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PubMed1996

The relationship of body mass index to reproductive factors in pre- and postmenopausal African-American women with and without breast cancer.

To date, there are virtually no existing data on the relationship between obesity, menopausal status, and breast cancer in African-Americans. Therefore, the present study was designed to test the following hypotheses in an African-American population: (1) there exists a positive association between BMI and breast cancer among postmenopausal women; (2) there exists an inverse association between BMI and breast cancer among premenopausal women; and (3) similar associations between BMI and reproductive factors exist for both pre- and postmenopausal breast cancer cases. The study population comprised 357 African-American women (n = 193 breast cancer cases; n = 164 controls). No significant differences were observed between premenopausal cases and controls for BMI, obesity categories, and reproductive factors. Among the postmenopausal women, the cases had significantly lower weight and BMI levels than the controls. Age at first pregnancy and parity were significantly lower among postmenopausal cases than their controls. No significant associations were revealed between body mass index and breast cancer for pre- and postmenopausal women. In the present study, early age at menarche was the only reproductive factor that was an independent predictor of BMI for both pre- and postmenopausal women, irrespective of breast cancer status. Also, these findings strongly suggest the need to consider reproductive factors, particularly age at menarche, as a covariate of BMI and other obesity-related diseases.

Adult↗

PubMed1996

Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: the OFELY Study.

Vitamin D receptor (VDR) gene polymorphisms have been reported to account for most of the well established genetic influence on bone mineral density (BMD). However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. In this study, we analyzed VDR gene polymorphisms, i.e., that of BsmI, ApaI, and TaqI restriction enzymes in 268 untreated postmenopausal women 1-26 years postmenopausal. There were 37 BBAA homozygote (absence of BsmI and ApaI restriction sites on both alleles), 55 bbaa homozygote (presence of restriction sites on both alleles), and 176 heterozygotes. At baseline, women between the three genotypes did not differ significantly in age, years since menopause, body mass index (BMI), nor dietary calcium intake. We found no relationship between VDR genotypes and bone turnover assessed by three serum markers of bone formation and three urinary bone resorption markers, nor with BMD measured at the spine, hip, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). Rates of bone loss assessed by repeated DXA measurements over 2 years were highly significant (p = 0.02-0.0001) at all skeletal sites except for the lumbar spine but did not differ between genotypes at any sites either before or after adjustment for potential confounding factors such as years since menopause, BMI, calcium intake, serum 25 hydroxyvitamin D levels, and baseline BMD. When we restricted the analysis to early postmenopausal women, within 10 years of menopause (n = 128), lumbar spine bone loss became significant, but no significant difference between VDR genotypes in the rate of bone loss measured at any site was found. We conclude that VDR genotypes are not predictive of bone turnover, rate of postmenopausal bone loss, and bone mass in either early or late postmenopausal women. In a subgroup of women with a low calcium intake (below 600 mg/day), we also found no significant differences between genotypes in BMD and the rate of bone loss measured at any site, although the sample size (n = 64) may be too small to detect small differences. In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.

Absorptiometry, Photon↗

PubMed1996

New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis.

The aim of this work was to perform a comparative study between three recently developed biochemical markers of bone resorption derived from collagen metabolism--(1) total urinary free pyridinolines (Pyr), (2) serum pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and (3) a urinary-specific sequence for a part of the C-telopeptide of the alpha 1 chain of type I collagen (CTX)--in the diagnosis and follow-up of postmenopausal osteoporosis. Results were also evaluated relative to the classical biochemical marker urinary hydroxyproline (Hyp). The study included 20 untreated osteoporotic postmenopausal women (OSP), age 60 +/- 6 years, range 46-69 years; 27 osteoporotic postmenopausal women treated (OSP-T) by cyclic therapy with disodium etidronate, 25-hydroxyvitamin D and calcium for a period between 3 months and 4 years (25 +/- 15 months), age 59 +/- 7 years, range 41-67 years; 17 osteopenic postmenopausal women, age 57 +/- 6 years, range 46 +/- 68 years; and 29 healthy control postmenopausal women, age 56 +/- 7 years, range 41-70 years. The diagnostic criterion for postmenopausal osteoporosis was a bone mineral density (BMD) (Hologic QDR-1000) in lumbar spine and/or femoral neck more than 2 SD below the mean value corresponding to an age- and sex-matched healthy control group. For inclusion in the osteopenic group BMD values had to be between 1 and 2 SD below the mean BMD value corresponding to the control group. We found a significant increase (p < 0.01) in the levels of Pyr/Cr and CTX/Cr (Cr = creatinine) in OSP patients with respect to the control group and we did not observe any significant difference between control and OSP-T or osteopenic women. It is interesting to note that there was a mean increase in CTX/Cr in OSP patients of 101% of the control values, while the mean increase found in Pyr/Cr concentration was only 33%. However, we did not find significant differences in the concentrations of ICTP and Hyp/Cr between groups. In a comparison of Pyr/Cr and CTX/Cr, urinary CTX showed the higher diagnostic accuracy, as can be deduced from the receiver operating characteristic (ROC) curves. CTX sensitivity was 40% with a specificity of 100%, whereas the sensitivity was 25% for urinary Pyr/Cr. In conclusion, the results of the present work suggest that in osteoporotic women CTX has the highest diagnostic accuracy among the markers of bone resporption studied.

Adult↗

PubMed1995

Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal, bone-active drug ipriflavone.

Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and tolerability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3 +/- 0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n = 24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n = 31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n = 28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%; p < 0.01). Both valid completers and intention to treat analyses revealed a significant difference (p < 0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.

Bone Density↗

PubMed1991

Potential risk factors for development of postmenopausal osteoporosis--examined over a 12-year period.

In a longitudinal study, we investigated the influence of risk factors on bone mass at menopause and postmenopausal bone loss in 121 healthy postmenopausal women. These women had completed a 2-year prospective study in 1979 and a follow-up examination in 1989. Measurements of the bone mineral content in the distal forearm (single photon absorptiometry) were performed 9 times during the initial study and once at the follow-up examination. Bone mass at menopause (initial measurement), rate of early postmenopausal bone loss, and the subsequent rate of bone loss over 10 years were thus determined. In addition, the bone mineral density of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DXA) in 1989. Information about risk factors was assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of alcohol and caffeine, smoking habits, and physical activity). Lactation, oral contraceptive use, and dietary calcium intake above 1500 mg per day was associated with significantly increased bone mass at menopause. The number of pregnancies reduced the rate of early postmenopausal bone loss, whereas moderate alcohol consumption reduced the subsequent rate of bone loss. Smoking significantly reduced femoral bone mineral density. In conclusion, the present prospective study showed that some of the examined putative risk factors positively influenced bone mass at menopause, especially calcium intake, whereas the postmenopausal bone loss was virtually unaffected. Assessment of risk factors in postmenopausal women thus seems to have limited value for reducing future risk of osteoporosis.

Aged↗

PubMed2002

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.

Blood Coagulation↗

PubMedDate not supplied

Sulfated glycosaminoglycans of the vagina and perineal skin in pre- and postmenopausal women, according to genital prolapse stage.

The aim of this study was to analyze the amount and types of sulfated glycosaminoglycans (GAGs) of the extracellular matrix (ECM) in the posterior vaginal wall and perineal skin in menacme and postmenopausal women, according to genital prolapse stage. Samples of vaginal tissue and perineal skin were obtained from 40 women who underwent vaginal surgery. Sulfated glycosaminoglycans were extracted by extensive tissue maxatase digestion, submitted to electrophoresis on agarose gel, and their concentrations were determined by densitometry. Dermatan sulphate (DS) was the predominant GAG, followed by chondroitin sulfate (CS) and heparan sulfate (HS). In the vagina there was a significant decrease in total GAGs, CS, DS and HS in postmenopausal women with prolapse stage 2 and 3 compared to the premenopausal group, independent of the stage. In stage 2 and 3 postmenopausal patients there was a significant decrease of DS and HS compared to the stage 1 postmenopausal group. In perineal skin there was no significant difference between total GAG amount, DS and HS. However, the amount of CS in premenopausal stage 1 patients was significantly than that in postmenopausal patients stage 1 and stages 2 and 3. In conclusions, there are quantitative and qualitative differences in GAGs of the ECM in vaginal wall and perineal skin between women in menacme and the postmenopause, according to genital prolapse stage.

Aged↗

PubMed2006

Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal women.

The aim of this study was to explore the relationship between biomechanical properties and the occurrence of pelvic organ prolapse (POP) through analysis on biomechanical properties of vaginal tissue. The biopsy specimens were obtained from 43 patients undergoing transvaginal hysterectomy, who were assigned into premenopausal POP, postmenopausal POP, premenopausal control and postmenopausal control groups. Tissue specimens were biomechanically assessed by a purpose-built tissue puller system, and stress-strain curves were digitally recorded. The Young's modulus, Poisson's ratio, maximum elongation, maximum fracture of vaginal tissue were 9.45 +/- 0.70, 0.43 +/- 0.01, 1.50 +/- 0.02, 0.60 +/- 0.02 in premenopausal POP group; 12.10 +/- 1.10, 0.39 +/- 0.01, 1.14 +/- 0.05, 0.27 +/- 0.03 in postmenopausal POP group; 6.65 +/- 1.48, 0.46 +/- 0.01, 1.68 +/- 0.11, 0.79 +/- 0.05 in premenopausal control group and 10.26 +/- 1.10, 0.42 +/- 0.01, 1.37 +/- 0.04, 0.42 +/- 0.03 in postmenopausal control group. There was significant difference in biomechanical properties between premenopausal POP group and premenopausal control group (p < 0.01). There was significant difference in biomechanical properties between postmenopausal POP group and postmenopausal control group (p < 0.01). Biomechanical properties in POP group were significantly lower than that in control group, suggesting that degeneration of biomechanical properties in pelvic support construction might lead to the occurrence of POP.

Adult↗

PubMed2002

Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal women.

The aim of this study was to biomechanically assess vaginal tissue from pre- and postmenopausal women with symptomatic prolapse. Vaginal tissue was collected at the time of surgery in women with symptomatic prolapse. Tissue specimens were biomechanically assessed by a purpose-built tissue puller system and stress-strain curves were digitally recorded. Tissue was stretched at a constant rate of 0.8 mm/s to an elongation of 8 mm. A force-stiffness relationship was obtained. All data were normalized for length and cross-sectional area of the specimens. Tissues from the anterior vaginal wall were analyzed in 10 postmenopausal and 8 premenopausal women. The mean age of the postmenopausal women was 69 years, compared to 41 years for premenopausal women. Pre- and postmenopausal groups show very little or no difference regarding elongation or long-term tissue deformation. A significantly higher elastic modulus was observed in postmenopausal vaginal tissue. This is most likely an age-related phenomenon. Apart from this, pre- and postmenopausal vaginal tissue showed few differences in biomechanical assessment.

Adult↗

PubMed2006

Computer-aided system for measuring the mandibular cortical width on dental panoramic radiographs in identifying postmenopausal women with low bone mineral density.

INTRODUCTION: Mandibular inferior cortical width manually measured on dental panoramic radiographs may be useful for identifying postmenopausal women with low skeletal bone mineral density (BMD). Automatic measurement of cortical width may enable us to identify a large number of postmenopausal women with suspected low skeletal BMD. The purposes of this study were to develop a computer-aided system for measuring mandibular cortical width on dental panoramic radiographs and clarify the diagnostic efficacy of this system. METHODS: Panoramic radiographs of 100 postmenopausal women who had had BMD assessments of the lumbar spine and the femoral neck were used in this study. Experienced oral radiologist determined the position of the mental foramen on 100 digitized dental panoramic radiographs. After determination of the mental foramen, mandibular cortical width below the mental foramen was measured automatically with a computer-aided system by identifying the area of interest, enhancing the original image, determining inner and outer margins of the cortex, and selecting an appropriate point. Cortical width measured by this system was compared with BMD of the lumbar spine and the femoral neck. RESULTS: There were statistically significant correlation between cortical width measured by the computer-aided system and spinal BMD (r=0.50) and femoral neck BMD (r=0.54). These correlations were similar with those between cortical width by manual measurement and skeletal BMD. Sensitivity and specificity for identifying postmenopausal women with low spinal BMD by the computer-aided system were about 88.0% and about 58.7%, respectively. Those for identifying postmenopausal women with low femoral neck BMD by this system were about 87.5% and about 56.3%, respectively. CONCLUSION: Our results suggest that our computer-aided system may be useful for identifying postmenopausal women with low skeletal BMD.

Aged↗

PubMed2005

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women.

OBJECTIVE: To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure. METHODS: Time-dependent Cox regression models were used to analyse information on postmenopausal women from a large-scale French cohort. Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive postmenopausal breast cancer cases were identified from 1992 to 2000. RESULTS: A non-significant decrease in risk of around 10% was associated with ever OC use as compared to never OC use in postmenopausal women. No significant interaction was found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer risk decreased significantly with increasing time since first OC use (test for trend: p=0.01); this was consistent after adjustment for duration of use or for time since last use. CONCLUSION: No increase in breast cancer risk was associated with previous OC exposure among postmenopausal women, probably because the induction window had closed. Some women may develop breast cancer soon after exposure to OCs, leading to a deficit of cases of older women. Further investigation is therefore required to identify young women at high risk.

Adult↗

PubMed2005

Women's quality of life in the premenopausal and postmenopausal periods.

PURPOSE: The purpose of this research was to determine the relationship between menopausal symptoms and quality of life in women in the pre and postmenopausal periods. METHODS AND INSTRUMENTS: All 171 women in the climacteric period who registered at the Pamukkale University Education and Research Hospital Obstetrics and Gynecology Clinic between January and July 2001 were included in the study. A questionnaire asking for sociodemographic information, complaints related to the climacteric period, and HRT use, as well as the WHOQOL brief, were used in order to obtain data. FINDINGS: One hundred of the women who participated in the study were premenopausal and 71 were postmenopausal and the mean age was 47.39 (SD=6.65). No significant difference was found in pre and postmenopausal women in the comparison of their quality of physical life, psychological, social relationships and environment scores (p>0.05). The physical quality of life scores for those without vasomotor complaints in the pre and postmenopausal periods were significantly higher in those with a high educational level and women who had been menopausal between 1-5 years and more than 10 years (p<0.05). Age and HRT use in postmenopausal women were not found to affect quality of life scores (p>0.05). RESULT: We did not find any significant difference in the quality of life of pre and postmenopausal women.

Adult↗

PubMed1994

Management of postmenopausal osteoporosis.

More than 25% of postmenopausal women are at risk of osteoporosis. In order to avoid its consequences, it is necessary to find an appropriate prevention and/or treatment. We studied: (1) 15 postmenopausal women treated with percutaneous estradiol (50 micrograms/24 h) plus MPA (10 mg/10 days/month); (2) 15 postmenopausal women treated with synthetic calcitonin nasal spray at the daily dose of 100 IU; (3) 10 postmenopausal women treated with nandrolone decanoate (50 mg every 3 weeks); (4) 10 postmenopausal women treated with ipriflavone (600 mg/day); and (5) 10 postmenopausal women treated with sodium fluoride (20 mg) plus calcium (600 mg). Clinical examination, bone mass measurement (total BMD), hematochemical and urinary parameters of bone metabolism (calcium, urinary hydroxyproline, PTH) and growth factors (as IGF-I and TNF-beta) were evaluated. After 6 months of therapy, a complete prevention of bone resorption was achieved. In agreement with current literature, we observed that the various therapeutic approaches have all some positive effect on BMD, with different results on pain, blood biochemical parameters and growth factors' concentrations.

Aged↗

PubMed1993

Hormonal treatments modulate pulsatile plasma growth hormone, gonadotrophin and osteocalcin levels in postmenopausal women.

Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1-5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.

Calcitonin↗

PubMed1992

A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus.

The potential influence of postmenopausal estrogen therapy on the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM) is relatively unexplored, despite postulated effects of these hormones on glucose tolerance. We examined the association between postmenopausal hormone use and the subsequent incidence of NIDDM in a prospective cohort of 21,028 postmenopausal US women aged 30 to 55 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1976. During 12 years of follow-up (422,991 person-years), we confirmed 1249 cases of NIDDM. Current users of postmenopausal hormones had a relative risk of NIDDM of 0.80 (95% confidence interval, 0.67 to 0.96) as compared with never users, after adjustment for age and body mass index (BMI). Past users of these hormones had an age- and BMI-adjusted relative risk of 1.07 (0.93 to 1.23). These results were not materially altered by multivariate adjustment for age, BMI, family history of diabetes, and coronary risk factors. Comparable results were obtained when the analysis was restricted to symptomatic NIDDM as the outcome. We observed no appreciable modification of these associations by family history of diabetes or category of BMI. Duration of current or past use of postmenopausal hormones and dose of conjugated estrogen were not significantly related to incidence of NIDDM. Type of hormone (estrogen alone, progesterone alone, or combination) also did not appear to influence NIDDM risk. These prospective data indicate that postmenopausal hormone therapy is unlikely to be associated with a material increase in the incidence of NIDDM among women.

Adult↗

PubMed2005

Exercise as an alternative to oral estrogen for amelioration of endothelial dysfunction in postmenopausal women.

BACKGROUND: Both exercise and postmenopausal estrogen therapy augment endothelial function. We hypothesized that their interaction would be additive. The study objectives were to determine in postmenopausal women (1) the effects of an acute bout of exercise on brachial artery endothelium-dependent flow-mediated vasodilation (FMD), (2) whether these responses to exercise are augmented by concurrent estrogen treatment, and (3) whether these 2 interventions, independently or together, achieve FMD values observed in premenopausal women. METHODS: In postmenopausal women (n = 13; age 54 +/- 2 [mean +/- SE] years), FMD was quantified during supine rest and again 60 minutes after treadmill exercise for 45 minutes at 60% V* O2max. Subjects were studied twice: before and after 4 weeks of oral estradiol. To obtain reference normal values, FMD was determined concurrently in 14 premenopausal (28 +/- 1 years) women under identical basal conditions. RESULTS: Flow-mediated vasodilation in postmenopausal women, markedly impaired when compared with premenopausal women (5.3% +/- 0.5% vs 12.1% +/- 1.5%, P < .01), was significantly increased by exercise (to 9.9% +/- 0.6%, P < .01). In contrast, after estrogen, FMD was augmented at rest (P < .01) but was not further enhanced after exercise (11.5% +/- 0.6% vs 9.9% +/- 0.5%, P = .3). Both interventions increased, independently, FMD to values in premenopausal women (P > .05). CONCLUSIONS: In postmenopausal women, both acute exercise and estrogen therapy normalize FMD. However, their effects are not additive, possibly because of redundancy of nitric oxide signaling pathways activated by these 2 interventions. When considered in the context of recent trials with adverse cardiovascular outcomes, these results reinforce the therapeutic potential of exercise as an alternative nonpharmacological intervention to estrogen in postmenopausal women with endothelial dysfunction.

Administration, Oral↗

PubMed2004

Small low-density lipoprotein particles and endothelium-dependent vasodilation in postmenopausal women.

Low concentrations of estrogen may decrease endothelial function in postmenopausal women. Elevated plasma triglycerides after menopause are frequently associated with a small, dense low-density lipoprotein (LDL) phenotype. Small LDL particles that are more susceptible to oxidation can also inhibit endothelium-dependent vasodilation. The purpose of the present study was to investigate whether hypertriglyceridemia-induced small LDL particles are associated with endothelial dysfunction in postmenopausal women. We studied 15 premenopausal and 41 postmenopausal women. Postmenopausal subjects were divided into those with LDL subclass pattern A (large particles) and those with pattern B (small particles). Plasma lipids, hormones, and diameter and oxidative susceptibility of LDL were measured. Vasodilatory responses of the brachial artery were evaluated by measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation (NID). FMD in both postmenopausal groups was significantly lower than in premenopausal women. FMD in subjects with pattern B was significantly smaller than in those with pattern A (4.9 +/- 1.9% versus 8.8 +/- 3.6%). NID did not differ significantly among the groups. Plasma triglyceride concentrations were higher, lag time for LDL oxidation was shortened, and LDL-derived thiobarbituric acid-reactive substance (TBARS) concentrations were significantly greater in subjects with pattern B than in premenopausal or pattern A subjects. LDL diameter correlated negatively with plasma triglycerides (r = -0.51) or LDL-derived TBARS (r = -0.44) and positively with LDL-lag time (r = 0.66). FMD correlated negatively with LDL-derived TBARS (r = -0.36) and positively with LDL diameter (r = 0.44) or LDL-lag time (r = 0.43). Vascular endothelial dysfunction may be associated with elevated triglyceride-induced small LDL particles that have enhanced oxidative susceptibility in postmenopausal women.

Endothelium, Vascular↗

PubMed2004

Development of novel steroid sulfatase inhibitors; II. TZS-8478 potently inhibits the growth of breast tumors in postmenopausal breast cancer model rats.

In postmenopausal breast cancer tissue, steroid sulfatase (STS) activity is high and much estrone sulfate also exists; these facts reveal that estrone sulfate may be involved in the growth of breast cancer as an estrogen source. Steroid sulfatase is an enzyme, which catalyzes hydrolysis from estrone sulfate to estrone, and the development of steroid sulfatase inhibitors is expected as novel therapeutic drugs for postmenopausal breast cancer. We have developed a novel compound 2',4'-dicyanobiphenyl-4-O-sulfamate (TZS-8478), which has potent steroid sulfatase-inhibitory activity and exhibits no estrogenicity in vitro and in vivo. To elucidate its usefulness as a therapeutic drug for postmenopausal breast cancer, we examined the breast cancer cell proliferation- and breast tumor growth-inhibitory activity of TZS-8478 in postmenopausal breast cancer model rats. TZS-8478 dose-dependently suppressed the estrone sulfate-stimulated proliferation of MCF-7 cells. Regarding nitrosomethylurea (NMU)-induced postmenopausal breast cancer models, furthermore, TZS-8478 (0.5 mg/kg per day) markedly inhibited the estrone sulfate-stimulated growth of breast tumors similarly to estrone sulfate-depletion. TZS-8478 completely inhibited steroid sulfatase activity in tumor, uterus and liver, and also markedly lowered plasma concentrations of estrone and estradiol. The above mentioned results suggested that TZS-8478 may be useful as a therapeutic drug for estrogen-dependent postmenopausal breast cancer.

Animals↗