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Relation between body mass and postmenopausal symptoms in surgically castrated women.

INTRODUCTION: Post-menopause androgens are the essential precursors for estrogen synthesis through their conversion in peripheral tissues. The main postmenopausal estrogen is estrone, which is also peripherally converted into estradiol. Concentrations of these two estrogens are directly proportional in circulation. We wanted to establish whether there is a direct correlation between body mass and postmenopausal symptoms in surgically castrated women. MATERIALS AND METHODS: We analyzed 30 patients with artificially induced menopause, 3-12 months after the operation (hysterectomy and bilateral adnexectomy). Prior to being put on hormone substitution therapy the following was obtained from the patients: Body Mass Index--BMI (kg/m(2)), measurement of estradiol (E(2)) by RIA method, and 12 subjective symptoms analyzed according to intensity and frequency. The relationship between BMI, E(2) level and subjective symptoms were assessed. RESULTS: By analyzing the correlation coefficient it was shown that there was statistically significant causal-consequential connection between the E(2) level and BMI (R(2)=0.1647, p<0.05). There is no strong correlation between BMI and symptoms (R(2)=0.004, p<0.05). However, E(2) level correlated with subjective symptoms (R(2)=0.2123, p<0.05). CONCLUSIONS: Estrogen production in postmenopause is dependent on the substrate availability, and thus with adiposity. Therefore, we were surprised by the lack of correlation between BMI and symptoms. This suggests that estrogen metabolism and biological effects are not primarily affected by BMI, and that expression of postmenopausal symptoms does not depend only on estrogen level.

Adult↗

Menopausal symptoms and associated risk factors among postmenopausal women screened for the metabolic syndrome.

BACKGROUND: Although the frequency of menopausal symptoms may vary according to the studied population, in general severe intensity has been related to lower quality of life. OBJECTIVE: To assess the frequency of menopausal symptoms and involved risk factors in an Ecuadorian postmenopausal population. METHODS: Postmenopausal women that participated in a metabolic syndrome screening program were interviewed with the Menopause-specific quality of life questionnaire (MENQOL) in order to determine the most frequently presenting menopausal symptoms and correlate these symptoms with socio-demographic data and the main results of the screening program. RESULTS: Three hundred and twenty-five postmenopausal women (n = 325) were surveyed with the MENQOL. Mean age of participants was 55.9 +/- 8.1 years (median: 54 years). The most frequently presenting symptoms were: hot flushes (53.3%), sweating (49.2%), poor memory (80.6%), feeling depressed (67.4%), aching in muscles and joints (84%), drying of their skin (85.5%), avoiding intimacy (76.2%) and change in their sexual desire (76.5%). Multivariate analysis determined that abdominal obesity was a significant risk factor for presenting hot flushes, depression and muscle and joint pain. High triglyceride levels were associated to higher rates of sweating and depression. While women with basal hyperglycemia were associated to dry skin and changes in sexual desire in a higher proportion, those who were older and with more years of menopause onset were related less frequently to vasomotor symptoms. Older age was also significantly associated in a higher rate to dry skin. CONCLUSION: In this postmenopausal Ecuadorian population, the frequency of menopausal symptoms, as assessed with the MENQOL, was found to be relatively similar to other Latin and non-Latin American populations and associated to age, hormonal status and related metabolic conditions.

Adult↗

Melatonin in postmenopausal females.

There is little information about the interaction between melatonin, sexual steroids and neuroendocrine system in postmenopausal females, even if former research showed that melatonin is clearly involved in human physiology and pathophysiology. We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin (6-SMT) using a radioimmunoassay in 60 postmenopausal women. The group has been divided into patients with insomnia (10), hyperprolactinemia (7), depression (9), obesity (7) and controls (27). Compared to controls 6-SMT values were significantly higher in depressive females. Patients with hyperprolactinemia showed a trend toward a significantly elevated average nocturnal melatonin concentration. Melatonin levels were significantly lower in patients with insomnia and obese postmenopausal females than in controls. Since previous studies described lower melatonin levels in postmenopausal than in premenopausal women, the indication of melatonin therapy, especially for sleep disorders in this collective, can be handled more generously. Melatonin should be prescribed restrictively in patients with depression and in those with hyperprolactinemia. The role of melatonin in obese females remains unclear.

Depression↗

Factors related to postmenopausal muscle performance: a cross-sectional population-based study.

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932-1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm(-2) kg(-1) and N kg(-1)). In addition, two performance tests, 'ability to stand on one foot' and 'ability to squat down to touch the floor' were carried out. A five-category self-assessment of overall health ('very good', 'good', 'moderate', 'bad', and 'very bad') was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts ( P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA ( P<0.001 between 'very good' and 'moderate' or poorer state of health) and regression model ( P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.

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Does raloxifene treatment influence back pain and disability among postmenopausal women with osteoporosis?

Clinical studies have suggested that postmenopausal women on estrogen replacement treatment are more likely to experience back pain and related disability compared to women who do not take estrogens. Raloxifene, a selective estrogen receptor modulator has estrogen-like effects on bone tissue, and antagonize the action of estrogens on endometrium and breast tissue. It is unknown if the treatment of osteoporosis with raloxifene has estrogen-like or opposite effects on back pain and functional capacity among postmenopausal women with osteoporosis. A total of 120 postmenopausal women with osteoporosis and chronic back pain were randomized to receive raloxifene 60 mg with 1,000 mg calcium, and 800 IU vitamin D daily or 1,000 mg calcium and 800 IU vitamin D daily. Pain intensity and pain-related disability were measured before treatment at 6 months and after 1 year. Repeated measures of ANOVA, did not reveal statistically significant differences over time, on pain intensity and disability scores, between groups studied. There was a trend in pain intensity changes during the follow-up period, but the differences between the groups were not statistically significant. It seems that treatment with raloxifene does not influence back pain and disability among postmenopausal women with osteoporosis. Raloxifene may have estrogenic agonist effects on nociceptive processing in the central nervous system.

Back Pain↗

The relationship of sodium intake to calcium and sodium excretion and bone mineral density of the hip in postmenopausal African-American and Caucasian women.

During the past several decades in the United States, there has been a shift in dietary habits, with an increased consumption of processed foods that are high in sodium. It is known that calcium and sodium metabolism are linked and that higher sodium intakes may increase calcium excretion. Epidemiological studies in patients with idiopathic hypercalciuria suggest that hypercalciuria is linked to low bone mass. However, the relationship of sodium intake to bone mineral density (BMD) is controversial in Caucasians and has not been explored in African-Americans. To determine the consequences of sodium intake on bone in African-American and Caucasian postmenopausal women, sodium and calcium excretion and BMD of the total hip were measured in 50 Caucasian and 39 African-American postmenopausal women. After adjustment for race and urine volume, sodium excretion was a significant predictor of calcium excretion (P < 0.01). This relationship was modulated by calcium intake (P < 0.01), but not by race (P = 0.63). There was no significant effect of sodium excretion (P = 0.42) or calcium excretion (P = 0.90) on BMD of the total hip after adjusting for race and urine volume. Sodium excretion is a significant predictor of calcium excretion in both postmenopausal African-American and Caucasian women. The relationship between sodium and calcium excretion is modulated by calcium intake, and the relationship is strongest at low calcium intakes (< or =1000 mg/day). However, sodium excretion in the range of 53.75-283.33 mmole/g/total volume (mmole/g/TV) is not a significant predictor of total hip BMD in elderly African-American and Caucasian postmenopausal women.

Aged↗

Body mass index and the risk of death following the diagnosis of colorectal cancer in postmenopausal women (United States).

OBJECTIVES: Although overweight body mass is an established risk factor for colorectal cancer incidence, few studies have examined the association between body mass index (BMI) and mortality after colorectal cancer diagnosis. We examined survival in a group of postmenopausal women according to BMI. METHODS: Using the Wisconsin Cancer Reporting System we identified and enrolled 633 postmenopausal women aged 38-74 years who were diagnosed with colorectal cancer in 1988-1991. These women were interviewed by telephone; vital status was ascertained via Wisconsin death certificates. Cox proportional hazards regression was used to estimate multivariate risks of colorectal cancer-specific and all-cause mortality. RESULTS: Both underweight (BMI <20.0 kg/m2) (Hazard Ratio (HR) 2.3, 95% Confidence Interval (CI) 1.0-5.4) and obese (BMI > or = 30.0 kg/m2) women (HR 2.1, 95% CI 1.1-3.8) were at increased risk of colon cancer death, as compared to normal weight women (BMI 20.0-24.9 kg/m2). No association was observed for those with rectal cancer. Approximately 50% increases in all-cause mortality were observed among underweight and obese women with colorectal cancer. Postmenopausal hormone use did not appear to modify these associations. CONCLUSIONS: Underweight and obese postmenopausal women with colon cancer were at increased risk of death, though comorbidities may partially account for this risk.

Adult↗

Role of the immune system in postmenopausal bone loss.

Postmenopausal osteoporosis stems from estrogen deficiency. The mechanisms by which estrogen deficiency drives bone destruction are complex and poorly understood. Recent findings from animal models suggest that postmenopausal bone loss may stem in large measure from a pathologic upregulation of the adaptive immune response. While the role of activated T cells in the bone loss driven by inflammatory conditions such as rheumatoid arthritis has been well documented, only recently has the role of T cells in the bone destruction associated with estrogen deficiency begun to be appreciated. In vivo and in vitro models of postmenopausal osteoporosis demonstrate that the activation and expansion of tumor necrosis factor-a producing T cells is a key step in estrogen deficiency driven bone loss and is regulated by multiple interacting cytokines including transforming growth factor-b, interleukin-7, and interferon-g, as well as by the process of antigen presentation. This paper presents recent findings pertaining to this new view of postmenopausal osteoporosis.

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The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗

Effects of estrogen replacement therapy on peripheral vasomotor function in postmenopausal women.

Hormone replacement therapy is associated with a reduction in cardiovascular events in postmenopausal women. We have recently found that acute 17 beta-estradiol administration improves endothelium-dependent vasodilation in both the peripheral and coronary circulations of postmenopausal women. The current study was undertaken in 33 estrogen-deficient postmenopausal women (mean age 59 +/- 7 years) to determine if short-term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intraarterial infusion of estradiol, which increased forearm venous estradiol levels from 16 +/- 11 to 345 +/- 202 pg/ml, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine by 49 +/- 67% (p < 0.001). Acute estradiol also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside by 5 +/- 31% (p = 0.04). However, after 3 weeks of transdermal estradiol administration (0.1 mg/day), which achieved an estradiol level of 120 +/- 57 pg/ml, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements obtained before acute administration of estradiol. Repeat intraarterial infusion of estradiol in 8 women, while receiving transdermal estradiol, increased forearm venous estradiol levels to 268 +/- 105 pg/ml and again potentiated the vasodilator response to acetylcholine to a similar degree as that observed in the initial study after acute administration of estradiol. Thus, although acute intraarterial infusion of 17 beta-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic estrogen administration.

Acetylcholine↗

Bone mineral density in Turkish postmenopausal women.

OBJECTIVE: To determine the bone mineral density curve in Turkish postmenopausal women and to evaluate the efficacy of estrogen replacement therapy in the prevention of bone loss. METHOD: Spinal bone mineral density was measured using dual photon absorptiometry in 118 postmenopausal women, prospectively. Parity, previous and current use of estrogen preparations were correlated with BMD using Student's t-test and the chi 2-test. RESULTS: With a mean BMD value of 0.967 +/- 0.013 g/cm2, 62.5% of our postmenopausal study population had a mean BMD value of < 1.0 g/cm2 and 33.7% were already osteoporotic (< 0.9 g/cm2). Bone loss was faster and more intense in the surgically menopausal than in the naturally menopausal group (P < 0.05). Parity after the fourth delivery dropped the mean BMD value (P < 0.05). Previous and current use of estrogen treatment seemed to decrease bone mineral loss in the postmenopausal years. CONCLUSION: Our data stress the need for locally obtained normal BMD values in every country in the world. High parity, surgical menopause and duration of 5 or more years of natural menopause are risk factors for bone loss. Estrogen replacement diminishes the annual bone loss.

Adult↗

Postmenopausal bone loss in Japanese women.

OBJECTIVES: Our purpose was to detect anatomic variations in postmenopausal bone loss and to determine the risk factors most affecting bone mass in Japanese women. METHODS: One hundred sixty-six Japanese women (54 premenopausal and 112 postmenopausal), aged 40-68 years, were enrolled in the study. Bone mineral densities (BMD) of the lumbar spine (L2-4) and total body were measured by dual energy X-ray absorptiometry and the results were subjected to statistical analysis. RESULTS: Among the various sites studied, the lumbar spine (L2-4) showed the fastest bone loss after menopause. Multiple regression analysis indicated that two factors, number of years since the menopause and body mass index (BMI), affected lumbar spine (L2-4) BMD. CONCLUSION: Measurement of lumbar spine (L2-4) BMD is suitable for evaluating postmenopausal osteoporosis. The risk factors for postmenopausal bone loss were a long period after menopause and a low BMI.

Adult↗

Endometrial assessment by transabdominal ultrasonography in postmenopausal women.

We evaluated the usefulness of transabdominal ultrasonography (TAS) for endometrial abnormalities in postmenopausal women. A total of 232 postmenopausal women were examined by TAS and endometrial sampling. Abnormal findings, including endometrial hyperplasia, atypical hyperplasia and endometrial cancer, were noted in 0.7% (1/41) of sonographically measured endometrium < 2 mm and in 15.4% (14/91) of measurements > or = 2 mm. Endometrial cancer was found in 5.9% in the postmenopausal bleeding group (n = 85) and in 1.4% in the symptom-free group (n = 147). With one exception, all endometrial abnormalities were in endometrial thickness > or = 2 mm. We conclude that TAS has limitations as a technique but is useful in deciding which postmenopausal women require endometrial biopsy.

Adult↗

Transvaginal sonography and endometrial thickness in patients with postmenopausal uterine bleeding.

The objective of the present study was to evaluate the usefulness of transvaginal ultrasonography in assessment of the endometrial thickness in patients with postmenopausal uterine bleeding in relation to the histopathological results of the endometrial biopsy. A total of 118 women with postmenopausal uterine bleeding were studied prospectively. Thirty postmenopausal women without vaginal bleeding and without gynaecological complaints served as a control group. In women with histopathological diagnosis of atrophic endometrium the mean endometrial thickness was 3.1 +/- 1.7 mm whereas the corresponding value for patients with endometrial carcinoma was 18.4 +/- 8.2 mm (P < 0.001). No endometrial carcinoma was diagnosed in endometrial thickness < or = 6 mm. The sensitivity was 100% and specificity 64% if a 6-mm cutoff limit was used. We consider that transvaginal ultrasonographic investigation for post-menopausal bleeding may provide useful information for selection of those patients who are under higher risk of endometrial abnormalities. When using vaginal sonography for measuring the endometrial thickness in women with postmenopausal bleeding, it is reasonable not to perform a dilatation and curettage if the endometrial thickness is < or = 6 mm.

Adult↗

Combining vaginal ultrasonography and office endometrial sampling in the diagnosis of endometrial disease in postmenopausal women.

OBJECTIVE: To investigate the value of the combined use of vaginal ultrasonography and endometrial sampling in the office for the diagnosis of endometrial disease in postmenopausal women. METHODS: One hundred forty consecutive postmenopausal women presenting with uterine bleeding or endometrial cells on cervical cytology entered the study. Vaginal ultrasonography was used to measure the endometrial thickness, followed by use of the Pipelle endometrial sampler. Pipelle biopsy was not feasible in two patients. The results of hysteroscopy with biopsy or hysterectomy, performed within 6 weeks in all but 12 patients, were considered the final diagnosis. The accuracy of ultrasound and Pipelle was measured against the final diagnosis. RESULTS: The sensitivity of vaginal ultrasonography for endometrial disease was 98.2 and 82.0% if cutoff points for endometrial thickness of 2 and 4 mm, respectively, were used. All six patients with endometrial carcinoma had endometrial thicknesses exceeding 12 mm. Pipelle endometrial sampling had a sensitivity of 44.6% and a specificity of 98.5% for endometrial disease. All cases of endometrial carcinoma were detected by sampling in the office setting. CONCLUSION: This study illustrates the value of vaginal scanning in the diagnosis of endometrial disease in symptomatic, postmenopausal women. A 4-mm cutoff point for endometrial thickness seemed appropriate. The sensitivity of Pipelle sampling for endometrial carcinoma was excellent, but relatively weak for other endometrial disease because it failed to detect endometrial polyps and submucous myomas. The combined use of ultrasound and Pipelle sampling offers sufficient diagnostic information for most symptomatic postmenopausal women.

Adult↗

The ovariectomized rat model of postmenopausal bone loss.

An animal model of postmenopausal bone loss can be defined as a living animal in which spontaneous or induced bone loss due to ovarian hormone deficiency can be studied, and in which the characteristics of the bone loss and its sequalae resemble those found in postmenopausal women in one or more respects. Although in comparison to humans, the skeletal mass of rats remains stable for a protracted period during their lifespan, rats can be ovariectomized to make them sex-hormone deficient, and to stimulate the accelerated loss of bone that occurs in women following menopause. Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics. These include: increased rate of bone turnover with resorption exceeding formation; and initial rapid phase of bone loss followed by a much slower phase; greater loss of cancellous than cortical bone; decreased intestinal absorption of calcium; some protection against bone loss by obesity; and similar skeletal response to therapy with estrogen, tamoxifen, bisphosphonates, parathyroid hormone, calcitonin and exercise. These wide-ranging similarities are strong evidence that the ovariectomized rat bone loss model is suitable for studying problems that are relevant to postmenopausal bone loss.

Aging↗

Salmon calcitonin reduces vertebral fracture rate in postmenopausal crush fracture syndrome.

The effectiveness of calcitonin on the vertebral fracture rate in postmenopausal osteoporosis was assessed through the skeletal deformity index (SDI) and the new vertebral fracture rate per 100 patient-years in a group of 32 women with postmenopausal osteoporosis treated by us with 100 IU of salmon calcitonin and 500 mg of elemental calcium for 10 consecutive days each month, and in another group of 28 women with postmenopausal osteoporosis treated with 500 mg of elemental calcium only for 10 consecutive days each month. Both groups were age-matched. The follow-up was a retrospective randomized study over 24 months. Thirty of the 32 women of the calcitonin group and 27 of 28 women of the calcium group finished treatment. The SDI was stabilized after six months in the calcitonin group (0.57 +/- 0.13, 0.62 +/- 0.18, 0.63 +/- 0.16 and 0.64 +/- 0.17, at base line, 6, 12 and 24 months respectively). The calcium group showed a significant increase only at 12 months (P less than 0.01) and 24 months (P less than 0.05) (0.61 +/- 0.16, 0.63 +/- 0.16, 0.69 +/- 0.16, and 0.73 +/- 0.15, at base line, 6, 12 and 24 months respectively). At 24 months, the new vertebral fracture rate decreased by 60% (20%, 14% and 8% at 6, 12 and 24 months respectively) in the calcitonin group and increased by 35% (31%, 33% and 42%, at 6, 12 and 24 months respectively) in the calcium group (P less than 0.025). These results show that calcitonin induced a significant reduction in postmenopausal osteoporotic vertebral fractures.

Aged↗

The incidental finding of abnormal cervical histology in postmenopausal patients.

A report is supplied on 216 samples of cervical tissue incidentally found in 684 endometrial specimens collected during hysteroscopic examination of postmenopausal women with uterine bleeding and a recent negative Pap smear. We found 43 (19.9%) specimens including cervical tissue with some histologic sign of pathology. Twenty-five (11.6%) had histologic features suggestive for human papillomavirus (HPV) infection, while 18 (8.3%) had cervical intraepithelial neoplasia (CIN). Of the 18 CIN cases, 9 were CIN I, 6 CIN II and 3 CIN III. Altogether, the prevalence of dysplasia in postmenopausal women with recently referred normal cervical cytology was impressive. A significant number of dysplastic lesions (14 out of 18, 77.7%) did not present any histologic sign of HPV. Also, none of the histologic diagnoses of sub-clinical HPV infection was confirmed by the in situ hybridization. Considering the significant prevalence of high grade lesions (9 CIN II and III, 4.2% of the analysed samples) found in this randomly selected patient population, our data strongly suggest the need for a regular follow-up of the transformation zone in all postmenopausal women. Although in women of postmenopausal age some low grade lesions seem to have only a reactive-reparative significance, a more accurate screening procedure, taking into account the peculiar modifications of the menopausal uterine cervix, is advisable.

Adult↗