Estrogen Replacement Therapy In Women Research Articles

Management of Hypopituitarism.

Hypopituitarism includes all clinical conditions that result in partial or complete failure of the anterior and posterior lobe of the pituitary gland’s ability to secrete hormones. The aim of management is usually to replace the target-hormone of hypothalamo-pituitary-endocrine gland axis with the exceptions of secondary hypogonadism when fertility is required, and growth hormone deficiency (GHD), and to safely minimise both symptoms and clinical signs. Adrenocorticotropic hormone deficiency replacement is best performed with the immediate-release oral glucocorticoid hydrocortisone (HC) in 2–3 divided doses. However, novel once-daily modified-release HC targets a more physiological exposure of glucocorticoids. GHD is treated currently with daily subcutaneous GH, but current research is focusing on the development of once-weekly administration of recombinant GH. Hypogonadism is targeted with testosterone replacement in men and on estrogen replacement therapy in women; when fertility is wanted, replacement targets secondary or tertiary levels of hormonal settings. Thyroid-stimulating hormone replacement therapy follows the rules of primary thyroid gland failure with L-thyroxine replacement. Central diabetes insipidus is nowadays replaced by desmopressin. Certain clinical scenarios may have to be promptly managed to avoid short-term or long-term sequelae such as pregnancy in patients with hypopituitarism, pituitary apoplexy, adrenal crisis, and pituitary metastases.

Uterine Development After Estrogen Replacement Therapy in Women with Different Etiologies of Primary Hypogonadism

Study ObjectiveTo evaluate uterine development with estrogen replacement therapy in patients with primary amenorrhea due to hypogonadism. Design and SettingRetrospective study. ParticipantsThirty-five women. Interventions and Main Outcome MeasuresWomen who were younger than 20 years of age and who had primary amenorrhea and an immaturely shaped uterus were included. Changes in uterine cross-sectional area (UXA) and uterine maturity in pelvic ultrasound after 2 year of estrogen replacement therapy were assessed on the basis of the etiology of primary hypogonadism. ResultsPatients were classified into three groups according to the etiology of primary hypogonadism: Turner syndrome (n = 19), hypogonadotropic hypogonadism after brain surgery (n = 10), and premature ovarian insufficiency after cancer treatment (n = 6). Overall, the mean UXA significantly increased (from 3.1 ± 1.8 to 11.6 ± 4.9 cm2) after estrogen replacement therapy (P < .001), but the final UXA was significantly smaller in patients with premature ovarian insufficiency compared with other etiologies. In logistic regression analysis, etiology and the cumulative dose of estrogen were associated with uterine maturation (P = .011 and .004, respectively). ConclusionEstrogen replacement therapy induced growth of the uterus in patients with primary hypogonadism. However, the response to estrogen replacement therapy varied on the basis of the total cumulative dose of estrogen and etiology of primary hypogonadism.

Metabolic Dysfunction Under Reduced Estrogen Levels

Loss of estrogen function leads to the development of metabolic dysfunction that spans numerous tissues. In this review, we explore the concept that estrogens are critical for defining metabolic function in adipose and hepatic tissues and also the possibility that exercise training should be considered a substitute for estrogen replacement therapy in women with impairments in estrogen levels.

Gender-related survival differences associated with polymorphic variants of estrogen receptor-β (ERβ) in patients with metastatic colon cancer

Estrogen replacement therapy in women has demonstrated a protective effect in the development of colonic carcinomas. Gender-related differences in the development of colonic carcinomas have also been reported. Estrogen receptor beta (ERβ) is expressed in colon carcinomas and has demonstrated prognostic value in colon cancer patients. This study investigated an ERβ 3’ non-coding polymorphism associated with transcriptional activity to determine clinical outcome in patients with metastatic colon cancer. Genomic DNA from 318 metastatic colon cancer patients, 177 males and 141 females, were collected from 1992 to 2003. These patients were analyzed for CA repeat polymorphism of the ERβ gene. Gender-related survival differences were associated with an ERβ (CA)n repeat polymorphism (P for interaction=0.003, the likelihood ratio test). Female patients with any short <22 (CA)n repeat alleles had shorter overall survival compared to female patients that had both long ≥22 (CA)n repeat alleles. In the male patients the opposite overall survival difference was found. This study supports the role of an ERβ (CA)n repeat polymorphism as a prognostic marker in metastatic colon cancer; however, this prognostic factor had opposite implications based on gender.

Role of oestrogen replacement therapy in women with diabetes

Role of oestrogen replacement therapy in women with diabetes

Estrogen replacement therapy after endometrial cancer: a survey of physicians' prescribing practice

Objective To determine whether the prescribing practice of physicians with regard to estrogen replacement therapy (ERT) in symptomatic women with previous endometrial cancer is consistent with the available evidence.Methods A descriptive survey was conducted among physicians in Germany, using a questionnaire containing two hypothetical cases of endometrial cancer patients (‘low-risk’ and ‘high-risk’ disease) and menopausal symptoms. Physicians were asked about their prescribing practice concerning moderate to severe menopausal symptoms.Results Four hundred and twenty questionnaires were sent out, with an overall response rate of 39.8%; 45.6% in the ‘low-risk’ case and 75.4% in the ‘high-risk’ case (p < 0.0001) stated that ERT is contraindicated. Only 12.9% were willing to prescribe ERT; 81.9% preferred to prescribe non-estrogenic alternatives (44.8% phytoestrogens, 29.0% selective serotonin reuptake inhibitors).Conclusion Despite the evidence that ERT does not increase the risk of recurrence of endometrial cancer, many physicians are reluctant to prescribe ERT in women suffering from moderate to severe menopausal symptoms.

Abdominal Aortic Calcification and Exostoses at the Hand and Lumbar Spine: The Framingham Study

Bony proliferation (exostoses) and vascular calcification are common in elderly men and women, but it is unclear whether they have a common etiology. Lateral lumbar and hand radiographs were obtained (1967-1970) in 777 men and 1,241 women (mean age 59, range 47-80 years) from the Framingham Heart Study. Each group of hand exostoses, specifically apiostoses (tufting), enthesophytes, and osteophytes, was graded on a scale of 0-3 (absent to severe) and summed across phalanges of digits 2-5. Anterior lumbar osteophytes were assessed in intervertebral spaces T12-L5 and abdominal aortic calcification (AAC) at lumbar segments L1-L4. Information on age, sex, body mass index, smoking, alcohol consumption, physical activity, systolic blood pressure, total cholesterol level, diabetes, and estrogen replacement therapy in women was obtained at the time of radiography and adjusted for in multivariate analyses. We used multivariable logistic regression models to assess the relationship between AAC (dependent variable) and exostoses for each sex. Multivariable adjusted logistic regression revealed a significant association between increased anterior lumbar osteophytes and prevalent AAC in men [odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.1-1.3 per unit increase in osteophytes] and in women (OR = 1.25, 95% CI 1.1-1.4). There also was an inverse association between enthesophytes and AAC in women only (OR = 0.82, 95% CI 0.73-0.92). Apiostoses were weakly associated with AAC in men only. Hand osteophytes were not associated with AAC. In conclusion, in this cross-sectional study, anterior lumbar osteophytes and AAC occurred in the same individuals after adjustment for age and other covariates. In general, hand exostoses were not associated with aortic calcification.

Serum adiponectin concentration and cardiovascular risk factors in climacteric women

Objective Adiponectin plays a significant role in the modulation of glucose tolerance and insulin sensitivity. We attempted to evaluate the relationship between adiponectin level and parameters of the menopausal metabolic syndrome: body mass index, waist-to-hip ratio, lipid profile and insulin resistance indices.Subjects and methods Thirty-two women and ten men aged 40–63 years were included. The percentage of body fat and of abdominal fat deposits were measured with dual-energy X-ray absorptiometry. Serum adiponectin, tumour necrosis factor-α (TNFα) and leptin were measured with commercially available radioimmunoassay kits. To exclude the influence of nutritional factors on adiponectin secretion, diet content was analysed in the preceding three days.Results Postmenopausal non-obese women had a non-significantly lower level of adiponectin compared with premenopausal women of corresponding body mass. Serum adiponectin level was significantly lower in postmenopausal obese women than in non-obese women (p = 0.0023). Men with similar age and body mass to the women had the lowest level of adiponectin (p = 0.06). Three months of estrogen replacement therapy in women with surgical menopause did not significantly change the serum level of adiponectin. We found a negative correlation of adiponectin with leptin, insulin resistance index and total cholesterol, and a positive correlation with high-density lipoprotein cholesterol. Adiponectin level was negatively correlated with free testosterone, but we did not find such a relationship with estradiol. There was no correlation of adiponectin level with TNFα; however, serum TNFα correlated positively with leptin. The dietary analysis showed no differences between the diets of obese and non-obese women over the preceding three days. Moreover, mean diastolic and systolic blood pressures were noted to be significantly lower in premenopausal women than in postmenopausal non-obese women (p = 0.05).Conclusions Our results suggest that adiponectin could be a marker of risk for developing menopausal metabolic syndrome. Moreover, it is possible that sex steroids have an influence on adiponectin secretion.

Neurobiological Consequences of Long-Term Estrogen Therapy

Postmenopausal women demonstrate an increased incidence of Alzheimer's disease (AD). Epidemiological evidence suggests that estrogen replacement therapy (ERT) may reduce the risk or delay the onset of AD, yet recent clinical trials found no cognitive benefits of ERT in women with mild to moderate AD. This review suggests that the timing of estrogen administration may explain these conflicting results. Chronic administration has neurobiological consequences that can affect neural and immune function, but a therapy designed to mimic the natural cycle of fluctuating hormones may more effectively slow the progression of AD in postmenopausal women.

Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome.

Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6-10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle-aged trisomic mice (9-15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17beta-estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full-length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS.

Estrogen receptor-mediated repression of human hepatic lipase gene transcription

Estrogen replacement therapy in women decreases hepatic lipase (HL) activity, which may account for the associated increase in HDL cholesterol. To investigate whether estrogen decreases HL transcription, transient cotransfection assays with HL promoter and estrogen receptor-α (ERα) expression constructs were performed in HepG2 cells. 17β-estradiol (E2) decreased transcription driven by the −1557/+41 human HL promoter by up to 50% at 10−7 M. Mutation of ERα by deletion of its transactivation domains or ligand-binding domain eliminated E2-induced repression of the promoter, whereas deletion of the DNA-binding domain of ERα resulted in a 7-fold activation by E2. The E2-induced repression was maintained after mutation of a potential estrogen-response element in the promoter. The region of estrogen responsiveness was localized to −1557/ −1175 of the HL promoter by deletion analysis. Mutation of an AP-1 site at −1493 resulted in a partial loss of E2-induced repression, similar to that caused by deletion of nucleotides −1557 to −1366. Gel shift assays with nuclear extracts from E2-treated HepG2 cells stably expressing ERα demonstrated an increase in binding to an AP-1 consensus oligonucleotide. The AP-1 activator, phorbol 12-myristate 13-acetate, inhibited the HL promoter by greater than 50%. Collectively, the data suggest that estrogen represses the transcription of the HL gene, possibly through an AP-1 pathway. —Jones, D. R., R. J. Schmidt, R. T. Pickard, P. S. Foxworthy, and P. I. Eacho. Estrogen receptor-mediated repression of human hepatic lipase gene transcription.

Overview of gender aspects of cardiac syndrome X.

Cardiac syndrome X, a condition defined by the presence of angina-like chest pain, a positive response to stress testing and normal coronary arteriograms, has been shown to occur in approximately 20--30% of angina patients undergoing coronary arteriography. The prevalence of syndrome X is significantly higher in women compared to men. In the majority of patients with chest pain and normal coronary arteriograms, symptoms are likely to be non-cardiac in origin. However, myocardial ischaemia may be the pathogenic mechanism in a proportion of syndrome X patients. Indeed, the clinical characteristics, the ischaemic electrocardiographic findings and the presence of myocardial perfusion defects during stress testing are similar in syndrome X and coronary artery disease patients. Moreover, coronary sinus oxygen saturation abnormalities and pH changes, as well as myocardial lactate production and alterations of cardiac high energy phosphate are seen during stress testing in patients with syndrome X and appear to endorse an ischaemic origin of symptoms in at least a proportion of these individuals. Patients with chest pain and normal coronary arteries have abnormal vasodilatory coronary blood flow responses and an increased sensitivity of the coronary microcirculation to vasoconstrictor stimuli (microvascular angina). Microvascular endothelial dysfunction appears to be responsible for these coronary microcirculation abnormalities. Given the high prevalence of peri- and post-menopausal women in cardiac syndrome X, it has been hypothesized that oestrogen deficiency may play a major role in the pathogenesis of this condition. Oestrogen vasoactive properties involve endothelium-dependent effects and, in postmenopausal women, forearm vasodilatation induced by acetylcholine is potentiated by the acute local administration of intravenous oestradiol. This suggests that endothelium-dependent responses in the peripheral circulation may be modulated by steroid hormones. Impairment of endothelial function in post-menopausal women with syndrome X has been reported by various groups and it could be hypothesized that oestrogen deficiency may contribute to the development of microvascular angina through endothelial dysfunction and that exogenous oestrogen administration may have a beneficial effect in syndrome X patients. This article reviews current knowledge regarding the role of oestrogen deficiency in the pathogenesis of syndrome X and the potential therapeutic role of oestrogen replacement therapy in women with chest pain and normal coronary arteriograms

Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease.

Previous studies have examined the relation between postmenopausal estrogen replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings have been inconsistent, since some studies have been interpreted as showing a protective effect while others have reported no effect. To determine whether exposure to ERT is associated with a reduced risk of AD. Population-based nested case-control study. The United Kingdom-based General Practice Research Database. The base cohort consisted of women who were recipients of ERT (n = 112 481) and a similar cohort of women who did not use estrogens (n = 108 925). The 2 cohorts were restricted to women born on or before January 1, 1950. From the 2 cohorts, we identified and verified 59 newly diagnosed cases of AD and 221 matched control subjects. Prior and current use of ERT in cases compared with controls. Among the 59 newly diagnosed cases of AD, 15 (25%) were current estrogen users, while among the controls, 53 (24%) were current users. The adjusted odds ratio comparing all current estrogen recipients with nonrecipients was 1.18 (95% confidence interval, 0.59-2.37). In estrogen users who took the drug for 5 years or longer compared with nonusers, the odds ratio was 1.05 (95% confidence interval, 0.32-3.44). Odds ratios were similar for estrogen recipients who received estrogens alone and recipients who received combined estrogen-progestin treatment. The use of ERT in women after the onset of menopause was not associated with a reduced risk of developing AD.

ESTROGEN AFTER ISCHEMIC STROKE: Effect of estrogen replacement on risk of recurrent stroke and death in the Women’s Estrogen for Stroke Trial (WEST)

71 Introduction: Observational research has produced conflicting findings concerning the effect of estrogen replacement therapy (ERT) on reducing risk for vascular events or death in women. To test the effect of ERT in women with established cerebrovascular disease, we designed a randomized trial of estradiol-17β(1 mg/day) vs. placebo. Methods: Participants were identified from 20 hospitals in New England. Eligibility criteria included age over 44, at least 1 year since last menstrual period, and TIA or non-disabling stroke within 90 days of entry. Randomization was stratified by baseline risk group and hospital. Primary trial outcomes were non-fatal stroke and all-cause death. Results: From December 1993-May 1998, 652 women were randomized (332 estradiol, 320 placebo). Index event was TIA in 164 subjects and stroke in 488. Mean age of subjects was 71 years (range 46–91); 84% were white, 13% black, and 4% other. Mean follow-up was 2.7 years (range: 18 days-5.8 years). At 1 year, 76% of subjects assigned to estradiol were on study drug. In the estradiol group, adverse events were diagnosed during follow-up in 8 subjects (1 pulmonary embolus (PE), 1 deep venous thrombosis (DVT), 5 breast cancers, 1 endometrial cancer) compared with 7 events in placebo subjects (2 PE, 1 DVT, and 4 breast cancers). Non-fatal strokes were confirmed in 51 subjects in the estradiol group vs. 52 in placebo subjects (rates at 3 years[R]: 16.8% estradiol vs. 17.4% placebo; logrank p-value[p]=.83). Death occurred in 46 estradiol subjects vs. 38 placebo subjects (R=13.0% vs. 12.6%, p=.89). At 3 years, combined rate of non-fatal stroke or death was 27.6% in the estradiol group vs. 27.7% in placebo [p=.80]. Conclusion: During an average follow-up of 2.7 years, estradiol treatment did not protect against recurrent cerebral ischemia or reduce all-cause mortality in postmenopausal women with pre-existing cerebrovascular disease. No increased risk for adverse events associated with estrogen was observed. This trial adds to the growing body of evidence that fails to confirm a protective role for ERT in populations with known vascular disease.

ESTROGEN AFTER ISCHEMIC STROKE: Effect of estrogen replacement on risk of recurrent stroke and death in the Women’s Estrogen for Stroke Trial (WEST)

71 Introduction: Observational research has produced conflicting findings concerning the effect of estrogen replacement therapy (ERT) on reducing risk for vascular events or death in women. To test the effect of ERT in women with established cerebrovascular disease, we designed a randomized trial of estradiol-17β(1 mg/day) vs. placebo. Methods: Participants were identified from 20 hospitals in New England. Eligibility criteria included age over 44, at least 1 year since last menstrual period, and TIA or non-disabling stroke within 90 days of entry. Randomization was stratified by baseline risk group and hospital. Primary trial outcomes were non-fatal stroke and all-cause death. Results: From December 1993-May 1998, 652 women were randomized (332 estradiol, 320 placebo). Index event was TIA in 164 subjects and stroke in 488. Mean age of subjects was 71 years (range 46–91); 84% were white, 13% black, and 4% other. Mean follow-up was 2.7 years (range: 18 days-5.8 years). At 1 year, 76% of subjects assigned to estradiol were on study drug. In the estradiol group, adverse events were diagnosed during follow-up in 8 subjects (1 pulmonary embolus (PE), 1 deep venous thrombosis (DVT), 5 breast cancers, 1 endometrial cancer) compared with 7 events in placebo subjects (2 PE, 1 DVT, and 4 breast cancers). Non-fatal strokes were confirmed in 51 subjects in the estradiol group vs. 52 in placebo subjects (rates at 3 years[R]: 16.8% estradiol vs. 17.4% placebo; logrank p-value[p]=.83). Death occurred in 46 estradiol subjects vs. 38 placebo subjects (R=13.0% vs. 12.6%, p=.89). At 3 years, combined rate of non-fatal stroke or death was 27.6% in the estradiol group vs. 27.7% in placebo [p=.80]. Conclusion: During an average follow-up of 2.7 years, estradiol treatment did not protect against recurrent cerebral ischemia or reduce all-cause mortality in postmenopausal women with pre-existing cerebrovascular disease. No increased risk for adverse events associated with estrogen was observed. This trial adds to the growing body of evidence that fails to confirm a protective role for ERT in populations with known vascular disease.

Estrogen replacement therapy for women with Alzheimer's disease

Estrogen replacement therapy for women with Alzheimer's disease

The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus

Estrogen replacement therapy in women is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. The present study indicates that estrogen is neuroprotective against N-methyl-d-aspartate (NMDA)- and kainate-mediated neurotoxicity, an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. Finally, estrogen-mediated enhancement of long-term potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. Thus, estrogen, by activating an src tyrosine kinase and the extracellular signal-related protein kinase/MAPK signaling pathway, both enhances NMDA receptor function and long-term potentiation and retains neuroprotective properties against excitotoxicity. These findings warrant further evaluation of the usefulness of estrogenic compounds for the treatment of Alzheimer's disease and other neurodegenerative diseases.

The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus.

Estrogen replacement therapy in women is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. The present study indicates that estrogen is neuroprotective against N-methyl-d-aspartate (NMDA)- and kainate-mediated neurotoxicity, an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. Finally, estrogen-mediated enhancement of long-term potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. Thus, estrogen, by activating an src tyrosine kinase and the extracellular signal-related protein kinase/MAPK signaling pathway, both enhances NMDA receptor function and long-term potentiation and retains neuroprotective properties against excitotoxicity. These findings warrant further evaluation of the usefulness of estrogenic compounds for the treatment of Alzheimer's disease and other neurodegenerative diseases.

Estrogen replacement therapy in women with amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) occurs more commonly in men than in women, and women get the disease later in life compared to men. This epidemiologic aspect of the disease raises the question as to whether estrogen may be neuroprotective in delaying or preventing ALS. Postmenopausal women with ALS were separated into two groups dependent upon whether or not they took estrogen replacement therapy. Women who used estrogen had onset of their disease at an earlier age compared to those not taking hormonal replacement. There was no difference in survival in those patients taking estrogen compared to those not on the medication. Women with ALS were more likely to take estrogen compared to a control group of patients with neurological diseases other than motor neuron disease. Therefore, no evidence for a neuroprotective role of estrogen in postmenopausal women with ALS was found.

Estrogen replacement therapy in women with previous breast cancer

Objective: We sought to review the status of patients with breast cancer who were treated with estrogen replacement therapy and compare the results with those of nonestrogenic hormone users and women not treated with hormone replacement. Study Design: The study group consisted of 76 patients with breast cancer, including 50 using estrogen replacement for up to 32 years, 8 using nonestrogenic hormone replacement for up to 6 years and followed for up to 11 years, and 18 using no hormones for up to 10 years. In addition to estrogen use, 40 of the 50 hormone users were treated with androgens, usually in the form of implantation of testosterone pellets. Forty-five subjects were also given progestogens, usually megestrol acetate 20 to 40 mg for 10 to 25 days each month. The 8 nonestrogen hormone users were treated with various combinations of testosterone pellets, tamoxifen, and progestogens. Forty-two of the 50 estrogen users are still being treated in our clinic, as are 2 of the 8 subjects using nonestrogen hormone. Follow-up was done through the tumor registry at University Hospital, and those whose tumor records were not current were telephoned. Results: Of the 50 estrogen users, 3 have died (a mortality rate of 6%), and the rest have been followed for 6 months to 32 years, with a mean duration of follow-up of 83.3 ± 8.81 months. One of the 8 nonestrogen hormone users has died (a mortality rate of 12.5%), and the rest have been followed for 2 to 11 years, with a mean duration of follow-up of 72.0 ± 5.93 months. Six of the 18 women not using hormone replacement have died (a mortality rate of 33.3%), and the rest have been followed for 6 months to 10 years, with a mean duration of follow-up of 50.5 ± 6.01 months. Conclusion: Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progestogens may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks, and controversies. (Am J Obstet Gynecol 1999;181:288-95.)