Healthy Early Postmenopausal Women Research Articles

Impact of combined hormone replacement therapy on serum lipid metabolism: New aspects

The objective of this study was to evaluate the impact of combined estrogen-progestogen therapy on low density lipoprotein (LDL) particle size (determined by the LDL cholesterol I apolipoprotein B ratio). The prospective study was carried out on 139 healthy Danish early postmenopausal women. The subjects were randomized to placebo or to 2 mg estradiol valerate equivalents, either sequentially combined with 75 μg levonorgestrel, 10 mg medroxyprogesterone acetate (MPA), or 150 μg deso-gestrel, or continuously combined with 1 mg cyproterone acetate. LDL particle size was calculated before treatment and at nine well-defined times during the subsequent 84 days.LDL particle size was reduced by all four treatments. This change was statistically significant for estradiol valerate combined with levonorgestrel and MPA (6.2 ± 2.7% and 5.6 ± 2.1% (mean ± SEM), respectively; p < 0.05for both, placebo-corrected). Estradiol valerate combined with MPA induced cyclic (progestogen-minus estrogen-related values) decreases (-6.3 ± 2.6%; p < 0.05), and with levonorgestrel there were cyclic increases (5.1 ± 2.7%; p = 0.067) in LDL particle size (placebo-corrected).In conclusion, combined estrogen-progestogen therapy causes a decrease in LDL particle size. A cyclic variation in LDL cholesterol/apolipoprotein B ratio was observed during sequential treatment.

Oral continuous clodronate in the prevention of early postmenopausal bone loss

The aim of this study was to investigate the effects of 12 months of continuous oral clodronate therapy on bone metabolism in healthy early postmenopausal women. A total of 137 evaluable healthy early postmenopausal women were given 400 mg/d oral clodronate continuously for 12 months. Thirty age-matched healthy early postmenopausal women were included as controls. Measures of lumbar L 2–L 4 and ultradistal radius bone mineral density (LBD and URBD, respectively) and bone turnover biochemical analyses were performed at baseline and after 6 and 12 months of therapy. After 12 months, statistically significant increases in LBD (+1.78 ± 0.87%) and in URBD (+4.23 ± 0.91%) were shown in the clodronate group versus the control group (−4.6 ± 0.96% and −2.80 ± 0.51%, respectively; P < 0.01). At the same time, significant decreases in serum osteocalcin (−4.2 ± 1.5%), free calcium (−2.5 ± 0.7%), and urinary hydroxyproline (−9.7 ± 3.8%) levels were observed in the treated group ( P < 0.01 vs baseline). Within the clodronate group, patients were divided into two subgroups on the basis of biochemical indexes indicating a normal (subgroup N) or high (subgroup H) bone turnover. Statistically significant differences between subgroups N and H were observed after 6 and 12 months in the percent change in ultradistal forearm mineral density, serum alkaline phosphatase, and urinary hydroxyproline excretion. Thus 12 months of oral clodronate treatment was shown to be effective in preventing bone loss in early postmenopausal women, and the drug was particularly effective in high bone turnover conditions.

Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease?

The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early post-menopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0.01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0.05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.

Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use

Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17β-oestradiol with I mg norethisterone acetate [E 2 + NEta]; 2 mg oestradiol valerate with 75 μg levonorgestrel [E 2V + Lng]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E 2V + Mpa]; or 1.5 mg 17β-oestradiol with 150 βg desogestrel [E 2 + DG]. A placebo-controlled study lasting 12–24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3–6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E 2V + LNG, 21% of the women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E 2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E 2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E 2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E 2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness.

Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss: do they exist?

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, but the prevalence of non-responders in healthy early postmenopausal women is not known. In order to study this, we reviewed data from three published studies, each carried out in a randomized, placebo-controlled, longitudinal design over 2 year, that used seven hormone replacement therapies. Bone mineral content (BMC) was measured in the distal forearm by single photon absorptiometry. A mathematical model for elimination of measurement errors was applied to published BMC data. After this correction, we found that only 1.2% of early healthy postmenopausal women who are receiving HRT in conventional doses will lose more than 1% of forearm BMC per year. In conclusion, most, if not all, healthy early postmenopausal women who might need HRT against loss of bone will respond positively in forearm BMC to such therapy.

Vertebral postmenopausal bone loss is reduced in overweight women: a longitudinal study in 155 early postmenopausal women.

To study the influence of excess body weight on vertebral postmenopausal bone loss, 155 healthy early postmenopausal women were divided into 2 groups according to their body mass index (BMI = weight/height2) and prospectively followed over a mean 31-month period. Spinal (L2-L4) bone mineral density was measured by dual photon absorptiometry. The annual rate of vertebral bone loss (percentage) was significantly reduced (-0.54 +/- 1.1% vs. -1.46 +/- 1.6%; P < 0.05) in the overweight group (BMI, > or = 25; n = 40) compared to that in the normal weight group (BMI, < 25; n = 115). At baseline, a significant decrease in the urinary calcium/creatinine ratio was observed in the overweight group, which suggested a decrease in bone turnover. A significant correlation was found between the annual rate of bone loss and the BMI (r = 0.21; P < 0.05), but not the body weight. The positive correlation between vertebral postmenopausal rate of bone loss and BMI was confirmed after adjustment for age and time since menopause. Moreover, plasma dehydroepiandrosterone sulfate levels were higher in the high BMI group than in the normal BMI group (P < 0.05). We conclude that within the first years after menopause, moderate excess body weight significantly reduces vertebral postmenopausal bone loss. This effect is probably related to excess adipose tissue through increased conversion of estrogen from adrenal precursors and/or increased production of adrenal androgens.

92301263 Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women

92301263 Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women

Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women.

The objective was to study the independent relationships of body mass index and endogenous estradiol to cortical bone mineral density and the rate of cortical bone loss at the radius in healthy early postmenopausal women. Fifty-one healthy early postmenopausal women (aged 58-66 years) participated. The women were a subset of a population participating in a 10-year longitudinal study to elucidate the influence of dietary calcium on the rate of cortical bone loss. Cortical bone mineral density at the radius, body weight and body height were measured annually (1979-89). Concentrations of sex steroids were measured in serum samples collected during the last year of follow-up (1989). Endogenous estradiol levels, although significantly positively correlated with body mass index, were not independently related to bone mass indices of the radius. Body mass index, on the other hand, was found to be positively related to cortical bone mineral density and negatively to the rate of bone loss, even after adjustments had been made for confounding factors. Our results suggest that the level of total estradiol is not an important determinant of cortical bone mass indices in healthy early postmenopausal women. Other factors of overweight such as mechanical loading may be important.

One measurement of serum total cholesterol is enough to predict future levels in healthy postmenopausal women

purpose: The purpose of this study was to investigate how well a single or double measurement of serum total cholesterol represents the spontaneous, future level in a particular person. subjects and methods: The spontaneous fluctuations in serum total cholesterol levels in 169 healthy early postmenopausal women were followed during the course of 12 years. Serum total cholesterol was measured enzymatically. results: The initial measurement and the long-term level of serum total cholesterol were highly related (p <0.0001). The long-term level (calculated for each woman as the area under the curve of serum total cholesterol versus time) was not statistically significantly different from the initial level (mean difference: 0.036 ± 0.046 mmol/L [mean ± SEM], NS). The initial serum total cholesterol level was then used to classify each woman into a high or a low cholesterol group, according to the current recommendations. The predictive value of an initial total cholesterol value in the high level (greater than or equal to 6.2 mmol/L) group was 84%, when compared with the long-term level. The predictive value of an initial total cholesterol level below 6.2 mmol/L was 80%. No improvement in these parameters was found when the average of the initial two (or three, when the difference exceeded 0.9 mmol/L) measurements were used as the baseline value. The fluctuations in serum total cholesterol levels were mainly due to short-term variations. conclusion: For screening purposes, one measurement of serum total cholesterol in a woman gives a good estimate of the long-term level. The current data indicate that repeated measurements of serum total cholesterol do not improve the predictability of future cholesterol levels. The data also suggest that, at least in postmenopausal women with an elevated level of serum total cholesterol, one should proceed immediately to lipoprotein analysis for further risk assessment.

Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.

To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss. Population based study. Outpatient clinic for research into osteoporosis. 178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism. Bone mineral content of the forearm and values of biochemical markers of bone turnover. The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles' fracture and 20 a spinal compression fracture. The group with Colles' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture). One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.

Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives

To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. One hundred thirty-nine healthy early postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 micrograms levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 micrograms desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A1 (Apo A1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A1 parallel those in HDL-C. All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.

Relation of axial bone mass to habitual calcium intake and to cortical bone loss in healthy early postmenopausal women : Bone 1990 11/1 (7–13)

A group of 60 healthy early postmenopausal women participating in an ongoing study on the effect of habitual calcium intake on the rate of cortical bone loss at the radius, were subjected to additional skeletal measurements at the lumbar spine and femoral neck. The women were between 58 and 64 years of age, and 3 to 10 years postmenopausal. No correlations were found between habitual calcium intake (range 560 to 2580 mg/day) and either bone mineral content of the radius, the lumbar spine and the femoral neck, or spine deformity index. Body mass index was found to be positively correlated with bone mass indices of the radius (decrease of BMD and BMD) and femoral neck (BMC), but not with of the lumbar spine (BMC, BMD and SDI), even after adjustments had been made for confounding factors. Although the rate of cortical bone loss at the radius correlated significantly with bone mineral content of lumbar spine and femoral neck, the error in predicting bone mass of the lumbar spine or the femoral neck from longitudinal measurements of cortical bone at the radius was high. The rate of cortical bone loss did not correlate with the spine deformity index. We conclude that in healthy women in early menopause, the bone mineral content of both the appendicular and the axial skeleton are not influenced by habitual calcium intake. A higher body mass index has a protective effect on the appendicular skeleton but appears to be less protective to the axial skeleton. Longitudinal measurements of cortical bone mass are of limited value to predict bone density of the appendicular and axial skeleton.

Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives

purpose: To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. patients and methods: One hundred thirtynine healthy early Postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 μg levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 μg desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. results: All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A 1 (Apo A 1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/ MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A 1 parallel those in HDL-C. conclusion: All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.

Assessment of osteoporotic spine deformity

For the objective assessment of the severity and progression of osteoporotic deformities of the spine, a mathematical model has been developed which permits evaluation of a single set of radiographs of the spine without reference to absolute values of vertebral height. The model was based on measurements of anterior, central and posterior heights of the vertebrae Th4 to L5 of 50 subjects, aged 20 to 50 years, without a history or radiologic signs of osteoporosis or other metabolic bone disease and without traumatic deformities. The model follows a simple sinusoidal function which describes the general form of the spine, adapted to the individual's height and build. A spine fracture index (SFI) is produced and the method allows calculation of the total number of vertebral deforming events (VDE), manner. The method has been used prospectively in 178 spine radiographs of 109 subjects (60 healthy early postmenopausal women and 49 with osteoporosis). Sensitivity and specificity of SFI in identifying osteoporotic patients were 94 and 88% respectively. In all 109 persons, densitometry of the spine was performed by dual photon absorptiometry at the same time. In the osteoporotic patients the examination was repeated once or twice during fluoride therapy for osteoporosis. The SFI and the total score of VDE and VDS correlated significantly with lumbar bone mineral content (r = -0.38 P less than 0.001). The method offers the advantage of being objective, not dependent on projection errors, and adaptable to the shape of the individual spine.

Relation of axial bone mass to habitual calcium intake and to cortical bone loss in healthy early postmenopausal women

A group of 60 healthy early postmenopausal women participating in an ongoing study on the effect of habitual calcium intake on the rate of cortical bone loss at the radius, were subjected to additional skeletal measurements at the lumbar spine and femoral neck. The women were between 58 and 64 years of age, and 3 to 10 years postmenopausal. No correlations were found between habitual calcium intake (range 560 to 2580 mg/day) and either bone mineral content of the radius, the lumbar spine and the femoral neck, or spine deformity index. Body mass index was found to be positively correlated with bone mass indices of the radius (decrease of BMD and BMD) and femoral neck (BMC), but not with of the lumbar spine (BMC, BMD and SDI), even after adjustments had been made for confounding factors. Although the rate of cortical bone loss at the radius correlated significantly with bone mineral content of lumbar spine and femoral neck, the error in predicting bone mass of the lumbar spine or the femoral neck from longitudinal measurements of cortical bone at the radius was high. The rate of cortical bone loss did not correlate with the spine deformity index. We conclude that in healthy women in early menopause, the bone mineral content of both the appendicular and the axial skeleton are not influenced by habitual calcium intake. A higher body mass index has a protective effect on the appendicular skeleton but appears to be less protective to the axial skeleton. Longitudinal measurements of cortical bone mass are of limited value to predict bone density of the appendicular and axial skeleton.

Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women

One hundred and ninety-one healthy early postmenopausal women, aged 45-54 years, were randomized to 2 years of treatment with (a) percutaneous 17 beta-oestradiol combined with progesterone (n = 29) or placebo (n = 28); (b) oral oestradiol valerate combined with cyproterone acetate (n = 37) or placebo (n = 39); (c) 24R, 25 (OH)2D3 (n = 29) or placebo (n = 29). We measured the plasma bone Gla-protein (BGP), bone mineral content of the proximal forearms (BMC), bone mineral density in the spine (BMDspine) and total body bone mineral (TBBM) in all the women before, and during, the study. In the groups of women receiving the oestrogen preparations, the plasma BGP decreased highly significantly (P less than 0.001) to a premenopausal level. The initial plasma BGP concentration was significantly related to the loss of BMC (P less than 0.001) in the placebo groups. The changes in plasma BGP were an indicator of the oestrogen response on BMC. We conclude that serial determinations of plasma BGP are useful for determination of the effect of oestrogen therapy in groups of patients, and that plasma BGP measured at the time of the menopause indicates what the rate of bone loss will be.

Climacteric symptoms after oral and percutaneous hormone replacement therapy

One hundred and ten (110) healthy early post-menopausal women with mild subjective vasomotor symptoms (mean Kupperman index score 11) participated in a long-term, double-blind, placebo-controlled therapeutic trial. The effects of 2 hormone regimens were evaluated. Group I received percutaneous oestrogen therapy for 2 yr, opposed by oral micronized progesterone (200 mg) during the second year, while Group II received oral 17β-oestradiol valerate together with cyproterone acetate (CPA). The serum oestrogen concentrations differed markedly in the 2 treatment groups. In Group I the serum/oestrone/oestradiol ratio was 1 (comparable to the pre-menopausal value), but in group II the ratio was > 5. Despite the difference in the serum oestradiol and oestrone concentrations, the mean symptom scores were rapidly and similarly reduced in both treatment groups ( P < 0.001). They remained low throughout the study and were not significantly different from pre-menopausal values.

UNCOUPLING OF BONE FORMATION AND RESORPTION BY COMBINED OESTROGEN AND PROGESTAGEN THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS

10 healthy early postmenopausal women were treated with oestrogen and progestagen for two cycles of 28 days. Serum alkaline phosphatase and bone Gla protein increased during progestagen administration, whereas urinary excretion of calcium and hydroxyproline fell significantly during treatment, independently of progestagen intake. Thus, bone formation increases when progestagen is added to oestrogen treatment, whereas bone resorption may be kept constantly low during oestrogen plus progestagen treatment, leading to a positive calcium balance. This makes possible effective treatment of postmenopausal osteoporosis—treatment of elderly postmenopausal women with substantial bone loss before their bones have fractured or when they have just started to fracture. This study design can be used for easy and rapid screening of potential drugs for the prevention and treatment of postmenopausal bone loss.