Bone density patterns after normal and premature menopause

Objectives: The investigation of the effect of time and type of menopause on bone mineral density (BMD) at different ages. Methods: Five hundred and fourteen women, who had never received any hormonal substitution were studied in a cross-sectional design: 177 with normal (NMP), 210 with surgical (SUMP) and 127 with premature natural (EMP) menopause. Age at menopause was 49.1±3.9, 38.3±4.7 and 38.1±4.2 years (mean±1 S.D.), respectively. BMD was measured at L2–L4 vertebrae and proximal femur by the DEXA method. Results: EMP women presented significantly lower vertebral BMD than NMP women in the 45–55-years segments (P<0.001), but did not differ from SUMP women. This group exhibited lower vertebral BMD than NMP between 45 and 50 years (P<0.001). Regarding femoral neck, EMP women exhibited lower values than SUMP in the 45–50 and 55–65 age segments (P<0.001) whereas SUMP women presented significantly higher BMD values than NMP women after 55 years of age (P<0.001). The percentages of women with vertebral BMD (T-score values) in the osteoporotic range were significantly greater in EMP compared with either NMP or SUMP groups (both P<0.001) whereas in femoral neck lower in SUMP than the other two categories. Conclusions: Women with either natural or surgical premature menopause exhibit lower BMD of trabecular bone compared with normal menopause women at the age segments 45–55 and 45–50, respectively. However, surgical menopause women exceed normal menopause women in their mixed bone BMD values after 60 years as well as premature natural menopause women at almost all age segments.     

Total and regional bone mineral content in relation to menopause

Total body bone mineral content (TBBM) and anatomical region bone mineral content (head, trunk and extremities) were measured using dual-energy X-ray absorptiometry in 188 women aged 60 ± 6 years, of whom 154 were normal and 34 were osteoporotic. Of the 154 normal subjects, 90 were premenopausal (40 aged 44 ± 3 years and 50 aged 34 ± 8 years), the remaining 64 being postmenopausal and aged 58 ± 7 years. There were no TBBM or regional changes in the premenopausal women, whereas there was a significant reduction in bone mineral content in the postmenopausal as compared with the premenopausal women in all regions. The osteoporotic subjects showed a general decrease (P < 0.001) in all measurements which was more marked in the trunk. The rate of TBBM reduction was 16% in the normal postmenopausal women and 29% in the osteoporotic subjects. All the postmenopausal women (both normal and osteoporotic) showed lower TBBM values than those in the Wisconsin trial, similar results being obtained in the case of the premenopausal group. Such differences can only be explained by hardship experienced by these now postmenopausal women during their childhood and adolescence.     

Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass

Objective: To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies. Methods: A total of 104 naturally or surgically postmenopausal women were studied, and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass, a factor overlooked in several studies. They were randomized into four groups of 26 patients each: the untreated control group (mean age 50 ± 5 years); the hormonal replacement treatment (HRT) group (mean age 48 ± 6 years), which was treated for 24 days each month with transdermal 17β-estradiol, 50 mg/day, together with medroxiprogesterone, 10 mg during 12 days; the calcium group (mean age 50 ± 4 years), which was treated with elemental calcium, 1 g/day; and the calcitonin group (mean age 50 ± 5 years), which was treated for 10 days each month with eel calcitonin, 40 IU/day and with elemental calcium, 500 mg/day. Full-body bone densitometry, for measuring total body bone mineral content (TBBMC), was carried out in all the women at baseline and 1 year. TBBMC was corrected for body weight by dividing its value by body weight (TBBMC/W). Results: After 1 year TBBMC/W was lower in every group: −2.14% (P < 0.001) in the control group; −0.14% (P = NS) in the HRT group (P < 0.05 vs. controls); −0.18% (P = NS) in the calcium group (P < 0.05 vs. controls); and −0.06% (P = NS) in the calcitonin group (P < 0.01 vs. controls; P < 0.05 vs. calcium and HRT). Conclusions: These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass.     

Difference in the effect of adiposity on bone density between pre- and postmenopausal women

Objectives: Elevated bone mineral density (BMD) in obese women is partially attributable to the higher circulating estrogen levels derived from extraglandular aromatization in adipose tissue. However, it remains unclear whether there is an effect of overall adiposity on BMD in both pre- and postmenopausal women. The difference in the effect of overall adiposity on BMD between pre- and postmenopausal women was investigated. Materials and methods: Subjects were 296 premenopausal women with regular menstruation and 233 postmenopausal women. Age, age at menarche, years since menopause (YSM, in postmenopausal women), weight, height, and body mass index were recorded. Total fat mass amount, lean mass amount, and percentage of body fat were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). Lumbar spine BMD (L2–L4) was measured by DEXA. In each group, significant determinants of BMD were investigated using univariate and stepwise multiple regression analysis. Results: In postmenopausal women, YSM, lean mass amount, total fat mass amount, and height were significant determinants of BMD (R²=0.273, P<0.001). In premenopausal women, only two variables including lean mass amount and age at menarche were significant determinants of lumbar spine BMD (R²=0.110, P<0.001), but total fat mass amount and percentage of body fat were not significant determinants of BMD. Conclusion: The effect of overall adiposity on BMD is more prominent in postmenopausal women than in premenopausal women.     

Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women

Objective: This study was to investigate whether the effect of lean and fat mass component on bone mineral density (BMD) differs between pre- and postmenopausal women. Materials and methods: Subjects were 360 pre- and 193 postmenopausal Japanese women with right side dominance. Age, height, and years since menopause (YSM, in postmenopausal women) were recorded. Body fat and lean body mass were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). BMD of the vertical axis (L2-4 of the lumbar spine, pelvis, bilateral legs, and total body) and horizontal axis (arms) were also measured by DEXA. Results: In premenopausal women, lean body mass was independently correlated with BMD of the left arm (partial correlation COEFFICIENT=0.417), right arm (0.430), L2-4 (0.285), pelvis (0.276), left leg (0.403), right leg (0.412), and total body (0.377) (P<0.001). However, body fat mass was not correlated with several BMD sites except for pelvis BMD (0.187, P<0.01). In postmenopausal women, body fat mass was independently correlated with BMD of the left arm (0.248, P<0.01), L2-4 (0.188, P<0.05), pelvis (0.263, P<0.01), left leg (0.228, P<0.01), right leg (0.319, P<0.001), and total body (0.188, P<0.01)). However, lean body mass was correlated with BMD in only three segmental regions including left arm (0.175), right arm (0.217), and left leg (0.210; P<0.05). Conclusion: Lean body mass is a significant determinant of BMD in premenopausal women, while body fat mass is a significant determinant in postmenopausal women.     

Relationship between skin collagen and bone changes during aging

There is evidence that skin collagen content and bone mass are influenced by estrogen deficiency, both of them declining in the years following menopause. The aim of our study was to analyze the relationship between changes in skin collagen content and bone mass during aging. A total of 76 nulliparous women who had been admitted for surgery of non-malignant processes were studied. All subjects were arranged into five age-groups (from 20 to 60 years). Bone mineral density was measured by dual photon absorptiometry and expressed in g/cm₂as the mean of the second to fourth lumbar vertebrae. Additionally, in all patients skin biopsies were taken from a non-sun exposed site in the lower abdomen (4 cm above the pubic symphysis) and osteocalcin levels were determined. Collagen decreased significantly with age after the 40s (P < 0.001) and after menopause (P < 0.001). Changes in bone mass were closely related to those detected in collagen (r = 0.586 P < 0.0001). In conclusion, our data suggest that bone mass and skin collagen decline in parallel with aging and that the hypoestrogenism developing in postmenopausal years has a significant effect on skin collagen content. Nevertheless, the question of whether osteoporosis is an intrinsic collagen disorder remains to be demonstrated.     

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women

Objective: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. Methods: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 μg/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. Results: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. Conclusion: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.     

The influence of physical activity on the response of bone mineral density to 5 years tibolone

Objectives: Menopausal hormone replacement therapy (HRT) maintains bone mineral density (BMD) and reduces risk of fracture in postmenopausal women. It has been suggested that sex steroids and loading may have synergistic effects on bone. We therefore investigated whether habitual physical activity influences the response of BMD to tibolone in postmenopausal women. Methods: The subjects were 42 postmenopausal women aged mean (SE) 65.8±6.2 year who had taken tibolone for prevention/ treatment of osteoporosis over 5 years. Bone mineral density was measured annually by dual X-ray absorptiometry and physical activity was assessed using accelerometers after 5 years therapy. Results: Twenty-six women were classified as having low physical activity (LPA; <15 min day⁻¹) and sixteen as high physical activity (HPA; >15 min day⁻¹). Spine BMD did not differ significantly between groups at baseline and increased significantly by 2 years of treatment with further increase to 5 years. The magnitude of increase did not differ between groups. Hip BMD at baseline was 7.3% higher in HPA women (P=0.07). Hip BMD increased over 2 years tibolone treatment in LPA women (+5.6%, P<0.01) whilst no significant change occurred in the HPA group (−0.5%). This difference in response between groups was statistically significant (P=0.002) and persisted after adjustment for age and body mass (P=0.002). Hip BMD was maintained in both groups over the subsequent 3 years of treatment. Conclusions: Spine BMD increased significantly in response to tibolone irrespective of physical activity participation. The more physically active women had higher hip BMD at baseline but the response to tibolone was greater in the less physically active women. The difference in response between groups may be due to physically active women having lower resorption at the hip and hence reduced response to anti-resorptive effects of HRT.     

Testosterone enhances estradiol''s effects on postmenopausal bone density and sexuality

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1–L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1–L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P<0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.     

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00±0.15, 5.36±0.17 (P<0.01), 5.63±0.13 (P<0.05) mmol/l, respectively for total cholesterol; 4.13±0.15, 3.64±0.15 (P<0.05), 3.82±0.12 (P<0.05) mmol/l, respectively for LDL-cholesterol; 48.19±9.90, 26.59±5.53 (P<0.03), 25.12±4.62 (P<0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r=−0.27, P<0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16±0.07 mmol/l) than in the premenopausal group (0.96±0.07) or postmenopausal group not using HRT (0.87±0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.     

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures

Objective: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). Method: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n=24), mean age 33.7±8.1 years; (2) postmenopausal women (n=32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than −2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7±7.9 years; and years since menopause (ysm), 12.6±8.3); (3) postmenopausal women (n=32, including 19 patients with fractures) whose BMD values in terms of T score, were below −2.5 S.D. (mean age 62.9±8.6 years; and ysm 15.9±9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. Results: There were significant differences amongst the three groups in mean ALP (P<0.001, by analysis of variance) TRAP (P<0.006) and NTx/Cr (P<0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r=−0.392, P<0.001; r=−0.447, P<0.001 and r=−0.327, P<0.002, respectively) and ysm (r=−0.374, P<0.001; r=−0.474, P<0.001 and r=−0.333, P<0.002). Conclusions: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.     

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

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.     

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.     

Influence of menopause on serum lipids and lipoproteins

The influence of the menopause on serum lipids and lipoproteins was examined longitudinally at 6-week intervals for 2–3 years in pre-menopausal women undergoing the menopause. Serum lipid and lipoprotein profiles were also examined cross-sectionally in 4 groups of pre-menopausal, perimenopausal and post-menopausal women, who were followed up longitudinally at 3-monthly examinations for 1–2 years. The results covering 1360 examinations and 270 woman-years are reported here.

Serum concentrations of total cholesterol (P = 0.001), low-density-lipoprotein (LDL) cholesterol (P = 0.001) and triglycerides (P < 0.05) increased significantly as a consequence of the menopause and all increases occurred within 6 months of cessation of menstrual periods. High-density-lipoprotein (HDL) cholesterol decreased significantly (P < 0.05) as a consequence of the menopause, but the decline occurred gradually over the 2 years preceding cessation of menses. In addition to the menopausal changes, serum concentrations of total cholesterol and LDL-cholesterol increased gradually in the pre-menopausal and post-menopausal years, but were significantly related to biological age only in the pre-menopausal groups (P < 0.05). Serum triglycerides and HDL-cholesterol levels remained virtually unchanged in the pre-menopausal as well as the post-menopausal groups and were only influenced by the actual menopause.

Serum lipids and lipoproteins are thus significantly altered as a consequence of the menopause. The result is a more atherogenic lipid profile which may partly explain the increased risk of cardiovascular disease observed in post-menopausal women.     

Beneficial effects of pravastatin in peri- and postmenopausal hyperlipidemic women: a 5-year study on serum lipid and sex hormone levels

Objectives: The aims of the present study are to assess the 5 year effects of pravastatin on serum lipids and lipoproteins in women around the menopause and to assess the effects of pravastatin on serum gonadotropins and sex steroid levels over a long-term period. Methods: We evaluated the long-term efficacy of pravastatin on serum lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride) in 121 patients (47 premenopausal and 74 postmenopausal women) suffering from primary hypercholesterolemia. The effects of this lipid-lowering drug on serum gonadotropins and sex steroids (estradiol, estrone, and testosterone) are also reported. Results: Pravastatin produced a remarkable reduction in the serum total cholesterol level of 19.2±9.3% (P<0.0001) and 18.9±11.8% (P<0.0001), and in LDLl-cholesterol of 25.1±18.7% (P<0.0001) and 24±18.0% (P<0.0001) after 24 and 60 months’ treatment, respectively. In hypertriglyceridemia, pravastatin also produced a remarkable reduction in triglyceride of 29.3±27.3% (P<0.0001) and 39.9±20.4% (P<0.0001) after 24 and 60 months of treatment, respectively. We found that serum gonadotropins and sex steroid levels changed naturally as a function of age from pre-therapy levels in the premenopausal patients after 60 months of treatment. Conclusions: Pravastatin was well tolerated over 5 years and was a very effective lipid-lowering agent for both hypercholesterolemia and hypertriglyceridemia with no effect on the biosynthesis of sex steroids. These findings suggest that pravastatin can be used in the treatment of hypercholesterolemia with/without high triglyceride levels in women around the menopause.     

The effect of menopause on regional and total body lean mass

Objectives: To investigate the effect of menopause on regional and total body lean mass. Methods: Evaluation of 123 healthy premenopausal women (40.6±10.8 years) and 123 healthy postmenopausal women (61.8±7.5 years). All subjects were right side dominant. Regional (head, bilateral arms, trunk, and bilateral legs) and total body lean mass were measured using whole-body scanning by dual-energy X-ray absorptiometry. Baseline characteristics including age, height, weight, and menopausal state were recorded. These variables were compared between pre- and postmenopausal women. In all subjects, correlations between regional or total body lean mass and baseline characteristics were investigated using univariate and multiple regression analyses. Results: Height, and lean mass of the trunk, bilateral legs and total body were significantly lower in postmenopausal women than in premenopausal women, while lean mass of the bilateral arms did not differ between the two groups. On univariate regression analysis, bilateral arms lean mass was positively correlated with height (P<0.001). Trunk, bilateral legs, and total body lean mass were inversely correlated with age and menopausal state (P<0.001), but were positively correlated with height (P<0.001). After adjusting for age and height, trunk lean mass was still correlated with menopausal state (P<0.01). Conclusions: Menopause induces lean mass loss, independent of aging and height. Trunk lean mass is more prone to decline with menopause than lean mass of other sites.     

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites

Objectives: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. Methods: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense™ (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). Results: 143 ERT users for 5.2±3.6 years were compared with 139 ERT non-users (age: 57.0±5.3 and 57.5±5.5, respectively). Both groups were 7.1±5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (−0.55±1.30 and −1.36±1.60, respectively, P<0.0001), and at the TIB (−0.73±1.34 and −1.28±1.45, respectively, P=0.003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). Conclusions: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.     

Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia

We sought to determine whether menopausal status or postmenopausal hypercholesterolemia affects forearm resistance artery endothelial function. We studied the forearm resistance artery endothelial function in 75 Japanese women: 25 premenopausal volunteers, 25 postmenopausal women with normal serum low-density lipoprotein (LDL) cholesterol concentrations, and 25 hypercholesterolemic postmenopausal women. Excluded from the study were patients with hypertriglyceridemia, hypertension, or diabetes, cigarette smokers. The forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. The serum concentrations of lipoprotein (a) [Lp(a)] were significantly higher in the hypercholesterolemic postmenopausal group than in the other two groups (P<0.01). These lipid parameters were similar between the premenopausal and postmenopausal women with normal cholesterol. The FBF responses to reactive hyperemia were significantly lower in the postmenopausal hypercholesterolemic women than in the other two groups (P<0.01). The reactive hyperemia also was impaired in the postmenopausal group with normal cholesterol as compared with the premenopausal group (P<0.01). Increases in FBF after NTG were similar between the three groups. By stepwise multivariate analysis, menopausal status and serum LDL cholesterol was the significant predictor of forearm endothelial function. These findings suggest that reactive hyperemia is impaired in forearm resistance arteries after menopause, especially in postmenopausal women with hypercholesterolemia.     

Plasma androstenedione and oestrone levels in the climacteric syndrome

Plasma androstenedione (A) and oestrone (E₁) levels were measured by radioimmunoassay in a group of 78 healthy women who had undergone a natural menopause. Of this total, 23 were symptomless (Group 1), 39 presented with a moderate climacteric syndrome (Group 2) and 16 had a severe climacteric syndrome (Group 3). The average body weight was found to be significantly higher in Groups 2 (P < 0.01) and 3 (P < 0.05), than in Group 1, but the age distribution and number of years since the menopause were similar in all three groups. Nevertheless, significantly lower levels of A (0.75± 0.06 ng/ml, P < 0.01, in Group 2; 0.24 ± 0.05 ng/ml, P < 0.001, in Group 3) and E₁ (20.80 ± 2.18 pg/ml, P < 0.05, in Group 2; 12.22 ± 1.65 pg/ml, P < 0.001, in Group 3) were observed in the women with climacteric symptoms than in those with no symptoms (A = 1.08 ± 0.08 ng/ml, E₁ = 27.73 ± 2.22 pg/ml in Group 1).

Since, after the menopause, the concentrations of A and E₁ in the plasma represent the most important source of oestrogens, these results suggest that climacteric symptoms are related to oestrogen deficiency which is secondary to low A production.