Changes in muscle strength in women following the menopause: a longitudinal assessment of the efficacy of hormone replacement therapy.
(25/2291)
The effects of hormone deficiency at the menopause on muscle strength was examined in 10 healthy middle-aged women (1-3 years post-menopause) in a longitudinal trial over 39 weeks. Performance was compared with that of age-matched females (n=11) taking a course of hormone replacement therapy (HRT). Muscle strength of the quadriceps was measured isometrically at 90 degrees of knee flexion and at angular velocities of 1.05, 2.09 and 3.13 rad/s using an isokinetic dynamometer. Hand grip strength was assessed by means of a portable dynamometer. Measurements were taken every 13 weeks for 39 weeks. Significant decreases in isometric strength (-10%) and dynamic leg strength at 1.05 rad/s (-9%) were found in the post-menopausal women over 39 weeks. There was no change in strength in the HRT group. There were also no changes in leg strength at higher angular velocities or in grip strength for either the post-menopausal group or those taking HRT. While HRT preserved muscle strength, there was no evidence of a strengthening effect on skeletal muscle within this short period of treatment. A rapid loss of leg strength occurs post-menopausally in hormone-depleted women. HRT may offer protection against muscle weakness, although the hormone responsible for regulating strength is not evident using this model. (+info)
Bone mineral density in patients with type 1 and type 2 diabetes.
(26/2291)
OBJECTIVE: To assess the effect of type 1 and type 2 diabetes and insulin treatment on bone mineral density (BMD) in middle-aged and elderly men and women. RESEARCH DESIGN AND METHODS: We measured BMD and evaluated known determinants of osteoporosis in 56 type 1 and 68 type 2 diabetic patients and 498 nondiabetic community control subjects. All patients, aged 52-72 years, developed diabetes after the age of 30 years (i.e., after achievement of peak bone mass) and were treated with insulin. BMD was measured at the proximal femur with dual-energy X-ray absorptiometry. RESULTS: Among both sexes, BMD values were significantly lower in type 1 diabetic patients than in type 2 diabetic patients or the control subjects. When adjusted for age and BMI, the differences between type 1 diabetic patients and control subjects remained essentially unchanged in both sexes, whereas the differences between type 1 and type 2 diabetic subjects were significant only in men. After further adjustments for confounding factors, the average BMD values were still lower in type 1 diabetic subjects than in type 2 diabetic subjects although with lesser significance. Past low-energy fractures were more common in type 1 diabetic women than in type 2 diabetic women. CONCLUSIONS: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes. This cannot be explained by insulin treatment, which was prescribed for both types of patients. Because the causes of low BMD in type 1 diabetes are unknown, these patients should be evaluated for the risk of osteoporosis and related fractures and offered appropriate preventive measures. (+info)
Species, interindividual, and tissue specificity in endocrine signaling.
(27/2291)
The activity of endocrine-active agents exhibits specificity at many levels. Differential responsiveness to these agents has been observed between different species and extends to interindividual differences within a species and between different tissues as well. In cases where they have been identified, the biologic and molecular mechanisms underlying this specificity are quite diverse. Determinants of species specificity include differences that exist in receptor binding, gene transcription, and cellular responses to endocrine-active compounds between species. Interindividual differences in responsiveness may be determined at the level of genetic polymorphisms in hormone-metabolizing enzymes, hormone receptors, and in those genes that are transactivated by these receptors, as well as during changing windows of susceptibility that occur as a function of age, such as prenatal and postmenopausal exposures. Extrinsic factors such as diet can also impact individual susceptibility to endocrine-active agents. Tissue-specific determinants of susceptibility are well documented, but little is known regarding the mechanisms underlying these different responses. Differences in the expression of accessory proteins for steroid hormone receptors and different patterns of receptor expression, estrogen receptor alpha and estrogen receptor beta; for example, may contribute to tissue specificity, as may differences in the pattern of expression of other genes such as hormone-metabolizing enzymes. The use of animal model systems and development of appropriate mathematical models has the potential to yield additional valuable information for elucidating the role of these determinants of specificity at low-dose exposures and for improved risk assessments for the adverse health effects of endocrine-active compounds. (+info)
Metalloproteinases and tissue inhibitor of metalloproteinase 1 (TIMP-1) in endometrial flushings from pre- and post-menopausal women and from women with endometrial adenocarcinoma.
(28/2291)
The presence of metalloproteinase activity in endometrial flushings obtained from premenopausal women, during the proliferative and secretory phases of the menstrual cycle, control post-menopausal women and women with post-menopausal bleeding (PMB) with or without adenocarcinoma was analysed by zymography. In addition, quantitative measurements of matrix metalloproteinase 2 (MMP-2), MMP-3, MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) in the flushings were obtained by ELISA. The zymography results showed eight bands of activity, with molecular weights ranging from 51 to 208 kDa in the flushings from pre-menopausal women and post-menopausal women, particularly those with adenocarcinoma. Both zymography and ELISA showed that MMP-2 and MMP-9 were the major metalloproteinases found in the flushings and only low concentrations of MMP-3 were found. Concentrations of MMP-2 in pre-menopausal women were higher in flushings obtained during the secretory phase of the menstrual cycle than those obtained in the proliferative phase (P < 0.05), suggesting that it may play a role in embryo implantation. Concentrations of MMP-2 (P < 0.001), MMP-9 (P < 0.05) and TIMP-1 (P < 0.001) in the flushings from post-menopausal control women were lower than those from pre-menopausal women. Concentrations of MMP-2 (P < 0.05) and TIMP-1 (P < 0.05) were higher in flushings from women with PMB without carcinoma compared with post-menopausal controls and concentrations of MMP-9 (P < 0.01) and TIMP-1 (P < 0.05) in flushings from women with adenocarcinoma were higher than in post-menopausal controls. Among subjects with PMB, concentrations of MMP-9 in women with adenocarcinoma were higher than those without carcinoma (P < 0.05). Our results show that concentrations of MMP-2, MMP-9 and TIMP-1, but not MMP-3, are associated with endometrial activity and, therefore, may have a role in the breakdown of endometrial tissue. In addition, the increased concentrations of MMP-9 in flushings of women with adenocarcinoma indicate that this particular proteinase is associated with the presence of endometrial neoplastic cells. (+info)
Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico.
(29/2291)
A case-control study was carried out in Mexico City during 1995-1997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 healthy women, matched according to age categories. In a multivariate analysis, the reproductive risk factors for ovarian and endometrial cancer are similar. The risk of ovarian cancer was inversely related to the number of full-term pregnancies; the odds ratio (OR) was 0.17 and the 95% confidence interval (CI) was 0.05-0.54 when comparing nulliparous women versus those with more than seven pregnancies. For endometrial cancer, a similar association was observed (OR, 0.11; 95% CI, 0.04-0.34). The use of oral contraceptive hormones was inversely associated with both ovarian (OR, 0.36; 95% CI, 0.15-0.83) and endometrial cancer risk (OR, 0.36; 95% CI, 0.14-0.90). In women with a history of more than 8.7 years without ovulation, the risk of ovarian cancer decreased four times (OR, 0.23; 95% CI, 0.10-0.50), and that of endometrial cancer decreased more than five times (OR, 0.17; 95% CI, 0.08-0.35). These two neoplasms are clearly typified as hormone dependent, and it is possible to establish that "ovulation" and "exfoliative" mechanisms jointly determine the level of risk for both ovarian and endometrial cancer. (+info)
Hypertension and hormone-related neoplasms in women.
(30/2291)
The relation between hypertension and the risk of selected hormone-related neoplasms in women was investigated in a network of case-control studies conducted in Italy during 1983-1996. Cases were women younger than 75 years with histologically confirmed cancer of the breast (n=3406), endometrium (n=745), ovary (n=970), and thyroid (n=145). Controls were 3054 women admitted in the same geographic area for acute, nonneoplastic, non-hormone-related diseases. Odds ratios (ORs) of treated hypertension were computed after allowance for sociodemographic factors, smoking habits, alcohol consumption, parity, menopausal status, and body mass index (BMI) by means of unconditional logistic regression. The ORs were 1.2 (95% CI, 1.1 to 1.4) for breast cancer and 1.6 (95% CI, 1.3 to 1.9) for endometrial cancer, and the elevated ORs persisted after >/=5 years since diagnosis of hypertension. No significant association was observed for ovarian and thyroid cancer. For breast cancer, the association was apparently stronger at age 55 years or over and consequently after menopause. No appreciable effect modification was evident for endometrial cancer. Allowance for BMI did not explain the association of postmenopausal breast cancer and endometrial cancer with hypertension. The OR of postmenopausal breast cancer was 1.5 (95% CI, 1.1 to 2.0) in hypertensive women with BMI >/=30 kg/m(2) compared with normotensive women with BMI <25 kg/m(2). The corresponding figure for all endometrial cancers was 4.9 (95% CI, 3. 4 to 6.9). Even in the absence of a clear understanding of biological mechanisms, the definition of a role of hypertension on female hormone-related cancers can have relevant implications on individual risk assessment. (+info)
Homocysteine, vitamin status and risk of vascular disease; effects of gender and menopausal status. European COMAC Group.
(31/2291)
BACKGROUND: Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B(6)and B(12)affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B(6)and B(12)with risk of vascular disease in men and women (pre- and post-menopausal). MATERIAL AND METHODS: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only. RESULTS: Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B(6)conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease. CONCLUSIONS: Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B(6)with vascular disease indicates that it will be advisable to test the effects of vitamin B(6)in clinical trials. (+info)
Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.
(32/2291)
PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain. (+info)