Postmenopausal Estrogen and Progestin Use and the Risk of Cardiovascular Disease
Francine Grodstein, Sc.D., Meir J. Stampfer, M.D., JoAnn E. Manson, M.D., Graham A. Colditz, M.B., B.S., Walter C. Willett, M.D., Bernard Rosner, Ph.D., Frank E. Speizer, M.D., and Charles H. Hennekens, M.D.
Background Estrogen therapy in postmenopausal women has beenassociated with a decreased risk of heart disease. There islittle information, however, about the effect of combined estrogenand progestin therapy on the risk of cardiovascular disease.
Methods We examined the relation between cardiovascular diseaseand postmenopausal hormone therapy during up to 16 years offollow-up in 59,337 women from the Nurses' Health Study, whowere 30 to 55 years of age at base line. Information on hormoneuse was ascertained with biennial questionnaires. From 1976to 1992, we documented 770 cases of myocardial infarction ordeath from coronary disease in this group and 572 strokes. Proportional-hazardsmodels were used to calculate relative risks and 95 percentconfidence intervals, adjusted for confounding variables.
Results We observed a marked decrease in the risk of major coronaryheart disease among women who took estrogen with progestin,as compared with the risk among women who did not use hormones(multivariate adjusted relative risk, 0.39; 95 percent confidenceinterval, 0.19 to 0.78) or estrogen alone (relative risk, 0.60;95 percent confidence interval, 0.43 to 0.83). However, therewas no significant association between stroke and use of combinedhormones (multivariate adjusted relative risk, 1.09; 95 percentconfidence interval, 0.66 to 1.80) or estrogen alone (relativerisk, 1.27; 95 percent confidence interval, 0.95 to 1.69).
Conclusions The addition of progestin does not appear to attenuatethe cardioprotective effects of postmenopausal estrogen therapy.
More than 30 epidemiologic studies have found that postmenopausalwomen who use estrogen are at lower risk for coronary diseasethan those who do not use estrogen1; however, most data arefor estrogen alone.2 Progestins added to estrogen reduce oreliminate the excess risk of endometrial cancer due to the unopposedeffect of estrogen.3 The use of progestins combined with estrogenis now common, but information about the risk of cardiovasculardisease associated with combined therapy is sparse.
Experimental data suggest that the addition of progestin maydiminish the apparent cardioprotective effect of hormone therapy.Progestins alone tend to raise low-density lipoprotein (LDL)cholesterol levels and lower high-density lipoprotein (HDL)cholesterol levels.4 In the Postmenopausal Estrogen/ProgestinInterventions trial,5 all hormone regimens lowered LDL cholesterollevels, but medroxyprogesterone acetate significantly attenuatedthe estrogen-induced increase in HDL cholesterol levels. Moreover,progestins tend to oppose estrogen's beneficial effects on arterialdilatation and blood flow.6
In an earlier report, we examined the relation between postmenopausalhormone therapy and cardiovascular disease on the basis of 10years of follow-up data from the Nurses' Health Study,2 butat the time of that analysis, few women were taking progestinwith estrogen. We now report on the relation between combinedhormone therapy and cardiovascular disease. Our analysis isbased on 16 years of follow-up data in 59,337 postmenopausalwomen participating in the Nurses' Health Study.
Methods
The Nurses' Health Study began in 1976, when 121,700 femalenurses, 30 to 55 years of age, completed a mailed questionnaireabout their use of postmenopausal hormones and their medicalhistory, including cardiovascular disease and associated riskfactors. We updated the information with biennial follow-upquestionnaires. Starting in 1980, we included questions aboutdiet and physical activity. Follow-up data were available forover 90 percent of the cohort.
Ascertainment of Hormone Use
In 1976, the study participants were asked whether they usedhormones after menopause and, if so, the duration of use. Beginningin 1978, we collected information on the type of hormone therapy,and beginning in 1980, we also asked about the dose of oralconjugated estrogen.
Documentation of Cardiovascular Disease
Cardiovascular disease was defined as nonfatal myocardial infarction,fatal coronary disease, coronary-bypass surgery or angioplasty,and fatal or nonfatal stroke occurring during the period betweenthe return of the 1976 questionnaire and June 1, 1992. Nurseswho reported a nonfatal infarction or stroke were asked forpermission to review their medical records. Nonfatal myocardialinfarctions were confirmed if the information in the medicalrecords met the criteria of the World Health Organization8 (symptomsplus either elevated cardiac-enzyme levels or diagnostic findingson electrocardiograms). Infarctions for which medical recordswere unavailable were defined as probable and included in theanalysis if they required hospitalization and were corroboratedby an interview or a letter from the subject. Infarctions ofindeterminate age discovered on routine examination were notincluded. Data on coronary-artery surgery were obtained fromthe study participants' reports alone.
Nonfatal strokes were confirmed if they were characterized inthe medical records as typical neurologic deficits that wererapid in onset and lasted at least 24 hours and if they metthe criteria of the National Survey of Stroke.9 We classifiedstrokes as ischemic strokes (defined as thrombotic or embolicocclusion of a cerebral artery), subarachnoid hemorrhages, orintraparenchymal hemorrhages. We excluded subdural hematomasand strokes caused by infection or neoplasia. Strokes for whichthe medical records were unavailable were defined as probablestrokes and included in the analysis if they required hospitalizationand were corroborated by letter or interview.
Most deaths were reported by the participants' families. Wesearched the National Death Index10 to identify deaths amongthe nonrespondents to each two-year questionnaire; data on mortalitywere more than 98 percent complete. For all deaths possiblyattributable to cardiovascular causes, we requested permissionfrom family members (subject to state regulations) to reviewthe medical records. A death was considered to be due to coronarydisease if the medical records or autopsy report confirmed afatal myocardial infarction or if coronary disease was listedon the death certificate as the underlying cause of death withoutanother, more plausible cause and if the nurse was known (fromhospital records, a family member's report, or another source)to have had coronary disease before death. In no case was thecause listed on the death certificate used as the sole criterionfor death due to coronary disease. Fatal strokes were confirmedon the basis of autopsy reports, hospital records, or deathcertificates listing stroke as the underlying cause.
The category of major coronary heart disease includes nonfatalmyocardial infarction and death due to coronary disease; similarly,the category of total stroke includes nonfatal and fatal casesof stroke. Confirmed and probable cases in each category wereanalyzed together; in this and previous analyses, the resultsfor probable cases were quite similar to those for confirmedcases.2 Eighty percent of the cases of major coronary diseaseand 73 percent of the cases of stroke were confirmed. All interviewsand reviews of medical records were conducted by investigatorswithout knowledge of the category of hormone use.
Study Population
Women who reported stroke, myocardial infarction, angina, orcancer (except skin cancer other than melanoma) on the 1976questionnaire were excluded from the analysis, because the diseasemay have caused them to alter their use of hormones. Similarly,women who reported such conditions on a subsequent questionnairewere excluded from further analysis. Thus, at the start of eachtwo-year interval, the base population included no women reportingthese conditions.
We classified women as postmenopausal from the time of naturalmenopause or a hysterectomy with a bilateral oophorectomy. Womenwho underwent a hysterectomy without a bilateral oophorectomywere considered postmenopausal when they reached the age atwhich natural menopause had occurred in 90 percent of the cohort(54 years among the smokers and 56 years among the nonsmokers).11The reported age at the time of menopause and the type of menopausewere highly accurate in this cohort.12
In 1976, a total of 21,726 postmenopausal women were includedin the analysis, and 37,611 women were added during follow-upas they became postmenopausal; 662,891 person-years of follow-upwere accrued from 1976 to 1992.
Statistical Analysis
For each participant, person-months were allocated to categoriesof hormone use according to the 1976 data and updated everytwo years (for progestin use and estrogen dose, follow-up beganin 1978 and 1980, respectively). Follow-up ended when cardiovasculardisease was first diagnosed, the participant died, or the lastquestionnaire was returned.
The primary analysis was based on incidence rates, with person-monthsof follow-up used as the denominator. We used relative riskas the measure of association; the relative risk was definedas the incidence rate of cardiovascular disease among womenin various categories of hormone use divided by the incidencerate among women who never used hormones. We computed age-specificrates using five-year categories and calculated age-adjustedrelative risks with 95 percent confidence intervals.13 Testsof trends across categories of exposure were calculated by treatingthe levels of exposure as a continuous, ordinal variable inthe regression model.
Proportional-hazards models14 were used to calculate relativerisks, with adjustments for age, age at menopause, body-massindex (the weight in kilograms divided by the square of theheight in meters), cigarette smoking, hypertension, diabetes,elevated cholesterol levels, myocardial infarction in a parentbefore the age of 60 years, prior use of oral contraceptives,type of menopause (natural or surgical), and two-year interval(eight categories). For certain analyses, saturated-fat intake(in quintiles), alcohol use (none, <5 g, 5 to 14.9 g, or>15 g per day), use of vitamin E (none, <100 IU, 100 to299 IU, 300 to 599 IU, or >600 IU per day) or multivitamins(yes or no), use of aspirin (none or 1 to 6 pills or >7 pillsa week), and physical activity (none or at least once per week)were added to the model (with follow-up from 1980 to 1992, becauseinformation on these additional variables was not availablebefore 1980). Rate differences (the excess number of cases attributableto the nonuse of hormones per 100,000 person-years) were calculatedin strata of risk groups (e.g., cigarette smokers and nonsmokers)as the difference between the incidence rates among hormoneusers and nonusers (i.e., those who had never used hormones),standardized to the age distribution among nonusers withoutthe specified risk factor (e.g., nonsmokers).
Results
We documented 584 nonfatal myocardial infarctions, 186 deathsdue to coronary disease, 572 strokes (285 ischemic events, 155subarachnoid hemorrhages, and 132 other or unspecified types),and 553 instances of coronary surgery or angioplasty. Womenwho had never used hormones accounted for 49.0 percent of theperson-years of follow-up, current users for 25.1 percent (threefourths of whom used estrogen alone, and one fourth estrogenwith progestin), and past users for 22.7 percent; informationwas missing for 3.2 percent of the follow-up time.
Current hormone users, regardless of whether they used estrogenalone or with progestin, tended to have a better risk profilethan women who had never used hormones (Table 1). Fewer currentusers had a parental history of myocardial infarction, had diabetes,or smoked cigarettes. Current users also took multivitamins,vitamin E, and aspirin more often than women who had never usedhormones, were slightly younger and leaner, and drank more alcohol.However, current users reported a greater intake of saturatedfat and were more likely to have high serum cholesterol levels.
Table 1. Age-Standardized Distribution of Characteristics of Women Participating in the Nurses' Health Study in 1990, According to the Use or Nonuse of Postmenopausal Hormones.
Among current users of oral conjugated estrogen alone, as comparedwith women who had never used hormones, the age-adjusted relativerisk of major coronary disease was 0.45 (95 percent confidenceinterval, 0.34 to 0.60) (Table 2). With adjustment for cardiovascularrisk factors, the relative risk was 0.60, largely because currentusers were leaner and less likely to smoke. However, adjustmentfor age as a continuous variable did not further change theestimates of relative risk. Among the women who used estrogenwith progestin, there was also a marked decrease in the riskof major coronary disease (multivariate adjusted relative risk,0.39; 95 percent confidence interval, 0.19 to 0.78).
Table 2. Relative Risk of Cardiovascular Disease among Current Users of Conjugated Estrogen Alone or with Progestin as Compared with Nonusers, 1978 to 1992.
We found little association between the risk of stroke of anytype and current use of estrogen alone (relative risk, 1.27,as compared with women who had never used hormones) or estrogenwith progestin (relative risk, 1.09). There was an increasein the risk of ischemic stroke among current users of estrogenalone (relative risk, 1.63; 95 percent confidence interval,1.10 to 2.39) and current users of the combined regimen (relativerisk, 1.42; 95 percent confidence interval, 0.73 to 2.75). Forsubarachnoid hemorrhage, we found no decrease in risk amongcurrent users of estrogen alone (relative risk, 1.35); amongusers of estrogen with progestin, there was a nonsignificantdecrease in the risk of hemorrhagic stroke (relative risk, 0.53),but the data were based on only three cases of stroke amongwomen using the combined regimen.
In subsequent analyses, we combined the data on use of estrogenalone and use of estrogen with progestin, since the resultswere similar for the two types of hormone therapy. The multivariateadjusted relative risk of major coronary disease was 0.60 forcurrent hormone use, but 0.85 for past use (Table 3). Thesefindings are similar to the results of our follow-up at 10 years.2Additional adjustment for dietary variables, use of vitaminsupplements, use of aspirin, and physical activity did not substantiallyalter these estimates (relative risk of major coronary diseaseamong current users, 0.65; 95 percent confidence interval, 0.50to 0.84). We did not include these factors in further analyses,because we would have had to limit the follow-up, since dietaryinformation was first requested in 1980. There was no relationbetween coronary bypass or angioplasty and current hormone use(relative risk, 0.99; 95 percent confidence interval, 0.78 to1.26), as was also noted in our 10-year follow-up.2
Table 3. Relative Risk of Cardiovascular Disease among Current and Past Hormone Users as Compared with Nonusers, 1976 to 1992.
We found no decrease in the risk of stroke among current orpast hormone users, as compared with nonusers; there was thesuggestion of an increased risk of ischemic stroke among currentusers (Table 3).
Among current users, a longer period of use was not associatedwith any apparent trend toward a further reduction in the riskof either major coronary disease or stroke (P for trend, 0.73for both). With less than 2 years of current use, the relativerisk of coronary disease was 0.53 (95 percent confidence interval,0.31 to 0.93), and with 10 or more years of use, the risk was0.70 (95 percent confidence interval, 0.47 to 1.04). The relativerisk of a stroke of any type among the long-term users was 1.01(95 percent confidence interval, 0.69 to 1.46). The data onthe duration of use are available elsewhere (*).
The benefit of hormone use in providing protection against coronarydisease appeared to diminish somewhat 3 or more years afterthe cessation of hormone use (Figure 1): the relative risk ofcoronary disease among women who had stopped using hormonesless than 3 years earlier as compared with women who had neverused hormones was 0.69 (95 percent confidence interval, 0.48to 1.00), and it was 0.81 (95 percent confidence interval, 0.54to 1.21) for those who had stopped using hormones 3 to 4.9 yearsearlier (P for trend, 0.05).
Figure 1. Relative Risk of Major Coronary Heart Disease among Current Hormone Users and among Past Users, According to the Interval since Last Use.
Data are for the period from 1976 to 1992. Horizontal bars indicate relative risks, and vertical bars 95 percent confidence intervals.
We also examined the risk of coronary disease according to thecurrent dose of oral conjugated estrogen (Table 4). There wasan inverse association between coronary disease and estrogentherapy at doses of 0.3 and 0.625 mg (relative risk, 0.57 and0.53, respectively), but this association was diminished athigher doses. Although we found little apparent overall relationbetween the risk of stroke and the dose of oral conjugated estrogen,there was a trend toward an increased risk with higher doses(P for trend, 0.047).
Table 4. Relative Risk of Cardiovascular Disease among Current Hormone Users as Compared with Women Who Never Used Hormones, According to the Dose of Estrogen, 1980 to 1992.
We performed an analysis to determine whether the effect ofhormones on the risk of major coronary disease varied in specificsubgroups of women (Table 5). The protective effect appearedto be similar in most subgroups. Even among women who were 60to 71 years old, the risk of coronary disease was lower amongcurrent users than among nonusers (relative risk, 0.66); inour 10-year follow-up,2 we had found a nonsignificant increasein the risk among the women in this age group, although thenumbers were small. In addition, estrogen use was inverselyrelated to the risk of coronary disease among women, regardlessof whether they had diabetes or a parental history of heartdisease, used aspirin daily, or exercised regularly. Among low-riskwomen (those who had a body-mass index in the first to fourthquintiles; did not have diabetes, hypertension, or hypercholesterolemia;and were not current smokers), the relative risk of coronarydisease was 0.67 (95 percent confidence interval, 0.34 to 1.32)for current hormone users, as compared with women who had neverused hormones.
Table 5. Relative Risk of Coronary Heart Disease and Rate Differences among Current Hormone Users as Compared with Women Who Never Used Hormones, According to Categories of Risk Factors.
Women who use hormones must see a physician, which may account,in part, for the apparent benefit of hormones. In 1978, 1988,and 1990, however, we asked the study participants whether theyhad visited a physician in the previous two years; in the subgroupof women who reported a visit in each period (accounting for50 percent of the follow-up time), the relative risk of majorcoronary disease among the current hormone users was 0.52 (95percent confidence interval, 0.37 to 0.74), as compared withthe women who had never used hormones.
Even though the relative risks were similar regardless of thepresence or absence of coronary risk factors, the number ofcases of coronary disease per 100,000 women-years that couldhave been avoided if hormones had been used was higher amongthe women with risk factors than among those without risk factors(Table 5).
Discussion
In this large prospective study, the risk of major coronarydisease was substantially decreased among current users of estrogenand progestin, as well as among current users of estrogen alone.Neither estrogen alone nor combined therapy substantially affectedthe risk of stroke, although there was a suggestion of an increasedrisk in the subgroup of women taking the highest doses of oralconjugated estrogen. The associations were unrelated to theduration of hormone use, and the protective benefit diminishedsomewhat three years after cessation of hormone therapy. Ingeneral, women with risk factors for heart disease and thosewithout risk factors had similar relative risks, but the absoluterate differences were greater among the women with risk factors.
Although we did not validate self-reported hormone use, we believethe reports were accurate, because all the study participantsare registered nurses with a demonstrated interest in medicalresearch. Moreover, the prospective design eliminates recallbias, which can be a problem in case–control studies.
A primary concern is whether hormone users are different fromnonusers (i.e., women who have never used hormones) in waysthat may influence the risk of heart disease. Women who takehormones see a physician regularly, and these visits may themselvesresult in a decreased risk of coronary disease. For example,in a study of upper-middle-class women, estrogen users reportedundergoing more screening tests, such as blood cholesterol measurementsand mammography, than nonusers.15 In our study, however, theproportions of women who reported having had blood pressureand blood cholesterol checks in 1988 were only slightly largeramong the hormone users (83 percent and 72 percent, respectively)than among the nonusers (78 percent and 61 percent, respectively).Furthermore, when we limited our analysis to women who reporteda visit to a physician in 1978, 1988, and 1990, the resultsstill showed a strong protective effect of hormone use.
Women who take hormones are a self-selected group and usuallyhave healthier lifestyles with fewer risk factors than womenwho do not take hormones. In general-population samples, hormoneusers, as compared with nonusers, have more years of education,are leaner, drink more alcohol, and participate in sports moreoften,16 even before starting to use hormones.17 However, thesecharacteristics are due primarily to socioeconomic factors,since women who take hormones can generally afford medical care.Participants in the Nurses' Health Study are relatively homogeneousin terms of education. Although the current hormone users hada somewhat better risk profile, an analysis adjusted for manyrisk factors still yielded a strong inverse association betweencurrent hormone use and major coronary disease. Unknown confoundersmay have influenced our results, but to explain the apparentbenefit on the basis of confounding variables, one must postulateunknown risk factors that are extremely strong predictors ofdisease and closely associated with hormone use.
A substantial body of biologic data supports the role of estrogenin reducing the risk of coronary disease,4,18,19,20,21,22,23,24but the effect of progestin added to estrogen is less clear.Miller et al.18 found that the estrogen-induced elevation inHDL cholesterol levels was attenuated by 14 to 17 percent withthe addition of progestin, although there was little changein the estrogen-induced reduction in LDL cholesterol levels.In the Postmenopausal Estrogen/Progestin Interventions trial,5875 women were randomly assigned to receive placebo, oral estrogenalone, or one of three estrogen–progestin regimens. HDLcholesterol levels were increased and LDL cholesterol levelswere decreased in all the treatment groups. The decreases inLDL cholesterol levels were similar for all regimens, but theHDL cholesterol levels were significantly less elevated in thewomen who took estrogen with medroxyprogesterone acetate thanin those who took estrogen alone.
In a study of monkeys given either estrogen alone or estrogencombined with progestin, there was a reduction of approximately50 percent in the extent of coronary atherosclerosis after 30months in both groups, as compared with monkeys given placebo.25In addition, cholesterol-fed rabbits given estrogen alone orestrogen with progestin had similar decreases in aortic cholesterolaccumulation, as compared with rabbits given placebo.26 In ovariectomizedewes, however, estrogen-induced increases in uterine blood flowwere reduced by 20 to 35 percent with the addition of progestin;the withdrawal of progestin immediately restored the flow.6
The few epidemiologic studies of estrogen with progestin forthe most part found an inverse association between combinedtherapy and the risk of coronary disease. In two British studies,compounds other than conjugated estrogen were frequently used;Hunt et al. reported a lower risk in hormone users than in thegeneral population,27 whereas Thompson et al. reported nullfindings in a case–control study.28 In a clinical trialinvolving 168 women, Nachtigall et al.29 reported a lower incidenceof myocardial infarction in women given estrogen and cyclicprogestin than in those given placebo (relative risk, 0.32;P>0.05), although there was only one case of infarction inthe treatment group. In a population-based case–controlstudy, Psaty et al.30 reported similarly decreased risks ofmyocardial infarction among current users of estrogen alone(relative risk, 0.69; 95 percent confidence interval, 0.47 to1.02) and current users of estrogen with progestin (relativerisk, 0.68; 95 percent confidence interval, 0.38 to 1.22). Ina prospective analysis of health care records in Uppsala, Sweden,Falkeborn et al. found that women given a prescription for anestradiol–levonorgestrel combination had a 50 percentlower risk of myocardial infarction than women in the generalpopulation of that region31; among the women given a prescriptionfor estrogen alone, the relative risk was 0.74.
The data on stroke are unclear. In the Leisure World study,32the relative risk of mortality from stroke was 0.3 among currentestrogen users as compared with women who had never used estrogen(P<0.05). Falkeborn et al.33 reported that the relative riskof stroke was 0.72 among women taking estrogen and 0.61 amongthose taking combined hormones. In our study, however, therewas no decrease in the risk of stroke among hormone users, regardlessof whether they used estrogen alone or with progestin, and therewas the suggestion of an increased risk associated with theuse of high doses of estrogen. Similarly, a large prospectivestudy in Copenhagen, Denmark,34 found little association betweenthe risk of stroke and hormone use (relative risk, 0.8; 95 percentconfidence interval, 0.4 to 1.4). At present, the data are stilltoo sparse to clarify the effect of hormones on the risk ofstroke.
In conclusion, the addition of progestin to estrogen does notappear to attenuate the cardioprotective effects of hormonetherapy in relatively young postmenopausal women. This issuewill be addressed more directly in the next decade, when theresults of clinical trials, such as the Women's Health Initiative,are known. Any cardiovascular benefits of postmenopausal hormoneuse, however, must be evaluated in the light of possible risks,such as an increased risk of breast cancer, particularly amonglong-term current users and older women.35
Supported by grants (CA 40356 and HL 30594) from the NationalInstitutes of Health.
* See NAPS document no. 05320 for 2 pages of supplementary material.To order, contact NAPS c/o Microfiche Publications, 248 HempsteadTpk., West Hempstead, NY 11552.
Source Information
From the Channing Laboratory (F.G., M.J.S., J.E.M., G.A.C., W.C.W., B.R., F.E.S.), the Division of Preventive Medicine (J.E.M., C.H.H.), and the Departments of Medicine and Ambulatory Care and Prevention (C.H.H.), Brigham and Women's Hospital and Harvard Medical School; and the Departments of Epidemiology (F.G., M.J.S., J.E.M., G.A.C., W.C.W.), Nutrition (M.J.S., W.C.W.), and Biostatistics (B.R.), Harvard School of Public Health — all in Boston.
Address reprint requests to Dr. Grodstein at the Channing Laboratory, 180 Longwood Ave., Boston, MA 02115.
References
Grodstein F, Stampfer MJ. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995;38:199-210. [CrossRef][Medline]
Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses' Health Study. N Engl J Med 1991;325:756-762. [Abstract]
Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-1037.
Bush TL, Miller VT. Effects of pharmacologic agents used during menopause: impact on lipids and lipoproteins. In: Mishell D Jr, ed. Menopause: physiology and pharmacology. Chicago: Year Book Medical, 1986:187-208.
The Postmenopausal Estrogen/Progestin Interventions Trial Writing Group. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. JAMA 1995;273:199-208. [Abstract]
Sarrel PM. Blood flow. In: Lobo RA, ed. Treatment of the postmenopausal woman: basic and clinical aspects. New York: Raven Press, 1994:251-62.
Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51-65. [Free Full Text]
IHD register: report of the fifth working group. Copenhagen, Denmark: World Health Organization, 1971.
Walker AE, Robins M, Weinfeld FD. The National Survey of Stroke: clinical findings. Stroke 1981;12:Suppl 1:I-13.
Stampfer MJ, Willett WC, Speizer FE, et al. Test of the National Death Index. Am J Epidemiol 1984;119:837-839. [Free Full Text]
Willett WC, Stampfer MJ, Bain C, et al. Cigarette smoking, relative weight, and menopause. Am J Epidemiol 1983;117:651-658. [Free Full Text]
Colditz GA, Stampfer MJ, Willett WC, et al. Reproducibility and validity of self-reported menopausal status in a prospective cohort study. Am J Epidemiol 1987;126:319-325. [Free Full Text]
Rothman KJ, Boice JD. Epidemiologic analysis with a programmable calculator. Washington, D.C.: Government Printing Office, 1979. (NIH publication no. (PHS) 79-1649.)
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med 1991;115:455-456.
Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG. Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol 1990;163:1438-1444. [Medline]
Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol 1996;143:971-978. [Free Full Text]
Miller VT, Muesing RA, LaRosa JC, Stoy DB, Phillips EA, Stillman RJ. Effects of conjugated equine estrogen with and without three different progestogens on lipoproteins, high-density lipoprotein subfractions, and apolipoprotein A-1. Obstet Gynecol 1991;77:235-240. [Free Full Text]
Wagner JD, Clarkson TB, St Clair RW, Schwenke DC, Shively CA, Adams MR. Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys. J Clin Invest 1991;88:1995-2002.
Sarrel PM, Lindsay D, Rosano GMC, Poole-Wilson PA. Angina and normal coronary arteries in women: gynecologic findings. Am J Obstet Gynecol 1992;167:467-471. [Medline]
Pines A, Fisman EZ, Levo Y, et al. The effects of hormone replace-ment therapy in normal postmenopausal women: measurements of Doppler-derived parameters of aortic flow. Am J Obstet Gynecol 1991;164:806-812. [Medline]
Gangar KF, Vyas S, Whitehead M, Crook D, Meire H, Campbell S. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet 1991;338:839-842. [CrossRef][Medline]
Sack MN, Rader DJ, Cannon RO III. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 1994;343:269-270. [CrossRef][Medline]
Adams MR, Kaplan JR, Manuck SB, et al. Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys: lack of an effect of added progesterone. Arteriosclerosis 1990;10:1051-1057. [Free Full Text]
Haarbo J, Leth-Espensen P, Stender S, Christiansen C. Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. J Clin Invest 1991;87:1274-1279.
Hunt K, Vessey M, McPherson K. Mortality in a cohort of long-term users of hormone replacement therapy: an updated analysis. Br J Obstet Gynaecol 1990;97:1080-1086. [Medline]
Thompson SG, Meade TW, Greenberg G. The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women. J Epidemiol Community Health 1989;43:173-178. [Free Full Text]
Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstet Gynecol 1979;54:74-79. [Medline]
Psaty BM, Heckbert SR, Atkins D, et al. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med 1994;154:1333-1339. [CrossRef][Medline]
Falkeborn M, Persson I, Adami HO, et al. The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. Br J Obstet Gynaecol 1992;99:821-828. [Medline]
Henderson BE, Paganini-Hill A, Ross RK. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med 1991;151:75-78. [CrossRef][Medline]
Falkeborn M, Persson I, Terent A, Adami HO, Lithell H, Bergstrom R. Hormone replacement therapy and the risk of stroke: follow-up of a population-based cohort in Sweden. Arch Intern Med 1993;153:1201-1209. [CrossRef][Medline]
Boysen G, Nyboe J, Appleyard M, et al. Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke 1988;19:1345-1353. [Free Full Text]
Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995;332:1589-1593. [Free Full Text]
Ho, P. M., Peterson, P. N., Masoudi, F. A.
(2008). Evaluating the Evidence: Is There a Rigid Hierarchy?. Circulation
118: 1675-1684
[Full Text]
Smith, A., Contreras, C., Ko, K. H., Chow, J., Dong, X., Tuo, B., Zhang, H.-h., Chen, D.-b., Dong, H.
(2008). Gender-Specific Protection of Estrogen against Gastric Acid-Induced Duodenal Injury: Stimulation of Duodenal Mucosal Bicarbonate Secretion. Endocrinology
149: 4554-4566
[Abstract][Full Text]
Sare, G. M., Gray, L. J., Bath, P. M.W.
(2008). Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis. Eur Heart J
29: 2031-2041
[Abstract][Full Text]
Bushnell, C. D., Lee, J., Duncan, P. W., Newby, L. K., Goldstein, L. B.
(2008). Impact of Comorbidities on Ischemic Stroke Outcomes in Women. Stroke
39: 2138-2140
[Abstract][Full Text]
Vitale, C., Mercuro, G., Cerquetani, E., Marazzi, G., Patrizi, R., Pelliccia, F., Volterrani, M., Fini, M., Collins, P., Rosano, G. M.C.
(2008). Time Since Menopause Influences the Acute and Chronic Effect of Estrogens on Endothelial Function. Arterioscler. Thromb. Vasc. Bio.
28: 348-352
[Abstract][Full Text]
Schutt, B., Kunz, M., Blode, H.
(2007). Coadministration of Estradiol/Drospirenone and Indomethacin Does Not Cause Hyperkalemia in Healthy Postmenopausal Women: A Randomized Open-Label Crossover Study. J Clin Pharmacol
47: 774-781
[Abstract][Full Text]
Warren, M. P.
(2007). Historical Perspectives in Postmenopausal Hormone Therapy: Defining the Right Dose and Duration. Mayo Clin. Proc.
82: 219-226
[Abstract][Full Text]
Paul, R. J., Bowman, P. S., Johnson, J., Martin, A. F.
(2007). Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta. Am. J. Physiol. Regul. Integr. Comp. Physiol.
292: R751-R757
[Abstract][Full Text]
Collins, P., Flather, M., Lees, B., Mister, R., Proudler, A. J., Stevenson, J. C., on behalf of the WHISP (Women's Hormone Interventi,
(2006). Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study. Eur Heart J
27: 2046-2053
[Abstract][Full Text]
Kim, J., Evans, S., Smeeth, L., Pocock, S.
(2006). Hormone replacement therapy and acute myocardial infarction: a large observational study exploring the influence of age. Int J Epidemiol
35: 731-738
[Abstract][Full Text]
Ouyang, P., Michos, E. D., Karas, R. H.
(2006). Hormone Replacement Therapy and the Cardiovascular System: Lessons Learned and Unanswered Questions. J Am Coll Cardiol
47: 1741-1753
[Abstract][Full Text]
Bots, M. L., Evans, G. W., Riley, W., McBride, K. H., Paskett, E. D., Helmond, F. A., Grobbee, D. E., for the OPAL Investigators,
(2006). The effect of tibolone and continuous combined conjugated equine oestrogens plus medroxyprogesterone acetate on progression of carotid intima-media thickness: the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study. Eur Heart J
27: 746-755
[Abstract][Full Text]
Jayachandran, M., Miller, V. M.
(2006). Mechanisms of estrogenic vascular protection. Am. J. Physiol. Heart Circ. Physiol.
290: H507-H508
[Full Text]
Caspard, H., Chan, A. K, Walker, A. M
(2006). Determinants of the Differences in LDL-Cholesterol After Initiation of Statin Treatment. The Annals of Pharmacotherapy
40: 21-26
[Abstract][Full Text]
Ballard, V. L., Edelberg, J. M.
(2005). Harnessing Hormonal Signaling for Cardioprotection. Sci Aging Knowl Environ
2005: re6-re6
[Abstract][Full Text]
Wassmann, K., Wassmann, S., Nickenig, G.
(2005). Progesterone Antagonizes the Vasoprotective Effect of Estrogen on Antioxidant Enzyme Expression and Function. Circ. Res.
97: 1046-1054
[Abstract][Full Text]
Sowers, M. R., Matthews, K. A., Jannausch, M., Randolph, J. F., McConnell, D., Sutton-Tyrrell, K., Little, R., Lasley, B., Pasternak, R.
(2005). Hemostatic Factors and Estrogen during the Menopausal Transition. J. Clin. Endocrinol. Metab.
90: 5942-5948
[Abstract][Full Text]
Petitti, D. B., Freedman, D. A.
(2005). Invited Commentary: How Far Can Epidemiologists Get with Statistical Adjustment?. Am J Epidemiol
162: 415-418
[Full Text]
Miller, V. M., Clarkson, T. B., Harman, S. M., Brinton, E. A., Cedars, M., Lobo, R., Manson, J. E., Merriam, G. R., Naftolin, F., Santoro, N.
(2005). Women, hormones, and clinical trials: a beginning, not an end. J. Appl. Physiol.
99: 381-383
[Full Text]
Davis, S R, Dinatale, I, Rivera-Woll, L, Davison, S
(2005). Postmenopausal hormone therapy: from monkey glands to transdermal patches. J Endocrinol
185: 207-222
[Abstract][Full Text]
Dubey, R. K., Imthurn, B., Barton, M., Jackson, E. K.
(2005). Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen. Cardiovasc Res
66: 295-306
[Abstract][Full Text]
Dubey, R. K., Imthurn, B., Zacharia, L. C., Jackson, E. K.
(2004). Hormone Replacement Therapy and Cardiovascular Disease: What Went Wrong and Where Do We Go From Here?. Hypertension
44: 789-795
[Abstract][Full Text]
Voci, P., Pizzuto, F., Romeo, F.
(2004). Coronary flow: a new asset for the echo lab?. Eur Heart J
25: 1867-1879
[Full Text]
Lochner, H. V., Einhorn, T. A.
(2004). Hormone Replacement Therapy. J Am Acad Orthop Surg
12: 291-294
[Full Text]
Smith, L. H., Coats, S. R., Qin, H., Petrie, M. S., Covington, J. W., Su, M., Eren, M., Vaughan, D. E.
(2004). Differential and Opposing Regulation of PAI-1 Promoter Activity by Estrogen Receptor {alpha} and Estrogen Receptor {beta} in Endothelial Cells. Circ. Res.
95: 269-275
[Abstract][Full Text]
Kalantaridou, S. N., Naka, K. K., Papanikolaou, E., Kazakos, N., Kravariti, M., Calis, K. A., Paraskevaidis, E. A., Sideris, D. A., Tsatsoulis, A., Chrousos, G. P., Michalis, L. K.
(2004). Impaired Endothelial Function in Young Women with Premature Ovarian Failure: Normalization with Hormone Therapy. J. Clin. Endocrinol. Metab.
89: 3907-3913
[Abstract][Full Text]
Jepsen, P, Johnsen, S P, Gillman, M W, Sorensen, H T
(2004). Interpretation of observational studies. Heart
90: 956-960
[Full Text]
Koh, K. K., Shin, M.-S., Sakuma, I., Ahn, J. Y., Jin, D. K., Kim, H. S., Kim, D. S., Han, S. H., Chung, W.-J., Shin, E. K.
(2004). Effects of Conventional or Lower Doses of Hormone Replacement Therapy in Postmenopausal Women. Arterioscler. Thromb. Vasc. Bio.
24: 1516-1521
[Abstract][Full Text]
Koga, M., Hirano, K., Nishimura, J., Nakano, H., Kanaide, H.
(2004). Endothelium-Dependent and Independent Enhancement of Vascular Contractility in the Ovariectomized Rabbit. Reproductive Sciences
11: 272-279
[Abstract]
Koh, K. K., Sakuma, I.
(2004). Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials?. Arterioscler. Thromb. Vasc. Bio.
24: 1171-1179
[Abstract][Full Text]
Col, N. F., Pauker, S. G.
(2004). The Discrepancy between Observational Studies and Randomized Trials of Menopausal Hormone Therapy. ANN INTERN MED
140: 765-766
[Full Text]
Canadian Task Force on Preventive Health Care,
(2004). Postmenopausal hormone replacement therapy for primary prevention of cardiovascular and cerebrovascular disease: Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ
170: 1388-1389
[Full Text]
Kirwan, L. D., MacLusky, N. J., Shapiro, H. M., Abramson, B. L., Thomas, S. G., Goodman, J. M.
(2004). Acute and Chronic Effects of Hormone Replacement Therapy on the Cardiovascular System in Healthy Postmenopausal Women. J. Clin. Endocrinol. Metab.
89: 1618-1629
[Abstract][Full Text]
Barr, R. G., Wentowski, C. C., Grodstein, F., Somers, S. C., Stampfer, M. J., Schwartz, J., Speizer, F. E., Camargo, C. A. Jr
(2004). Prospective Study of Postmenopausal Hormone Use and Newly Diagnosed Asthma and Chronic Obstructive Pulmonary Disease. Arch Intern Med
164: 379-386
[Abstract][Full Text]
Orshal, J. M., Khalil, R. A.
(2004). Gender, sex hormones, and vascular tone. Am. J. Physiol. Regul. Integr. Comp. Physiol.
286: R233-R249
[Abstract][Full Text]
Wynne, F. L., Payne, J. A., Cain, A. E., Reckelhoff, J. F., Khalil, R. A.
(2004). Age-Related Reduction in Estrogen Receptor-Mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats. Hypertension
43: 405-412
[Abstract][Full Text]
Kida, Y.
(2003). Age and Sex as Independent Risk Factors for Stroke Among Patients With Atrial Fibrillation. JAMA
290: 2937-2937
[Full Text]
Col, N. F., Pauker, S. G.
(2003). The Discrepancy between Observational Studies and Randomized Trials of Menopausal Hormone Therapy: Did Expectations Shape Experience?. ANN INTERN MED
139: 923-929
[Abstract][Full Text]
Fitzpatrick, L. A.
(2003). Hormones and the Heart: Controversies and Conundrums. J. Clin. Endocrinol. Metab.
88: 5609-5610
[Full Text]
Machens, K., Schmidt-Gollwitzer, K.
(2003). Issues to debate on the Women's Health Initiative (WHI) study. Hormone replacement therapy: an epidemiological dilemma?. Hum Reprod
18: 1992-1999
[Abstract][Full Text]
Mercier, I., Mader, S., Calderone, A.
(2003). Tamoxifen and ICI 182,780 negatively influenced cardiac cell growth via an estrogen receptor-independent mechanism. Cardiovasc Res
59: 883-892
[Abstract][Full Text]
Jokela, H., Dastidar, P., Rontu, R., Salomaki, A., Teisala, K., Lehtimaki, T., Punnonen, R.
(2003). Effects of Long-Term Estrogen Replacement Therapy Versus Combined Hormone Replacement Therapy on Nitric Oxide-Dependent Vasomotor Function. J. Clin. Endocrinol. Metab.
88: 4348-4354
[Abstract][Full Text]
Macleod, J, Davey Smith, G
(2003). Psychosocial factors and public health: a suitable case for treatment?. J. Epidemiol. Community Health
57: 565-570
[Abstract][Full Text]
Kishida, T., Miyazato, S., Ogawa, H., Ebihara, K.
(2003). Taurine Prevents Hypercholesterolemia in Ovariectomized Rats Fed Corn Oil but Not in Those Fed Coconut Oil. J. Nutr.
133: 2616-2621
[Abstract][Full Text]
Krieger, N., Grodstein, F., Manson, J., Clarkson, T. B.
(2003). Postmenopausal Hormone Therapy. NEJM
348: 2363-2364
[Full Text]
Colacurci, N., Manzella, D., Fornaro, F., Carbonella, M., Paolisso, G.
(2003). Endothelial Function and Menopause: Effects of Raloxifene Administration. J. Clin. Endocrinol. Metab.
88: 2135-2140
[Abstract][Full Text]
Lambert, L J, Straton, J A Y, Knuiman, M W, Bartholomew, H C
(2003). Health status of users of hormone replacement therapy by hysterectomy status in Western Australia. J. Epidemiol. Community Health
57: 294-300
[Abstract][Full Text]
Grodstein, F., Clarkson, T. B., Manson, J. E.
(2003). Understanding the Divergent Data on Postmenopausal Hormone Therapy. NEJM
348: 645-650
[Full Text]
Hurn, P. D., Brass, L. M.
(2003). Estrogen and Stroke: A Balanced Analysis. Stroke
34: 338-341
[Full Text]
Mize, A. L., Shapiro, R. A., Dorsa, D. M.
(2003). Estrogen Receptor-Mediated Neuroprotection from Oxidative Stress Requires Activation of the Mitogen-Activated Protein Kinase Pathway. Endocrinology
144: 306-312
[Abstract][Full Text]
Nussmeier, N. A., Marino, M. R., Vaughn, W. K.
(2002). Hormone replacement therapy is associated with improved survival in women undergoing coronary artery bypass grafting. J. Thorac. Cardiovasc. Surg.
124: 1225-1229
[Abstract][Full Text]
Bladbjerg, E.M., Skouby, S.O., Andersen, L.F., Jespersen, J.
(2002). Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor. Hum Reprod
17: 3235-3241
[Abstract][Full Text]
Stangl, V., Baumann, G., Stangl, K.
(2002). Coronary atherogenic risk factors in women. Eur Heart J
23: 1738-1752
[Full Text]
Busserolles, J., Mazur, A., Gueux, E., Rock, E., Rayssiguier, Y.
(2002). Metabolic Syndrome in the Rat: Females Are Protected Against the Pro-Oxidant Effect of a High Sucrose Diet. Exp. Biol. Med.
227: 837-842
[Abstract][Full Text]
Moreau, K. L., Donato, A. J., Seals, D. R., Dinenno, F. A., Blackett, S. D., Hoetzer, G. L., Desouza, C. A., Tanaka, H.
(2002). Arterial intima-media thickness: site-specific associations with HRT and habitual exercise. Am. J. Physiol. Heart Circ. Physiol.
283: H1409-H1417
[Abstract][Full Text]
Molero, L., Garcia-Duran, M., Diaz-Recasens, J., Rico, L., Casado, S., Lopez-Farre, A.
(2002). Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men: Regulation by estrogen. Cardiovasc Res
56: 43-51
[Abstract][Full Text]
Humphrey, L. L., Chan, B. K.S., Sox, H. C.
(2002). Postmenopausal Hormone Replacement Therapy and the Primary Prevention of Cardiovascular Disease. ANN INTERN MED
137: 273-284
[Abstract][Full Text]
Wakatsuki, A., Ogawa, Y., Saibara, T., Okatani, Y., Fukaya, T.
(2002). Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Breast Cancer Patients with Tamoxifen-Induced Fatty Liver. J. Clin. Endocrinol. Metab.
87: 3676-3681
[Abstract][Full Text]
Simoncini, T., Varone, G., Fornari, L., Mannella, P., Luisi, M., Labrie, F., Genazzani, A. R.
(2002). Genomic and Nongenomic Mechanisms of Nitric Oxide Synthesis Induction in Human Endothelial Cells by a Fourth-Generation Selective Estrogen Receptor Modulator. Endocrinology
143: 2052-2061
[Abstract][Full Text]
Ling, S., Dai, A., Williams, M. R. I., Myles, K., Dilley, R. J., Komesaroff, P. A., Sudhir, K.
(2002). Testosterone (T) Enhances Apoptosis-Related Damage in Human Vascular Endothelial Cells. Endocrinology
143: 1119-1125
[Abstract][Full Text]
Rossouw, J. E
(2002). Hormones, genetic factors, and gender differences in cardiovascular disease. Cardiovasc Res
53: 550-557
[Full Text]
Mikkola, T. S, Clarkson, T. B
(2002). Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res
53: 605-619
[Abstract][Full Text]
Babiker, F. A, De Windt, L. J, van Eickels, M., Grohe, C., Meyer, R., Doevendans, P. A
(2002). Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res
53: 709-719
[Abstract][Full Text]
Perera, M., Petrie, J.R., Hillier, C., Small, M., Sattar, N., Connell, J.M.C., Lumsden, M.A.
(2002). Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes. Hum Reprod
17: 497-502
[Abstract][Full Text]
Ospina, J. A., Krause, D. N., Duckles, S. P.
(2002). 17{beta}-Estradiol Increases Rat Cerebrovascular Prostacyclin Synthesis by Elevating Cyclooxygenase-1 and Prostacyclin Synthase. Stroke
33: 600-605
[Abstract][Full Text]
Brown, N. J., Abbas, A., Byrne, D., Schoenhard, J. A., Vaughan, D. E.
(2002). Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women. Circulation
105: 304-309
[Abstract][Full Text]
Hundrup, Y. A., Thoning, H., Obel, E. B., Rasmussen, N. K., Philip, J.
(2002). Lifestyle factors and choice of hormone replacement therapy among Danish nurses. Scand J Public Health
30: 47-53
[Abstract]
Nussmeier, N.A., Thong, W.Y., Marino, M.R., Williams, C.L., Vaughn, W.K.
(2002). Hormone replacement therapy improves the survival of women undergoing coronary artery bypass grafting. Ann. Thorac. Surg.
73: S371-371
[Full Text]
Voci, P., Pizzuto, F.
(2001). Coronary flow: how far can we go with echocardiography?. J Am Coll Cardiol
38: 1885-1887
[Full Text]
Mendelsohn, M. E., Karas, R. H.
(2001). The Time Has Come to Stop Letting the HERS Tale Wag the Dogma. Circulation
104: 2256-2259
[Full Text]
Shlipak, M. G., Angeja, B. G., Go, A. S., Frederick, P. D., Canto, J. G., Grady, D.
(2001). Hormone Therapy and In-Hospital Survival After Myocardial Infarction in Postmenopausal Women. Circulation
104: 2300-2304
[Abstract][Full Text]
Sitges, M, Heras, M, Roig, E, Duran, M, Masotti, M, Zurbano, M.J, Roque, M, Sanz, G
(2001). Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries. Eur Heart J
22: 2116-2124
[Abstract]
Viscoli, C. M., Brass, L. M., Kernan, W. N., Sarrel, P. M., Suissa, S., Horwitz, R. I.
(2001). A Clinical Trial of Estrogen-Replacement Therapy after Ischemic Stroke. NEJM
345: 1243-1249
[Abstract][Full Text]
Vega-Lopez, S., Vidal-Quintanar, R. L., Fernandez, M. L.
(2001). Sex and hormonal status influence plasma lipid responses to psyllium. Am. J. Clin. Nutr.
74: 435-441
[Abstract][Full Text]
Minshall, R. D., Pavcnik, D., Halushka, P. V., Hermsmeyer, K.
(2001). Progesterone regulation of vascular thromboxane A2 receptors in rhesus monkeys. Am. J. Physiol. Heart Circ. Physiol.
281: H1498-H1507
[Abstract][Full Text]
Liu, Y., Ding, J., Bush, T. L., Longenecker, J. C., Nieto, F. J., Golden, S. H., Szklo, M.
(2001). Relative Androgen Excess and Increased Cardiovascular Risk after Menopause: A Hypothesized Relation. Am J Epidemiol
154: 489-494
[Abstract][Full Text]
Monster, T. B. M., Janssen, W. M. T., de Jong, P. E., de Jong-van den Berg, L. T. W., for the Prevention of Renal and Vascular End Stage,
(2001). Oral Contraceptive Use and Hormone Replacement Therapy Are Associated With Microalbuminuria. Arch Intern Med
161: 2000-2005
[Abstract][Full Text]
Grodstein, F., Manson, J. E., Stampfer, M. J.
(2001). Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses' Health Study: A Prospective, Observational Study. ANN INTERN MED
135: 1-8
[Abstract][Full Text]
Alexander, K. P., Newby, L. K., Hellkamp, A. S., Harrington, R. A., Peterson, E. D., Kopecky, S., Langer, A., O'Gara, P., O'Connor, C. M., Daly, R. N., Califf, R. M., Khan, S., Fuster, V.
(2001). Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up. J Am Coll Cardiol
38: 1-7
[Abstract][Full Text]
Bushnell, C. D., Samsa, G. P., Goldstein, L. B.
(2001). Hormone replacement therapy and ischemic stroke severity in women: A case-control study. Neurology
56: 1304-1307
[Abstract][Full Text]
Harris, S. T., Eriksen, E. F., Davidson, M., Ettinger, M. P., Moffett, A. H. Jr., Baylink, D. J., Crusan, C. E., Chines, A. A.
(2001). Effect of Combined Risedronate and Hormone Replacement Therapies on Bone Mineral Density in Postmenopausal Women. J. Clin. Endocrinol. Metab.
86: 1890-1897
[Abstract][Full Text]
Matthews, K. A., Kuller, L. H., Sutton-Tyrrell, K., Chang, Y.-F., Tietjen, G. E., Brey, R. L.
(2001). Changes in Cardiovascular Risk Factors During the Perimenopause and Postmenopause and Carotid Artery Atherosclerosis in Healthy Women Editorial Comment : Premenopausal Risk Continuum for Carotid Atherosclerosis After Menopause. Stroke
32: 1104-1111
[Abstract][Full Text]
Koh, K. K., Jin, D. K., Yang, S. H., Lee, S.-K., Hwang, H. Y., Kang, M. H., Kim, W., Kim, D. S., Choi, I. S., Shin, E. K.
(2001). Vascular Effects of Synthetic or Natural Progestagen Combined With Conjugated Equine Estrogen in Healthy Postmenopausal Women. Circulation
103: 1961-1966
[Abstract][Full Text]
Harms, C., Lautenschlager, M., Bergk, A., Katchanov, J., Freyer, D., Kapinya, K., Herwig, U., Megow, D., Dirnagl, U., Weber, J. R., Hortnagl, H.
(2001). Differential Mechanisms of Neuroprotection by 17 {beta}-Estradiol in Apoptotic versus Necrotic Neurodegeneration. J. Neurosci.
21: 2600-2609
[Abstract][Full Text]
Li, C., Briggs, M. R., Ahlborn, T. E., Kraemer, F. B., Liu, J.
(2001). Requirement of Sp1 and Estrogen Receptor {{alpha}} Interaction in 17{beta}-Estradiol-Mediated Transcriptional Activation of the Low Density Lipoprotein Receptor Gene Expression. Endocrinology
142: 1546-1553
[Abstract][Full Text]
Rozenberg, S., Ham, H., Mosca, L.
(2001). The Role of HRT in Cardiovascular Disease. Arch Intern Med
161: 773-773
[Full Text]
Rosano, G.M.C., Simon, T., Mercuro, G., Sans., S., Schenck-Gustaffson, K., Stevenson, J.C., Swahn, E., Jaillon, P.
(2001). Hormone replacement therapy: where we stand in Europe. Eur Heart J
22: 439-441
Kawano, H., Motoyama, T., Hirai, N., Kugiyama, K., Ogawa, H., Yasue, H.
(2001). Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina. J Am Coll Cardiol
37: 735-740
[Abstract][Full Text]
Mhurchu, C. N., Anderson, C., Jamrozik, K., Hankey, G., Dunbabin, D., Longstreth, W.T. Jr, Nelson, L. M.
(2001). Hormonal Factors and Risk of Aneurysmal Subarachnoid Hemorrhage : An International Population-Based, Case-Control Study Editorial Comment : The Gender Gap in Aneurysmal Subarachnoid Hemorrhage. Stroke
32: 606-612
[Abstract][Full Text]
Tolbert, T., Oparil, S.
(2001). Hormone Replacement Therapy and Stroke: Are the Results Surprising?. Circulation
103: 620-622
[Full Text]
Simon, J. A., Hsia, J., Cauley, J. A., Richards, C., Harris, F., Fong, J., Barrett-Connor, E., Hulley, S. B.
(2001). Postmenopausal Hormone Therapy and Risk of Stroke : The Heart and Estrogen-progestin Replacement Study (HERS). Circulation
103: 638-642
[Abstract][Full Text]
Wakatsuki, A., Ikenoue, N., Okatani, Y., Fukaya, T.
(2001). Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women. J Am Coll Cardiol
37: 425-430
[Abstract][Full Text]
Otsuki, M., Saito, H., Xu, X., Sumitani, S., Kouhara, H., Kishimoto, T., Kasayama, S.
(2001). Progesterone, but Not Medroxyprogesterone, Inhibits Vascular Cell Adhesion Molecule-1 Expression in Human Vascular Endothelial Cells. Arterioscler. Thromb. Vasc. Bio.
21: 243-248
[Abstract][Full Text]
Goldstein, L. B., Adams, R., Becker, K., Furberg, C. D., Gorelick, P. B., Hademenos, G., Hill, M., Howard, G., Howard, V. J., Jacobs, B., Levine, S. R., Mosca, L., Sacco, R. L., Sherman, D. G., Wolf, P. A., del Zoppo, G. J., Members,
(2001). Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association. Circulation
103: 163-182
[Full Text]
Santen, R. J., Pinkerton, J., McCartney, C., Petroni, G. R.
(2001). Risk of Breast Cancer with Progestins in Combination with Estrogen as Hormone Replacement Therapy. J. Clin. Endocrinol. Metab.
86: 16-23
[Full Text]
Friday, K. E., Dong, C., Fontenot, R. U.
(2001). Conjugated Equine Estrogen Improves Glycemic Control and Blood Lipoproteins in Postmenopausal Women with Type 2 Diabetes. J. Clin. Endocrinol. Metab.
86: 48-52
[Abstract][Full Text]
Goldstein, L. B., Adams, R., Becker, K., Furberg, C. D., Gorelick, P. B., Hademenos, G., Hill, M., Howard, G., Howard, V. J., Jacobs, B., Levine, S. R., Mosca, L., Sacco, R. L., Sherman, D. G., Wolf, P. A., del Zoppo, G. J.
(2001). Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association. Stroke
32: 280-299
[Full Text]
A correction has been published: N Engl J Med 1996;335(18):1406.
