Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality

OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality. DESIGN: Retrospective observational study. PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics. RESULTS: 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73). CONCLUSION: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.     

Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer

CONTEXT: Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. OBJECTIVE: To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. DESIGN AND SETTING: Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. PARTICIPANTS: A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. RESULTS: After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. CONCLUSIONS: These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.     

Hormone replacement therapy and high S phase in breast cancer

CONTEXT: Prolonged postmenopausal hormone replacement therapy (HRT) is associated with increased incidence of breast cancer and, paradoxically, reduced breast cancer mortality. The biological rationale for this discrepancy has not been explored. OBJECTIVE: To compare the prognostic characteristics of cancers arising in women who have used HRT with those in women who never have used HRT. DESIGN: Prospective cohort study from December 1989 to November 1996. SETTING: Teaching hospital in a large midwestern metropolitan area. PATIENTS: Cohort of 331 postmenopausal women who presented consecutively with 349 invasive breast cancers. MAIN OUTCOME MEASURES: Estrogen receptor (ER) status (ER positive vs ER negative) and S phase (low vs high) for current HRT users vs never users. RESULTS: The frequency of high S-phase fraction among cancers in women who were using HRT was markedly increased compared with that in women who had never used HRT (adjusted odds ratio [OR], 2.82; 95% confidence interval [CI], 1.04-7.66). However, the greater frequency of high S-phase fraction was limited to women with ER-positive cancers (for HRT users vs never users, OR, 5.25; 95% CI, 1.36-20.28; for ER-negative cancers in HRT users vs never users, OR, 1.08; 95% CI, 0.20-5.86). CONCLUSIONS: Use of HRT appears to stimulate growth of ER-positive but not ER-negative breast cancer as measured by S-phase fraction. The prognostic significance of high S-phase fraction in current HRT users who have ER-positive tumors is unknown.     

Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women

CONTEXT: Estrogens are known to be prothrombotic, and findings from the Heart and Estrogen/progestin Replacement Study suggest that in women with clinically recognized heart disease, hormone replacement therapy (HRT) may be associated with early harm and late benefit in terms of coronary events. OBJECTIVE: To assess whether, as hypothesized, prothrombotic mutations modify the association between HRT use and incidence of first myocardial infarction (MI). DESIGN AND SETTING: Population-based, case-control study conducted in a Seattle-based health maintenance organization. PARTICIPANTS: Cases were 232 postmenopausal women aged 30 to 79 years who had their first nonfatal MI between 1995 and 1998. Controls were a stratified random sample of 723 postmenopausal women without MI who were frequency-matched to cases by age, calendar year, and hypertension status. MAIN OUTCOME MEASURE: Risk of first nonfatal MI based on current use of HRT and the presence or absence of coagulation factor V Leiden and prothrombin 20210 G-->A variants among cases and controls, stratified by hypertension. RESULTS: One hundred eight MI cases and 387 controls had hypertension and 124 MI cases and 336 controls did not. Among hypertensive women, the prothrombin variant was a risk factor for MI (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.52-12.1) and, in this stratum, there was also a significant interaction between use of HRT and presence of the prothrombin variant on risk of MI. Compared with nonusers of HRT with wild-type genotype, women who were current users and who had the prothrombin variant (n = 8) had a nearly 11-fold increase in risk of a nonfatal MI (OR, 10.9; 95% CI, 2.15-55.2). The interaction with the prothrombin variant was more pronounced in analyses assuming 100% compliance than in those assuming 80% compliance with HRT. The interaction was absent among nonhypertensive women and was less pronounced if hypertensive and nonhypertensive women were combined into 1 group. No interaction was found for factor V Leiden in either hypertensive or nonhypertensive women. Among hypertensive women, the estimates were affected only in trivial ways by adjustment, and the interaction with the prothrombin variant was specific to HRT. CONCLUSIONS: Our results suggest that among postmenopausal hypertensive women, the association between HRT use and MI risk differed between those with and without the prothrombin 20210 G-->A variant. If these findings are confirmed in other studies, screening for the prothrombin variant may permit a better assessment of the risks and benefits associated with HRT in postmenopausal women.     

Hormone replacement therapy and dry eye syndrome.

CONTEXT: Postmenopausal hormone replacement therapy (HRT) use is common in the United States. Some research suggests that estrogen may have detrimental effects on the tear film and could influence the development of dry eye syndrome, but few data are available on this relationship. OBJECTIVE: To determine the relationship of HRT and dry eye syndrome. DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Study, a large cohort study in which 25 665 postmenopausal women provided information about use of HRT at baseline (1992), 12, and 36 months and dry eye syndrome at 48 months. MAIN OUTCOME MEASURES: (1) Clinically diagnosed dry eye syndrome, as reported by participants; (2) severe symptoms (both ocular dryness and irritation either constantly or often); and (3) either clinically diagnosed dry eye syndrome or severe symptoms, compared between women who used HRT vs those who did not. RESULTS: For the combined end point of either clinically diagnosed dry eye syndrome or severe symptoms, the multivariable-adjusted odds ratios were 1.69 (95% confidence interval [CI], 1.49-1.91) for estrogen use alone and 1.29 (95% CI, 1.13-1.48) for estrogen plus progesterone/progestin use compared with no HRT use. Each 3-year increase in the duration of HRT use was associated with a significant 15% (95% CI, 11%-19%) elevation in risk of clinically diagnosed dry eye syndrome or severe symptoms. Results were similar for the combined end point of clinically diagnosed dry eye syndrome and severe symptoms. CONCLUSIONS: These data suggest that women who use HRT, particularly estrogen alone, are at increased risk of dry eye syndrome. Physicians caring for women who are taking or considering HRT should be apprised of this potential complication.     

Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials

CONTEXT: Hormone replacement therapy (HRT) is widely considered to reduce fractures, but this belief is based on observational data; evidence from randomized trials is lacking. OBJECTIVE: To conduct a systematic review of all randomized trials of HRT that have reported or collected nonvertebral fracture data but that may not have focused on fracture prevention. DATA SOURCES: The MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trials Register databases were searched from 1997 through 2000 and a search was conducted of all recent systematic reviews to identify older studies. Authors were contacted to establish whether fracture data had been collected but not reported. Researchers in the field and pharmaceutical companies also were contacted to try to identify unpublished studies. STUDY SELECTION: Trials were included in which participants had been randomized to at least 12 months of therapy and data on nonvertebral fractures at any other site and due to any cause were available. Of 70 initially identified studies, 22 were included in the analysis. DATA EXTRACTION: Both investigators extracted data independently and appraised trial quality according to the Jadad scale, which assesses the methods of randomization, concealment allocation, and reporting of withdrawals and dropouts. Disagreements were resolved by discussion. DATA SYNTHESIS: There was an overall 27% reduction in nonvertebral fractures in a pooled analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.94; P =.02). This effect was greater among women randomized to HRT who had a mean age younger than 60 years (RR, 0.67; 95% CI, 0.46-0.98; P =.03). Among women with a mean age of 60 years or older, there was a reduced effect (RR, 0.88; 95% CI, 0.71-1.08; P =.22). For hip and wrist fractures alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P =.02), particularly for women younger than 60 years (RR, 0.45; 95% CI, 0.26-0.79; P =.005). CONCLUSIONS: Our meta-analysis of randomized controlled trials of HRT noted a statistically significant reduction in nonvertebral fractures. However, this effect may be attenuated in older women.     

Decrease in breast cancer incidence following a rapid fall in use of hormone replacement therapy in Australia

OBJECTIVE: To determine if the recent rapid fall in use of hormone replacement therapy (HRT) in Australia has been followed by a reduction in breast cancer incidence among women aged 50 years or older, but not among younger women. DESIGN AND SETTING: Analysis of trends in annual prescribing of HRT, using Pharmaceutical Benefits Scheme data, and in annual age-standardised breast cancer incidence rates in Australian women for the period 1996-2003. RESULTS: In Australia, prescribing of HRT increased from 1996 to 2001, but dropped by 40% from 2001 to 2003. Age-standardised breast cancer incidence rates in women aged > or = 50 years also increased to 2001 but declined thereafter. The incidence rates in this age group were lower by 6.7% (95% CI, 3.9%-9.3%; P < 0.001) in 2003 compared with 2001, equivalent to 600 (95% CI, 350-830) fewer breast cancers (out of about 9000 incident breast cancers annually for women this age). There was no significant change in breast cancer incidence for women aged < 50 years. CONCLUSIONS: While other factors may have contributed to a recent reduction in breast cancer incidence among Australian women aged > or = 50 years, the available evidence suggests that much of the decrease is due to the recent fall in use of HRT. This is consistent with other evidence that the HRT-associated increase in risk of breast cancer is reversible after ceasing use of HRT.     

A prospective study of folate intake and the risk of breast cancer

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.     

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk

CONTEXT: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. OBJECTIVE: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. DESIGN: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine screening centers throughout the United States. PARTICIPANTS: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). MAIN OUTCOME MEASURE: Incident breast cancers by recency, duration, and type of hormone use. RESULTS: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. CONCLUSION: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.     

Use of hormone replacement therapy among cardiac patients at a Canadian academic centre

BACKGROUND: Although hormone replacement therapy (HRT) is associated with a reduced risk of coronary artery disease (CAD), use of this treatment among post-menopausal women is not widespread. The authors sought to determine the extent of HRT use in a select population of women at high risk for CAD. METHODS: A cross-sectional survey was performed involving all consecutive post-menopausal women who attended a cardiology clinic in a Toronto teaching hospital between January 1996 and August 1997. A chart review was followed by a telephone interview with the patients or their physicians. The utilization rate of HRT was obtained. Predictors of HRT use were identified using a multivariate logistic regression model. RESULTS: A total of 80 women with risk factors for CAD, symptoms suspicious of CAD or definite CAD diagnosed after cardiac investigations were included in the survey. Information on HRT use or nonuse was documented in 17 (21%) of the charts. Of the 72 women for whom data on HRT were available 16 (22%) were currently using it, 41 (57%) were not, and 15 (21%) had used it in the past. Five women (7%) were receiving HRT but there was no chart documentation. On multivariate analysis, younger women were more likely than older women to use HRT (odds ratio 0.91, 95% confidence interval 0.22-0.96; p < 0.05). Coronary risk profile, CAD diagnosis and history of hysterectomy were not associated with HRT use. Of the 41 women who had never received HRT 10 (24%) had possible contraindications (e.g., breast cancer or deep vein thrombosis); the proportion was similar in the group of women who were current or past users of HRT (29%). INTERPRETATION: Documentation of HRT use in patient charts is lacking. Few women in the study who were at risk for CAD were currently using HRT. The data support the need for better adherence to optimal practices in the management of women at high risk for CAD.     

Hormone Replacement Therapy and Risk of Breast Cancer With a Favorable Histology: Results of the Iowa Women's Health Study

Context  Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown. Objective  To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma. Design  Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996. Setting and Participants  Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37,105 women. Main Outcome Measures  Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use. Results  Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend=.005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85). Conclusions  Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use.      

Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women

CONTEXT: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. OBJECTIVES: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. DESIGN AND SETTING: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. PARTICIPANTS: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. MAIN OUTCOME MEASURE: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). RESULTS: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17). CONCLUSIONS: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.     

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.     

Treatment patterns for cancer in Western Australia: does being Indigenous make a difference?

OBJECTIVE: To examine whether hospital patients with cancer who were identified as Indigenous were as likely to receive surgery for the cancer as non-Indigenous patients. DESIGN, SETTING AND PATIENTS: Epidemiological survey of all Western Australian (WA) patients who had a cancer registration in the state-based WA Record Linkage Project that mentioned cancer of the breast (1982-2000) or cancer of the lung or prostate (1982-2001). MAIN OUTCOME MEASURES: The likelihoods of receiving breast-conserving surgery or mastectomy for breast cancer, lung surgery for lung cancer, or radical or non-radical prostatectomy for prostate cancer were compared between the Indigenous and non-Indigenous populations using adjusted logistic regression analyses. RESULTS: Indigenous people were less likely to receive surgery for their lung cancer (odds ratio [OR], 0.64; 95% CI, 0.41-0.98). Indigenous men were as likely as non-Indigenous men to receive non-radical prostatectomy (OR, 0.69; 95% CI, 0.40-1.17); only one Indigenous man out of 64 received radical prostatectomy. Indigenous women were as likely as non-Indigenous women to undergo breast-conserving surgery (OR, 0.86; 95% CI, 0.60-1.21). CONCLUSIONS: These results indicate a different pattern of surgical care for Indigenous patients in relation to lung and prostate, but not breast, cancer. Reasons for these disparities, such as treatment choice and barriers to care, require further investigation.     

高碘对儿童甲状腺肿大影响的Meta分析

目的：综合评价高碘对甲状腺功能的影响。方法系统检索2014年以前在中国生物医学文献数据库（CBM）、万方数据库、维普数据库（VIP）、中国知网数据库（CNKI）、PubMed、EMbase、Ovid、CochraneLibrary里发表的关于高碘对甲状腺肿大影响的文献。文献研究类型为随机对照试验或半随机对照试验。使用RevMan5．0软件对相关文献进行统计分析,计算合并RR及95％CI。采用Begg′s检验、Egger′s检验和Macaskill′s检验方法评价Meta分析的“发表偏倚”。敏感性分析检验Meta分析结果的稳定性。结果该研究共纳入10篇文献。Meta分析结果显示高碘在150～300μg／L（RR：1．54;95％CI：1．14～2．07）;301～600μg／L（RR：2．33;95％CI：1．43～3．82）;601～900μg／L（RR：2．72;95％CI：1．01～7．33）和≥900μg／L（RR：2．41;95％CI：1．38～4．23）时都会导致儿童甲状腺肿大。结论碘含量超过150μg／L会引起儿童甲状腺肿大。     

Prevalence of gestational diabetes mellitus among Swampy Cree women in Moose Factory, James Bay

BACKGROUND: Although high rates of gestational diabetes mellitus have been documented in native populations, few studies have examined rates of the disease among native Indians in Canada. The authors conducted a study to estimate the prevalence of gestational diabetes among Swampy Cree women, to identify factors predictive of the occurrence of gestational diabetes, and to identify delivery and infant outcomes related to the presence of the disease. METHODS: Information on Swampy Cree women who gave birth at Weeneebayko Hospital, Moose Factory, James Bay, Ont., between 1987 and 1995 was obtained from medical charts. Patients with and without gestational diabetes were compared. Logistic regression analysis was used to identify independent predictors of gestational diabetes. Delivery and infant outcomes that occurred secondary to gestational diabetes were also identified by means of logistic regression. RESULTS: A total of 1401 deliveries occurred at Weeneebayko Hospital over the study period, of which 1298 were included in the study. Gestational diabetes was diagnosed in 110 (8.5% [95% confidence interval (CI) 6.9%-9.9%]) of the 1298 pregnancies. Factors predictive of gestational diabetes were age 35 years or more (relative risk [RR] 4.1, 95% CI 1.5-11.7), a history of gestational diabetes in a previous pregnancy (RR 6.4, 95% CI 3.5-11.7), diastolic blood pressure of 80 mm Hg or higher at the first prenatal visit (RR 1.7, 95% CI 1.1-2.8), weight greater than 80 kg at the first prenatal visit (RR 4.9, 95% CI 1.8-12.9) and having a first-degree relative with diabetes (RR 3.0, 95% CI 1.4-6.1). The only delivery outcome independently associated with the presence of gestational diabetes was an increased likelihood of needing assisted delivery (forceps or vacuum extraction) (RR 2.8, 95% CI 1.1-7.0). Shoulder dystocia was indirectly associated with gestational diabetes owing to increased infant birth weight. Infant outcomes associated with the presence of gestational diabetes were birth weight greater than 4500 g (RR 2.4, 95% CI 1.4-3.8), hyperbilirubinemia (RR 2.9, 95% CI 1.4-6.1), hypoglycemia (RR 7.3, 95% CI 3.7-14.4) and hypocalcemia (RR 8.9, 95% CI 2.3-33.7). INTERPRETATION: Gestational diabetes occurred in a significant minority of Swampy Cree women and was associated with a number of adverse outcomes.     

Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial

CONTEXT: Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women. OBJECTIVE: To determine whether HRT increases bone mineral density (BMD) in frail elderly women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000. PARTICIPANTS: Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. INTERVENTION: Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months. MAIN OUTCOME MEASURES: The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. RESULTS: Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%). CONCLUSIONS: In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.     

激素替代治疗前乳腺X线检查的重要性

目的 探讨激素替代治疗(HRT)前行双侧乳腺X线检查的重要意义。方法 对2001年5月至2003年4月妇科门诊要求HRT的268名患者行双侧乳腺X线片检查，并对其结果进行分析。结果 X线片显示268例中117例正常；良性乳腺疾病144例；6例患者恶性病变不能排除，活检确诊为良性肿块；1例为恶性肿瘤，自行用HRT4年。结论 HRT前行双乳X线检查十分重要。     

Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study

Context  Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. Objective  To examine the relationship between use of HRT and risk of AD among elderly women. Design, Setting, and Participants  Prospective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. Main Outcome Measure  Diagnosis of incident AD. Results  Thirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]). Conclusions  Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.      

Use of statins and risk of fractures

CONTEXT: Previous studies have reported lower fracture risks in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To investigate risk of fracture among statin users. DESIGN: Case-control study of data from the General Practice Research Database (GPRD). SETTING: A total of 683 general clinical practices in the United Kingdom. PATIENTS: Cases were 81 880 patients aged 50 years or older who had a fracture of the vertebrae, clavicle, humerus, radius/ulna, carpus, hip, ankle, or foot occurring between the enrollment date of their practice into the GPRD and July 1999, paired with 81 880 age-, sex-, and practice-matched controls. MAIN OUTCOME MEASURE: Risk of fracture in current users vs nonusers of statins. Odds ratios were estimated from conditional logistic regression and adjusted for smoking, medications and illnesses associated with fracture risk, and body mass index when known. RESULTS: The adjusted odds ratio (OR) for current use of statins compared with nonuse was 1.01 (95% confidence interval [CI], 0.88-1.16). For forearm, hip, and vertebral fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and 1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of 0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95% CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for durations of more than 12 months. CONCLUSION: In this study, use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture.