Computer-aided measurement of mandibular cortical width on dental panoramic radiographs for identifying osteoporosis.

AIM: To develop a computer-aided diagnosis system to continuously measure mandibular inferior cortical width on dental panoramic radiographs and evaluate the system's efficacy in identifying postmenopausal women with low-skeletal bone mineral density. METHODS: Mandibular inferior cortical width was continuously measured by enhancing the original X-ray image, determining cortical boundaries, and evaluating all distances between the upper and lower boundaries in the region of interest. The system's efficacy in identifying osteoporosis at the lumbar spine and the femoral neck was evaluated for 100 women (≥50 years): 50 in the development of the tool and 50 in its validation. RESULTS: The sensitivity and specificity of the cortical measurements for identifying the development patients were 90% (95% confidence interval shown in parentheses) (63.0-87.0) in women with low spinal bone mineral density, and 81.8% (70.1-91.8) and 69.2% (56.2-81.8) in those with low femoral bone mineral density, respectively. Corresponding values in the validation patients were 93.3% (85.9-100) and 82.9% (71.4-92.7) at the lumbar spine, and 92.3% (84.5-99.5) and 75.7% (63.0-87.0) at the femoral neck, respectively. CONCLUSION: Our new computer-aided diagnosis system is a useful procedure in triage screening for osteoporosis.

Diagnosis of osteoporosis from dental panoramic radiographs using the support vector machine method in a computer-aided system.

BACKGROUND: Early diagnosis of osteoporosis can potentially decrease the risk of fractures and improve the quality of life. Detection of thin inferior cortices of the mandible on dental panoramic radiographs could be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The aim of our study was to assess the diagnostic efficacy of using kernel-based support vector machine (SVM) learning regarding the cortical width of the mandible on dental panoramic radiographs to identify postmenopausal women with low BMD. METHODS: We employed our newly adopted SVM method for continuous measurement of the cortical width of the mandible on dental panoramic radiographs to identify women with low BMD or osteoporosis. The original X-ray image was enhanced, cortical boundaries were determined, distances among the upper and lower boundaries were evaluated and discrimination was performed by a radial basis function. We evaluated the diagnostic efficacy of this newly developed method for identifying women with low BMD (BMD T-score of -1.0 or less) at the lumbar spine and femoral neck in 100 postmenopausal women (≥50 years old) with no previous diagnosis of osteoporosis. Sixty women were used for system training, and 40 were used in testing. RESULTS: The sensitivity and specificity using RBF kernel-SVM method for identifying women with low BMD were 90.9% [95% confidence interval (CI), 85.3-96.5] and 83.8% (95% CI, 76.6-91.0), respectively at the lumbar spine and 90.0% (95% CI, 84.1-95.9) and 69.1% (95% CI, 60.1-78.6), respectively at the femoral neck. The sensitivity and specificity for identifying women with low BMD at either the lumbar spine or femoral neck were 90.6% (95% CI, 92.0-100) and 80.9% (95% CI, 71.0-86.9), respectively. CONCLUSION: Our results suggest that the newly developed system with the SVM method would be useful for identifying postmenopausal women with low skeletal BMD.

Use of dental panoramic radiographs in identifying younger postmenopausal women with osteoporosis.

INTRODUCTION: Eroded or thin inferior cortex of the mandible detected on dental panoramic radiographs may be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The purpose of this study was to evaluate whether these panoramic measurements are useful for identifying low BMD or osteoporosis in postmenopausal women younger than 65 years. METHODS: We compared the diagnostic performances of panoramic measurements with those of the osteoporosis self-assessment tool (OST) for identifying women with low BMD (T-score of -2.0 or less at either the lumbar spine or the femoral neck) and osteoporosis (T score of -2.5 or less) in 158 healthy Japanese postmenopausal women aged 46 years to 64 years. Mandibular cortical shape (erosion) and width were evaluated on dental panoramic radiographs. Receiver operating characteristic curve analysis was used to determine the optimal cutoff thresholds for cortical width and OST index. RESULTS: The sensitivity and specificity, respectively, for identifying women with low BMD were 82.3% and 55.2% for OST index, 79.0% and 50.0% for cortical width, and 72.6% and 74.0% for cortical shape. The sensitivity and specificity, respectively, for identifying women with osteoporosis were 86.7% and 46.9% for OST index, 90.0% and 45.3% for cortical width, and 86.7% and 65.6% for cortical shape. Likelihood ratio for identifying women with low BMD was 13.90 for thin cortical width (<3.0 mm) and 10.84 for severely eroded cortex. That for identifying women with osteoporosis was 6.40 for thin cortical width and 7.11 for severely eroded cortex. CONCLUSIONS: Dentists may be able to refer postmenopausal women younger than 65 years for bone densitometry on the basis of incidental findings on dental panoramic radiographs.

Visual assessment of the mandibular cortex on panoramic radiographs to identify postmenopausal women with low bone mineral densities.

OBJECTIVE: The purpose of this study was to determine whether simple visual estimation of the mandibular inferior cortex width on panoramic radiographs is useful for identifying postmenopausal women with low skeletal bone mineral density (BMD). STUDY DESIGN: Panoramic radiographs were made on 100 women aged 50-84 years who also had BMD assessment of the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. The panoramic images were examined twice by 4 observers to evaluate the thickness of the mandibular inferior cortex. RESULTS: Intraobserver agreement varied from moderate to almost perfect. Interobserver agreements varied from fair to almost perfect. Overall mean sensitivity, specificity and positive predictive value in identifying women with low BMD were 54.7%, 82.0%, and 72.5% in the lumbar spine and 51.8%, 82.2%, and 75.7% in the femoral neck, respectively. CONCLUSIONS: Our results suggest that simple visual estimation of the mandibular inferior cortex on panoramic radiographs may be useful for identifying postmenopausal women with low BMD.

Relationship between self-reported periodontal status and skeletal bone mineral density in Japanese postmenopausal women.

OBJECTIVE: Several investigators have linked periodontal disease progression and low skeletal bone mineral density in postmenopausal women. However, little is known about whether self-reported periodontal status is the reflection of skeletal bone mineral density. We investigated whether self-reported poor periodontal status is associated with low skeletal bone mineral density in postmenopausal women. DESIGN: Relationships among self-reported periodontal status, number of teeth remaining, and bone mineral density of the lumbar spine and the femoral neck were evaluated in 253 Japanese postmenopausal women (mean +/- SD, 56.6 +/- 7.7) recruited from the patients who visited our clinic for bone mineral assessment between 1997 and 2003. Self-reported periodontal symptoms included gingival swelling, gingival bleeding, purulent discharge, and tooth mobility at the time of bone mineral assessment. RESULTS: Analysis of covariance adjusted for age, height, weight, years since menopause, duration of estrogen use, and regular oral care revealed that subjects without periodontal symptoms had significantly higher BMD of the lumbar spine than did those with periodontal symptoms (mean +/- SEM, 0.962 +/- 0.014 vs 0.921 +/- 0.013; P = 0.038); however, there were no significant differences in the number of remaining teeth and bone mineral density of the femoral neck between them. The odds of low spine bone mineral density in subjects with periodontal symptoms was 2.01 (95% CI = 1.15 to 3.50). CONCLUSION: Our results suggest that self-reported poor periodontal status may be associated with low bone mineral density of the lumbar spine in postmenopausal women.

Validation of dental panoramic radiography measures for identifying postmenopausal women with spinal osteoporosis.

OBJECTIVE: Measurements of mandibular inferior cortical shape and width detected on dental panoramic radiographs may be a useful screening tool for spinal osteoporosis in postmenopausal women. The purposes of this study were to clarify whether these measures are validated compared with simple screening tools based on questionnaires, such as the osteoporosis self-assessment tool (OST) and whether these measures can be used in postmenopausal women with histories of hysterectomy, oophorectomy, or estrogen use. SUBJECTS AND METHODS: We calculated the diagnostic performances of panoramic measurements and the OST for identifying women with spinal osteoporosis in both 159 healthy postmenopausal and 157 postmenopausal women with histories of hysterectomy, oophorectomy, or estrogen use. Spinal osteoporosis was defined as a bone mineral density T score of -2.5 or less at the lumbar spine. Cortical shape and width were evaluated on dental panoramic radiographs. Receiver operating characteristic curve analyses were used to determine the optimal cutoff thresholds for cortical width and the OST in healthy postmenopausal women. RESULTS: The sensitivity and specificity, respectively, for identifying women with spinal osteoporosis were 89.5% and 33.9% for cortical width, 86.8% and 57.8% for the OST, and 86.8% and 63.6% for cortical shape in healthy postmenopausal women. Sensitivity and specificity, respectively, were 92.5% and 35.0% for cortical width, 72.5% and 58.1% for the OST, and 80.0% and 64.1% for cortical shape in postmenopausal women with histories of hysterectomy, oophorectomy, or estrogen use. CONCLUSION: Dentists may be able to refer postmenopausal women with suspected spinal osteoporosis for bone densitometry on the basis of dental panoramic radiographs with diagnostic performance similar to that of osteoporosis screening tools based on questionnaires.

Apolipoprotein E phenotype affects the malondialdehyde-modified LDL concentration and forearm endothelial function in postmenopausal women.

OBJECTIVE: We investigated whether the apolipoprotein E (apo E) phenotype affects the serum concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) or forearm endothelial function in postmenopausal women. PATIENTS AND MEASUREMENTS: Individuals were divided into three groups according to their apo E phenotype: E2 (E2/2 and E2/3, n = 12); E3 (E3/3, n = 71); and E4 (E3/4 and E4/4, n = 27). The serum concentrations of lipids and MDA-LDL were measured. Forearm blood flow during reactive hyperaemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. RESULTS: The serum concentrations of total and LDL cholesterol were significantly higher in the E4 group than in the E2 group (P < 0.05) or in the E3 group (P < 0.05). The serum apo B concentration was significantly higher in the E4 group than in the E2 group (P < 0.05). The serum concentrations of high density lipoprotein (HDL) cholesterol and nitrite/nitrate were significantly lower in the E4 group than in the E2 group (P < 0.05). Other lipid concentrations did not differ in the three groups. The serum MDA-LDL concentration was highest in the E4 group, and was lowest in the E2 group (E2: 91.1 +/- 6.9 IU/l, E3: 112.3 +/- 5.9 IU/l, E4: 128.8 +/- 9.9 IU/l; P < 0.05). The forearm blood flow response to reactive hyperaemia was lowest in the E4 group, and highest in the E2 group (E2: 52.2 +/- 5.8 ml/min per 100 ml tissue, E3: 40.7 +/- 1.7 ml/min per 100 ml tissue, E4: 33.4 +/- 2.4 ml/min per 100 ml tissue; P < 0.05). The forearm blood flow changes in response to nitroglycerine were similar between all three groups. CONCLUSIONS: The apo E phenotype affects the serum MDA-LDL concentration and forearm endothelial function in postmenopausal women.

Effect of estrogen use on tooth retention, oral bone height, and oral bone porosity in Japanese postmenopausal women.

OBJECTIVE: Recent studies in the United States support the protective effect of estrogen use on tooth retention; however, little is known as to how estrogen promotes tooth retention. The aims of this study were to investigate the effects of estrogen use on tooth retention, oral bone height, and oral bone porosity in Japanese postmenopausal women and to clarify how estrogen promotes tooth retention. DESIGN: Relationships among the number of teeth remaining (total, anterior, and posterior teeth), oral bone height, oral bone porosity, bone mineral density of the lumbar spine and the femoral neck, estrogen use status, and the duration of estrogen use were evaluated in 330 Japanese postmenopausal women (mean age +/- SD, 56.8 +/- 7.6 y). RESULTS: Analysis of covariance adjusted for confounding variables revealed that estrogen users (66 women) tended to have more posterior teeth than did nonusers (264 women) (P = 0.065), although there were no significant differences in number of total (P = 0.196) and anterior (P = 0.751) teeth remaining, oral bone height (P = 0.970), oral bone porosity (P = 0.745), and bone mineral density of the lumbar spine (P = 0.459) and the femoral neck (P = 0.749) between estrogen users and nonusers. Multiple regression analysis showed that the duration of estrogen use was significantly associated with number of total (P = 0.019) and posterior (P = 0.007) teeth remaining, independent of age and oral bone height. CONCLUSION: Our results suggest that estrogen may promote tooth retention by strengthening the periodontal attachment surrounding the teeth, but not increasing oral bone height and not decreasing oral bone porosity.

Forearm endothelial function and bone mineral loss in postmenopausal women.

It is widely believed that the vasculature plays an important role in bone remodeling. We investigated the relationship between forearm endothelial function and bone mass in the lumbar spine in early postmenopausal women without a history of smoking or diabetes mellitus. We studied the forearm resistance artery endothelial function in 110 Japanese women-52 postmenopausal women with normal spinal bone mineral density (BMD), 36 postmenopausal women with osteopenia, and 22 osteoporotic postmenopausal women. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry. After adjustment for age, body mass index, years since the start of menopause, and basal FBF, women with osteoporosis had a lower maximal FBF response to reactive hyperemia (28.4 +/- 3.8 mL/min per 100 mL tissue) than those with normal BMD (39.8 +/- 2.8 mL/min per 100mL tissue) or osteopenia (35.6 +/- 2.5 mL/min per 100mL tissue) (P = 0.029). A significant increase in serum angiotensin-converting enzyme (ACE) activity (P = 0.042) and a significant decrease in the serum concentrations of nitrite/nitrate (P = 0.041) were noted in osteoporotic women compared to women with normal BMD or osteopenia. The present findings suggest that postmenopausal women with low BMD, especially those with osteoporosis, have impaired endothelial function in the forearm resistance arteries.

Tooth loss is associated with an increased risk of hypertension in postmenopausal women.

Tooth loss has been associated with an increased risk of vascular diseases such as coronary heart disease and cerebrovascular disease. Little is known whether hypertension is an important factor linking 2 phenomena in postmenopausal women. We compared an incidence of hypertension and traditional risk factors for vascular diseases between 2 age-matched groups: 67 postmenopausal women with missing teeth and 31 without missing teeth. In addition to blood pressure, serum concentration of total cholesterol, high- and low-density lipoprotein cholesterol and triglycerides, plasma angiotensin-converting enzyme activity, plasma angiotensin II concentration, plasma renin activity, and resting heart rate were measured as traditional risk factors for vascular diseases. Subjects without missing teeth had significantly lower diastolic blood pressure than did subjects with missing teeth (P=0.021). The former tended to have lower systolic blood pressure than did the latter (P=0.058). There were no significant differences in other variables between subjects with and without missing teeth. The odds ratio of having hypertension in subjects with missing teeth was 3.59 (95% confidence interval, 1.10 to 11.7) after adjustment of obesity, hypercholesterolemia, and hypertriglyceridemia. Our results suggest that hypertension may be an important factor linking tooth loss and an increased risk of vascular diseases in postmenopausal women.

Substitution of transdermal estradiol during oral estrogen-progestin therapy in postmenopausal women: effects on hypertriglyceridemia.

OBJECTIVE: We investigated effects of changing from oral estrogen to transdermal estradiol on the lipid and lipoprotein profile of postmenopausal women who developed hypertriglyceridemia (serum concentrations exceeding 150 mg/dL) during estrogen-progestin therapy. DESIGN: Sixty-one postmenopausal Japanese women receiving 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate daily for 12 months had developed serum triglyceride concentrations exceeding 150 mg/dL after 12 months of treatment. Thirty-six of them, chosen randomly for study, were assigned at random to either a group that continued this oral regimen or another that changed to transdermal estradiol while continuing 2.5 mg of oral medroxyprogesterone acetate for the next 3 months (n = 18 for each). Blood lipids were compared between groups. RESULTS: Serum concentrations of triglyceride and very-low-density lipoprotein triglyceride decreased significantly after changing to transdermal estradiol (triglyceride, from 226.0 +/- 43.9 to 110.5 +/- 44.1 mg/dL, P < 0.01). No changes were seen in concentrations of low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. CONCLUSION: Changing to transdermal estradiol may improve triglyceride metabolism in women who developed hypertriglyceridemia during oral estrogen-progestin therapy, with minimal effect on cholesterol profiles.

Estrogen regulates the production of VEGF for osteoclast formation and activity in op/op mice.

UNLABELLED: Op/op mice have a severe deficiency of osteoclasts because of lacking functional M-CSF that is an essential factor of osteoclast differentiation and function. We now report that OVX induces osteoclast formation and cures osteopetrosis by increasing the VEGF that regulates osteoclast formation in these mice. INTRODUCTION: We have found that estrogen deficiency induced by ovariectomy (OVX) upregulated osteoclast formation in op/op mice. We have recently demonstrated that vascular endothelial growth factor (VEGF) could substitute for macrophage colony-stimulating factor (M-CSF) in the support of osteoclastic bone resorption in these mice. Therefore, in this study, we wished to assess the effects of VEGF on bone loss induced by OVX in these mice. MATERIALS AND METHODS: Eight-week-old op/op mice were bilateral OVX or sham-operated. Mice were killed at 8, 10, and 12 weeks of age, and femurs were removed for preparations. Some OVX mice were treated with three consecutive injections of 120 microl/body of VEGF-neutralizing antibody at 12-h intervals starting from 36 h before death at 4 weeks after OVX. VEGFR-1/Fc chimeric protein (600 microg/kg/day) or 17beta-estradiol (0.16 microg/day) was administered in a dorsal subcutaneous pocket of the mice at the time of OVX. These mice were killed 2 weeks after surgery. Changes of serum levels of VEGF were measured by ELISA. Changes of mRNA levels of VEGF, Flt-1, interleukin-6, and osteoclast differentiation factor (ODF/TRANCE/RANKL) in bone tissue were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In OVX op/op mice, trabecular bone volume of the femur was decreased, and the number of osteoclasts was significantly increased. Serum levels of VEGF were demonstrated to be higher in OVX mice than in sham-operated mice. VEGF mRNA, Flt-1 mRNA, interleukin-6 mRNA, and RANKL mRNA levels in bone tissue were elevated in OVX mice over that in sham-operated mice. The increase in osteoclast number was inhibited by VEGF antagonist treatment in OVX mice. CONCLUSIONS: In this study, we have demonstrated that the production of VEGF and RANKL stimulated by OVX results in increased osteoclast formation in op/op mice.

Relationship between dental panoramic radiographic findings and biochemical markers of bone turnover.

UNLABELLED: We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs. INTRODUCTION: Recent studies suggest that mandibular inferior cortical shape and width on dental panoramic radiographs may be useful screening tools for low skeletal bone mineral density (BMD) or increased risk of osteoporotic fracture. However, little is known as to whether these measures are associated with bone turnover. We investigated relationships among dental panoramic radiographic findings, spine BMD, and biochemical markers of bone turnover in postmenopausal women. MATERIALS AND METHODS: Of 609 women who visited our clinic for BMD assessment between 1996 and 2002, 82 Japanese postmenopausal women, 46-68 years of age (54.1 +/- 4.9 years), were recruited for this study. Mandibular inferior cortical shape (normal, mild/moderate erosion, severe erosion) and width were evaluated on dental panoramic radiographs. BMD at the lumbar spine (L2-L4) was measured by DXA and categorized as normal (T-score > -1.0), osteopenia (T-score, -1.0 to -2.5), or osteoporosis (T-score < -2.5). Bone turnover was estimated by serum total alkaline phosphatase (ALP) and urinary N-telopeptide cross-links of type I collagen (NTx), corrected for creatinine. RESULTS: The odds of low spine BMD in subjects with any cortical erosion were 3.8 (95% CI, 1.2-12.5). Mandibular cortical erosion was significantly associated with increased NTx (p < 0.001) and ALP (p < 0.05) levels. The associations of spine BMD with NTx and ALP were similar. Mandibular cortical width was significantly associated with spine BMD but not with NTx and ALP levels. CONCLUSIONS: Our results suggest that mandibular inferior cortical shape on dental panoramic radiographs may be an indicator of bone turnover and spine BMD in postmenopausal women. Dentists may be able to identify postmenopausal women with increased risk of osteopenia and osteoporosis on routine dental panoramic radiographs.

Dental panoramic radiograph as a tool to detect postmenopausal women with low bone mineral density: untrained general dental practitioners' diagnostic performance.

The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra-and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77% and 40%, respectively, when BMD of the lumbar spine was used as standard and 75% and 39%, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70%) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.

Association of estrogen and vitamin D receptor gene polymorphisms with tooth loss and oral bone loss in Japanese postmenopausal women.

OBJECTIVE: To investigate the relationship between estrogen receptor (ER) and vitamin D receptor (VDR) gene polymorphisms and tooth loss, oral bone loss, and postcranial bone mineral density (BMD) in Japanese postmenopausal women. DESIGN: Polymorphisms at the ER PvuII and XbaI and VDR BsmI gene sites, number of teeth remaining, oral bone mass, and BMD of the lumbar spine and the hip were evaluated in 149 Japanese postmenopausal women. RESULTS: The distribution of ER PvuII and XbaI and VDR BsmI restriction fragment length polymorphisms was as follows: pp, 30.2%; Pp, 49.7%; PP, 20.1%; xx, 71.8%; Xx, 22.5%; XX, 2.7%; bb, 76.5%; Bb, 22.2%; and BB, 1.3%. Analysis of covariance adjusted for confounding variables revealed that participants with pp allele had fewer teeth remaining than did those with P allele. There were no significant differences in oral bone mass and postcranial BMD among three alleles at the PvuII site. Participants with X and bb allele had less oral bone mass and lower postcranial BMD than did those with xx and B allele, respectively. We could not clarify the positive associations between XbaI and BsmI polymorphism and number of teeth. CONCLUSIONS: PvuII polymorphism was associated with tooth loss, but not with oral bone mass and postcranial BMD. XbaI and BsmI polymorphisms may be associated with bone mass or density; however, PvuII polymorphism might contribute to another unknown pathway related to tooth loss.

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.

A comparison of low-dose and standard-dose oral estrogen on forearm endothelial function in early postmenopausal women.

We investigated the effects of low-dose estrogen plus progestin on endothelial function. Postmenopausal women received daily doses of conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) (standard-dose group, n = 18), CEE (0.3 mg) plus MPA (2.5 mg) (low-dose group, n = 18), or no treatment (control group, n = 15) for 3 months. Serum concentrations of lipids and malondialdehyde (MDA)-modified low-density lipoprotein (LDL) were measured. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Decreases in serum concentrations of LDL cholesterol and MDA-modified LDL and increases in high-density lipoprotein cholesterol and nitrite/nitrate were observed in both treatment groups. After 3 months of treatment, similar increases in the maximal FBF response during reactive hyperemia were observed in both treatment groups (standard-dose group, from 35.8 +/- 3.0 to 47.5 +/- 2.8 ml/min per 100 ml tissue; and low-dose group, from 35.2 +/- 2.2 to 46.8 +/- 3.4 ml/min per 100 ml tissue, P < 0.01). FBF levels in the control group were unchanged. Treatment did not affect nitroglycerin-induced dilation. The incidences of vaginal bleeding and breast tenderness were lower with the low-dose group than with the standard-dose group. Low-dose CEE plus MPA augments endothelial function in forearm resistance arteries and decreased MDA-modified LDL levels similarly to standard doses of CEE plus MPA, with fewer side effects.

Hormone replacement effects on endothelial function measured in the forearm resistance artery in normocholesterolemic and hypercholesterolemic postmenopausal women.

We investigated whether forearm resistance artery endothelial function differed between hypercholesterolemic postmenopausal women (n = 41) and normocholesterolemic postmenopausal women (n = 37), both generally and in terms of effects of long-term hormone replacement therapy (HRT) on endothelial function. Both menopause and hypercholesterolemia are associated with endothelial dysfunction and increased coronary risk. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. Treated women received conjugated equine estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) daily for 6 months. Nitrite/nitrate, angiotensin-converting enzyme, and lipids were measured in serum. FBF during reactive hyperemia as well as serum nitrite/nitrate concentrations were significantly lower in hypercholesterolemic than normocholesterolemic subjects. Increases in the FBF induced by NTG were similar in the two groups. HRT significantly increased estradiol, high-density lipoprotein cholesterol, and serum nitrite/nitrate, while decreasing circulating angiotensin-converting enzyme activity in both groups. Reduction in total and low-density lipoprotein cholesterol was seen only in hypercholesterolemic subjects. After 6 months of HRT, maximal FBF response during reactive hyperemia increased in both groups. Augmentation of this response was greater in hypercholesterolemic than in normocholesterolemic subjects (maximal FBF, 55.4 +/- 11.2 vs. 25.9 +/- 11.5%; P < 0.05). Changes in the FBF with NTG were not altered by HRT in either group. Long-term HRT augments endothelial function in forearm resistance artery. This beneficial effect is greater in patients with hypercholesterolemia.

Combination therapy of low-dose medroxyprogesterone acetate and oral estrogen does not affect endothelial function in the forearms of postmenopausal women.

OBJECTIVE: We investigated whether low-dose medroxyprogesterone acetate (MPA) combined with oral estrogen had adverse effects on endothelial function compared with oral estrogen alone in postmenopausal women with mild hypercholesterolemia. DESIGN: Subjects were divided into two groups. One group received conjugated equine estrogen (CEE, 0.625 mg daily) orally for the first 3 months, followed by estrogen combined with MPA (2.5 mg daily) orally for an additional 3 months ( = 26). The other group received no treatment (control group, = 12). Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Nitrite/nitrate, angiotensin-converting enzyme, and lipid concentrations were measured in the serum. RESULTS: Both CEE and CEE combined with MPA significantly increased the FBF during reactive hyperemia. This increase was similar in both active treatment phases. No changes were seen in controls. FBF after sublingual nitroglycerin did not change over 6 months in either group. Significant and similar increases in serum concentration of nitrite/nitrate and plasma renin activity as well as decreases in angiotensin-converting enzyme activity were found in both treatment phases. No such changes occurred in the control group. There was no significant increase in high-density lipoprotein cholesterol or decrease in low-density lipoprotein cholesterol between the treatment phases. Likewise, no such changes were observed in the control group. CONCLUSIONS: Our 6-month study suggests that the addition of low-dose MPA with CEE had no adverse effects on forearm resistance artery endothelial function compared with CEE alone.

Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate.

OBJECTIVE: Estrogen replacement therapy (ERT) in postmenopausal women reduces the risk of cardiovascular diseases. Beneficial changes in lipid profiles account for only one part, thereby raising the question of other estrogen induced benefit that may be lost at menopause. The purpose of this study was to determine the effects of estrogen replacement therapy (ERT) on platelet function of postmenopausal women. METHODS: The effect of 4 weeks ERT (conjugated estrogens 0.625 mg/day) on platelet function was evaluated ex vivo in 18 postmenopausal women (mean age 53 +/- 5 years, after menopause 3.8 +/- 1.9 years). RESULTS: After ERT, (1) plasma concentrations of estrone and estradiol significantly increased (estrone: 16 +/- 7-211+/- 80 pg/ml, estradiol: 14+/- 3-125 +/- 49 pg/ml, P<0.05) and LDL-cholesterol decreased (129 +/- 23-94 +/- 25 mg/dl, P<0.05). Plasma 6-keto-PG F(1) alpha significantly increased (7.2 +/- 3.4-13.3 +/- 6.7 pg/dl, P<0.05). (2) platelet aggregation and positive staining for P-selectin in thrombin- (0.1 and 1.0 U/ml) stimulated platelets were inhibited (Th 0.1 U/ml: 4.0 +/- 0.9-2.4 +/- 1.0/control, P<0.05), but positive staining for GP IIb-IIIa complex did not alter significantly. (3) Ca(2+) influx induced by thrombin decreased (Th 0.3 U/ml: 345 +/- 29-298 +/- 24 nmol/l, P<0.05). The baseline [Ca(2+)](i), the release of Ca(2+) from internal stores induced by thrombin and the size of internal Ca(2+) stores did not alter. (4) platelet c-AMP increased (Th 0.3 U/ml: 66.4 +/- 9.4-82.6 +/- 13.0 fmol/l, P<0.05), but platelet nitrite/nitrate (NO(x)) or c-GMP did not alter significantly. CONCLUSIONS: These results suggest that modulation of platelet function by decreasing Ca influx and increased production of c-AMP may account in part for the cardiovascular benefit of ERT.