Japanese women after menopause or oophorectomy. These women were divided into four groups of 20 women each as follows: early postmenopausal stage (early physiologic menopause < 3 years before study entry); late postmenopausal stage (physiologic menopause > or = 3 years before study entry); early postoophorectomy stage (oophorectomy < or = 03 years before study entry); or late oophorectomy stage (oophorectomy > 3 years before study entry). RESULTS: Lumbar BMD was significantly lower in the late groups compared to their respective early groups and was lowest in the late postoophorectomy group. The ratio of D-pyr/creatinine (Cr) was not significantly different among the four groups. The ratio of Pyr/Cr was significantly higher in the early postoophorectomy subjects compared with either late group. The serum level of ICTP was significantly higher in the early postoophorectomy group compared to all other groups. CONCLUSIONS: These findings suggest that serum ICTP may be useful in detecting changes in bone resorption after oophorectomy and that women are at greater risk for bone resorption after oophorectomy than after physiologic menopause, although this difference appears to diminish with time.     

Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.