Changes in serum levels of type I collagen-related proteins after surgically induced menopause and correlations with bone loss in the lumbar spine.
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The purpose of this prospective study was to characterize the changes in serum levels of two proteins produced during the synthesis and degradation of type I collagen, i.e., the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), respectively, after oophorectomy, and to assess the degree of correlation between changes in the serum values of these proteins and changes in bone mineral density (BMD) of the lumbar spine. Serum levels of PICP, ICTP and bone gla protein (BGP) were determined in 18 women before oophorectomy (baseline) and at 7 days, and 1, 2, 3, 6, 9 and 12 months post-oophorectomy (PO). The BMD of the lumbar spine was measured at baseline, and at 6 months and 12 months PO. ICTP had increased significantly at 7 days PO and peaked between 1 and 3 months PO. PICP and BGP had increased significantly at 2 months PO and remained at high levels thereafter. The percent changes in lumbar BMD from baseline values (% CFB) at 6 months and at 12 months PO were significantly correlated with % CFB in ICTP, but not with % CFB in PICP or BGP. Accordingly, bone resorption is a main determinant of bone mineral loss after oophorectomy and the change in recently-developed bone resorption markers, such as ICTP, is of clinical utility in predicting a degree of subsequent bone loss after surgical menopause. (+info)
Validity of self-reports of fractures in perimenopausal women.
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The validity of self-report of fractures in postal inquiry among perimenopausal women was evaluated. Self-reports of fractures in the 1989 baseline postal inquiry data of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were compared with information in patient records. The study population consisted of 373 women who reported fractures sustained during the last 10 years and 200 randomly selected women who did not report fractures from a population base of 2,007 women aged 47-56 years. Self-report as a screening test for fracture was evaluated in the total sample of 2,007 women by estimating the number of false negative reports in all the women who did not report a fracture with the information on these 200 women. Of the self-reports of fractures, 84% proved to be true fractures, 12% soft tissue injuries, and the rest either self-diagnoses or misnomers. Self-report of wrist fracture was more accurate (95%). The sensitivity of self-report to detect fracture was 78% for all fractures and 95% for wrist fracture, while the respective specificities were 96 and 99%. Self-report is a relatively accurate way to obtain information about past major fractures in perimenopausal women. However, it is rather insensitive in the detection of minor fractures, if the reporting period is several years. (+info)
Aging, body composition, and lifestyle: the Fels Longitudinal Study.
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BACKGROUND: Changes in body composition in men and women occur with age, but these changes are affected by numerous covariate factors. OBJECTIVE: The study examined patterns of change in body composition and determined the effects of long-term patterns of change in physical activity in older men and women and in menopausal status and estrogen use in women. DESIGN: Serial measures of height, weight, body mass index (BMI), total body fat (BF), percentage BF, and fat-free mass (FFM) from underwater weighing of 102 men and 108 women enrolled in the Fels Longitudinal Study were analyzed. Physical activity levels and menopausal status were included as covariates. RESULTS: There were significant age-related decreases in FFM and height and increases in total BF, percentage BF, weight, and BMI. Physical activity was associated with decreases in total BF, percentage BF, weight, and BMI in men and were associated with increases in FFM and decreases in total BF and percentage BF in women. Postmenopausal women had significantly higher total BF and percentage BF than did pre- and perimenopausal women. The longer the time since menopause the greater were the increases in weight, BMI, total BF, and percentage BF; however, estrogen use attenuated these increases. CONCLUSIONS: Low FFM can be improved by increased physical activity. The effects of an intervention program on body composition can be masked if only body weight or BMI is measured. The effects of physical activity were more profound in postmenopausal than in premenopausal women, and estrogen use had beneficial effects on body composition. (+info)
Interactions of familial and hormonal risk factors for large bowel cancer in women.
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BACKGROUND: Family history of colorectal cancer has been consistently associated with an increased personal risk of this disease. Since evidence suggests that hormones are related to colon cancer risk in women, the effect of family history on large bowel incidence may be modified according to endogenous and exogenous hormone levels. METHODS: We analysed data from a population-based case-control study of female colorectal cancer to evaluate family history and cancer risk. Cases (n = 702) were female residents of Wisconsin with a new diagnosis of colorectal cancer, identified through a statewide tumour registry. Controls (n = 2274) were randomly selected from lists of licensed drivers and from rosters of Medicare beneficiaries. All relative risks (RR) were adjusted for age, body mass index, smoking and alcohol history, education, and use of hormone replacement therapy. RESULTS: Compared with women who reported no history of cancer in a first degree relative, women with a family history had an RR of 2.07 (95% confidence interval [CI]: 1.60-2.68). Regardless of which parent was affected, risks were increased about twofold, while sibling history was associated with about a 50% increase in risk. Risk was greater if more than one family member was affected (RR 3.65, 95% CI: 1.81-7.37). The association between family history and risk was stronger for colon cancer than for rectal cancer. There were no indications that exogenous hormonal factors, notably hormone replacement use, modified these risks. There was a suggestion that high parity attenuated the risks associated with family history (P = 0.07). CONCLUSIONS: These results confirm that family history of colorectal cancer is associated with a doubling of risk for large bowel cancer in women; some histories were associated with greater risk. This relation was not substantially different among subgroups of women with varying exogenous and endogenous hormone exposures. (+info)
Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions.
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We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast. (+info)
Overexpression of BRCA2 gene in sporadic breast tumours.
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The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript that encodes a 3418-amino acid protein involved in the response to DNA damage. To obtain better a molecular characterization of BRCA2 expression in sporadic breast cancer, we quantified BRCA2 mRNA by means of RT - PCR in a large series of human primary breast tumours. BRCA2 expression showed wide variations in tumour tissues, being underexpressed in 14/127 (11%) and overexpressed in 25/127 (20%). BRCA2 overexpression (but not underexpression) correlated significantly with Scarff, Bloom and Richardson (SBR) histopathological grade III (P=0.007) and was mainly attributed to nuclear polymorphism (P=0.005) and mitotic index (P=0.048), suggesting that the BRCA2 gene contributes to the proliferation rate in breast tumours. BRCA2 status (under and/or overexpression versus normal expression) was not associated with subsequent relapse and with significantly shorter disease-free survival. The observed disruption of BRCA2 expression is not due to allelic loss, because the latter did not correlate with altered BRCA2 mRNA expression in our tumour series. Taken together, these data suggest the involvement, especially by overexpression, of the BRCA2 gene in sporadic breast tumours, and the existence of another important tumour-suppressor gene in breast cancer, in the 13q12-q13 region. (+info)
Androgen replacement for women.
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OBJECTIVES: To determine whether a postmenopausal syndrome comprising specific changes in sexual desire and response associated with low free testosterone exists. To determine whether this syndrome is ameliorated by testosterone replacement. QUALITY OF EVIDENCE: Literature documenting that replacement of physiological levels of testosterone is beneficial and safe is scant. Only one randomized prospective blinded study examines sexual outcome in detail. MAIN MESSAGE: Testosterone is an important metabolic and sex hormone produced by the ovary throughout life. The variable reduction in ovarian testosterone production coincident with menopause is sometimes associated with a syndrome of specific changes in sexual desire and sexual response. Estrogen deficiency also impairs sexual response, but its replacement will not improve and might exacerbate sexual symptoms from androgen loss. Diagnosis of androgen deficiency is clinical, based on accurate assessment of a woman's sexual status before and after menopause and only confirmed (rather than diagnosed) by a low level of free testosterone. Partial androgen replacement restores much of the sexual response and facilitates sexual desire that is triggered by external cues. Avoiding supraphysiological levels of testosterone lessens risk of masculinization. Avoiding alkylated testosterone lessens hepatic or lipid impairment. CONCLUSION: Further prospective randomized studies of replacement of physiological levels of testosterone in women with androgen deficiency syndrome are needed, using formulations of testosterone available in Canada. The consistency of sexual changes, the associated personal and relationship distress, together with our clinical experience of the gratifying response to physiological replacement, make further studies urgently needed. (+info)
Can estrogen keep you smart? Evidence from clinical studies.
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OBJECTIVE: To review and critically analyze the biological plausibility of and the clinical empirical evidence concerning a link between estrogen levels and memory in women. DATA SOURCES: MEDLINE search of the literature published from 1980 to 1998. Studies published between 1952 and 1980 that were known to the author were also included. STUDY SELECTION: Sixteen prospective, placebo-controlled studies in humans. DATA SYNTHESIS: Most of the studies that used neuropsychological tests with known reliability and validity found that estrogen maintained aspects of memory in women. CONCLUSIONS: Estrogen specifically maintains verbal memory in women and may prevent or forestall the deterioration in short- and long-term memory that occurs with normal aging. There is also evidence that estrogen decreases the incidence of Alzheimer disease or retards its onset or both. (+info)