Estrogen Replacement Therapy Group Research Articles

The Relationships Between Reproductive History, Ethnicity and Alzheimer’s Disease Incidence

Introduction: In recent years, it has been shown that postmenopausal women have a greater risk of developing Alzheimer’s Disease (AD) than their male counterparts. Additionally, greater parity in postmenopausal women is associated with increased AD prevalence. Menopause and childbirth, two factors that affect estrogen levels, are believed to contribute to this health disparity, as estrogen plays an important role in neuroprotection. In addition, few studies have considered the effect of ethnicity on AD incidence in postmenopausal women. It is important to consider the role of ethnicity in the development of effective AD prevention methods for diverse ethnicities. This study seeks to a) investigate the link between increased parity and the development of AD in postmenopausal women of different ethnicities, and b) investigate the effectiveness of estrogen replacement therapy (ERT) in reducing the risk of AD. Methods: This protocol comprises two studies. Study 1 will include neurological assessment of 200 postmenopausal women to determine AD incidence. These women will be from African, Caucasian, Asian, and Latin ethnicities. The second study will be a randomized, placebo-controlled clinical trial providing ERT to a cohort of 200 menopausal women of the same ethnicities as part A. The treatment will be monitored for AD incidence once every 3 years for 15 years post-intervention. Results: Based on prior literature, we hypothesize that women of African and Latin ethnicities in Study 1 will have higher AD incidence than Caucasian and Asian women. In Study 2, we expect overall AD incidence to be lower in the ERT group than the control group. We also expect AD incidence to be higher in African and Latino participants than Caucasian and Asian participants post-ERT. Discussion: The relationship between ethnicity and AD incidence can be confounded by factors such as migratory status and the indirect relationship between racial and genetic groupings. Future studies are required to investigate these factors. Conclusion: This study will pave the path for further estrogen therapies that can reduce the risk of AD through exogenous estrogen exposure. As AD is prevalent amongst the aging population, findings will also help to reduce health disparities among postmenopausal women of multiple ethnicities.

Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors

The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown. To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors. Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 μg/24h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured. No difference between groups was found for change in plasma HDL-C (p=0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus+5.8 (-6.3,+16.9)% placebo group, p=0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus+7.4 (-1.5,+18.1)% placebo group, p=0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p<0.0001) and insulin resistance (p=0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (β=-0.26, p=0.004). Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.

Effects of resveratrol combined with soy isoflavones on apoptosis induced by oxidative stress in hippocampus of aging model rats

To investigate the effect of resveratrol(Res) combined with soy isoflavones(SIF) on apoptosisinduced by oxidative stress in hippocampus in aging model rats. Sixty female SD rats were randomly divided into the Sham control group, aging model group, Res treatment group, SIF treatment group, Res combined with SIF treatment group and estrogen replacement therapy group(ERT group). Rats with aging were induced by bilateral ovariectomy combined with intraperitoneal injection of D-galactose. TUNEL and transmission electron microscopy were used to observe apoptosis and ultrastructural changes of mitochondrion in hippocampus, respectively. The activities of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-Px) and content of Malonaldehyde(MDA) were detected in the hippocampal homogenate. The protein expressions of cytochrome C oxidase(COX) Ⅰ, Bcl-2 associated X protein(Bax)、B-cell leukemia/lymphoma 2(Bcl-2) and cytochrome C were detected by Western blot. Compared with the Sham control group, the number of TUNEL-positive cells and the apoptotic index(AI) in the model group increased. Marked increase of mitochondrial swelling and vacuolation, decrease of mitochondrial integrity were also observed in the model group. Additionally, the levels of SOD, CAT and GSH-Px were decreased and the level of MDA was increased in the model group in the hippocampus, Bax and cytochrome C protein expression increased, and the COX Ⅰ protein expression and the ratio of Bcl-2/Bax decreased(P&lt;0. 05). In compared with the model group, the number of TUNEL-positive cells and AI significantly decreased, mitochondrial integrity improved in all of the treatment groups, the COX Ⅰ protein expression significantly up-regulated, Bax and cytochrome C protein expression down-regulated, and the protein expression ratio of Bcl-2/Bax increased(P&lt;0. 05 or P&lt;0. 01). Compared with the Res alone and SIF alone treatment group, Res combined SIF treatment decreased the AI and Bax, cytochrome C protein expression, moreover, increased the mitochondrial integrity rate, COX Ⅰ and Bcl-2/Bax protein expression ratio(P&lt;0. 05). There was no statistically significant difference in Bcl-2 protein expression among all the groups(P&gt;0. 05). Res and SIF alone and in combination decreased apoptosisinduced by oxidative stress in hippocampus of aging model rats, and beneficial effect in the Res combined SIF treatment group is more significant than that in the alone administration. Improving the antioxidant capacity, increasing the protein expressions of COX Ⅰ andthe ratio of Bcl-2 and Bax, and inhibiting the release of cytochrome C may be the mechanisms by which Res and SIF improve apoptosis in aging rats.

Estrogen replacement therapy is not a recommended therapy for postmenopausal women with coronary heart disease: a meta-analysis

Aim: This study was to investigate the effect of estrogen replacement therapy (ERT) on clinical outcomes for postmenopausal women with established coronary heart disease (CHD). Materials and Methods: The authors conducted a meta-analysis using 12 eligible studies. The overall odds ratios (OR) or standardized mean difference (SMD) and their corresponding 95% confidence interval (CI) were calculated. Results: For the incidence of adverse events, significant difference was observed in the occurrence rates of CHD death (OR = 1.166, 95% CI: 1.000-1.360, p = 0.050) and death of any cause (OR = 1.221, 95% CI: 1.057-1.410, p = 0.007) in postmenopausal women with CHD between ERT and placebo groups, whereas there was no significant difference (p &gt; 0.05) in the occurrence rates of CHD events, myocardial infarction (MI), revascularization, unstable angina (UA), venous thromboembolic event, stroke/transient ischemic attack, and congestive heart failure between two groups. With respect to the alterations of other clinical outcomes, the SMD for the alteration of TC level was -0.192 (95% CI: -0.346—0.047, p = 0.015), and a significant difference was detected between the two groups, whereas there was no significant difference (p &gt; 0.05) in the alterations of MLD and TG in patients between the two groups. Additionally, patients treated with ERT had lower LDL and higher HDL levels. Conclusion: This meta-analysis suggests that postmenopausal women with CHD receiving ERT are more likely to suffer from CHD death, death of any cause, lower LDL, and higher HDL and TC levels. Therefore, ERT should not be recommended to postmenopausal women with CHD for the secondary prevention of cardiovascular disease (CVD) clinically.

Security of hormone replacement therapy among postoperative patients with endometrial carcinoma: a Meta-analysis

To systematically evaluate the security of hormone replacement therapy (HRT) among postoperative patients with endometrial carcinoma (EC). A systematic review and Meta-analysis of studies on security of HRT among EC patients after operation was done by Revman 5.2 software. Studies were mainly searched from the CENTRAL, Medline, Embase, Ovid, Wanfang, CNKI databases. A total of 7 studies with 2 038 stageⅠand stageⅡ endometrial carcinoma patients were included. The quality of 6 studies included were medium, and 1 study was high. The endometrial carcinoma patients on HRT did not have a statistically increased incidence in the EC recurrence (RR=0.69, 95%CI (0.42-1.15), P=0.16) and cancer-induced death (RR=0.55, 95%CI (0.25-1.21), P=0.14). Subgroup analysis for the start of HRT within 6 months from time of surgery group and only estrogen replacement therapy group found no statistical different in the risk of the EC recurrence and cancer-induced death, compared with control group. No statistically increased risk of the EC recurrence was observed for estrogen plus progestin replacement therapy group. There is no statistical difference in the recurrence rate and cancer-induced death rate of EC whether the early stage postoperative patients used HRT or not.

Effects of ultrasound on estradiol level, bone mineral density, bone biomechanics and matrix metalloproteinase-13 expression in ovariectomized rabbits.

The aim of the present study was to observe the effect of ultrasound (US) on estradiol level, bone mineral density (BMD), bone biomechanics and matrix metalloproteinase-13 (MMP-13) expression in ovariectomized (OVX) rabbits. A total of 28 virgin New Zealand white rabbits were randomly assigned into the following groups: Control (control group), ovariectomy (OVX group), ovariectomy with ultrasound therapy (US group) and ovariectomy with estrogen replacement therapy group (ERT group). At 8 weeks after ovariectomy, the US group received ultrasound treatment while the ERT group were orally treated with conjugated estrogens, and the control and OVX groups remained untreated. The estradiol level, BMD and bone biomechanics, cartilage histology and the MMP-13 expression were analyzed after the intervention. The results indicate that the US treatment increased estradiol level, BMD and bone biomechanical function. Furthermore, the US treatment appeared to improve the recovery of cartilage morphology and decreased the expression of MMP-13 in OVX models. Furthermore, the results suggest that 10 days of US therapy was sufficient to prevent the reduction of estradiol, BMD and bone biomechanical function, to protect osteoarthritis cartilage structure, and to reduce MMP-13 transcription and expression in OVX rabbits. Therefore, US treatment may be a potential treatment for postmenopausal osteoarthritis and osteoporosis.

The ocular benefits of estrogen replacement therapy: a population-based study in postmenopausal Korean women.

PurposeTo elucidate the prevalence of cataract, glaucoma, pterygia, and diabetic retinopathy among Korean postmenopausal women with or without estrogen replacement therapy (ERT).MethodsA cross-sectional, nationally representative sample from the 4th Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007–2009) was used. Participants were interviewed for the determination of socioeconomic and gynecologic factors. Each woman also underwent an ophthalmologic examination and provided a blood sample for risk factor assessment.ResultsOf 3968 postmenopausal women enrolled, 3390 had never received estrogen, and 578 were undergoing estrogen treatment. After adjusting for age, diabetes, hypertension, high cholesterol levels, and high low-density lipoprotein levels, the prevalence of anterior polar cataract, retinal nerve fiber layer (RNFL) defect, and flesh pterygium was higher in the non-ERT group (OR, 3.24; 95% CI, 1.12–9.35, OR 1.70; 95% CI, 1.04–2.78, OR 3.725; 95% CI, 1.21–11.45, respectively). Further, the prevalence of atrophic pterygium was lower in the non-ERT group compared to that in the ERT group (OR, 0.21, 95% CI, 0.07–0.63).ConclusionsThese data suggest that ERT has a protective effect against the development of anterior polar cataract, flesh pterygium, and RNFL defect.

Time and dose-dependent effects of Labisia pumila on bone oxidative status of postmenopausal osteoporosis rat model.

Postmenopausal osteoporosis can be associated with oxidative stress and deterioration of antioxidant enzymes. It is mainly treated with estrogen replacement therapy (ERT). Although effective, ERT may cause adverse effects such as breast cancer and pulmonary embolism. Labisia pumila var. alata (LP), a herb used traditionally for women’s health was found to protect against estrogen-deficient osteoporosis. An extensive study was conducted in a postmenopausal osteoporosis rat model using several LP doses and duration of treatments to determine if anti-oxidative mechanisms were involved in its bone protective effects. Ninety-six female Sprague-Dawley rats were randomly divided into six groups; baseline group (BL), sham-operated (Sham), ovariectomised control (OVXC), ovariectomised (OVX) and given 64.5 μg/kg of Premarin (ERT), ovariectomised and given 20 mg/kg of LP (LP20) and ovariectomised and given 100 mg/kg of LP (LP100). The groups were further subdivided to receive their respective treatments via daily oral gavages for three, six or nine weeks of treatment periods. Following euthanization, the femora were dissected out for bone oxidative measurements which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) levels. Results: The SOD levels of the sham-operated and all the treatment groups were significantly higher than the OVX groups at all treatment periods. The GPx level of ERT and LP100 groups at the 9th week of treatment were significantly higher than the baseline and OVX groups. MDA level of the OVX group was significantly higher than all the other groups at weeks 6 and 9. The LP20 and LP100 groups at the 9th week of treatment had significantly lower MDA levels than the ERT group. There were no significant differences between LP20 and LP100 for all parameters. Thus, LP supplementations at both doses, which showed the best results at 9 weeks, may reduce oxidative stress which in turn may prevent bone loss via its anti-oxidative property.

The effects of Labisia pumila var. alata on bone markers and bone calcium in a rat model of post-menopausal osteoporosis

Postmenopausal osteoporosis is mainly treated with estrogen replacement therapy (ERT). However, ERT causes side effects, mainly breast cancer, uterine cancer and thromboembolic problems. Labisia pumila var. arata (LPva), a herb with phytoestrogenic effects has the potential to be used as an alternative agent to ERT. This study was conducted to determine the effects of LPva on bone biochemical markers and bone calcium content in ovariectomised rats. Thirty two Wistar rats were divided into 4 groups, with 8 rats in each group. The first group was sham operated (Sham), the second group was ovariectomised (OVX), the third (LPva) and fourth group (ERT) were also ovariectomised and given LPva 17.5 mg/kg and Premarin(®) 64.5 μg/kg, respectively. Blood samples were taken before and after treatment to measure osteocalcin and C-terminal telopeptide of type 1 collagen levels using ELISA while the fifth lumbar bone samples were taken to measure bone calcium content using the Atomic Absorption Spectrophotometer (AAS). The osteocalcin levels were significantly higher in both the LPva and ERT groups compared to the OVX group. The CTX levels were significantly lower in both the LPva and ERT groups compared to the OVX group. However, only the ERT group had significantly higher bone calcium level compared to the OVX group. The supplementation of 17.5 mg/kg of LPva to ovariectomised rats for 8 weeks was able to prevent the changes in bone biochemical markers but failed to prevent the bone calcium loss induced by ovariectomy.

Effects of synaptic plasticity regulated by 17beta-estradiol on learning and memory in rats with Alzheimer's disease.

To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer's disease (AD). The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 microL (10 microg/microL) amyloid-beta peptide 1-40(Abeta1-40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P< 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P< 0.01). ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.

Effects of estrogen replacement therapy on estrogen receptor expression and immunoregulatory cytokine secretion in surgically induced menopausal women

To investigate the effect of oral and transdermal estrogen replacement therapy (ERT) on the expression of different estrogen receptor (ER) subtypes and the secretion of immunoregulatory cytokines, we performed a clinical investigation on previously healthy women who had undergone a total hysterectomy and bilateral salpingo-oopherectomy. These women were randomly distributed into two groups: an oral ERT group and transdermal ERT group. Before and after ERT, the serum levels of estradiol (E 2) and follicle stimulating hormone (FSH) were measured, ERα and ERβ expression of peripheral blood T lymphocytes was tested, and secretion of specific immunoregulatory cytokines (IFNγ, IL-2 and IL-4) by T lymphocytes was examined. Our results confirm that for both groups, the serum E 2 level was increased after ERT ( P < 0.01) and the serum FSH level was decreased after ERT ( P < 0.01), with no significant difference in hormone levels between the two groups. ERα expression by T lymphocytes was significantly higher after ERT than before ( P < 0.01) in both groups. Levels of type 1 cytokines (IL-2 and IFNγ), which were secreted by T helper 1 (Th1), after ERT were substantially decreased. The level of type 2 cytokine (IL-4), which were secreted by T helper 2 (Th2), was significantly increased after ERT ( P < 0.01 for the oral group and P < 0.05 for the transdermal group). In summary, both oral and transdermal ERT increased serum E 2 levels, decreased serum FSH levels and relieved the effects of peri-menopausal symptoms. These data suggest that both oral and transdermal ERT act to improve the balance of Th1/Th2 cytokines by the effects of estrogen potentially acting in T lymphocytes mainly through ERα.

Racial disparities in recurrence among patients with early‐stage endometrial cancer

AbstractBACKGROUND.Population‐based studies suggest that, because of inequalities in treatment, black women with localized endometrial cancer have shorter survival compared with white women. The objective of the current investigation was to determine whether there is a racial disparity in outcome between black patients and white patients with early‐stage endometrial cancer treated similarly in a clinical trial setting.METHODS.A retrospective review of 110 black patients and 1049 white patients with stage I and II endometrial cancer (graded according to the International Federation of Gynecology and Obstetrics grading system) was performed using data from a randomized, placebo‐controlled trial performed by the Gynecologic Oncology Group that evaluated postoperative estrogen replacement therapy (ERT) and the risk of cancer recurrence. Demographic, pathologic, treatment, and outcome‐related data were collected and analyzed using regression and survival analysis.RESULTS.Estimates of recurrence‐free survival suggested that black patients may be more likely to have disease recurrence, particularly those receiving ERT. Within a median follow‐up of 3 years, 5 of 56 black patients with endometrial cancer in the ERT group were identified with recurrent disease compared with only 8 of 521 white patients. Adjusted for age, body mass index, and tumor grade, the relative risk of recurrence among blacks in the ERT group was 11.2 (95% confidence interval, 2.86‐43.59; P = .0005).CONCLUSIONS.The findings of the current study suggested that recurrence‐free survival may be shorter among black women with stage I endometrial cancer, even in a clinical trials setting in which patients receive similar treatment and follow‐up. This increased risk of recurrence appeared to be most evident in black women with endometrial cancer who maintained ERT after primary treatment. Cancer 2008. Published 2008 by the American Cancer Society.

Effects of long-term estrogen replacement therapy on the prevalence and area of periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

Osteoarthritis (OA) occurs naturally in cynomolgus macaques. The purposes of the present study were to: 1) develop histological measurement schemes to measure the cross-sectional area of axial and abaxial osteophytes in the proximal tibia; 2) determine the effects of long-term estrogen replacement therapy (ERT) on osteophyte prevalence and area; and 3) assess relationships between osteophyte size and risk factors of OA (age and body weight) and concurrent bone and cartilage lesions. Adult female cynomolgus macaques ( n = 180) were bilaterally ovariectomized (OVX) and were treated for 3 years with ERT, soy phytoestrogens (SPE), or no hormones (OVX controls). At necropsy, the prevalence and cross-sectional area of periarticular tibial osteophytes were evaluated histologically. Treatment effects on osteophyte prevalence and area were evaluated using Chi-square analyses and Kruskal–Wallis test, respectively; other comparisons were evaluated using regression analyses. The prevalence of abaxial osteophytes in the medial tibial plateau was not significantly affected by treatment group; however, the prevalence of abaxial osteophytes in the lateral tibial plateau was significantly lower in ERT group than SPE group ( p < 0.01). The total number of abaxial osteophytes (sum of lateral and medial) was significantly lower in ERT group compared to OVX and SPE groups. Neither the prevalence of axial osteophytes nor the sum of lateral and medial axial osteophytes was significantly affected by treatment in either tibial plateau. There were no significant treatment effects on axial or abaxial osteophyte cross-sectional area in either tibial plateau. There was a significant positive correlation between abaxial osteophyte area and SCB thickness in the medial tibial plateau ( p = 0.048); however, there were no significant correlations between abaxial osteophyte area ( medial or lateral) and age or body weight. In this model of naturally occurring OA, long-term ERT does not consistently reduce the prevalence, and has no significant effects on cross-sectional area, of periarticular tibial osteophytes.

Low-dose estradiol alters brain activity

Although several studies have examined the effects of estrogen replacement therapy (ERT) on neural activity associated with tasks of learning and memory, no study has examined such effects on a sustained attention task. This study examined the effect of low-dose estrogen replacement therapy on hemodynamic activity elicited by a visual three-stimulus oddball task recorded using event-related functional magnetic resonance imaging (fMRI). Participants included 16 women between the ages of 73 and 84 who were part of a randomized controlled double-blind study to evaluate the effect of an ultralow dose micronized estradiol on bone. No significant differences in behavioral performance were found with ERT. However, there was evidence that ERT group participants had both reductions and increases in the amplitude of hemodynamic response in a variety of subcortical and cortical brain regions. These included regions involved in perception and attention such as the occipital and parietal lobes, motor cortex, anterior cingulate and prefrontal cortex. These findings suggest that estrogen may facilitate the efficiency of brain function during the performance of sustained attention tasks in post-menopausal elderly women.

The effects of exercise training on abdominal visceral fat, body composition, and indicators of the metabolic syndrome in postmenopausal women with and without estrogen replacement therapy: The HERITAGE family study

The purpose of this research was to investigate the effects of apriori estrogen replacement therapy (ERT) and endurance exercise training in postmenopausal women on abdominal visceral fat (AFV) and other selected variables related to body composition and the metabolic syndrome (MS). Forty-eight healthy and previously sedentary postmenopausal women (mean age, 54.3 years) who were enrolled in the HERITAGE Family Study (HFS) served as subjects. Of these 48 women, 18 were currently taking ERT and the remaining 30 were taking no supplemental estrogen (NHRT). Computed tomography (CT) scans were used to assess AVF as well as total abdominal fat (TAF) and abdominal subcutaneous fat (ASF). Body mass index (BMI) and waist-to-hip ratios (WHR) were calculated while body fat percentage (%FAT) and total fat mass (FATM) was assessed using underwater weighing. Blood assays for HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG) were conducted at a Centers for Disease Control (CDC) certified laboratory, while blood pressure measurements were assessed using an automated system. All measurements were obtained in duplicate before and after a regimen of endurance exercise training. Analysis of variance (ANOVA) showed AVF to be an average of 31.6 cm 2 less in the women receiving ERT, but lost statistical significance when AVF was adjusted for FATM. Mean values for TAF, ASF, and waist girth were also less in the women receiving ERT, but only waist girth achieved statistical significance. No differences were found in BMI or %FAT, but mean WHR was 5% smaller in the ERT group. Baseline values for HDL-C was higher and LDL-C lower in the ERT group. Prevalence of the MS tended to be greater in the NHRT group, but did not achieve statistical significance. There were no differences in training responses in any of the body composition variables between groups, however, in the ERT group LDL-C decreased with training while TG increased. It was concluded that postmenopausal women taking ERT tended to have lower values of AVF and other indicators of body composition, a more favorable lipid profile, and a slightly reduced risk of the MS when compared with women not taking supplemental hormones. Also exercise training did not improve the overall MS status of either group, as LDL-C status improved in the ERT group while TG decreased in the NHRT group.

Estrogen replacement therapy mitigates the loss of joint cartilage proteoglycans and bone mineral density induced by ovariectomy and osteoarthritis

AbstractAims: To investigate the effects of ovariectomy and estrogen replacement therapy (ERT) on the structural integrity and proteoglycan (PG) content of articular cartilage (AC) and bone mineral density (BMD) in an ovine model of osteoarthritis (OA) induced by meniscectomy.Method: Thirty aged ewes were used for the study. Six had ovariectomy alone (OVX), 6 meniscectomy alone (OA) and 12 ovariectomy and meniscectomy (OVX + OA). Six of the (OVX + OA) sheep received Femtran‐50 (3M) estrogen (50 µg/day) patches (OVX + OA + ERT). Six animals were used as non‐operated controls (NOC). Three months post‐surgery all animals were sacrificed, the stifle joints dissected through the site of lesions, and coronal sections of the lateral femoral condyle (LFC) and lateral tibial plateau (LTP) were cut which were each subdivided into inner (I), middle (M) and outer (O) zones. Toluidine blue stained sections were examined using a modified Mankin scoring system, and AC–PG content determined via computer image analysis.Results: There were no significant differences between lesion scores among the OA, OVX + OA and OVX + OA + ERT groups, yet all had significantly higher scores than NOC and OVX in each region (P &lt; 0.005). Computer image analysis of PG content in stained sections showed no difference between OVX and NOC. However, in LFC‐AC the loss of PG was highest in the OVX + OA group (P &lt; 0.005) compared to the NOC or OVX groups. The bone mineral density (BMD) of the LFC averaged for all zones was higher in the OVX + OA + ERT group than the OVX + OA group (P &lt; 0.02) with the most significant rise being in the I‐zone (P &lt; 0.002). Significantly in this same zone of the OVX + OA + ERT group the AC‐PG content was higher than in the corresponding zone of the OVX + OA group (P &lt; 0.05).Conclusions: While ERT did not reduce the focal AC lesions scores in the lateral compartment of this OA model it did mitigate the loss of PG from adjacent joint cartilage and increase the bone mineral density (BMD), especially in the I‐zone. These findings are consistent with epidemiological studies which suggest that ERT may slow the progression of OA in postmenopausal women.

Estrogen replacement therapy in breast cancer survivors: a matched-controlled series.

We prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group. Two hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (+/- 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (+/- 3.01) years, with a median of 3.05 years. Hot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P = 0.01), to have received prior ERT (P < 0.001), and to have received no adjuvant tamoxifen (P < 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143; P = 0.85), contralateral breast cancers (10/258 v 9/260; P = 0.99), or systemic metastasis (8/277 v 15/277; P = 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P = 0.03). Overall survival favored the ERT group (P = 0.02). In these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases.

Estrogen Replacement Therapy, Subsyndromal Depression, and Orthostatic Blood Pressure Regulation

Although estrogen replacement therapy (ERT) alleviates depressed moods in postmenopausal women, it is not known whether ERT is equally effective in reducing affective and somatic depressive complaints. One of the authors' goals in this study was to examine possible differences between women receiving and not receiving ERT. The authors studied a group of postmenopausal women. Somatic symptoms in the ERT group were significantly lower than in the Non-ERT group. Affective scores were only marginally lower in the ERT group (p = .06). After controlling for affective depression, the advantage of ERT remained significant with respect to somatic levels, but control for somatic levels essentially eliminated the effects of ERT on affective depression values. Second, in response to orthostatic challenge, the change in systolic blood pressure was significantly smaller in the ERT group. Apparently ERT is associated with more effective blood pressure regulation. Thus there are several potential benefits of ERT, despite recent evidence finding several untoward effects of long-term treatment.

Estrogen replacement therapy in patients with early breast cancer

Objective: Most physicians believe that estrogen replacement therapy is contraindicated once a patient is diagnosed with breast cancer. Recently, several studies have shown that estrogen replacement therapy may be safely used in patients with early breast cancer that has been treated successfully. These women can have severe menopausal symptoms and are at risk for osteoporosis. We reviewed the current status of women in our practice with breast cancer who received estrogen replacement therapy, who did not receive hormone replacement therapy, and who did not receive estrogenic hormone replacement therapy. Study Design: The study group consisted of 123 women (mean age, 65.4 ± 8.85 years) who were diagnosed with breast cancer in our practice, including 69 patients who received estrogen replacement therapy for ≤32 years after diagnosis. The comparative groups were 22 women who used nonestrogenic hormones for ≤18 years and 32 women who used no hormones for ≤12 years. The group who did not receive estrogenic hormone replacement therapy received androgens with or without progestogens (such as megestrol acetate). Of the 63 living hormone users, 56 women are still being treated in our clinic, as are 15 of the 22 subjects who receive nonestrogenic hormone replacement therapy. Follow-up was done through the tumor registry at University Hospital; those patients whose tumor records were not current were contacted by telephone. Results: There were 18 deaths in the 123 patients: 6 patients who received estrogen replacement therapy (8.69%), 2 patients who received nonestrogenic hormone replacement therapy (9.09%), and 10 patients who received no hormone replacement therapy (31.25%). Of the 18 deaths, 9 deaths were from breast cancer (mortality rate, 7.3%); 3 deaths were from lung cancer; 1 death was from endometrial cancer; 1 death was from myocardial infarction; 1 death was from renal failure; and 3 deaths were from cerebrovascular accidents. The 9 deaths from breast cancer included one patient who received nonestrogenic hormone replacement therapy (mortality rate, 4.5%), 6 patients who received no hormone replacement therapy (mortality rate, 11.3%), and 2 patients who received estrogen replacement therapy (mortality rate, 4.28%). The 9 non-breast cancer deaths included 4 patients who received estrogen replacement therapy (endometrial cancer [1 death], lung cancer [1 death], cerebrovascular accident [1 death], and renal failure [1 death]), 1 patient who did not receive estrogenic hormone replacement therapy group (myocardial infarction), and 4 patients who used no hormones (lung cancer, 2 deaths; stroke, 2 deaths). Carcinoma developed in one patient in the estrogen replacement therapy group in the contralateral breast after 4 years of hormone replacement therapy; she is living and well 2.5 years later with no evidence of disease. Metastatic breast cancer developed in one patient after 8 years of hormone replacement therapy; she is living with disease. Conclusion: Estrogen replacement therapy apparently does not increase either the risk of recurrence or of death in patients with early breast cancer. These patients may be offered estrogen replacement therapy after a full explanation of the benefits, risks, and controversies. (Am J Obstet Gynecol 2002;187:289-95.)

Estrogen replacement therapy moderates the sleep disruption associated with nocturnal blood sampling.

To determine whether chronic oral estrogen replacement therapy (ERT) (1) improves the sleep of older, non-symptomatic postmenopausal women; and (2) reduces the sleep disruption associated with a stressor (frequent remote nocturnal blood-sampling through an intravenous catheter). Descriptive, cross-sectional, secondary analysis of a larger study. The General Clinical Research Center at the University of Washington Medical Center. Women aged 57-80 (mean age = 70) at least 5 years past menopause were recruited from the community. Hot flashes and significant sleep difficulties were exclusion criteria. The ERT group (n=37) consisted of women on chronic oral ERT for > or = 2 years. The NERT group (n=56) consisted of women not using estrogen (NERT) for > or = 2 years. N/A. Following an adaptation night, polysomnographic measures were collected for 2 consecutive nights. A blood sample was collected every 20 minutes for the last 24 hours (including Night 2), through an intravenous catheter. The only group difference in sleep on the baseline (non-catheter) night was that NERT women had a shorter sleep latency. Sleep on the catheter night was characterized by increased wakefulness, longer sleep latency, and decreased REM sleep for both groups relative to the baseline. However, the impact of nocturnal blood sampling was much greater for NERT than for ERT women: they experienced significantly greater percent changes in more sleep-wake variables, particularly slow-wave sleep (SWS). In this cross-sectional study, the use of chronic oral ERT was associated with little effect on the sleep of older postmenopausal women not experiencing hot flashes, except in the presence of a challenge to sleep. ERT ameliorated the disruptive effect of nocturnal blood sampling on both objectively assessed and subjectively assessed sleep.