A cohort study of acute pancreatitis in relation to exenatide use

Aim: Reports of acute pancreatitis associated with exenatide treatment prompted this study to estimate the association between acute pancreatitis and exenatide use relative to other antihyperglycaemic drugs. Methods: This cohort study included patients without claims for prior pancreatic disease who initiated exenatide or other antihyperglycaemic drugs between June 2005 and December 2007. Acute pancreatitis was identified with diagnosis codes and confirmed through review of blinded medical records. Poisson regression models provided estimates of rate ratios (RRs) and 95% confidence intervals (CIs) comparing the rate of acute pancreatitis during periods of current (days supplied + 31 days), recent (current definition + 31 days) and past use (≥32 days beyond current definition) of exenatide relative to other antihyperglycaemic drugs, adjusted for propensity scores. A prespecified nested case–control analysis provided RR estimates adjusted for patient characteristics abstracted from medical records. Results: Initiators of exenatide (N = 25719) had more baseline claims for obesity and concomitant diabetes drugs than comparators (N = 234536). There were 40 confirmed cases of acute pancreatitis in the exenatide cohort and 254 among other antihyperglycaemic drug initiators. Compared to other antihyperglycaemic drugs, the propensity score‐adjusted RR for exenatide was 0.5 (95% CI 0.2–0.9) for current use, 1.1 (95% CI 0.4–3.2) for recent use and 2.8 (95% CI 1.6–4.7) for past use. The case–control analysis resulted in a RR of 0.2 for current use (95% CI 0.0–1.4) and 0.1 for recent use (95% CI 0.0–1.3), but an attenuated RR in the past use association (RR 1.1; 95% CI 0.1–11.0). Conclusions: Exenatide use was not associated with an increased risk of acute pancreatitis.     

Exogenous sex hormones and the risk of rheumatoid arthritis

The use of exogenous sex hormones in relation to the risk of rheumatoid arthritis (RA) was examined in a cohort of married nurses 30-55 years of age followed since 1976 in the Nurses' Health Study. Baseline information on the use of oral contraceptives, replacement estrogens, and other potential risk factors was obtained in 1976 and updated every 2 years. During 8 years of followup, 217 incident cases of polyarthritis were ascertained (115 RA and 102 undifferentiated polyarthritis). When compared with women who had never used oral contraceptives, the age-adjusted relative risk was 1.0 (95% confidence interval [CI] 0.7-1.3) for past users; however, too few women were currently using oral contraceptives for a reliable estimate of its effect. Among postmenopausal women, 123 cases of RA were reported. Compared with postmenopausal women who never used replacement estrogens, current users had an age-adjusted relative risk of 1.3 (95% CI 0.9-2.0), past users had an age-adjusted relative risk of 0.7 (95% CI 0.5-1.2), and ever users had a relative risk of 1.0 (95% CI 0.7-1.4). These data do not show a protective effect of past use of oral contraceptives or replacement estrogens for RA; however, a modest protective effect of current oral contraceptive use cannot be excluded.     

Smoking, smoking cessation, and risk of hip fracture in women

PURPOSE: To examine the effects of cigarette smoking and smoking cessation on the risk of hip fracture in women. PATIENTS AND METHODS: We studied 116,229 female nurses, 34 to 59 years of age at baseline in 1980, who were followed for up to 12 years. Smoking habits and the occurrence of incident hip fractures (n = 377) due to low or moderate trauma were self-reported on biennial mailed questionnaires. RESULTS: Compared with women who had never smoked, the age-adjusted relative risk (RR) of hip fracture among current smokers was 1.3 (95% confidence interval [CI] 1.0 to 1.7). The risk of hip fracture increased linearly (P = 0.09) with greater cigarette consumption (RR = 1.6, 95% CI 1.1 to 2.3 for 25 or more cigarettes per day). These associations were somewhat reduced by adjusting for other risk factors for osteoporosis (menopausal status, use of postmenopausal estrogen, physical activity, and intakes of calcium, alcohol, and caffeine): RR = 1.2, 95% CI 0.8 to 1.3 for all current smokers; RR = 1.4, 95% CI 0.9 to 2.1 for 25 or more cigarettes per day. Relative risks were further reduced when body mass index was added to the model. There was no apparent benefit from quitting smoking until 10 years after cessation. After 10 years, former smokers had a reduced risk of hip fracture (adjusted RR = 0.7, 95% CI 0.5 to 0.9) compared with current smokers. CONCLUSION: Smokers are at increased risk of hip fracture and their risk rises with greater cigarette consumption. Risk declines among former smokers, but the benefit is not observed until 10 years after cessation. Both the increased risk among current smokers and the decline in risk after smoking cessation are in part accounted for by differences in body weight.     

Cardiovascular Risks of Hormonal Contraceptives

In 2012, new information about arterial thrombosis (thrombotic stroke and myocardial infarction) and venous thromboembolism in users of hormonal contraceptives was published. A Danish study representing the experience of more than 1.6 million women reported only small, and statistically indistinguishable, differences in the relative risks of thrombotic stroke and acute myocardial infarction between current users of combined estrogen/progestin oral hormonal contraceptives containing different progestins and low (30–40 microgram) or very low (20–40 micrograms) doses of ethinyl estradiol. A United States study also found no differences in the risks of arterial thrombosis between users of low estrogen dose oral contraceptives containing levonorgestrel, norethrindrone, or norgestimate and formulations that deliver hormones transdermally or vaginally. The United States study provided further evidence about the risk of venous thromboembolism in users drosperinone-containing oral contraceptives and the norelgestromin—containing transdermal patch compared with other low estrogen hormonal contraceptives, although the aggregate of data remains inconclusive.     

Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: The Kame Project

BACKGROUND: The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin. OBJECTIVE: To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women. METHODS: A prospective observational study in a population-based cohort of older Japanese Americans (aged > or =65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use. RESULTS: Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, -0.41; SEM, 0.50; P =.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35). CONCLUSIONS: Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.     

Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study

BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1) and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION: Patients with chronic inflammatory bowel disease seem to be at increased risk of acute pancreatitis. Further validation and refinement of this registration-based study are needed.     

Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies

BackgroundTobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association.MethodsPubMed and Embase databases were searched for relevant studies up to April 13th^, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model.ResultsTen prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29–1.72, I² = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15–1.34, I² = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25–1.54, I² = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18–1.42, I² = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08–1.17, I² = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined.ConclusionsThese results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.     

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease

BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.     

Postmenopausal hormone therapy and cognitive function in healthy older women

OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.     

Unopposed estrogen therapy and the risk of invasive breast cancer

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.     

Genetic variants of coagulation factor XIII,postmenopausal estrogen therapy,and risk of nonfatal myocardial infarction

We hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction =.03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy.     

Antihypertensive medication and the risk of acute pancreatitis: the European case-control study on drug-induced acute pancreatitis (EDIP)

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors and diuretics have been associated with acute pancreatitis. We quantified the risk of acute pancreatitis associated with the use of antihypertensive medication in the European study on drug-induced acute pancreatitis (EDIP). MATERIAL AND METHODS: The EDIP study is a multicenter population-based European case-control investigation of the association between drug use and acute pancreatitis. Patients between 40 and 85 years of age hospitalized for acute pancreatitis were included in the study between 1 October 1994 and 31 December 1998. For each case, age- and gender-matched community controls were recruited. Detailed information on drug use and potential confounders (e.g. comorbidity, alcohol use) was obtained through a structured interview. RESULTS: In all, 724 patients with acute pancreatitis and 1791 community controls were identified and interviewed. Use of ACE inhibitors in the week prior to the index date was associated with an increased risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1-2.2). The risk of acute pancreatitis associated with ACE inhibitors increased with higher daily doses and was highest in the first 6 months of therapy. Calcium channel blockers increased the risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1-2.1) without an apparent dose- or response relationship. Loop and thiazide diuretic use was not associated with an increased risk of acute pancreatitis. Potassium-sparing diuretics elevated the risk of acute pancreatitis, albeit non-significantly. CONCLUSION: Use of ACE inhibitors is associated with a modest increase in the risk of acute pancreatitis during the first months of treatment.     

Decreased mortality in users of estrogen replacement therapy

In a prospective study of 8881 postmenopausal female residents of a retirement community in southern California, we evaluated in detail the relationship between estrogen use and overall mortality. After 7 1/2 years of follow-up, there had been 1447 deaths. Women with a history of estrogen use had 20% lower age-adjusted, all-cause mortality than lifetime nonusers (95% confidence interval, 0.70 to 0.87). Mortality decreased with increasing duration of use and was lower among current users than among women who used estrogens only in the distant past. Current users with more than 15 years of estrogen use had a 40% reduction in their overall mortality. Among oral estrogen users, relative risks of death could not be distinguished by specific dosages of the oral estrogen taken for the longest time. Women who had used estrogen replacement therapy had a reduced mortality from all categories of acute and chronic arteriosclerotic disease and cerebrovascular disease. This group of women had a reduced mortality from cancer, although this reduction was not statistically significant. The mortality from all remaining causes combined was the same in estrogen users and lifetime nonusers.     

Estrogen therapies,lipids, and the heart disease prevention controversy

One of the most highly unexpected reports in recent medical literature was the lack of benefit of estrogen-progestin replacement therapy in cardiovascular disease prevention in postmenopausal women. The ensuing negative view of hormone replacement therapy has now extended to all forms of postmenopausal hormone treatment, including estrogen alone. Is this pessimism justified? A review of the effects of estrogens and progestins on the estrogen-sensitive systems of the body can help explain why combined oral estrogen and low-dose continuous medroxyprogesterone acetate administration may not be the paradigm for all other forms of postmenopausal hormone replacement. Some of these effects include the following: progestins are anti-estrogens, as evidenced in their divergent effects on plasma lipids; not all progestins are equal in their effect on lipids and other physiologic functions; administration of any hormone by mouth is not physiologic; giving estrogen 10 to 15 years postmenopausally may be too late to prevent atherosclerosis. On the other hand, high doses of oral estrogen/progestin in the presence of high cardiovascular risk appear to promote atherosclerosis risk. Given the current evidence the common sense answer to the question of the benefit of estrogen is “it depends.” Until these and other points are formally addressed, the hypothesis that estrogen prevents heart disease remains open.     

Risk factors for mortality in middle-aged women

BACKGROUND: Many factors contribute to mortality in older women, but their relative importance and independent contribution have been poorly characterized. METHODS: From 1990 to 1992, we assessed demographics, lifestyle measures, prevalent disease, medication use, anthropometrics, vital signs, and physical function in 17 748 postmenopausal women. We used proportional hazards modeling to evaluate their association with mortality. RESULTS: During 9 years of follow-up, 1886 women (10.6%) died. The relative hazard (RH) of death was approximately 1.5 (95% confidence interval [CI], 1.5-1.6) per 5 years of age, 1.4 (95% CI, 1.2-1.6) for a history of heart disease, and 1.9 (95% CI, 1.6-2.3) for a history of breast cancer. Modifiable risk factors associated with mortality included smoking (RH, 3.7 [95% CI, 3.1-4.5] for current smokers with a > or =50 pack-year history) and systolic blood pressure (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile). Elevated waist-hip ratio was associated with higher mortality (RH, 1.3 [95% CI, 1.1-1.5], fifth vs first quintile), but obesity was associated with lower mortality (RH, 0.7 [95% CI, 0.6-0.9] for body mass index [calculated as weight in kilograms divided by the square of height in meters] of >35.0 vs 18.5-25.0). Poor results on the timed Up and Go Test, a measure of physical function, were also strongly associated with mortality (RH, 1.7 [95% CI, 1.4-2.0], fifth vs first quintile). CONCLUSIONS: Simple measures are sufficient to stratify postmenopausal women into groups at high and low risk of dying. Smoking, central obesity, blood pressure, and physical function are potentially modifiable risk factors, although clinical trials are required to demonstrate that change in these factors affects mortality.     

Postmenopausal hormone use and secondary prevention of coronary events in the nurses' health study. a prospective, observational study.

BACKGROUND: The Heart and Estrogen/progestin Replacement Study (HERS) was the first randomized clinical trial of combined hormone therapy and secondary prevention of coronary events. The trial had overall null results but reported an unexpected increased risk for recurrent events in the initial year, followed by a decrease during the final years. OBJECTIVE: To provide additional data on a time trend in risk for recurrent heart disease. DESIGN: A prospective, observational cohort study of secondary prevention of coronary heart disease. SETTING: Nurses' Health Study. PATIENTS: 2489 postmenopausal women with previous myocardial infarction or documented atherosclerosis; 213 cases of recurrent nonfatal myocardial infarction or coronary death were identified from 1976 through 1996. MEASUREMENTS: Information on hormone status and on recurrent disease was collected by using biennial questionnaires. Multivariable-adjusted relative risks and 95% CIs were calculated from logistic regression models. RESULTS: A trend of decreasing risk for recurrent major coronary heart disease events with increasing duration of hormone use was observed (P for trend = 0.002). For short-term current users, the multivariate-adjusted relative risk for major coronary heart disease was 1.25 (95% CI, 0.78 to 2.00) compared with never-users. However, after longer-term hormone use, the rate of second events was lower in current users than in never-users (relative risk, 0.38 [CI, 0.22 to 0.66]). No clear differences emerged between users of estrogen alone and users of estrogen combined with progestin. Overall, with up to 20 years of follow-up, the relative risk for a second event among current users of hormone therapy was 0.65 (CI, 0.45 to 0.95) compared with never-users. CONCLUSIONS: The risk for recurrent major coronary events seems to increase among short-term hormone users with previous coronary disease but to decrease with longer-term use.     

Postmenopausal estrogen therapy and depressive symptoms in older women

BACKGROUND: Evidence regarding the effect of postmenopausal estrogen therapy on mood is limited. METHODS: To determine whether postmenopausal estrogen therapy is associated with fewer depressive symptoms in elderly women, we conducted a cross-sectional study of 6,602 white women ages 71 years or older who were recruited from population-based listings in Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley, Pa. Use of estrogen and progestin was determined by interview. Participants completed the Geriatric Depression Scale short form (GDS) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. RESULTS: A total of 6.3% (72/1,150) of current estrogen users, 7.2% (142/1,964) of past estrogen users, and 9.0% (313/3,488) of never users reported 6 or more symptoms of depression (P=.004). Current estrogen users had a decreased risk of reporting 6 or more depressive symptoms, compared with not current (past or never) users of estrogen (odds ratio [OR], 0.7; 95% CI, 0.5 to 0.9; P=.01), adjusted for living alone, bilateral oophorectomy, current smoking, physical activity, social network, self-perceived health, cognitive function, functional status, and antidepressant use. However, excluding women who use estrogen or progestin alone, we were unable to find an association between current use of combined estrogen plus progestin therapy and depressive symptoms (adjusted OR, 0.8; 95% CI, 0.5 to 1.4; P=.5). CONCLUSIONS: This cross-sectional study found that current use of unopposed estrogen was associated with a decreased risk of depressive symptoms in older women. Additional studies are needed to understand the effect of combined estrogen and progestin therapy on the prevalence of depressive symptoms in older women. The members of the Study of Osteoporotic Fractures Research Group are listed in the Appendix. Dr. Whooley is supported by a Research Career Development Award from the Department of Veterans Affairs Health Services Research and Development Service. This study was supported by a grant from the American Federation for Aging Research and by Public Health Service grants AG05394, AG05407, AR35582, AR35583, AR35584, and NS36016.     

Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study

BACKGROUND: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. METHODS: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA-IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59-71 have been followed during 4 years. Among these women, 166 had already used HRT. RESULTS: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21-0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47-0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA-IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users (P=0.61). CONCLUSION: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.     

Timing of estrogen replacement therapy for optimal osteoporosis prevention.

To determine whether estrogen initiated at age 60 yr or later reduces rates of bone loss and fracture incidence, we performed a prospective cohort study of 6910 nonosteoporotic women, 65 yr of age or older. Estrogen use, medical history, lifestyle, and anthropometric data were obtained by questionnaire, interview and examination. We identified five patterns of estrogen use: never users (67%); past early users (started under age 60 yr with no current use; 23%); past late users (started at age 60 or later with no current use; 2%); current early users (started under age 60 yr with use both at baseline and 6 yr later; 6.7%); and current late users (started at age 60 or later with use at baseline and 6 yr later; 1.5%). Bone mineral density was measured at the total hip twice, an average of 3.5 yr apart, and at the calcaneus, an average of 5.7 yr apart. Incident nonspine fractures were validated by radiographic report. Bone mineral density was significantly higher among current users, compared with never and past users. The annual rate of hip bone loss was significantly lower in current early users (-0.22%/yr) and current late users (-0.35%/yr) in comparison with never users (-0.6%/yr), past early users (-0.6%/yr), and past late users (-0.72%/yr). During an average of 11.0 yr of follow-up, 1953 nonspine fractures were confirmed. The multiple-adjusted relative risk of nonspine fracture was 0.63 (95% confidence interval 0.51-0.78) among current early users and 0.75 (0.50-1.12) among current late users, compared with never users. Early initiation and long-term continuation of estrogen is associated with a reduction in the risk of nonspine fractures, and initiation at or after age 60 yr with long-term continuation may also be associated with a reduced fracture risk.