Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study

A 3-year, open-label, monocenter study was performed on 60 patients with postmenopausal established osteoporosis treated with monofluorophosphate and calcium supplement (MFP/Ca) combined with hormone replacement therapy (HRT). Bone mineral density (BMD) after 3 years increased by 15.5% in the lumbar spine (L2-L4) and by 2.3% in the femur neck. During the 3 years, a total of six new vertebral fractures (NewVF) occurred in five patients (8.3% incidence) and a total of six nonvertebral fractures (Non-VF) occurred in six patients (10% incidence). Back pain score already decreased significantly after 6 months of treatment and, at the end of the 3rd treatment year, the pain score had decreased by 84%. The treatment was well tolerated, with only few mild or moderate adverse events. The results were compared with those of a previous study conducted in the same center with a similar protocol with a calcium supplement on patients suffering from postmenopausal established osteoporosis and treated with MFP/Ca but without HRT. It could be inferred that with the 3-year treatment, the combination of MFP/Ca with HRT protects from NewVF in one patient of every two treated. The comparison suggests that the MFP/Ca with HRT combination could be more effective than MFP/Ca alone in protecting from NewVF and from Non-VF, justifying further double blind, prospective randomized studies pursuing this investigation.     

Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy,as evidenced by reducing bone resorption and urinary calcium excretion

Recent reports suggest that soy protein may reduce the risk of osteoporosis in peri- and postmenopausal women. The objective of this study was to examine whether soy supplementation exerts beneficial effects on serum and urinary biomarkers of bone metabolism in postmenopausal women, regardless of whether or not they are on hormone replacement therapy (HRT). A total of 71 women were randomly assigned to either soy protein (SP) or milk-based protein (MBP), 40 g daily for 3 months, in a double-blind parallel design. Forty-two women completed the study (20 on SP and 22 on MBP). Overall, both protein supplements positively influenced serum IGF-I, known to correlate with bone formation. However, SP had a more pronounced effect on IGF-I than MBP. Urinary deoxypyridinoline (Dpd) excretion, a specific biomarker of bone resorption, was significantly reduced by SP, but not by MBP when all women were included. Furthermore, women on MBP experienced a 33% increase in urinary calcium excretion, whereas SP did not have such an effect. To evaluate whether SP affects women differently on the basis of their HRT status, data from women on HRT (n = 22) and those not on HRT (n = 20) were analyzed separately. The subanalysis of the data indicated that SP had the greatest impact on serum IGF-I (an increase of 97%) in the women not on HRT. The changes in urinary Dpd due to SP were only observed in women not on HRT, indicating that the overall decrease in Dpd occurred with SP in the absence of HRT. These results indicate that soy protein may positively influence bone and calcium homeostasis in postmenopausal women, particularly those not on HRT.     

The effect of continuous combined hormone replacement therapy on arterial reactivity in postmenopausal women with established angina pectoris.

Most epidemiological studies have suggested that the administration of estrogen reduces cardiovascular risk in healthy postmenopausal women. More recently, however, in the large Heart Estrogen/progestin Replacement Study (HERS), it was unexpectedly found that in women with established cardiovascular disease, there was overall no difference in cardiovascular events between those treated with combined oestrogen/progestin hormone replacement therapy and those on placebo. The aim of this study was to examine the effect of combined hormone replacement therapy on arterial reactivity in women with existing angina pectoris. Seventy-four postmenopausal women with angina pectoris were recruited into a 16 week double-blind, placebo-controlled study of treatment with 2 mg of estradiol combined with 1 mg of norethisterone acetate daily. The median endothelium-dependent change in arterial relaxation increased from 5.00 to 7.69% in the treatment group and decreased from 5.57 to 3.64% in the controls. The median endothelium-independent change in arterial relaxation increased from 6.49 to 7.27% in the treatment group and decreased from 4.39 to 2.07% in the controls. The changes in arterial relaxation between the treatment and control groups were not statistically significant. The administration of estrogen/progestin did not significantly improve either endothelium-dependent or -independent arterial relaxation in postmenopausal women with established cardiovascular disease. We have previously shown that estrogen/progestin treatment improves endothelium dependent relaxation in healthy women. The results of our study provide one possible explanation for the clinical findings of the HERS study. In women with established cardiovascular disease, arterial relaxation does not increase significantly in response to treatment with combined hormone replacement therapy.     

Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women

To evaluate the effect of alendronate combined with hormone replacement therapy (HRT) on postmenopausal osteoporotic Chinese women living in Taiwan, we treated 151 women (age range, 47-70 years; mean, 61 years) with conjugated equine estrogen (0.625 mg), medroxyprogesterone 5 mg, and elemental calcium 500 mg daily with either alendronate 10 mg (n = 79) or placebo (n = 72), and measured their bone mineral density (BMD) at the lumbar spine and hip every 6 months for 3 years. Urine N-telopeptide of type I collagen corrected by concentration of urine creatinine (NTx/Cr) and serum osteocalcin (OC) concentration was also measured at weeks 2, 4, and every 3 months from month 3 for 2 years. Significantly higher percentage increases in BMD at the lumbar spine (P < .0001, 2-way analysis of variance) throughout the 36-month treatment period were found in the alendronate plus HRT group than in the HRT-only group. However, there was no difference in BMD at the femoral neck and trochanter between these 2 groups. Treatment with alendronate plus HRT resulted in a 10.1% increase at the L-spine BMD and a 7.7% increase at the trochanter BMD at the end of the 3-year study period (P < .01, compared with baseline at both sites). A significant decline in urine NTx/Cr was observed at week 4 in the alendronate plus HRT group, whereas in the HRT-only group, a significant decline in urine NTx/Cr occurred at month 9. By the end of 24 months, urine NTx/Cr decreased by 49.7% in the alendronate plus HRT group (P = .001 compared with a 20.4% increase in the HRT group). A significant decline in serum OC level occurred at month 3 in the alendronate plus HRT group, whereas a similar decline was observed at month 6 in the HRT-only group. By the end of 24 months, serum OC decreased by 52.2% in the alendronate plus HRT group (P < .001 compared with a 1.5% increase in the HRT-only group). Subjects treated with alendronate plus HRT had a significantly greater percentage decrease in urine NTx/Cr (P = .0001) and serum OC (P = .0007) than subjects treated with HRT only throughout the 24-month treatment period by 2-way analysis of variance comparison. There was no difference in upper gastrointestinal or drug-related side effects between groups. In conclusion, our data suggest that the use of alendronate combined with HRT for 3 years was well tolerated and it significantly increased BMD at the L-spine and hip in postmenopausal Chinese women with osteoporosis. This regimen is safe and can be used in subjects who have no satisfactory response to a single agent or who have very low BMD with multiple risks. However, this study does not indicate whether HRT plus alendronate has any greater effect on BMD than alendronate alone.     

Effects of tibolone and cyclic hormone replacement therapy on glucose metabolism in non-diabetic obese postmenopausal women: a randomized study

OBJECTIVE AND METHODS: To study the effects of hormone replacement therapy on glucose metabolism, 31 obese (body mass index > or =27 kg/m(2)) postmenopausal women were randomized to treatment with tibolone (2.5 mg once daily; TIB; n=16) or to oestradiol valerate (2 mg daily)-dydrogesterone (20 mg daily for 2 weeks every 3 months; ED; n=15) for 12 months. Oral (OGTTs) and intravenous glucose tolerance tests (IVGTTs) and a euglycaemic hyperinsulinaemic clamp were performed before and at 6 and 12 months of treatment. RESULTS: TIB decreased the rates of whole body glucose uptake (WBGU) at 6 (P=0.04) and 12 months (P<0.001), but it did not have a significant effect on glucose tolerance. In OGTTs, serum insulin and C-peptide concentrations 2 h after the oral glucose load were increased (P<0.001 and P=0.05 respectively) at 12 months of treatment with TIB, but no changes in the areas under the curve (AUC) of insulin or C-peptide were observed. Furthermore, TIB did not have a significant effect on insulin secretion, the metabolic clearance rate (MCR) of insulin or hepatic insulin extraction. Treatment with ED did not modify the rates of WBGU, but it increased the MCR of insulin (P=0.017) and hepatic insulin extraction (P<0.001) and tended to decrease the insulin AUC (P=0.07). Moreover, glucose tolerance slightly deteriorated during this treatment (P=0.02). Although early phase insulin secretion evaluated by the serum C-peptide response at 30 min in the OGTT increased (P=0.046), the first-phase insulin response during the IVGTT decreased (P=0.05) during ED treatment. CONCLUSIONS: Despite the impairment in peripheral insulin sensitivity, TIB treatment had a neutral effect on glucose tolerance, possibly due to a compensatory decrease in endogenous glucose production. The increased demand on insulin induced by ED, due to both a stimulatory effect on pancreatic beta cells and increased insulin metabolism, may explain the slightly detrimental effect on glucose tolerance with this treatment.     

Additive effect of alfacalcidol on bone mineral density of the lumbar spine in Taiwanese postmenopausal women treated with hormone replacement therapy and calcium supplementation: a randomized 2-year study

OBJECTIVE: To evaluate the effect of 1alpha-hydroxyvitamin D3 on bone mineral density of the lumbar spine in postmenopausal women receiving hormone replacement therapy and calcium supplement. DESIGN: A randomized, prospective 2-year clinical trial. PATIENTS AND MEASUREMENTS: A total of 240 postmenopausal women were enrolled with randomized assignment of 120 patients to each treatment group (the D + E group of 1alpha-hydroxyvitamin D3 + sequential combined HRT + calcium supplement; the E group: sequential combined HRT + calcium supplement). None of the patients had received HRT for menopausal syndrome or osteoporosis before being enrolled in our study. Serum biochemical assays, electrolytes and calcitonin were performed at baseline and after 6 and 12 months of treatment. Bone mineral density (BMD) of L2-L4 was measured by dual energy X-ray absorptiometry (DXA) at the initial assessment and after 12 and 24 months of treatment. RESULTS: One hundred and five patients (87.5%) in the D + E group and 92 patients (76.7%) in the E group completed the first 1-year study. Ninety-six patients (80%) in the D + E group and 80 patients (66.7%) in the E group completed the 2-year trial. Renal function, liver function, electrolytes and calcitonin showed no significant changes during the first year of follow-up. In the D + E group, the BMD of L2-4 increased 3.24 +/- 0.32% from baseline after 1 year (P < 0.05) and 5.32 +/- 0.23% after 2 years of treatment (P < 0.05). On the other hand, the changes of BMD in the E group were 1.12 +/- 0.34% after 1 year (P < 0.05) and 2.42 +/- 0.26% after 2 years of treatment (P < 0.05). The changes of BMD of L2-L4 of the D + E group were higher than the changes of the E group after both 1 and 2 years of treatment (P < 0.05). CONCLUSIONS: Our study demonstrated that combination of 1alpha-hydroxyvitamin D3 with HRT is superior to HRT alone for the preservation of bone mineral density in postmenopausal women under calcium supplementation.     

Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women

BACKGROUND: Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial, but the presence of osteoporosis is regarded as an indication for parathyroidectomy. Hormone replacement therapy (HRT) is a possible alternative therapy in osteopenic postmenopausal women with the disorder, and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy. Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism. METHODS: We report the results of the extension from 2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism. Of 23 postmenopausal women with primary hyperparathyroidism, 11 received active HRT with conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo. Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects. None of the 23 patients withdrew during the extension period. RESULTS: Changes in bone mineral density were more positive in those taking HRT than placebo, with the between-group differences at 4 years being 4.6% in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At skeletal sites composed predominantly of cortical bone, there was a progressive divergence of the 2 groups. Biochemical markers of bone turnover remained lower throughout the study in women taking HRT. When rates of bone loss were compared between the placebo group and healthy women of comparable age, bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism, but only in the total body and its legs subregion was this difference significant. CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery. Bone loss seems to be accelerated in untreated primary hyperparathyroidism.     

Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women

Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined therapy with bisphosphonate and HRT is likely to be used in clinical practice, and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postmenopausal women received daily treatment with conjugated equine estrogens (0.625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion of the investigator. The primary efficacy end point was the percent change from baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were also assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spine BMD were observed in both treatment groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between the two groups was not statistically significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant (P < 0.05) at the femoral neck and midshaft radius. Both combined risedronate-HRT and HRT-only produced significant decreases in the biochemical markers of bone turnover, with somewhat greater decreases in the combined treatment group. Bone biopsy data showed normal bone structure and normal mineralization with either treatment. Expected decreases in bone turnover were observed and were greater in the combined treatment group (68-79% reduction relative to baseline values, P < 0.005). Overall, combined treatment had a safety profile similar to that of HRT-only, including bone and gastrointestinal safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favorable effect on BMD similar to that of HRT alone at the lumbar spine and slightly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.     

Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized,double-blind,placebo-controlled trial

BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass. METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo. All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (400 [corrected] IU/d) supplements. The primary efficacy end points were the changes in alveolar crest height and alveolar bone density. Alveolar crest height was measured on bite-wing radiographs, and changes in alveolar bone mass were assessed by means of digital-subtraction radiography. Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry. RESULTS: Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo (+1.84% vs +0.95% [P =.04]), and tended to improve alveolar crest height (+4.83% vs +3.46% [P =.34]). Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group (total proximal femur, +3.59% vs +0.22% [P =.001]; neck, +2.05% vs -0.34% [P =.02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P =.39]). Changes in alveolar bone mass correlated with bone density changes in the total femur (r = 0.28 [P =.02]) and femoral trochanter (r = 0.25 [P =.04]) in the H/ERT but not in the placebo group. CONCLUSIONS: Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT. Improvement in oral bone health constitutes an additional benefit of H/ERT.     

Bone mass and bone resorption in postmenopausal women with type 2 diabetes mellitus

The aim of the present study was to examine the relationships between bone mass or bone resorption evaluated by urinary cross-linked N-telopeptides of type I collagen (NTx) concentration and known and potential contributors to bone mass or bone resorption such as sex hormones, age, duration of diabetes, glycemic control (hemoglobin A(1c) [HbA(1c)]), body mass index (BMI), severity of diabetic complications, smoking status, and current treatment of diabetes in postmenopausal women with type 2 diabetes mellitus (n = 196). In addition, the relationship of bone mass to pulse wave velocity, which is an earlier indicator of cardiovascular disease, was investigated in a subgroup of patients (n = 120). Bone mass was evaluated by the quantitative ultrasound method. A higher stiffness index indicates higher bone mass. Inverse correlations were found between the stiffness index and age (r = -0.374, P < .0001) and between the stiffness index and log (urinary albumin excretion) (r = -0.170, P = .0398), and a positive correlation was found between the stiffness index and serum dehydroepiandrosterone sulfate (DHEA-S) concentration (r = 0.201, P = .0136). No significant correlations were found between the stiffness index and duration of diabetes, HbA(1c), BMI, or serum estradiol concentration. No significant correlations were found between urinary NTx concentration and age, duration of diabetes, HbA(1c), BMI, serum estradiol concentration, or serum DHEA-S concentration. The stiffness index correlated inversely with urinary NTx concentration (r = -0.262, P = .0002). No significant correlation was found between the stiffness index and pulse wave velocity (r = -0.165, P = .0714). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of the stiffness index (beta = .207, P = .0428). In conclusion, serum DHEA-S concentration correlated positively with bone mass, whereas glycemic control, BMI, or duration of diabetes did not correlate with bone mass or urinary NTx concentration in postmenopausal women with type 2 diabetes mellitus.     

Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women

BACKGROUND: Menopause is associated with decreases in lean mass and increases in fat mass. Serum hormone levels and hormone replacement therapy (HRT) may modify the effects of exercise training on body composition in postmenopausal women. METHODS: We assessed the changes in total body and regional lean soft tissue and fat mass (using dual-energy x-ray absorptiometry) in 94 sedentary postmenopausal women, aged 40-65 years, after 12 months of resistance and weight-bearing aerobic exercise training. Women currently on oral HRT (n = 39) and not on HRT (n = 55) were randomized within groups to exercise and no exercise, resulting in four groups: exercise + HRT (n = 20), HRT (n = 22), exercise (n = 24), and control (n = 28). Fasting blood samples were measured for resting serum total levels of estrone, estradiol, cortisol, androstenedione, growth hormone, and insulin-like growth factor 1 at baseline and 12 months. RESULTS: We found significant effects of exercise on increases in total body, arm, and leg lean soft tissue mass, and decreases in leg fat mass and percentage of body fat. There were no interaction effects of exercise and HRT on the changes in muscle strength and body composition. No significant changes in total hormone levels were found after 12 months. CONCLUSIONS: Exercise training resulted in significant beneficial changes in lean soft tissue and fat mass in early postmenopausal women. These changes in body composition were neither influenced by prolonged HRT use nor accompanied by changes in total levels of the hormones determined in this study.     

Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial

The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2-L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment. Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both). This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.     

Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women

We investigated the effects of transdermal 17β-estradiol, combined with standard antihypertensive therapy, on the modification of the cardiovascular risk profile in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 200 postmenopausal women with mild to moderate hypertension. Patients received 17β-estradiol (50 μg/day, transdermal) and norethisterone acetate (2.5 mg/day, orally) or placebo. At baseline serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and fibrinogen plasma levels were measured and all subjects underwent complete M-mode and 2-D echocardiograms, which were repeated after 6, 12, and 18 months of hormonal replacement therapy. Compared with placebo, all values decreased significantly except for HDL cholesterol. In both groups, no modifications were observed in echocardiographic parameters, except for left ventricular mean diastolic and systolic wall thickness and left ventricular mass index, which showed a significant decrease in both groups. The reduction was greater in the treated group; the percentage of patients with left ventricular hypertrophy was 46% before randomization and 17.2% after 18 months of treatment (P < .0001), whereas in group II the percentage was 48% at baseline and 31.5% after 18 months (P < .05).In conclusion, transdermal 17β-estradiol, associated with antihypertensive therapy, may contribute to the reduction of cardiovascular risk profile in hypertensive postmenopausal women.     

Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study

It is well recognized that estrogen (E(2)) prevents postmenopausal bone loss by suppressing bone resorption. Despite evidence that E(2) may also stimulate bone formation in animals, an anabolic effect in humans is still controversial. To investigate this, we studied 22 older postmenopausal females, with a mean age of 65.4 yr and mean interval of 16.9 yr since menopause and low bone mineral density. Transcortical iliac bone biopsies were performed before and 6 yr after E(2) replacement therapy (ERT) [75 mg percutaneous E(2) replaced 6-monthly plus oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month]. The mean serum E(2) level after 6 yr of treatment was 1077 (range, 180-2568) pmol/L. Bone mineral density improved in every patient, with a median increase of 31.4% at the lumbar spine and 15.1% at the proximal femur. Bone histomorphometry showed an increase in cancellous bone volume from 10.75% to 17.31% (P < 0.001). The wall thickness after 6 yr of E(2) treatment was 38.30 micrometer compared with 31.20 micrometer before commencement of ERT (P < 0.0005), indicating net bone gain. This is the first report showing histological evidence for an increase in cancellous bone volume, together with an increase in wall thickness, in a longitudinal follow-up study of ERT in older postmenopausal women. Our results show that E(2) is capable of exerting an anabolic effect in women with osteoporosis, even when started well into the menopause.     

Use of hormone replacement therapy by postmenopausal women in the United States

BACKGROUND: The benefits and risks of hormone replacement therapy (HRT) in postmenopausal women are not fully defined, and individual characteristics and preferences may influence decisions to use this therapy. Previous studies of postmenopausal women who use HRT have been conducted in local or highly selected cohorts or have not focused on current use. OBJECTIVE: To examine sociodemographic, clinical, and psychological factors associated with current use of HRT in a national population-based cohort. DESIGN: Random-digit telephone survey. SETTING: Probability sample of U.S. households with a telephone. PARTICIPANTS: 495 postmenopausal women 50 to 74 years of age in 1995. MEASUREMENTS: Current use of HRT. RESULTS: Current use of HRT was reported by 37.6% of women (58.7% of those who underwent hysterectomy and 19.6% of those who did not undergo hysterectomy; P = 0.001). In multivariable analyses, use of HRT was more common among women in the South (adjusted odds ratio, 2.67 [95% CI, 1.08 to 6.59]) and West (odds ratio, 2.76 [CI, 1.01 to 7.53]) than the Northeast. Use was more common among college graduates (odds ratio, 3.72 [CI, 1.29 to 10.71]) and less common among women with diabetes mellitus (odds ratio, 0.17 [CI, 0.05 to 0.51]). Other cardiac risk factors and most psychological characteristics were not associated with HRT use. CONCLUSIONS: Sociodemographic factors, such as region and education, may be more strongly associated with use of HRT than clinical factors, such as risk for cardiovascular disease. Future efforts should focus on understanding sociodemographic variations, defining which women are most likely to benefit, and targeting therapy to them.     

Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2～4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/ progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F₁₊₂ levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.     

Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.