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PubMedDate not supplied

The effects of transdermal estradiol alone or with cyclical dydrogesterone on markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes: a pilot study.

The objective of this open, longitudinal, controlled study was to assess the effect of transdermal estradiol alone or combined with cyclical dydrogesterone on the markers of cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes. The control group consisted of postmenopausal diabetic women who declined menopausal hormone replacement therapy (HRT). Twenty-eight postmenopausal women (19 on HRT and 9 controls) with type 2 diabetes were followed up for 12 months. From the active treatment group 14 women with a uterus in situ had 80 microg/24 hr transdermal estradiol (Fematrix 80; Solvay Healthcare Ltd, Southampton, UK) and oral dydrogesterone 10 mg daily for the first 12 days of the calendar month, whereas 5 women with previous hysterectomy had 80 microg/24 hr transdermal estradiol (Fematrix 80) alone. CVD risk markers were measured before and at regular intervals after starting HRT. The main outcome measures were weight, systolic and diastolic blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), glucose/insulin ratio, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein (a), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and endothelin-1. Transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk. There was a significant decrease in HbA1c, total cholesterol, and LDL cholesterol at 6 months in women receiving HRT. Some of the cardiovascular disease risk markers may improve in postmenopausal women with type 2 diabetes with transdermal estradiol. This effect may have important clinical implications and it deserves further investigation in appropriately designed trials.

Administration, Cutaneous↗

PubMedDate not supplied

Beliefs about breast cancer risk and use of postmenopausal hormone replacement therapy.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) decreases the risks of coronary heart disease and osteoporosis, but increases the risk of breast cancer. Although only 20-30% of postmenopausal women in the United States take HRT, the relationship between breast cancer risk perception and use of HRT is not known. OBJECTIVE: To assess the impact of belief that HRT increases breast cancer risk and high perceived risk of breast cancer on the use of HRT. DESIGN: Cross-sectional mailed survey. PARTICIPANTS: 189 randomly selected postmenopausal women from a general internal medicine practice in the Philadelphia area. MAIN RESULTS: Of the 268 women (67%) who returned surveys, 189 were postmenopausal; 70 (37%) were currently using HRT and 21 (11 %) had previously used HRT. Respondents' mean age was 59.6 years; 64% were Caucasian, and 33% had completed college. Fifty-nine women (33%) thought HRT increased the risk of breast cancer, 22 (12%) thought it did not, and 100 (55%) were unsure. Mean perceived lifetime risk of breast cancer was 31% (range 0%-100%). After multivariate adjustment, current use of HRT was inversely associated with age (OR 0.96 for each one-year increase, 95% CI 0.940.98), and positively associated with Caucasian race (OR 2.73, 95% CI 1.40-5.32). Use of HRT was not associated with belief that HRT increases the risk of breast cancer, breast cancer risk perception, or perceived severity of breast cancer. CONCLUSIONS: Belief that HRT increases the risk of breast cancer and high perceptions of breast cancer risk may not be important barriers to use of HRT. Efforts to improve decision making about HRT should focus on previously established barriers, such as perceptions of menopause and lack of physician discussion, rather than misconceptions about breast cancer risk.

Attitude to Health↗

PubMed1994

Epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal patients.

AIMS AND BACKGROUND: The purpose of our research was to investigate the relations between the levels of epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal Polish women. METHODS: Cell membrane levels of epidermal growth factor receptor (EGF-R), and cytosol (c) estrogen (ER) and progesterone (PR) receptors were determined in 221 specimens of primary breast cancers. ERc and PRc were assayed using the dextran-coated charcoal procedure, and EGF-R were assayed by the radioligand method of specific saturation of the crude membrane fraction with 125I-EGF RESULTS: A statistically significant inverse correlation was found in all tumors between the concentrations of EGF-R and ERc, whereas for PRc significance of this correlation was not fully confirmed. ERc concentrations in tumors were positively correlated with age of patients, whereas EGF-R and PRc were not. In all, in premenopausal, and in postmenopausal EGF-R-positive tumors (> or = 10 fmol/mg of membrane protein), mean concentrations of ERc did not differ significantly. These groups of tumors seem to be homogeneous with respect to ERc concentrations. In EGF-R-negative (< 10 fmol/mg of membrane protein) postmenopausal tumors, the mean ERc concentration was significantly higher than in premenopausal tumors, hence these groups of tumors appear to be heterogeneous with regard to ERc contents: CONCLUSIONS: The present findings may have significance in differentiation of postmenopausal breast cancer.

Adult↗

PubMed2003

Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women.

PURPOSE: To investigate the effect of hormone replacement therapy (HRT) on postmenopausal tear function and the conjunctival epithelium. METHODS: Schirmer I-Jones test, tear film break-up time (BUT), and impression cytology findings were analyzed in 34 eyes of 17 women who were at least two years postmenopausal and not taking HRT: This series of tests was repeated after three months on HRT. RESULTS: The patients' average age was 53.82 +/- 3.6 years, and the mean time postmenopause was 35.29 +/- 11.59 months. There was no significant difference in the Schirmer I-Jones test results before and after three months of HRT (p > 0.05). However, the BUT (p < 0.05) and impression cytology (p < 0.05) findings were significantly affected by HRT. CONCLUSIONS: HRT may alleviate postmenopausal dry eye symptoms by increasing goblet cell density.

Cell Count↗

PubMed2004

Risk factors for osteoporosis in postmenopausal African-American women.

BACKGROUND: Although postmenopausal African-American women are at lower risk for osteoporosis-related fractures compared with white women, fractures in African-American women are associated with significantly higher morbidity and mortality. Therefore, early diagnosis and treatment of osteoporosis in this population is just as important as it is for other ethnic groups and worthy of the attention of physicians and healthcare organizations. OBJECTIVE: The purpose of this study was to evaluate risk factors for osteoporosis in postmenopausal African-American women. DESIGN: This was a retrospective, case-control study in 201 postmenopausal African-American women at a community-based osteoporosis center. Spine and hip bone mineral density measurements were obtained by dual-energy x-ray absorptiometry. Patient and family medical history, past and present pharmaceutical use, and dietary and exercise habits were collected using a patient self-administered questionnaire. RESULTS: Using the manufacturer's African-American referent database, 56 women had osteoporosis, 99 had osteopenia, and 46 had normal bone mineral density. Risk factors more common in the osteoporotic group compared with the normal group included sedentary lifestyle (P < 0.03), family history of osteoporosis (P < 0.03), low body mass index (P < 0.05), and history of bilateral oophorectomy (P < 0.03). Polyarthritis was more prevalent in the normal versus the osteoporotic group (P < 0.001). In addition, premenopausal use of oral contraceptives (P < 0.005) and postmenopausal use of estrogen therapy (P < 0.05) were more common in the normal compared with the osteoporotic group. CONCLUSIONS: Many risk factors for osteoporosis in African-American women are similar to those in white women and can aid in the selection of patients in need of bone density testing.

Black or African American↗

PubMed2005

Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis.

OBJECTIVE: Poor compliance and persistence with bisphosphonates is a concern in postmenopausal osteoporosis due to its negative impact on fracture risk and healthcare costs as well as quality of life. Reducing oral bisphosphonate dosing frequency is one measure available to increase therapy convenience and practicality, with the hope of improving compliance and persistence. This study compared compliance and persistence with weekly and daily bisphosphonate regimens for postmenopausal osteoporosis. METHODS: Administrative claims data (1997-2002) from 30 health plans were used to identify postmenopausal women (> 45 years) with osteoporosis, who had been newly prescribed a once-weekly (QW alendronate 35 mg or 70 mg) or once-daily (QD alendronate 5 mg or 10 mg or risedronate 5 mg) bisphosphonate. QW and QD cohorts were followed for 12 months from initial prescription. Medication possession ratios (MPRs) measured refill compliance during follow-up. Persistence was calculated as the number of days from the initial prescription to a lapse of > 30 days after completion of the previous refill. RESULTS: Data were available for 2741 women (QW, N = 731, QD, N = 2010). QW users had significantly higher medication compliance than QD users (69.2% vs. 57.6% MPR, p < or = 0.0001). QW users persisted with therapy significantly longer than QD users (p < 0.0001) and had higher rates of retention on treatment at 12 months than QD users (44.2% QW; 31.7% QD). Dosing frequency was the strongest predictor of time to discontinuation (p < 0.0001). CONCLUSIONS: Postmenopausal women prescribed a weekly bisphosphonate had significantly better compliance and persistence than those taking more frequent, daily bisphosphonate doses. However, compliance and persistence rates for both regimens were suboptimal, suggesting that less frequent dosing intervals may provide an opportunity to further improve the consistent use of bisphosphonate therapy.

Age Factors↗

PubMed2007

Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study.

BACKGROUND: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. METHODS: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. RESULTS AND DISCUSSION: In multivariate analysis, women who were overweight (BMI > 25 to < or = 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI < or =25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. CONCLUSION: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.

Absorptiometry, Photon↗

PubMed2005

Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study.

INTRODUCTION: Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD. METHODS: In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal. Mammographic breast density (percentage of the breast composed of dense tissue), the outcome, was assessed with a computer-assisted percentage-density method. BMD, the primary predictor, was measured with dual-energy X-ray absorptiometry. Women quitting menopausal hormone therapy to join PEPI were designated recent hormone users. RESULTS: The mean age of the 594 women was 56 years. The average time since menopause was 5.6 years. After adjustment for age, body mass index, and cigarette smoking, in women who were not recent hormone users before trial enrollment (n = 415), mammographic density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08) BMD. Mammographic density of recent hormone users (n = 171) was not significantly related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants who were not recent hormone users, mammographic density was 4% greater in the highest quartile of total hip BMD than in the lowest. In participants who were not recent hormone users, mammographic density was 5% greater in the highest quartile of lumbar spine BMD than in the lowest. CONCLUSION: Mammographic density and BMD are positively associated in women who have not recently used postmenopausal hormones. A unifying biological mechanism may link mammographic density and BMD. Recent exogenous postmenopausal hormone use may obscure the association between mammographic density and BMD by having a persistent effect on breast tissue.

Bone Density↗

PubMed2003

Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population.

PURPOSE: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. METHODS: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. RESULTS: Compared with nonusers, women using estrogen and progestin for >/= 5 years were at increased risk of breast tumors of stage 0 or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size </= 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77), grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive (RR, 1.72; 95% CI, 1.55 to 1.90). Estrogen-only users were slightly more likely to have estrogen receptor-positive breast cancer compared with nonusers (RR, 1.14; 95% CI, 1.06 to 1.23). CONCLUSION: Use of estrogen and progestin postmenopausal hormone therapy for five years or more increased the likelihood of developing breast cancer, including both tumors with favorable prognostic features and tumors with unfavorable prognostic features.

Aged↗

PubMed2000

Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women.

Conjugated linoleic acid (CLA) is anticarcinogenic in experimental animal studies. We studied dietary and serum CLA in Finnish patients with breast cancer in 1992-1995. Participants were consecutive women with breast cancer (68 premenopausal and 127 postmenopausal) and population-based control women (75 premenopausal and 133 postmenopausal), matched for age and area of residence. Diet was assessed by a validated food frequency questionnaire and the fatty acid composition of serum by gas-liquid chromatography. In postmenopausal women, dietary CLA, serum CLA, myristic acid, and trans-vaccenic acid were significantly lower in cases than in controls. The odds ratio for breast cancer in the highest quintile vs. the lowest was 0.4 [95% confidence interval (CI) = 0.2-0.9]for CLA, 0.3 (95% CI = 0.1-0.7) for myristic acid, and 0.3 (95% CI = 0.1-0.7) for trans-vaccenic acid in serum. The odds ratios remained similar after adjustment for known risk factors of breast cancer. A diet composed of CLA-rich foods, particularly cheese, may protect against breast cancer in postmenopausal women, but it is impossible to assess the independent effects of CLA in this study. The findings may be of relevance for food production, inasmuch as it is possible to increase CLA and its precursor trans-vaccenic acid in foods by modifying the feeding of ruminants.

Adult↗

PubMed2002

Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women.

Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (+/-SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 +/- 39%) and 100-mg dose groups (242 +/- 184%) than in the control group (-29 +/- 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 +/- 72%) and 100-mg dose groups (116 +/- 119%) than in the control group (-5 +/- 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 +/- 17%, 2.8 +/- 34%, -11 +/- 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 +/- 146%) and 100-mg dose groups (457 +/- 601%) than in the control group (-27 +/- 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during long-term administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects.

Administration, Oral↗

PubMed2004

Myocardial blood flow and flow reserve in response to hormone therapy in postmenopausal women with risk factors for coronary disease.

Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD. We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after i.v. adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively. Response to CPT was neutral in all women at baseline (-0.51 +/- 27%). Adenosine induced a marked increase in MBF (161 +/- 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well. In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.

Aged↗

PubMed2004

Comparison of hormone levels in nipple aspirate fluid of pre- and postmenopausal women: effect of oral contraceptives and hormone replacement.

The effects of ovarian suppression by oral contraceptives as well as hormone replacement therapy were studied on hormone levels and on products of hormone action in nipple aspirate fluid (NAF) from breasts of pre- and postmenopausal women. Multiple samples per subject revealed high consistency (intraclass correlation coefficients) for all products measured. Compared with premenopausal women, NAF progesterone was much lower in postmenopausal women, but NAF androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate concentrations were not different. With oral contraceptive use, estradiol, estrone sulfate, and progesterone levels were similarly lower in serum and NAF. In postmenopausal women, NAF estradiol and estrone sulfate were not significantly less than those in premenopausal women, nor were epidermal growth factor or cathepsin D levels, but IL-6 was elevated. Despite corresponding changes in hormones in serum and NAF over time, correlations based on simultaneous sampling were not significant. It is concluded that: 1) potential precursors of estradiol remain at comparable levels in the breast after menopause; 2) local synthesis is important for maintenance of estradiol levels in NAF of postmenopausal women but less important for progesterone; and 3) changes in the serum parameters are accurately reflected in NAF, but only after a matter of days. These findings provide additional validation for the physiological relevance of NAF hormone levels as potential breast cancer risk markers.

Adult↗

PubMed2005

Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women.

CONTEXT: The endocrine and metabolic functions of the liver are affected by estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation despite augmenting GH secretion. The aim of this study was to determine whether selective estrogen receptor modulators display similar effects and whether these effects are magnified in GH-deficient (GHD) women because of the loss of GH feedback. DESIGN: This was an open-label, randomized, two-period, crossover study comparing treatment (raloxifene vs. estradiol) and group (normal vs. GHD). SETTING: The setting of this study was a clinical research unit. PARTICIPANTS: Twelve postmenopausal women and 12 women with hypopituitarism participated in this study. INTERVENTION: Two 4-wk treatments with 17beta-estradiol (E2; 2 mg, followed by 4 mg) or raloxifene (60 mg, followed by 120 mg) were given, crossing over to the alternate treatment after a 4-wk washout period. OUTCOME MEASURES: Endocrine [GH, IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein, and SHBG] and metabolic (fat oxidation) end points were used as outcome measures. RESULTS: E2 reduced serum IGF-I levels in a dose-dependent manner in both groups, with effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels in the GHD group (P < 0.001), but not in the postmenopausal group. E2 reduced (P < 0.05), and raloxifene increased (P < 0.05), IGFBP-3 levels in both groups. E2, but not raloxifene, increased GH (P < 0.05) in postmenopausal women. The effects of E2 and raloxifene on IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GH-binding protein, and SHBG were significantly different (P < 0.05). E2 and raloxifene reduced (P < 0.05) fat oxidation equally in GHD, whereas the decrease in postmenopausal women was not significant. CONCLUSION: E2 and raloxifene exert different hepatic endocrine, but not lipid oxidative, effects. The greater effects seen in GHD women may be explained by the loss of endogenous GH feedback.

Adolescent↗

PubMed2005

Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type II.

CONTEXT: Genetic factors are important determinants of bone mineral density (BMD). The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density. OBJECTIVE: The objective of the study was to investigate the association between polymorphisms in the CLCN7 gene and BMD in postmenopausal women and with clinical variability in ADOII. DESIGN: This was a genetic association study using five single-nucleotide polymorphisms and a variable number tandem repeat (VNTR) polymorphism in the CLCN7 gene. PARTICIPANTS: A total of 425 postmenopausal women aged 64 +/- 7 yr participated in the study. We also investigated an ADOII family with low penetrance comprising 18 mutation carriers. MAIN OUTCOME MEASURE(S): In our postmenopausal cohort, individual single-nucleotide polymorphism genotypes and haplotypes were analyzed for association with BMD at the lumbar spine and the femoral neck and with the bone resorption marker deoxypyridinoline (D-Pyr/Crea). The same polymorphisms on the nonmutated CLCN7 allele were investigated for association with the variability of the ADOII phenotype. RESULTS: Analysis by multiple linear regression revealed a significant association between the ss genotype of the VNTR and higher Z-score values (P = 0.029). The haplotype 4, which comprises the long allele of the VNTR, was found to be significantly associated with lower femoral neck Z-score values (P = 0.011). Furthermore, we found an association of the ss genotype of the VNTR with lower levels of the bone resorption marker D-Pyr/Crea (P = 0.015), whereas haplotype 4 was associated with higher D-Pyr/Crea levels (P = 0.039). In the ADOII family, we could demonstrate that haplotype 3, which contains the s-allele of the VNTR, is associated with a slightly higher probability that mutation carriers develop osteopetrosis (P = 0.029). In both cases the association seems largely to be driven by the VNTR genotype but is further strengthened if surrounding polymorphisms are added to the analysis. CONCLUSION: We observed a significant association of CLCN7 polymorphisms with the variance of BMD and bone resorption marker levels in postmenopausal women and with the variability of the ADOII phenotype.

Aged↗

PubMed2006

Intimal estrogen receptor (ER)beta, but not ERalpha expression, is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women.

BACKGROUND: Controversy exists over the association of estrogen and cardiovascular disease. Estrogen receptors (ERs) alpha and beta are expressed in the endothelial cells and vascular smooth muscle cells (VSMCs) of many arteries, but the relative importance of ERalpha or ERbeta in mediating the vascular response to estrogens is not well defined, particularly in humans. We have shown previously that postmenopausal women receiving hormone therapy (HT) had lower mean coronary artery calcium, plaque area, and calcium-to-plaque ratio compared with untreated women. In this study, we examined coronary artery ERalpha and ERbeta expression in pre- and postmenopausal women as a function of plaque area, calcium area, calcium-to-plaque ratio, and estrogen status. METHODS: Coronary arteries were obtained at autopsy from a total of 55 women: nine premenopausal women, 13 postmenopausal women on HT and 33 untreated postmenopausal women (non-HT). Coronary calcification was quantified by contact microradiography, and atherosclerotic plaque area was measured histologically. Coronary artery cross-sections were immunostained for ERalpha and ERbeta, and the amount of receptors was estimated semiquantitatively in each arterial wall layer (intima, adventitia, and media). Double immunofluorescence was used to colocalize ERalpha and ERbeta with smooth muscle actin, a marker of VSMCs. RESULTS: ERbeta and ERalpha were expressed in all artery wall layers, but most avidly in the media (P = 0.001), and colocalized with VSMCs. ERbeta expression exceeded ERalpha expression in all wall layers (P < 0.001) and was adjacent to areas of calcium deposition. ERbeta expression in the intimal layer correlated with calcium content, plaque area, and calcium-to-plaque ratio (all P < 0.01) and tended to be greater in non-HT than in HT women (P = 0.06). ERalpha expression did not vary significantly among groups, nor did it correlate with calcium content, plaque area or calcium-to-plaque ratio. Expression of ERalpha but not ERbeta declined with age (P < 0.01) in HT women only. Age had no effect on ERalpha or ERbeta expression in non-HT or premenopausal women. CONCLUSIONS: ERbeta is the predominant ER in human coronary arteries and correlates with coronary calcification, a marker of severe atherosclerosis. Increased ERbeta expression is linked to advanced atherosclerosis and calcification independent of age or hormone status. Future pharmacogenetic studies that target this receptor are needed to confirm causality.

Adult↗

PubMed2006

Clinical review: Controversies regarding transdermal androgen therapy in postmenopausal women.

CONTEXT: Recently, the field of androgen therapy in postmenopausal women has received much attention and press. Although the ovary ceases to produce follicles and estrogen at menopause, it continues to produce androgens. Hence, many oophorectomized women complain of sexual dysfunction (despite adequate estrogenization). Previous studies of nontransdermal testosterone replacement have shown an improvement in libido and sexual frequency, although at the cost of supraphysiological testosterone levels. Transdermal testosterone patch (Intrinsa) was developed to deliver a physiological amount of testosterone. In 2004, the Food and Drug Administration voted not to approve Intrinsa until long-term safety data are available. EVIDENCE ACQUISITION: Recent trials of Intrinsa in postmenopausal women were included. A MEDLINE search was conducted for articles published over the last 40 yr based on the key words androgen therapy/replacement and postmenopausal women. Relevant placebo-controlled trials of nontransdermal androgen therapy in postmenopausal women were also reviewed. EVIDENCE SYNTHESIS: Early results from industry-funded trials show that transdermal testosterone therapy results in only moderate (although statistically significant) improvement in libido in surgically menopausal women (on estrogen). However, the published data are of short duration (24 wk). Hence, long-term safety in these women remains unclear. CONCLUSION: We recommend a short-term trial (not to exceed 24 wk) of transdermal testosterone therapy (once approved) in surgically menopausal (estrogenized) women with distressful sexual dysfunction. Until the patch gets approval, a short trial of oral methyltestosterone in deserving estrogenized women may be justified.

Administration, Cutaneous↗

PubMed1989

Bone responsiveness to parathyroid hormone in normal and osteoporotic postmenopausal women.

Increased bone loss in estrogen-deficient normal and osteoporotic postmenopausal women may be due mainly to increased sensitivity of bone-resorbing cells to circulating PTH, but this is supported only by indirect data. Therefore, we tested the responsiveness of bone to PTH directly by using a 3-day iv infusion of bovine PTH-(1-34) at 400 U/day in 9 normal premenopausal women, 10 normal postmenopausal women, and 12 osteoporotic postmenopausal women. Serum calcium and urinary hydroxyproline concentrations increased (P less than 0.001) over baseline values during infusion, but the mean increases in both variables did not differ among groups. The data do not support the hypothesis that estrogen deficiency increases the sensitivity of bone to PTH or that the sensitivity in osteoporotic women is greater than that in normal postmenopausal women. Within the constraints imposed by the method of testing, we conclude that the additional bone resorption induced by menopause and by osteoporosis may be due to mechanisms that are not due to enhanced responsiveness of bone to PTH.

Age Factors↗