Longer-term Users Research Articles

Effects of Medication Period and Gastrin Levels on Endoscopic Gastric Mucosal Changes in Long-Term Proton Pump Inhibitor Users.

Background/Objectives: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. Methods: We enrolled 57 patients who received a PPI (>1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 < 5, 5-10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (<250, 250-500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. Results: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 < 5, 5-10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46-29.75; p = 0.014) and high (OR, 9.00; 95% CI, 1.79-45.23; p = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. Conclusions: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study

BackgroundTo investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. MethodWe conducted a case-control study using Taiwan’s National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. ResultsCompared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12–1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90–365 (OR: 1.07,95% CI: 0.87–1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12–3.31), venlafaxine (OR: 1.62, 95% CI: 1.13–2.31), mirtazapine (OR: 1.56, 95% CI: 1.00–2.43), paroxetine (OR: 1.44, 95% CI: 1.08–1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01–1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. ConclusionsThe study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.

Abstract 825: Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions

Abstract Purpose: Immune-related etiologic pathways in the development of colorectal cancer (CRC) have not been convincingly determined and may be confounded by lifestyle factors or reverse causality. We investigated the genetically predicted C-reactive protein (CRP) phenotype in the potential causal pathway of primary CRC risk in postmenopausal women in a Mendelian randomization (MR) framework. Methods: We employed individual-level data of the Women's Health Initiative Database for Genotypes and Phenotypes Study, which consists of 5 genome-wide association (GWA) studies, including 10,142 women, 737 of whom developed primary CRC. We examined 61 GWA single-nucleotide polymorphisms (SNPs) associated with CRP by using weighted/penalized MR weighted-medians and MR gene-environment interactions that allow some relaxation of the strict variable requirements and attenuate the heterogeneous estimates of outlying SNPs. Results: In lifestyle-stratification analyses, genetically determined CRP exhibited its effects on the decreased CRC risk in non-viscerally obese and high-fat diet subgroups. In contrast, genetically driven CRP was associated with an increased risk for CRC in women who smoked 15 or more cigarettes/day, with significant interaction of the gene-smoking relationship. Further, a substantially increased risk of CRC induced by CRP was observed in relatively short-term users (less than 5 years) of estrogen (E)-only and also longer-term users (longer than 5 years) of E plus progestin. Conclusions: Our findings may provide novel evidence on immune-related etiologic pathways connected to CRC risk and suggest the possible use of CRP as a CRC-predictive biomarker in women with particular behaviors and CRP marker-informed interventions to reduce CRC risk. Citation Format: Su Yon Jung, Herbert Yu, Matteo Pellegrini, Jeanette C. Papp, Eric M. Sobel, Zuo-Feng Zhang. Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 825.

Aspirin associated with a decreased incidence of uterine cancer: A retrospective population-based cohort study.

Aspirin (ASA) exerts an anti-tumor effect via the COX pathway. Clinical studies on the chemopreventive effects of ASA on uterine cancer (UC) remain inconsistent. We used population-based retrospective cohort study to evaluate the UC in ASA users in Taiwanese women. From insurance claims data, we identified 23,342 women received ASA treatment between 2000 and 2010 and a comparison group of same sample size randomly selected from the same database matched by the propensity score. The incidence of UC in the ASA cohort was 10% of that in the comparison group (0.28 vs 2.73 per 10,000 person-years). The Poisson regression analysis estimated adjusted incidence rate ratio (IRR) was 0.10 (95% confidence interval (CI) = 0.09–0.11) for ASA users relatives to comparisons after controlling for covariates. The UC incidence in ASA users decreased with age, from 0.61 per 10,000 person-years in the 20 to 39 years old (adjusted IRR = 0.21, 95% CI = 0.15–0.29) to 0.21 per 10,000 person-years in the 65 to 80 years old (adjusted IRR = 0.15, 95% CI = 0.12–0.16). The incidence was higher in longer term users. Hormone therapy of estradiol was associated with the increase of UC risk in both cohorts, but less in ASA users than comparisons (1.34 vs 4.75 per 10,000 person-years). This study suggests that ASA use was associated with a decreased risk of UC. Further prospective randomized clinical trials are warranted to confirm the association.

Cigar package quantity and smoking behavior

BackgroundSeveral jurisdictions in the US and abroad limit the minimum number of cigars that can be sold per package. Research has not evaluated whether small packages might result in cigar use initiation, or whether adding cigars to packages might result in purchasers smoking more cigars.MethodsUsing nationally representative US adult data from Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study, we assessed links between cigar package quantity (number of cigars in the package a person usually buys) and (1) price, and (2) cigar and cigarette use over time, for three cigar types: filtered cigars, cigarillos, and large cigars.ResultsSmaller quantity packages (i.e., packages with fewer cigars) were cheaper per-pack than larger quantity packages but more expensive per-stick for all three cigar types. For filtered cigars, past-year starters tended to buy smaller quantity packages compared to longer-term users (geometric mean = 6.31 vs. 11.75, respectively; b = −.18, 95%CI: −.32, −.04). Also, those who bought smaller quantity packages of filtered cigars tended to smoke fewer cigars over time compared to those who bought larger quantity packages (b = 1.16, 95%CI: 0.45, 1.87). Neither of these associations was observed for cigarillos or large cigars. We also found little evidence that buying larger quantity packages predicted continuing to use cigars or using cigarettes.ConclusionsAlthough we found consistent associations between package quantity and price, we found few associations between package quantity and changes in cigar smoking behaviors over time, particularly for cigarillos and large cigars. Key limitations include our adult-only analyses and inability to determine the package quantity that cigar users initiated with. Future studies could examine whether package quantity plays a causal role in filtered cigar use initiation or consumption rates.

Safety and Effectiveness of Longer‐Term Phentermine Use: Clinical Outcomes from an Electronic Health Record Cohort

The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer-term phentermine use. Using electronic health record data, 13,972 adults were identified with a first phentermine fill in 2010 to 2015, creating exposure categories according to a patient's duration of use (referent: ≤ 3months). Multivariable linear models were used to compare percent weight loss across categories at 6, 12, and 24months, and Cox proportional hazards models were used to compare risk of composite CVD or death, up to 3years after starting phentermine. The cohort was 84% female and 45% white, with a mean (SD) baseline age 43.5 (10.7)years and BMI of 37.8 (7.2)kg/m2 . In multivariable models, longer-term users of phentermine experienced more weight loss; patients using continuously for > 12months lost 7.4% more than the referent group at 24months (P<0.001). The composite CVD or death outcome was rare (0.3%, 41 events), with no significant difference in hazard ratios between groups. Greater weight loss without increased risk of incident CVD or death was observed in patients using phentermine monotherapy for longer than 3months. Despite the limitations of the observational design, this study supports the effectiveness and safety of longer-term phentermine use for low-risk individuals.

The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related Macular Degeneration

To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P= .029). New users of any NSAIDs (HR= 0.79, 95% CI 0.68-0.93, P= .0039) and aspirin (HR= 0.82, 95% CI 0.70-0.97, P= .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.

Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk.

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden. The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.

Discontinuing Psychiatric Medications: A Survey of Long-Term Users.

Individuals undergoing long-term psychiatric treatment frequently choose to stop taking psychiatric medications. To enhance service user choice and prevent undesirable outcomes, this first U.S. survey of a large sample of longer-term users sought to increase knowledge about users' experience of medication discontinuation. A sample of 250 U.S. adults with a diagnosis of serious mental illness and a recent goal to stop up to two prescribed psychiatric medications, which they had taken for at least nine months, completed a web-based survey about experiences, strategies, and supports during discontinuation. About half (54%) met their goal of completely discontinuing one or more medications; 46% reported another outcome (use was reduced, use increased, or use stayed the same). Concerns about medications' effects (for example, long-term effects and side effects) prompted the decision to discontinue for 74% of respondents. They used various strategies to cope with withdrawal symptoms, which 54% rated as severe. Self-education and contact with friends and with others who had discontinued or reduced medications were most frequently cited as helpful. Although more than half rated the initial medication decision with prescribers as largely collaborative, only 45% rated prescribers as helpful during discontinuation. Of respondents who completely discontinued, 82% were satisfied with their decision. Discontinuing psychiatric medication appears to be a complicated and difficult process, although most respondents reported satisfaction with their decision. Future research should guide health care systems and providers to better support patient choice and self-determination regarding the use and discontinuation of psychiatric medication.

Correlates of Trail Use for Recreation and Transportation on 5 Massachusetts Trails.

Promoting use of community trails is a recommended strategy for increasing population levels of physical activity. Correlates of walking and cycling for recreation or transportation differ, though few studies have compared correlates of trail-based physical activity for recreation and transportation purposes. This study examined associations of demographic, social, and perceived built environmental factors with trail use for recreation and transportation and whether associations were moderated by age, gender, and prior trail use. Adults (N = 1195) using 1 of 5 trails in Massachusetts responded to an intercept survey. We used multiple linear and logistic regression models to examine associations with trail use. Respondents' mean age was 44.9 years (standard deviation = 12.5), 55.3% were female, and 82.0% were white. Age (longer-term users only), trail use with others, travel time to the trail, and trail design were significantly associated with use for recreation (P < .05). Age, gender, trail safety (longer-term users only), travel time to the trail, trail design (younger users only), and trail beauty were associated with use for transportation (P < .05). Some common correlates were found for recreational and transportation trail use, whereas some variables were uniquely associated with use for 1 purpose. Tailored strategies are suggested to promote trail use for recreation and transportation.

In patients with minimally symptomatic OSA can baseline characteristics and early patterns of CPAP usage predict those who are likely to be longer-term users of CPAP.

Long-term continuous positive airway pressure (CPAP) usage varies between individuals. It would be of value to be able to identify those who are likely to benefit from CPAP (and use it long term), versus those who would not, and might therefore benefit from additional help early on. First, we explored whether baseline characteristics predicted CPAP usage in minimally symptomatic obstructive sleep apnoea (OSA) patients, a group who would be expected to have low usage. Second, we explored if early CPAP usage was predictive of longer-term usage, as has been shown in more symptomatic OSA patients. The MOSAIC trial was a multi-centre randomised controlled trial where minimally symptomatic OSA patients were randomised to CPAP, or standard care, for 6 months. Here we have studied only those patients randomised to CPAP treatment. Baseline characteristics including symptoms, questionnaires [including the Epworth sleepiness score (ESS)] and sleep study parameters were recorded. CPAP usage was recorded at 2-4 weeks after initiation and after 6 months. The correlation and association between baseline characteristics and 6 months CPAP usage was assessed, as was the correlation between 2 and 4 weeks CPAP usage and 6 months CPAP usage. One hundred and ninety-five patients randomised to CPAP therapy had median [interquartile range (IQR)] CPAP usage of 2:49 (0:44, 5:13) h:min/night (h/n) at the 2-4 weeks visit, and 2:17 (0:08, 4:54) h/n at the 6 months follow-up visit. Only male gender was associated with increased long-term CPAP use (male usage 2:56 h/n, female 1:57 h/n; P=0.02). There was a moderate correlation between the usage of CPAP at 2-4 weeks and 6 months, with about 50% of the variability in long-term use being predicted by the short-term use. In patients with minimally symptomatic OSA, our study has shown that male gender (and not OSA severity or symptom burden) is associated with increased long-term use of CPAP at 6 months. Although, in general, early patterns of CPAP usage predicted longer term use, there are patients in whom this is not the case, and patients with low initial usage may need to extend their CPAP trial before a decision about longer-term use is made.

Prevalence of NRT use and associated nicotine intake in smokers, recent ex-smokers and longer-term ex-smokers.

BackgroundNicotine replacement therapy (NRT) is used by smokers wanting to reduce their smoking and to quit. However, there are very little data on nicotine intake associated with NRT use in representative population samples. This study aimed to provide estimates for NRT use and associated nicotine exposure among smokers, recent and longer-term ex-smokers in England, a country with a permissive regulatory regime for nicotine substitution.MethodsIn the Smoking Toolkit Study, a monthly series of representative household surveys of adults aged 16+ in England, current and recent ex-smokers who agreed to be re-contacted were followed up 6 months later and standard socio-demographic and smoking characteristics assessed (N = 5,467, response rate 25.1%). A random sub-sample (N = 1,614; 29.5%) also provided saliva, analysed for cotinine.ResultsThe sample followed up was broadly representative of the original sample. At follow-up, 11.8% (95%CI 10.9–12.8, N = 565) of current smokers, 34.8% (95%CI 28.9–41.3, N = 77) of recent (≤3 months) ex-smokers, and 7.8% (95%CI 5.6–10.6, N = 36) of longer-term (>3 months) ex-smokers reported using NRT. Smokers who used NRT had similar saliva cotinine concentrations to smokers who did not use NRT (mean ± sd = 356.0±198.6 ng/ml vs. 313.1±178.4 ng/ml). Recent ex-smokers who used NRT had levels that were somewhat lower, but not significantly so, than current smokers (216.7±179.3 ng/ml). Longer-term ex-smokers using NRT had still lower levels (157.3±227.1 ng/ml), which differed significantly from smokers using NRT (p = 0.024).ConclusionsConcurrent use of nicotine replacement therapy while smoking is relatively uncommon and is not associated with higher levels of nicotine intake. Among ex-smokers, NRT use is common in the short but not longer-term and among longer-term users is associated with lower nicotine intake than in smokers.

PC-FACS

PC-FACS

Measuring Clinical Change in Routine Mental Health Care: Differences Between First Time and Longer Term Service Users

The aims were to assess the feasibility of routinely collecting outcome data in everyday mental health services across Italy and to evaluate clinical change in a cohort of patients stratified by illness duration. A prevalence sample of patients attending nine Italian community mental health services (CMHS) was assessed over one year with the Health of the Nation Outcome Scales (HoNOS). The patients were classified on the basis of the duration of their contact with services. Clinical outcome was evaluated taking into account parameters of reliable and clinically significant change (RCSC). Predictors of change included clinical and socio-demographic characteristics at first assessment and six month reliable improvement. 2059 patients were evaluated with only 3% attrition at follow up; 22% of first time and about 7% of longer term users achieved reliable improvement at one year. First contacts had a better outcome than longer term users and significant differences were seen at both group and individual level. Reliable improvement at six months was the best predictor of clinical improvement at one year for the whole cohort. The study demonstrated the feasibility of routine outcome assessment and gave an expected and realistic picture of the one-year outcome of a representative sample of patients attending a group of Italian CMHS. RCSC showed potential utility as a means of communicating with clinicians and decision makers.

Cohesive subgroups and drug user networks in Dhaka City, Bangladesh

The purpose of this paper was to explore group drug taking behaviour in a slum area of Dhaka, Bangladesh. We set out to examine the relationships between those who met, at least weekly, to take illegal drugs together, and how these relationships might shape their drug behaviour. Sociometric and behavioural data were collected using questionnaires via semi-structured interviews. We found that the likelihood of injecting drugs and sharing needles increased with age, duration of group membership and length of drug use. Drug users were classified into two clusters: one was more cohesive and comprised longer-term users, who were more likely to inject drugs and had poorer physical and mental health. The other cluster comprised younger, better educated members who were more transient, less cohesive, less likely to inject drugs and had better health. Qualitative data suggested that members of the first cluster were less accepting of outsiders and confirmed more to group norms. We conclude that emotionally bonded cohesive subgroups acquire norms, which reinforce problematic drug-using behaviour. Thus, health initiatives need to consider group relationships and norms and those initiatives which work with networks may be more effective and more appropriate for low-income countries.

The informal use of ketum ( Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy

Background Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used. Methods A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use. Findings Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance. Conclusions No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.

Epidemiologic Evidence on Mobile Phones and Tumor Risk

This review summarizes and interprets epidemiologic evidence bearing on a possible causal relation between radiofrequency field exposure from mobile phone use and tumor risk. In the last few years, epidemiologic evidence on mobile phone use and the risk of brain and other tumors of the head in adults has grown in volume, geographic diversity of study settings, and the amount of data on longer-term users. However, some key methodologic problems remain, particularly with regard to selective nonresponse and inaccuracy and bias in recall of phone use. Most studies of glioma show small increased or decreased risks among users, although a subset of studies show appreciably elevated risks. We considered methodologic features that might explain the deviant results, but found no clear explanation. Overall the studies published to date do not demonstrate an increased risk within approximately 10 years of use for any tumor of the brain or any other head tumor. Despite the methodologic shortcomings and the limited data on long latency and long-term use, the available data do not suggest a causal association between mobile phone use and fast-growing tumors such as malignant glioma in adults (at least for tumors with short induction periods). For slow-growing tumors such as meningioma and acoustic neuroma, as well as for glioma among long-term users, the absence of association reported thus far is less conclusive because the observation period has been too short.

Unopposed Estrogen Therapy and the Risk of Invasive Breast Cancer

Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period. Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline (1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer. A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor (ER+) and progesterone receptor (PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 (95% CI, 0.75-1.22), 0.90 (95% CI, 0.73-1.12), 1.06 (95% CI, 0.87-1.30), 1.18 (95% CI, 0.95-1.48), and 1.42 (95% CI, 1.13-1.77) (P for trend <.001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07). Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.

Hormone replacement therapy regimens and breast cancer risk

Objective: Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women’s Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use. Methods A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 con-trols) aged 35–64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. Results Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users ( P = .01). There were no positive associations between breast cancer risk and other HRT regimens. Conclusion Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

Third generation oral contraceptives and risk of venous thrombosis: meta-analysis

Objective: To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis.Design: Meta-analysis.Studies: Cohort and case-control studies assessing risk of venous thromboembolism...