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PubMed1999

A mouse model to study the effects of hormone replacement therapy on normal mammary gland during menopause: enhanced proliferative response to estrogen in late postmenopausal mice.

Hormone replacement therapy (HRT) with estrogen alleviates menopausal symptoms and is effective in reducing osteoporosis and cardiovascular disease when taken in early postmenopause. Older, late postmenopausal women who never previously received HRT are also believed to benefit from estrogen treatment. On the other hand, increased lifetime exposure of the mammary gland to estrogen may increase the risk of breast cancer. The development of suitable experimental animal model systems can advance our understanding of the effects of estrogen and the timing of HRT on the postmenopausal breast. Toward this end, early and late postmenopausal states were induced in mice by short vs. long term ovariectomy (1 vs. 5 weeks), and the effects of 17beta-estradiol (E) on mammary gland morphology, cell proliferation, and progesterone receptor (PR) levels were investigated. We report that in late postmenopausal mice, E caused a pronounced enlargement of duct ends and 6.5- and 4-fold greater mitogenic responses in the duct end epithelium and adjacent stromal cells, respectively, compared with the response in early postmenopausal mice. Furthermore, after long term, daily treatment with E, steady state levels of proliferation remained 2-fold higher than those of similarly treated, early postmenopausal mice. E failed to increase mammary PR levels in late postmenopausal, but not in early postmenopausal mice. Stimulation of duct ends by E and lack of PR inducibility are characteristics of the immature pubertal mammary gland and indicate that the late postmenopausal mammary gland resembled the immature state. In contrast, minimal E-induced proliferation and increased PR inducibility, characteristics of the adult, sexually mature mammary gland, were retained in early postmenopausal mice. The lack of difference in the numbers of estrogen receptor-positive epithelial or stromal cells or in estrogen receptor cellular concentration after short vs. long term ovariectomy indicates that the observed greater efficacy of E is mediated at a step beyond receptor-ligand binding. This mouse model of experimentally induced early vs. late postmenopausal states should prove useful in better understanding alterations in hormone responsiveness and their implications for timing of HRT on the human breast.

Age Factors↗

PubMed1998

Metacarpal radiogrammetry by computed radiography in postmenopausal women with Colles' fracture and vertebral crush fracture syndrome.

Based on the hypothesis that the underlying osteoporotic mechanism of Colles' fracture in postmenopausal women is similar to that of other osteoporotic fractures, that is, cortical bone resorption as opposed to cancellous bone resorption, the rate of corticoendosteal bone loss was compared in 40 normal postmenopausal women [average age 68.4 +/- 7.1 years; 20 +/- 4 years since menopause (YSM)], in 35 postmenopausal women with Colles' fracture (age 69.4 +/- 7.5 years, 22 +/- 8 YSM), in 35 normal postmenopausal women with vertebral crush fracture (age 69.4 +/- 7.5 years, 22 +/- 8 YSM, and in 35 normal premenopausal women (age 36.1 +/- 7.9 years). Radiogrammetry by digital radiography of the second metacarpal was used to measure external (ED) and internal (ID) diameter, cortical thickness (CCT), cortical area (CA), and the ratio of cortical area to total area (CA/TA). The ID values of the groups of postmenopausal women were subtracted from the ID value of the premenopausal women and the result was divided by YSM to obtain the rate of corticoendosteal resorption/year (DeltaC), CA resorption year (DeltaCA) and CA/TA resorption/year (DeltaCA/TA). ID, DeltaC, DeltaCA, and DeltaCA/TA all were larger in the postmenopausal women with Colles' and vertebral crush fractures than in the normal postmenopausal women (ANOVA: all P < 0.0001). ID, CCT, DeltaC, CA, DeltaCA, and DeltaCA/TA did not differ between the two groups of postmenopausal women with fractures. DeltaC was 87% greater in postmenopausal women with vertebral crush fracture and 116% greater in women with Colles' fracture than in normal postmenopausal women. These results indicate that the loss of cortical bone is an important factor in Colles' fracture in postmenopausal women.

Adult↗

PubMed1997

Comparison of endometrial changes among symptomatic tamoxifen-treated and nontreated premenopausal and postmenopausal breast cancer patients.

Breast cancer patients who received tamoxifen as adjuvant therapy have been reported to have more endometrial lesions such as polyps, hyperplasia, or carcinoma. We conducted a prospective study to elucidate the endometrial changes of premenopausal and postmenopausal breast cancer patients with tamoxifen. Sixty-seven symptomatic breast cancer patients who had been on tamoxifen treatment, including 34 premenopausal and 33 postmenopausal patients, and another group of 48 patients who had not been on tamoxifen, including 25 premenopausal and 23 postmenopausal patients, were recruited. Symptomatic patients were defined as having hypermenorrhea or abnormal vaginal bleeding among premenopausal patients or postmenopausal bleeding among postmenopausal patients. Endometrial thickness and uterine size determined by vaginal ultrasonography, histologic findings, and risk factors for endometrial cancer were compared. The mean endometrial thickness and uterine size showed no statistically significant difference in premenopausal patients with (n = 34) or without (n = 25) tamoxifen treatment, whereas there was a significant difference in the postmenopausal patients with (n = 33) or without (n = 23) tamoxifen treatment (12.11 +/- 12.38 mm vs 5.41 +/- 2.70 mm, P = 0.025; 234.71 +/- 76.36 cm3 vs 108.81 +/- 81.27 cm3, P = 0.0018, respectively). The frequency of endometrial histopathologic findings was 23.5% (8/34) in tamoxifen-treated women compared with 12.0% (3/25) in nontreated women (P = 0.269) in the premenopausal groups. In contrast, it was remarkably high with 66.7% (22/33) in tamoxifen-treated women compared with 30.4% (7/23) in the nontreated women in the postmenopausal groups (P = 0.025). There were four postmenopausal patients with tamoxifen, including three with atypical endometrial hyperplasia and one endometrial carcinoma, in contrast to no postmenopausal nontreated patients, although this difference did not reach statistical significance in this study (P = 0.096). There was a remarkably high prevalence of endometrial histopathologic findings in symptomatic tamoxifen-treated breast cancer patients, especially postmenopausal women. Tamoxifen might be associated with premalignant or malignant changes in postmenopausal endometrium. Thus timely, aggressive histologic assessment such as curettage or hysteroscope should be performed to detect the endometrial lesions when symptoms occur. Vaginal ultrasonography could be a useful tool to detect the endometrial lesions.

Aged↗

PubMed2006

Cognitive function in late versus early postmenopausal stage.

OBJECTIVES: There are relatively few studies of cognitive performance in the first few postmenopausal years and insufficient data on whether there is differential decline in different cognitive abilities. The aim of the present analysis was to determine the nature of cognitive decline across a range of functions within a period of 5 years from early to late postmenopausal stage. METHODS: In a cross-sectional study, 189 postmenopausal women, who had experienced a natural menopause, were not taking hormonal medication and had not done so in the previous 12 months, were divided according to their postmenopausal stage into early (stage +1, < or =5 years since the last menstrual period, aged 55.4+/-0.3 years, n=80), or late (stage +2, >5 years since the last menstrual period, aged 59.8+/-0.4 years, n=109) postmenopausal stages. Participants completed a comprehensive battery of tests measuring attention, episodic and semantic memory, planning and mental flexibility. Participants also completed self-ratings of mood, sleepiness and menopausal symptoms. RESULTS: There were no differences between the groups in their performance in tests of attention, verbal fluency or memory. However, in the two tests of executive function (planning and mental flexibility) the women in the late postmenopausal stage performed significantly worse than the women in the early postmenopausal stage. These differences remained significant when effects of age and IQ were taken into account by analyses of covariance. There were no differences between the groups in their ratings of mood or of habitual sleepiness, or of feeling sleepy at the start of testing. However, by the end of testing the women in the late postmenopausal stage rated themselves as feeling sleepier than did the women in the early postmenopausal stage. The group differences in executive function remained significant when these differences in sleepiness were accounted for. CONCLUSIONS: Although there were no differences in attention, verbal fluency and memory, executive function was significantly poorer in the late postmenopausal stage women, suggesting that this aspect of cognition deteriorates more rapidly than other functions. This change was independent of change in age, suggesting that hormonal changes between the early and late postmenopausal stages may be responsible.

Affect↗

PubMed1997

Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.

In women, sex hormone-binding globulin (SHBG) concentrations are the result of a balanced effect of stimulatory and inhibitory factors. Estrogens represent the principal stimulatory hormones, whereas androgens, insulin, excess body fat, and the pattern of body fat distribution have inhibitory effects. Menopause is characterized by major changes in blood sex steroid concentrations, notably a marked reduction of estradiol levels. In this study, we therefore investigated the relationship between hormonal and nonhormonal regulatory factors of SHBG and its blood levels in two groups of premenopausal and postmenopausal women characterized by normal-high or reduced estrogen concentrations. The data were obtained from an analysis of the cross-sectional database obtained during the first survey of the Virgilio-Menopause-Health Project, an epidemiologic longitudinal study aimed at investigating the impact of menopause on body weight, fat distribution, and related major metabolic, hormonal, and cardiovascular risk factors. A total of 329 women, 133 in premenopause and 196 in postmenopause without diabetes, thyroid diseases, or relevant cardiovascular, renal, and hepatic dysfunction, were included in the study. A clinical history (including dietary and physical-activity habits), anthropometry (body mass index [BMI], waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and morning blood samples in the fasting state for sex hormones, insulin, and biochemistry were available for all the women. Premenopausal and postmenopausal women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v 36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were characterized by a marked reduction of estradiol levels and significantly lower levels of testosterone. After adjusting for age, insulin was lower and the glucose to insulin ratio was higher in postmenopause than in premenopause. Age-adjusted values for all anthropometric parameters were not significantly different in the two groups. In simple correlation models, SHBG was significantly and negatively correlated with BMI, WHR, and insulin and testosterone levels in both premenopausal and postmenopausal women, whereas estradiol levels correlated positively and significantly with SHBG only in the premenopausal group. A significant positive correlation between the glucose to insulin ratio and SHBG was present in both groups. Using multiple regression models, in the premenopausal group, SHBG levels were correlated positively with estradiol and negatively with testosterone and insulin, but not with the WHR. On the contrary, in the postmenopausal group, SHBG values had a significant negative correlation with the WHR, whereas the relationship with estradiol was not significant; moreover, the relationship with testosterone and insulin, although significant, became less marked. In conclusion, this study indicates that (1) there is no significant difference in SHBG blood concentrations between premenopause and postmenopause; (2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in the postmenopausal group. Therefore, determinants of SHBG blood concentrations are likely to change on passing from premenopausal to postmenopausal status. In particular, there seems to be a threshold level for which estradiol is an important determinant of SHBG blood concentrations.

Adult↗

PubMed2003

Pre- and postmenopausal high-risk women undergoing screening for ovarian cancer: anxiety, risk perceptions, and quality of life.

OBJECTIVE: Recommendations for women at high risk of ovarian cancer include prophylactic salpingo-oophorectomy (PSO) or screening with transvaginal ultrasonography (TVUS) and CA125 levels. The best strategy for improving survival and maintaining quality of life in high-risk women is not known. Premenopausal women may be more reluctant than postmenopausal women to undergo PSO. However, the risk of false-positive screening results may be more likely in premenopausal women, posing potential psychological risk for those enrolled in high-risk ovarian cancer surveillance programs. We sought to determine whether anxiety, depression, perception of ovarian cancer risk, and false-positive test frequency differed between high-risk premenopausal and postmenopausal women initiating ovarian cancer screening. METHODS: High-risk women aged > or = 30 years enrolling in a TVUS plus CA125 ovarian cancer screening study completed standard QOL (SF-36), cancer-specific anxiety (IES), depression (CES-D), and ovarian cancer risk perception measures. CA125 > 35 and TVUS showing solid or complex cystic ovarian masses were considered abnormal. Abnormal tests were repeated after 4-6 weeks. Persistently abnormal tests prompted a search for malignancy. Tests that normalized on repeat were considered false positive. RESULTS: One hundred forty-seven high-risk women, median age 46 (range, 30-78), 78 premenopausal and 69 postmenopausal, had > or = 1 TVUS/CA125/outcome assessment. Premenopausal women were more likely than postmenopausal women to consider themselves at higher risk of ovarian cancer compared with women their age (P < 0.001) and compared with women with similar family histories (P < 0.001). Mean personal perception of lifetime risk of ovarian cancer among premenopausal women was 37% (range, 0-90%) versus 26% (range, 0-60%) among postmenopausal women (P = 0.02). While general QOL and depression scores were similar, 38% of premenopausal women reported high anxiety versus 27% of postmenopausal women (P = 0.03). Thirty percent of women required repeat CA125 or TVUS after first screening; 10.8% of premenopausal women versus 4.6% of postmenopausal women required repeat CA125; and 23.3% of premenopausal and 20.6% of postmenopausal women required repeat TVUS. One postmenopausal woman with persistently rising CA125 >100 had negative mammography, colonoscopy, and dilation and curettage/bilateral salpingo-oophorectomy. All other abnormal tests normalized on repeat. Two premenopausal women withdrew due to anxiety following false-positive CA125 results. Five women (2 premenopausal, 3 postmenopausal) with normal TVUS/CA125 screening tests elected PSO, with benign findings. CONCLUSION: Premenopausal women perceive their ovarian cancer risk to be higher, report greater ovarian cancer risk-related anxiety, and are more likely to have false-positive screening results than postmenopausal women. Few high-risk women elect PSO in the short term. Knowledge of the frequency of false-positive screening results and psychosocial outcomes is important for high-risk women choosing strategies for managing ovarian cancer risk.

Adult↗

PubMedDate not supplied

Relationship among leptin, neuropeptide Y, and galanin in young women and in postmenopausal women.

OBJECTIVE: To determine whether hormonal status may affect neuropeptide Y (NPY), galanin, and leptin release in postmenopausal women and in young women. DESIGN: Forty-eight postmenopausal women aged 47-65 years and 35 young women aged 26-39 years were investigated. RESULTS: Plasma leptin concentrations increased with increasing body mass index in both young and postmenopausal women and were significantly higher in obese postmenopausal women than in obese young women (p < 0.01). Plasma NPY levels in obese young and postmenopausal women were significantly higher than in lean women (p < 0.01 and p < 0.01, respectively) and were significantly higher in obese and nonobese postmenopausal women than in young women (p < 0.05 and p < 0.001, respectively). Plasma galanin levels in postmenopausal women, both lean and overweight, were significantly lower than in young women (p < 0.01 andp < 0.01, respectively). In obese postmenopausal women, plasma galanin concentrations were lower without differing significantly from those in obese young women. However, they were significantly higher than that in lean postmenopausal women (p < 0.001). CONCLUSIONS: Our results suggest that the differences is plasma leptin, NPY, and galanin between postmenopausal women and young women may be related to body mass index rather than to differences in hormonal status and that the higher NPY levels in both lean and obese postmenopausal women than in young women indicate that factors other than body mass index may be involved.

Adult↗

PubMed2002

Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women.

Various hormones can influence the expression of interleukin-6 (IL-6) and oestrogens are the most extensively studied. There is, however, controversy about the nature of the IL-6 secreted by human cells and its regulation by 17beta-oestradiol. The aim of this work was to clarify whether oestrogen deprivation after menopause may contribute to an enhanced IL-6 production by peripheral blood mononuclear cells (PBMC) in postmenopausal women. Twenty-two healthy postmenopausal women, age range 45-63 years, with clinical symptoms of oestrogen deficiency were enrolled in the study. The control group consisted of 16 healthy young women, age range 22-31 years, with regular menses and who were not taking oral contraceptives. Levels of IL-6 in the sera and PBMC culture supernatants were measured by the biological B9 cell-proliferation assay and expression of the IL-6 gene in non-stimulated PBMC was detected by RT-PCR. The effect of 17beta-oestradiol on spontaneous IL-6 production by the PBMC of postmenopausal women was also studied in vitro and in vivo. Seventeen out of the twenty-two postmenopausal women were given hormonal replacement therapy of 50 microg 17beta-oestradiol/day transdermally and the spontaneous production of IL-6 by the PBMC was analysed after 6 and 12 months of treatment. The postmenopausal women had significantly higher serum levels of IL-6 than the young controls. The spontaneous production of IL-6 by non-stimulated PBMC into the culture supernatants was also significantly higher in the postmenopausal women compared with the young. We also found that IL-6 gene expression was present in the non-stimulated PBMC isolated directly from the venous blood of the majority of the postmenopausal women. Women with IL-6 gene expression in the non-stimulated PBMC had significantly lower serum levels of 17beta-oestradiol compared with those where the IL-6 gene was not expressed in the PBMC. Our in vitro experiments showed that 17beta-oestradiol at concentrations of 10(-9) M and 10(-10) M decreased spontaneous IL-6 production by the PBMC of postmenopausal women. In vivo treatment with 17beta-oestradiol transdermally also significantly decreased spontaneous IL-6 production by the PBMC of postmenopausal women after 12 months of the therapy. Our results indicate that oestrogen deprivation after menopause may enhance IL-6 production by the PBMC of postmenopausal women. We suspect that the late complications of oestrogen deficiency, such as osteoporosis, coronary heart disease and Alzheimer's disease, may be mediated by an exaggerated production of IL-6 - a cytokine which seems to play a pivotal role in the pathogenesis of these age-related diseases.

Administration, Cutaneous↗

PubMed1999

Bone mineral in pre- and postmenopausal women with insulin-dependent and non-insulin-dependent diabetes mellitus.

The aim of the study was to compare bone mineral density (BMD) and bone turnover in pre- and postmenopausal women with insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and normal reference women. In a cross-sectional study 31 and 11 premenopausal and 22 and 21 postmenopausal IDDM and NIDDM patients, respectively, were recruited from an outpatient clinic. BMD in the forearm, spine, femur and total body and biochemical markers of bone turnover were measured and compared with reference values obtained from measurements of normal healthy pre- and postmenopausal women. Postmenopausally, but not premenopausally, IDDM patients had lower BMD values than NIDDM patients. Postmenopausal NIDDM patients had higher BMD value than normal women. The differences in BMD between IDDM and NIDDM patients could be explained statistically by differences in body weight between the NIDMM (obese) and IDDM (lean) women. Markers of bone turnover were significantly higher postmenopausally than premenopausally in both IDDM and NIDDM patients. Osteocalcin was significantly lower in postmenopausal NIDDM compared with postmenopausal IDDM patients and reference values. Otherwise there were no differences in the markers of bone turnover between NIDDM and IDDM patients. In conclusion, postmenopausal IDDM patients have a relatively decreased BMD, whereas NIDDM patients seem to be relatively protected from postmenopausal bone loss.

Adult↗

PubMed2003

Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation.

In the present study, to determine a possible role of nitric oxide (NO) in the regulation of membrane functions, we examined the relationship between plasma NO level and membrane fluidity of erythrocytes in postmenopausal women. We evaluated the membrane fluidity of erythrocytes obtained from hypertensive and normotensive postmenopausal women by means of an electron paramagnetic resonance (EPR) and spin labeling method. The EPR study revealed that the order parameter (S) for 5-nitroxide stearate in erythrocyte membranes was significantly greater in hypertensive postmenopausal women than in normotensive postmenopausal women. The finding indicated that the membrane fluidity of erythrocytes was decreased in hypertensive postmenopausal women compared with normotensive postmenopausal women. The plasma level of the NO metabolites (nitrite and nitrate) while fasting was significantly lower in hypertensive postmenopausal women than in normotensive postmenopausal women. In addition, the order parameter (S) in the EPR spectra of erythrocyte membranes was inversely correlated with the plasma NO metabolite level, which indicated that the lower membrane fluidity of erythrocytes was associated with the lower plasma NO level in postmenopausal women. These results are consistent with the hypothesis that NO may have a crucial role in the regulation of membrane fluidity of erythrocytes in postmenopausal women.

Aged↗

PubMed1999

Estrogen improves abnormal norepinephrine-induced vasoconstriction in postmenopausal women.

OBJECTIVE: An exaggerated blood pressure response to mental stress in postmenopausal women has been reported but the underlying mechanism is not clear. In the present study, we examined the role of estrogen in the blood pressure response to mental stress. SUBJECTS AND METHODS: Hemodynamic responses to mental stress and constrictor responses to norepinephrine were compared in 18 premenopausal (mean +/- SD age 33 +/- 5 years), 22 postmenopausal women (62 +/- 7 years) and 13 postmenopausal women with estrogen replacement therapy (58 +/- 8 years). Premarin was infused in 10 postmenopausal women to determine whether estrogen attenuates norepinephrine-induced vasoconstriction. The hemodynamic responses to a standard mental arithmetic test were measured. Norepinephrine (12.5, 25, 50, 100 ng/min) was infused at 0.5 ml/min for 5 min via the dorsal hand vein. Norepinephrine (100 ng/min) combined with premarin (200 microg/min) was infused into the dorsal hand vein of postmenopausal women. Changes in venous diameter were measured by ultrasonography using a 7.5 MHz transducer. RESULTS: All study subjects were healthy, normotensive and had normal lipid profiles. The postmenopausal women showed a significantly greater blood pressure response to the mental arithmetic test than the premenopausal women or those taking estrogen replacement therapy (P < 0.01). Norepinephrine induced significant dose-dependent vasoconstriction in all three groups (P < 0.001). The postmenopausal women showed significantly greater constriction in response to norepinephrine than the premenopausal women and those taking estrogen replacement therapy (P = 0.02). Premarin significantly attenuated the norepinephrine-induced vasoconstriction in the postmenopausal women (P< 0.001). CONCLUSION: Healthy, normotensive postmenopausal women showed an exaggerated blood pressure response to mental stress. An increased vasoconstriction in response to norepinephrine and loss of estrogen-mediated vasodilation may contribute to the increased blood pressure response to stress in postmenopausal women without estrogen replacement therapy.

Adult↗

PubMed1997

Effects of oestrogen on the extracellular matrix in the endometrium of postmenopausal women.

AIM: To obtain insight into the effects of oestrogen on extracellular matrix (ECM) in the postmenopausal endometrium. METHODS: The distribution of the components of the ECM, including collagen types I, III, IV, and VI, and laminin, was investigated in the human postmenopausal endometrium by an indirect immunofluorescence method with specific monoclonal antibodies and a polyclonal antibody. Collagens were also extracted from the endometrial tissues of postmenopausal women who had or had not been treated with oestrogen for three weeks. RESULTS: Immunohistochemical studies demonstrated that type I collagen was the predominant interstitial collagen, and that types III and VI collagens were absent or very sparsely distributed in the stroma of the postmenopausal endometrium. However, types I, III, and VI collagens were diffusely localised in the stroma of the postmenopausal endometrium after administration of oestrogen. Even though type IV collagen was not seen in the basement membrane of the endometrial glands in the endometrium of postmenopausal women in the absence of oestrogen treatment, both type IV collagen and laminin were localised exclusively in the basement membrane of the endometrial glands in the postmenopausal endometrium after three weeks of oestrogen treatment. The level of type III collagen relative to that of type I collagen was significantly increased (p < 0.01) in the endometrium of oestrogen treated postmenopausal women compared with non-treated postmenopausal women. CONCLUSIONS: Conjugated equine oestrogen might induce changes in the distribution of components and in the composition of the ECM in the endometrium of postmenopausal women.

Aged↗

PubMed2001

Transient increase in the levels of T-helper 1 cytokines in postmenopausal women and the effects of hormone replacement therapy.

The aim of this study was to determine, at least in part, T-cell function in postmenopausal women and the effects of hormone replacement therapy (HRT). Levels of T-helper 1 (Th1) cytokines (IL-2 and IFN-gamma) and T-helper 2 (Th2) cytokines (IL-4 and IL-10) produced by phytohemagglutinin-stimulated whole blood cells from 72 untreated and 44 HRT-treated women were measured by ELISA. Thirteen of the 44 HRT-treated women were examined before and during HRT. The production of IL-2 increased gradually with advance of the postmenopausal period. The levels of IL-2 in women in the early (< or =10 years) and mid (>10 and <30 years) postmenopausal stages were significantly higher than those in women in their second, third and fourth decades. The level in women in the late (> or =30 years) postmenopausal stage, however, was significantly lower than those in women in the early and mid postmenopausal stages. The level of IFN-gamma was highest in women in the mid postmenopausal stage. On the other hand, the levels of Th2 cytokines did not change with age or after menopause until the mid postmenopausal period but were significantly lower in women in the late postmenopausal stage. IFN-gamma levels in women on HRT were significantly lower than those in untreated postmenopausal women at all postmenopausal stages. HRT induced a significant decrease in the production of IL-2 and IL-4. In conclusion, production of Th1 cytokines is augmented in women after menopause. HRT prevents this increase, thereby improving the aberration of Th1/Th2 balance that is implicated in an inadequate immune response and pathological conditions.

Adolescent↗

PubMed2005

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.

Adult↗

PubMed2002

Body fat distribution and cardiovascular disease risk factors in pre- and postmenopausal obese women with similar BMI.

The aim of this study is to determine the body fat distribution and cardiovascular disease risk factors in pre- and postmenopausal obese women matched for weight, height and body mass index (BMI). Study group consisted of 405 premenopausal overweight/obese (BMI > 27 kg/m2, mean 37.83 +/- 6.91 kg/m2) and 405 postmenopausal overweight/obese (BMI > 27 kg/m2), BMI-matched (mean 37.77 +/- 6.84 kg/m2) women. None of the women were on hormone replacement therapy. Insulin resistance was evaluated by "homeostasis model assessment" (HOMA) formula. Intraabdominal fat volume was calculated according to the following formula: IAF (L) = [(0.370 x abdominal sagittal diameter) - 4.85]. Age, waist circumference, waist to hip ratio (WHR) and intraabdominal fat volume were significantly higher in postmenopausals compared with BMI-matched premenopausal women (p < 0.001). Systolic and diastolic blood pressure, glucose, uric acid, cholesterol and triglyceride were significantly higher (p < 0.001) and HDL-cholesterol was significantly lower (p < 0.05) in postmenopausals. No significant differences were observed with respect to insulin and HOMA. When age-matched pre- and postmenopausal women were compared, only total cholesterol was significantly higher in the postmenopausal group. However, older postmenopausal women (> 50 years) had significantly higher systolic blood pressure, waist circumference, WHR, glucose and uric acid concentrations compared with younger (< or = 50 years) postmenopausals. It is concluded that an increase in abdominal fat accumulation and unfavorable alterations in risk factors disturb postmenopausal obese women even if total body weight and BMI do not change during menopause transition. Ageing, particularly throughout the postmenopausal years, has important effects on the detrimental changes associated with menopause.

Abdomen↗

PubMed2001

Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement.

OBJECTIVES: A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects. SETTING: October 24 and 25, 2000, Washington, DC, preceding the annual Society of Radiologists in Ultrasound Advances in Sonography conference. PROCEDURE: Specific questions to the panel included the following: (1) What are the relative effectiveness and cost-effectiveness of using transvaginal sonography versus office (nondirected) endometrial biopsy as the initial examination for a woman with postmenopausal bleeding? (2) What are the sonographic standards for evaluating a woman with postmenopausal bleeding? (3) What are the abnormal sonographic findings in a woman with postmenopausal bleeding? (4) When should saline infusion sonohysterography or hysteroscopy be used in the evaluation of postmenopausal bleeding? (5) Should the diagnostic approach be modified for patients taking hormone replacement medications, tamoxifen, or other selective estrogen receptor modulators? CONCLUSIONS: Consensus recommendations were used to create an algorithm for evaluating women with postmenopausal bleeding. All panelists agreed that because postmenopausal bleeding is the most common presenting symptom of endometrial cancer, when postmenopausal bleeding occurs, clinical evaluation is indicated. The panelists also agreed that either transvaginal sonography or endometrial biopsy could be used safely and effectively as the first diagnostic step. Whether sonography or endometrial biopsy is used initially depends on the physician's assessment of patient risk, the nature of the physician's practice, the availability of high-quality sonography, and patient preference. Similar sensitivities for detecting endometrial carcinoma are reported for transvaginal sonography when an endometrial thickness of greater than 5 mm is considered abnormal and for endometrial biopsy when "sufficient" tissue is obtained. Currently, with respect to mortality, morbidity, and quality-of-life end points, there are insufficient data to comment as to which approach is more effective. The conference concluded by identifying several important unanswered questions and suggestions that could be addressed by future research projects.

Algorithms↗

PubMed2001

[Relationship between serum 1,25-dihydroxyvitamin D and bone loss in postmenopausal women].

OBJECTIVE: To study the correlations between loss of activity and/or amont of serum 1,25-dihydroxyvitamin D(1,25(OH)2D) and 25-dihydroxyvitamin D(1,25(OH)2D) and bone loss in postmenopausal women, in order to reveal the possible pathophysiology of postmenopausal osteoporosis. METHODS: The serum levels of 1,25 (OH)2D, 25 (OH) D, PTH, and E2 in 57 postmenopausal women with osteoporosis and 37 postmenopausal women without osteoporosis were measured by radioimmunology. Their Dpd/Cr in urine was measured by ELISA. The bone mineral density (BMD) at lumbar spine (L2-4) was measured in each subject by DEXA. RESULTS: The serum 1,25(OH)2D in postmenopausal oeteoporotic women and non-osteoporotic women were 18 pg/ml +/- 6 pg/ml and 31 pg/ml +/- 14 pg/ml respectively (P < 0.01) The serum 25 (OH)2D in postmenopausal oeteoporotic women and non-osteoporotic women were 32 ng/ml +/- 9 ng/ml and 46 ng/ml +/- 17 ng/ml respectively (P < 0.01). Postmenopausal osteoporotic women had a lower estrogen concentration (P < 0.01), higher serum parathyroid hormone (PTH) (P < 0.01) and higher urinary Dpd/Cr level (P < 0.01). The level of serum 1,25(OH)2D was highly correlated with BMD in L2-4 for postmenopausal women (r = 0.693, P < 0.001). There was a close relationship between the serum level of 1,25(OH)2D and serum level of 25(OH)2D, suggesting an association between the two factors. CONCLUSION: The lower bone mass density was associated with lower level of serum 1,25-dihydroxyvitamin D, accompanied by reduced serum estrogen and elevated serum PTH in postmenopausal women. Those may be among the important pathphysiological changes of postmenopausal osteoporosis.

Aged↗

PubMed1996

[Very low density lipoproteins and subclasses of intermediate density lipoproteins in postmenopausal women].

Post menopausal women present an increase of cardiovascular risk associated with the atherogenic plasma lipoproteins IDL and LDL. Our purpose was to study the composition of VLDL, IDL and the subfractions IDL-1 and IDL-2, and the Lipoprotein Lipase and Hepatic Lipase activities in a group of twelve healthy post menopausal women as compared with eleven fertile controls. The mean values of total cholesterol and LDL cholesterol were significantly increased in the post menopausal group compared to the controls (p < 0.005 and p < 0.001 respectively). The contribution of the HDL-cholesterol plasma concentration to total cholesterol was lower in the postmenopausal women (p < 0.02) although no one had HDL-cholesterol lower than 35 mg/dl and the mean value was 50 mg/dl. Postmenopausal women had increased concentrations of VLDL, total IDL and IDL-2 compared to controls (p < 0.05, p < 0.005 and p < 0.001 respectively). Plasma concentrations of total IDL was increased in postmenopausal women (33.6 +/- 3.4 vs 22.6 +/- 0.8 mg/dl, p < 0.005). The increase in total IDL was due to IDL-2 (19.9 +/- 1.7 vs 11.5 +/- 0.8 mg/dl, p < 0.001, in postmenopausal women vs controls). The IDL-2 subfraction was 60 +/- 2.6% of total IDL in postmenopausal women and 51 +/- 2.0% in controls (p < 0.02). In postmenopausal women and in controls the ratio triglyceride/protein (which indicates particles size) was significantly higher in IDL-1 than in IDL-2 (p < 0.005 and p < 0.01 respectively), but this ratio did not show differences when VLDL, total IDL and IDL-2 were compared between postmenopausal and control women. Then, the increased plasma concentration of these lipoproteins would show an increased number of particles in the postmenopausal women vs controls. There were no differences in the Lipoprotein Lipase and Hepatic Lipase activities between both groups. Lipoprotein Lipase vs total IDL-triglycerides and IDL-2-triglycerides showed a significant inverse correlation in controls (p < 0.05) but not in postmenopausal women. We conclude that the qualitative and quantitative study of the lipoproteins shows a more atherogenic profile in the postmenopausal group, with an increase in the concentration and number of particles of VLDL, total IDL and IDL-2.

Cholesterol, HDL↗