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Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women.

OBJECTIVE: The cardioprotective effects of postmenopausal estrogen replacement therapy are mediated by several mechanisms, including favorable effects on lipids and lipoproteins. The extent to which the latter reflects modification of body fat distribution by sex steroids is not known. Hence, we investigated the relationships between changes in lipids and measures of body composition in postmenopausal women who were administered estrogen therapy with and without testosterone. DESIGN: We randomized 33 postmenopausal women to treatment with either estradiol 50 mg (E) alone or estradiol 50 mg plus testosterone 50 mg implants (E&T) administered every 3 months for 2 years in conjunction with cyclic oral progestins for women with an intact uterus. RESULTS: Both therapies were associated with sustained reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. In women who received E but not E&T, hip (p < 0.001) and abdominal circumferences (p < 0.05) and fat mass:fat-free mass (FM:FFM) ratio over the abdomen (p < 0.05) declined. E&T but not E resulted in increased FFM (p < 0.001) and a reduced FM:FFM ratio (p < 0.05). For E but not E&T, the decrease in LDL cholesterol was significantly related to changes in total and compartmental body fat and to change in the FM:FFM ratio (p < 0.05). CONCLUSION: Estrogen replacement has effects on body fat distribution in postmenopausal women that are associated with improved lipid parameters. Addition ofparenteral testosterone does not negate the favorable effects of estrogen on LDL cholesterol levels but may attenuate the reduction in centralized body fat achieved with E implants.

Absorptiometry, Photon↗

Concomitant medication use in postmenopausal women using estrogen therapy.

OBJECTIVE: To determine whether long-term postmenopausal estrogen therapy is associated with use of other prescription medications. METHODS: Using computer pharmacy records from 1969 to 1973 for members of the Kaiser Permanente Medical Care Program in San Francisco, we identified the 215 most commonly used prescription medications in the pharmacy database and recorded their use by 232 postmenopausal long-term estrogen users and by 222 postmenopausal age-matched nonusers. These medications were grouped into 39 therapeutic classes. Classes of medications used by estrogen users and nonusers were compared. RESULTS: A statistically significant difference in use was seen for 21 of the 39 medication classes; of these 21 classes, 20 (95%) were used more frequently and 1 less frequently by estrogen users. Differences between estrogen users and nonusers were greatest for thyroid hormone preparations (estrogen user/nonuser multivariate odds ratio = 25.6, 95% confidence interval 5.9-112) and antimigraine preparations (11 recipients among estrogen users, none among nonusers). Postmenopausal women using estrogen were more likely than nonusers to use additional medications. CONCLUSION: Greater use of certain prescription medications by estrogen users than by nonusers should be considered in studying the health effects of estrogen replacement therapy.

Analgesics↗

Circadian rhythm of objectively recorded hot flashes in postmenopausal breast cancer survivors.

OBJECTIVE: Similar to the circadian rhythm of core body temperature, hot flashes have been found to exhibit a circadian rhythm in healthy, naturally postmenopausal women, with a peak in frequency at 18:25 h. However, to date, no studies have evaluated whether this same pattern is found among breast cancer survivors reporting hot flashes. DESIGN: Daily hot flash frequencies were measured among 21 postmenopausal breast cancer survivors using validated 24-h sternal skin conductance monitoring. RESULTS: Hot flashes were noted in all women, ranging in frequency from 1 to 30 per 24-h period. A majority of the sample (86%) experienced > or = 1 nighttime hot flash, with 48% exhibiting > or = 3 but < or = 7 nighttime hot flashes. For the total sample, a modest circadian rhythm was noted with a peak in hot flash frequency occurring at 16:10 h. However, significant variability was observed across individual women, and, as a whole, breast cancer survivors demonstrated distorted to obliterated rhythms. CONCLUSIONS: Data suggest that hot flashes in postmenopausal breast cancer survivors do not follow the same circadian pattern as previously seen in healthy, naturally postmenopausal women. Findings have implications for (1) understanding the potential for sleep disturbances and fatigue in breast cancer survivors experiencing hot flashes, and (2) future research examining circadian rhythms of core body temperature and hot flashes in breast cancer survivors.

Body Temperature↗

Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women.

OBJECTIVE: Oxidized low-density lipoprotein (LDL) seems to play an important role in the etiology of atherosclerosis. To further study this, we performed two studies: (1) we determined the ability of 10 estrogen components of the drug, conjugated equine estrogen (CEE), trans-resveratrol (t-resveratrol) and quercetin (red wine components), trolox (vitamin E analog), and probucol (a serum cholesterol-lowering drug) to delay or prevent the oxidation of plasma LDL isolated from untreated postmenopausal women, and (2) we assessed the effect of long-term (>1 year) estrogen replacement therapy and hormone replacement therapy on LDL oxidation by ex vivo methods. DESIGN: For the in vivo study, three groups of postmenopausal women were selected based on whether they were on long-term CEE therapy (group A: 0.625 mg CEE; n = 21), on combination CEE plus progestogen therapy (group B: 0.625 mg CEE + 5.0 mg medroxyprogesterone acetate, 10 days; n = 20), or not on any hormone therapy (group C; n = 37). For the in vitro study, only LDL samples obtained from group C were used. The kinetics of LDL oxidation were measured by continuously monitoring the formation of conjugated dienes followed by determination of the lag time. RESULTS: All compounds tested protected the LDL from oxidative damage. The relative antioxidant potency of estrogen components was generally greater than that of the other compounds. The minimum dose (nmoles) required to double the lag time from the control lag time of 57 +/- 2 min was 0.47 for 17beta-dihydroequilenin, 17alpha-dihydroequilenin, Delta 8 -estrone; 0.6 to 0.7 for Delta 8 -17beta-estradiol, equilenin, and quercetin; 0.9 for 17beta-dihydroequilin and 17alpha-dihydroequilin; 1.3 for equilin, estrone, 17beta-estradiol, 17alpha-estradiol; 1.4 for trolox; 1.9 for probucol; and 3.0 for t-resveratrol. The data from the in vivo study indicate that after long-term estrogen replacement therapy (group A) and hormone replacement therapy (group B), the LDL was significantly ( p < 0.01) protected (higher lag time) against oxidation compared with the control (group C). There was no difference between groups A and B. CONCLUSIONS: The oxidation of LDL isolated from postmenopausal women is inhibited differentially by various estrogens and other antioxidants. The unique ring B unsaturated estrogen components of CEE were the most potent, and t-resveratrol, the red wine component, was the least potent. Long-term CEE or CEE + medroxyprogesterone acetate administration to postmenopausal women protects the LDL against oxidation to the same extent. These combined data support the hypothesis that some of the cardioprotective benefits associated with CEE therapy and perhaps red wine consumption may be due to the ability of their components to protect LDL against oxidative modifications.

Antioxidants↗

High density lipoproteins (HDL) in women with postmenopausal osteoporosis: a preliminary study.

OBJECTIVE: Since a previous study showed an inverse correlation between high density lipoproteins (HDL) and bone mineral density (BMD), we searched for a possible relationship between HDL level and the presence of postmenopausal osteoporosis. DESIGN: We measured HDL levels in 37 women with postmenopausal osteoporosis, and compared them with a control group of 43 healthy postmenopausal women. The HDL levels were compared between the two groups using Student's t test and were correlated with BMD by Pearson's coefficient. To avoid possible selection bias, we compared patients and controls for body mass index by chi 2 test. The sensitivity and specificity of HDL level higher than 65 mg% (positive test) or lower than 45 mg% (negative test) was compared with double emission x-ray absorptiometry (considered the gold standard in the measurement of BMD). RESULTS: The level of HDL was significantly higher in the osteoporotic patients than in the controls (67.7 +/- 15.5 mg% vs 58.3 +/- 11.6 mg%, p = 0.0039). HDL was inversely correlated with BMD (r = -0.29, p = 0.0083). HDL higher than 65 mg% has a high specificity (77%) for patients with osteoporosis, while HDL lower than 45 mg% has a high sensitivity (97%) in detecting subject without osteoporosis. CONCLUSIONS: Our preliminary data suggest an interesting, as yet unexplained association between HDL and bone mineral density in postmenopausal women.

Absorptiometry, Photon↗

Should we consider performing oral glucose tolerance tests more frequently in postmenopausal women for optimal screening of impaired glucose tolerance?

OBJECTIVE: To investigate an optimal screening protocol for impaired glucose tolerance (IGT) and type II or non-insulin-dependent diabetes mellitus (DM) by using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in postmenopausal women. DESIGN: One hundred consecutive postmenopausal women were screened with FPG determination, and then all underwent an OGTT. Basal serum lipid and insulin levels of these women were also determined. Insulin sensitivity was determined by using the homeostasis model assessment. Receiver operating characteristic analysis was performed to determine the efficacy of these variables in detecting women with IGT and DM, and optimal cutoff values were determined. RESULTS: FPG with a cutoff value of 98 mg/dL had the best combination of sensitivity (71%) and specificity (76%) for the detection of IGT and DM. Combined FPG and body mass index screening (with the optimal cutoff value of 26.5 kg/m2) improved the sensitivity to 96% but decreased the specificity to 47%. This combined screening protocol detected 94% of the women with IGT and all diabetic women. CONCLUSIONS: Given that IGT and DM are common among postmenopausal women and DM can be prevented by nonpharmacologic interventions in women with IGT, OGTT may be used more frequently among these women. Our data indicate that for optimal screening of non-insulin-dependent DM and IGT, OGTT should be considered in postmenopausal women, especially when risk factors in addition to age are present. This model may detect most of the women with IGT and almost all diabetic women.

Aged↗

Core body temperature variation in symptomatic and asymptomatic postmenopausal women: brief report.

OBJECTIVE: To determine if core body temperature (T) fluctuations occur in asymptomatic as well as symptomatic postmenopausal women. DESIGN: Tc was recorded with an ingested radiotelemetry pill in symptomatic postmenopausal women who had a hot flash in the laboratory, in symptomatic women who did not have a hot flash in the laboratory, and in asymptomatic postmenopausal women. RESULTS: There were no significant differences in mean Tc or Tc variation, as measured by the standard deviation, among the three groups. CONCLUSION: Tc fluctuations are not unique to symptomatic postmenopausal women.

Analysis of Variance↗

Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society.

OBJECTIVE: To create an evidence-based position statement regarding the role of progestogen in postmenopausal hormone therapy (estrogen plus a progestogen, or EPT) for the management of menopause-related symptoms. DESIGN: NAMS followed the general principles established for evidence-based guidelines to create this document. Clinicians and researchers acknowledged to be experts in the field of postmenopausal hormone therapy were enlisted to review the evidence obtained from the medical literature and develop a position statement for approval by the NAMS Board of Trustees. RESULTS: The primary role of progestogen in postmenopausal hormone therapy is endometrial protection. Unopposed estrogen therapy (ET) is associated with a significantly increased risk of endometrial hyperplasia and adenocarcinoma. Adding the appropriate dose and duration of progestogen to ET has been shown to lower that risk to the level found in never-users of ET. The clinical goal of progestogen in EPT is to provide endometrial protection while maintaining estrogen benefits and minimizing progestogen-induced side effects, particularly uterine bleeding. EPT discontinuance correlates with uterine bleeding-women with more days of amenorrhea have higher rates of continuance. All US Food and Drug Administration-approved progestogen formulations will provide endometrial protection if the dose and duration are adequate. Progestogens may diminish the beneficial effects of ET on cardiovascular risk factors. However, no EPT (or ET) regimen should be initiated for the primary or secondary prevention of cardiovascular heart disease. Some progestogens may negatively affect mood. Adding progestogen to ET does not decrease the breast cancer risk, although it does not seem to increase mortality. Progestogen increases mammographic density, which is reversed after discontinuation of use. Progestogen has limited effect on the bone-enhancing action of ET. In general, the side effects of added progestogen are mild, although they may be severe in a small percentage of women. CONCLUSIONS: Progestogen should be added to ET for all postmenopausal women with an intact uterus to prevent the elevated risk of estrogen-induced endometrial hyperplasia and adenocarcinoma. There is no consensus on a preferred regimen for all women. By changing the progestogen type, route, or regimen, clinicians can individualize therapy to minimize side effects, especially uterine bleeding, and limit any effects on ET benefits while providing adequate endometrial protection.

Endometrial Hyperplasia↗

Relationship between self-reported periodontal status and skeletal bone mineral density in Japanese postmenopausal women.

OBJECTIVE: Several investigators have linked periodontal disease progression and low skeletal bone mineral density in postmenopausal women. However, little is known about whether self-reported periodontal status is the reflection of skeletal bone mineral density. We investigated whether self-reported poor periodontal status is associated with low skeletal bone mineral density in postmenopausal women. DESIGN: Relationships among self-reported periodontal status, number of teeth remaining, and bone mineral density of the lumbar spine and the femoral neck were evaluated in 253 Japanese postmenopausal women (mean +/- SD, 56.6 +/- 7.7) recruited from the patients who visited our clinic for bone mineral assessment between 1997 and 2003. Self-reported periodontal symptoms included gingival swelling, gingival bleeding, purulent discharge, and tooth mobility at the time of bone mineral assessment. RESULTS: Analysis of covariance adjusted for age, height, weight, years since menopause, duration of estrogen use, and regular oral care revealed that subjects without periodontal symptoms had significantly higher BMD of the lumbar spine than did those with periodontal symptoms (mean +/- SEM, 0.962 +/- 0.014 vs 0.921 +/- 0.013; P = 0.038); however, there were no significant differences in the number of remaining teeth and bone mineral density of the femoral neck between them. The odds of low spine bone mineral density in subjects with periodontal symptoms was 2.01 (95% CI = 1.15 to 3.50). CONCLUSION: Our results suggest that self-reported poor periodontal status may be associated with low bone mineral density of the lumbar spine in postmenopausal women.

Asian People↗

Effects of postmenopausal hormone therapy every day and every other day on lipid levels according to difference in body mass index.

OBJECTIVE: The objective of this study was to determine the effects of postmenopausal estrogen and progestogen therapy (EPT) every day and every other day on lipid levels, particularly triglyceride (TG) levels, according to difference in body mass index (BMI). DESIGN: Ninety-nine postmenopausal women (mean age, 53.9 +/- 5.6 years; mean BMI, 22.8 +/- 2.8 kg/m) were randomly treated with EPT every other day or every day for 1 year. Fifty women received oral administration of 0.625 mg of conjugated equine estrogen (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) every other day, and 49 women received oral administration of 0.625 mg of CEE and 2.5 mg of MPA every day. Blood samples were collected at baseline and after 1 year of therapy for measurement of fasting TG, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and apolipoproteins. Data from 88 of the 99 postmenopausal women were used for analysis. RESULTS: In women whose BMI was 25 kg/m or higher, TG levels during EPT every day increased by 26.8%, while TG levels during EPT every other day decreased by 12.3%. There was a significant (P < 0.05) difference between percentage changes in TG during EPT every day and every other day. In women whose BMI was less than 25 kg/m, TG levels during EPT every day increased by 21.7%, while during EPT every other day TG levels did not change. The mean levels of estradiol during EPT every day in women whose BMI was less than 25 kg/m and in women whose BMI was 25 kg/m or higher were 28.5 and 38.7 pg/mL, respectively, the difference between these levels was significant (P < 0.01). On the other hand, there was no significant difference between levels of estradiol during EPT every other day in these two BMI groups. CONCLUSIONS: Triglyceride levels during EPT every day with conventional doses of CEE and MPA increased more in overweight and obese postmenopausal women in association with increased estrogen levels.

Administration, Oral↗

The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study.

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.

Bone Density↗

Alcohol, estrogen replacement therapy, and visuospatial processes in postmenopausal women.

BACKGROUND: Studies suggest that moderate drinking may benefit cognition and the effect may favor women. This study investigated effects of moderate drinking on visuospatial functioning in postmenopausal women. Visuospatial processes are sensitive to alcohol abuse and are thought to be sensitive to hormonal fluctuations. Three questions were posed in order to: explore visuospatial processes in moderate-drinking and abstaining postmenopausal women, assess visuospatial differences in women using no estrogen replacement therapy (No-ERT), ERT alone (ERT-only), and ERT with progestin (ERT+Pro), and identify alcohol/ERT interactions associated with visuospatial performance. METHODS: Two hundred fourteen postmenopausal women participated (75 No-ERT; 63 ERT-only; 76 ERT+Pro. All were moderate drinkers or teetotalers and all received the Block Design test from the Wechsler Adult Intelligence Scale-Revised. A raw score was calculated and progress at 30-sec intervals was assessed. RESULTS: ANOVA revealed an alcohol main effect [F(3,202) = 4.74; p < 0.004] on 60- to 120-sec change scores. Teetotalers had significantly smaller change scores (less improvement) compared with all levels of drinkers. ANOVA on design 9 (the most difficult trial) revealed an ERT main effect [F(3,202) = 4.37; p < 0.02]. ERT nonusers scored significantly lower than ERT-only and ERT+Pro groups. A design 9 trend toward an alcohol x ERT interaction was noted [F(6,202) = 1.93; p < 0.08], and a design 9 time x alcohol interaction was revealed [F(6,404) = 2.65; p < 0.02]. CONCLUSIONS: These data suggest that moderate drinking may be positively associated with visuospatial processes in postmenopausal women. They also suggest that ERT, alone and with progestin, is positively associated with visuospatial processes, but only when the task is difficult. These findings support Kaplan's assertion that subtle performance deficits may not be detectible with traditional endpoint measures. A provocative alcohol x ERT trend suggests that alcohol consumption should be considered in studies of ERT effects on cognitive ability.

Aged↗

Effect of moderate alcohol consumption on parameters of reverse cholesterol transport in postmenopausal women.

BACKGROUND: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma cholesterol esterification (EST), and (3) cholesteryl ester transfer (CET) to apolipoprotein B-containing lipoproteins. Our previous study in healthy middle-aged men showed that moderate alcohol consumption increases cellular cholesterol efflux and EST. This study investigated the effect of moderate alcohol consumption on three early steps of reverse cholesterol transport in postmenopausal women. METHODS: In a randomized crossover study, 18 postmenopausal women--all apparently healthy, non-smoking, and moderate alcohol drinkers--consumed white wine or white grape juice with evening dinner during 2 successive periods of 3 weeks. During the white wine period, alcohol intake equaled 24 g/day. At the end of each of the two experimental periods, blood samples were collected. RESULTS: Three weeks of alcohol consumption increased serum HDL cholesterol levels (5.0%; p < 0.05), serum HDL phospholipid levels (5.8%; p < 0.05), and the ex vivo cellular cholesterol efflux capacity of plasma, measured with Fu5AH cells (3.4%; p < 0.05). Plasma EST and CET did not change. CONCLUSIONS: Moderate alcohol intake increases serum HDL cholesterol level and stimulates cellular cholesterol efflux in postmenopausal women. Moderate alcohol consumption does not seem to affect two other early steps of reverse cholesterol transport at this level of alcohol intake. Our data suggest that the relative protection of moderate alcohol consumption against cardiovascular disease in postmenopausal women may involve the stimulation of reverse cholesterol transport through increased HDL.

ATP-Binding Cassette Transporters↗

Alcohol intake, type of beverage, and risk of breast cancer in pre- and postmenopausal women.

BACKGROUND: Most studies of the relation between alcohol consumption and breast cancer have shown a modestly increased risk, although the results are still conflicting. METHODS: The aim of this prospective population-based cohort study was to assess the influence of alcohol intake and type of beverage (beer, wine, or spirits) on breast cancer risk in relation to menopausal status. Among 13,074 women aged 20 to 91 years, we examined the relationship between breast cancer risk, total alcohol intake, and type of alcohol in relation to menopausal status. The women were classified as premenopausal or as postmenopausal at younger than 70 years or 70 years or more. RESULTS: During follow-up, 76 premenopausal and 397 postmenopausal women developed breast cancer. Premenopausal women who had an intake of more than 27 drinks per week had a relative risk of breast cancer of 3.49 (95% confidence limits, 1.36-8.99) compared with light drinkers (p = 0.011), whereas there were no differences in risk in the lower-intake categories. The increased risk of breast cancer among premenopausal women was independent of the type of alcohol. Postmenopausal women older than 70 years of age who had an intake of more than six drinks per week of spirits had a relative risk of breast cancer of 2.43 (95% confidence limits, 1.41-4.20) compared with women who consumed less than one drink of spirits per week (p = 0.0014). CONCLUSIONS: Total alcohol intake of more than 27 drinks per week increases breast cancer risk in premenopausal women independently of the type of alcohol. Among postmenopausal women, an intake of spirits of more than six drinks per week increases breast cancer risk.

Adult↗

Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects.

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular beta2-adrenoceptor responsivity. METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and beta-adrenoceptor responsivity. RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular beta2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.

Administration, Cutaneous↗

Postmenopausal hormone therapy and risk of developing urinary incontinence.

OBJECTIVE: To better understand associations between post-menopausal hormone therapy and the development of urinary incontinence. METHODS: Postmenopausal hormone use was assessed via biennial mailed questionnaires beginning in 1976 among Nurses' Health Study participants. In 1996, 39,436 post-menopausal women aged 50-75 years reported no leaking of urine and were followed-up for 4 years to identify incident cases of incontinence. We used logistic regression to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relation of postmenopausal hormone use from 1976 to 1996 to the development of incontinence from 1996 to 2000. RESULTS: We identified 5,060 incident cases of occasional (leaking urine 1-3 times/month) and 2,495 cases of frequent incontinence (leaking at least weekly) for average yearly incidence rates of 3.2% and 1.6%, respectively. The risk of incontinence was elevated among women taking postmenopausal hormones compared with women who had never taken hormones (oral estrogen: RR 1.54, 95% CI 1.44, 1.65; transdermal estrogen: RR 1.68, 95% CI 1.41, 2.00; oral estrogen with progestin: RR 1.34, 95% CI 1.24, 1.44; transdermal estrogen with progestin: RR 1.46, 95% CI 1.16, 1.84). There was little risk after the cessation of hormones (RR 1.14, 95% CI 1.06, 1.23) and a decreasing risk of incontinence with increasing time since last hormone use; 10 years after stopping hormones, the risk was identical in women who had and had never taken hormone therapy (RR 1.02, 95% CI 0.91, 1.14). CONCLUSION: Postmenopausal hormone therapy appears to increase risk of developing urinary incontinence. This risk does not vary by route of administration, type of hormones, or dose taken, but is diminished upon cessation of use. LEVEL OF EVIDENCE: II-2

Age Distribution↗

The effects of antihypertensive agents on endometrial thickness in asymptomatic, hypertensive, postmenopausal women.

OBJECTIVE: The aim of this study was to investigate, by using transvaginal ultrasonography, the possible effects on endometrial thickness of antihypertensive agents in asymptomatic postmenopausal women. DESIGN: A prospective study in an outpatient menopause clinic of a university hospital. We included 288 postmenopausal women in this study, and we compared three groups of postmenopausal women as follows: (1) normotensive postmenopausal women, (2) hypertensive women treated with an antihypertensive drug (beta-blocker, non-beta-blocker, or beta-blocker plus non-beta-blocker), and (3) untreated hypertensive women who had had hypertension for at least 1 year. Hypertensive women treated with a drug had been receiving treatment for 1 year. All women were interviewed and examined. Measurements of endometrial thickness were carried out by vaginal ultrasonography. RESULTS: Sixty-two women (22%) were normotensive, and 226 (78%) of 288 women were hypertensive. Of the 226 women, 122 (54%) were receiving an antihypertensive drug. The mean (+/- SD) endometrial thicknesses in groups A, B, and C were 4.5 (+/- 1.3), 5.4 (+/- 1.5), and 6.4 (+/- 1.7) mm, respectively. Significant difference was obtained among the groups (P = 0.004). CONCLUSIONS: Our data indicate that the mean endometrial thickness is significantly greater in asymptomatic, hypertensive women receiving antihypertensive drugs than among untreated hypertensive and normotensive women.

Antihypertensive Agents↗

Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen.

OBJECTIVE: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability. DESIGN: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task. RESULTS: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group. CONCLUSION: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.

Adult↗