Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial.

PURPOSE: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. DESIGN: Secondary analysis of randomized controlled trial data. METHODS: We linked Medicare claims data to 25 535 women in the Women's Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625 mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625 mg/day + MPA 2.5 mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval. RESULTS: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age = 68.5 ± 4.8 years). The OAG incidence was 7.6% (mean follow-up = 11.5 ± 5.2 years; mean HT duration = 4.4 ± 2.3 years). Increased age (P trend = .01) and African-American race (HR = 2.69, 95% CI = 2.13-3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR = 1.01, 95% CI = 0.79-1.29 in the CEE trial, and HR = 1.05, 95% CI = 0.85-1.29 in the CEE + MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction = .01), and risk was reduced in African-American women treated with CEE (HR = 0.49, 95% CI = 0.27-0.88), compared to placebo. Race did not modify the relation between CEE + MPA use and OAG risk (P interaction = .68). CONCLUSIONS: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed.

Conjugated estrogens and bazedoxifene in minority populations: pooled analysis of four phase 3 trials.

OBJECTIVE: The aim of the study was to compare efficacy of conjugated estrogens (CE)/bazedoxifene (BZA) for treatment of menopausal symptoms and prevention of postmenopausal osteoporosis in minorities (black/Hispanic) versus whites. METHODS: In a post hoc analysis, data were pooled from 3,424 white or minority nonhysterectomized postmenopausal women randomized to CE 0.45 or 0.625 mg/BZA 20 mg or placebo in four double-blind, phase 3 Selective Estrogens, Menopause, and Response to Therapy (SMART) trials. Outcomes included hot flush frequency/severity (daily diary) in women with at least seven moderate-to-severe hot flushes per day (SMART-1, -2), vaginal cytology in women with at most 5% superficial cells (SMART-1, -3), lumbar spine and total hip bone mineral density (BMD) (SMART-1, -5), and the Menopause-Specific Quality of Life (MENQOL) questionnaire (SMART-1, -2, -3, -5). RESULTS: The analysis included 2,907 white (84.9%), 315 black (9.2%), and 202 Hispanic (5.9%) women. The reduction in hot flush frequency/severity versus placebo (P < 0.05; week 12) was similar in white and minority women. In both populations, both doses significantly (P < 0.05 vs placebo) improved MENQOL vasomotor function, sexual function, and total scores at 3 months; decreased the percentage of parabasal cells at 2 years; and increased the percentage of BMD responders at 12 and 24 months. Significant differential treatment effects by race/ethnicity were observed only for effects on vaginal superficial cells at month 24 and vaginal pH at month 3. CONCLUSIONS: Notwithstanding a limited sample size, CE/BZA had a similar and beneficial impact on hot flushes, MENQOL, and BMD in minorities and whites.

Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

OBJECTIVE: This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. METHODS: Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. RESULTS: Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture. CONCLUSIONS: The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.

OBJECTIVE: The aim of this study was to assess risks and benefits of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal Chinese women. METHODS: A retrospective cohort study was undertaken using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women aged 50 to 79 years were classified as exposed to CEE 0.625 mg/day with MPA 5.0 mg/day (estrogen [E] + progestin [P], n = 4,712) or CEE 0.625 mg/day only (E-only, n = 1,208) and were age-matched to unexposed women (n = 10,125). Follow-up was complete in 96% of the participants. The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. The global index summarized risks of primary outcomes, stroke, pulmonary embolism, colon and endometrial cancers, hip fractures, and death. Time-to-event analyses were performed. RESULTS: Median durations of exposure in the E + P and E-only groups were 6.9 and 9 months, respectively. Median follow-up was 110 months. Hazard ratios (95% CI) for E + P exposure were as follows: myocardial infarction, 0.78 (0.51-1.19); CHD death, 1.21 (0.53-2.70); breast cancer, 1.48 (1.20-1.83); global index, 0.79 (0.72-0.87). Hazard ratios for E-only exposure were as follows: myocardial infarction, 0.76 (0.35-1.68); CHD death, 0.57 (0.11-2.80); breast cancer, 1.44 (0.99-2.10); global index, 1.09 (0.92-1.28). Per 10,000 person-years, there were 12 excess breast cancer cases with E + P exposure; there were 39 fewer global index events with E + P exposure. Adjusting for age, statin and aspirin use, hypercholesterolemia, diabetes, and hypertension did not significantly change estimates. CONCLUSIONS: In postmenopausal Chinese women, CEE with or without MPA was not associated with increased rates of CHD, but CEE with MPA may be associated with a higher breast cancer rate. E + P exposure conferred lower global index event rates.

Assessment of DNA nucleo base oxidation and antioxidant defense in postmenopausal women under hormone replacement therapy.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate oxidative stress by investing oxidatively damaged DNA AS Formamidopyrimidine DNA glycosylase (Fpg) -sensitive sites, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities reduced glutathione (GSH) level and nitrite level as satble end product of in women receiving hormone replacement therapy (HRT). MATERIALS AND METHODS: 127 healthy postmenopausal women receiving HRT and 25 healthy control postmenopausal women were included in this study. Women receiving HRT, comprised surgical menopausal women who underwent surgery for benign conditions and received conjugated equine estrogen, 0.625 mg/day for 1 year (group 1), 5 years (group 2) and more than 10 years (group 3), spontaneous postmenopausal women received conjugated equine estrogen, 0.625 (Premarin) mg/day and medroxyprogesterone acetate, 2.5 mg/day (Premelle) for 1 year (group 4), 5 years (group 5) and more than 5 years (group 6).We investigated in the present study the effects of HRT on nitrite level and GSH level, activities of SOD and GPx and oxidative damage to DNA by comet assays by measuring levels of Fpg-sensitive sites. RESULTS: Although no significant differences were found in the SOD activities, in total group receiving HRT, increased DNA oxidation (P<0.001) together with an increased GPx activity (P<0.001) and nitrite level (P<0.001) as well as a decreased GSH level (P < 0.05) as compared with controls were observed. CONCLUSION: Estrogen alone or oestrogen in combination with progesterone and duration of use did not significantly alter the results. We evaluated that caused oxidative stress by investigating oxidative DNA damage as Fp-sensitive sites and GSH.NO levels in women receiving HRT.

Assessment of myoelectrical signal parameters in estrogen, progesterone, and human chorionic gonadotropin administered in nonpregnant rat myometrium after ovariectomy.

OBJECTIVE: To investigate the correlation of myoelectrical signals with spontaneous contractile events and physiological states in the nonisolated uterine horn of rats. DESIGN: In vivo uterine myoelectrical activity recording study. SETTING: Animal and pharmacology laboratory at Inonu University. ANIMAL(S): Thirty-six female Wistar albino rats. INTERVENTION(S): Six animals were not castrated and served as a sham-operated control group; the other 30 were ovariectomized (OVX) and put into groups: unbiased OVX subjects, estrogen (E)-biased OVX subjects, P-biased OVX subjects, E-plus-P-biased OVX subjects, and hCG-biased OVX subjects. An MP100 A-CE was used for data acquisition, and a personal computer was used for processing. MAIN OUTCOME MEASURE(S): Besides the temporal, spectral, and joint time-frequency (spectrotemporal) analysis, some quantitative measures such as standard deviation and mark to space power ratios of myoelectrical signals were measured. RESULT(S): Progesterone, E, and hCG administration down-regulated the power and contraction frequency of the uterine electrical signal. The spectral concentrations that occurred around the 0.9, 0.35, and 0.7 Hz frequency ranges may be distinguishing characteristics for P, E, and hCG, respectively. CONCLUSION(S): Based on the obtained results, uterine contractions change with ovariectomy and administration of hormones. Progesterone, E, and hCG particularly prolong the quiescent periods of the uterus by reducing the frequency of uterine contractions as well as the power of the myoelectrical activity. Individual or combined use of P, E, or hCG might favor quiescence of the uterine muscle and the maintenance of pregnancy.

Attitudes of Korean clinicians to postmenopausal hormone therapy after the Women's Health Initiative study.

OBJECTIVE: To assess the attitudes of Korean physicians toward hormone therapy (HT) after publication of the Women's Health Initiative (WHI) study. DESIGN: Self-administered questionnaires, consisting of 22 items, were sent by mail to the members of the Korean Society of Menopause. RESULTS: More than 95% of Korean physicians were aware of the WHI study. The HT prescription rate decreased by 16% after publication of the WHI report; approximately half of the physicians who continued prescribing HT changed their prescriptions. The largest decreases occurred in regimens using conjugated equine estrogens and medroxyprogesterone acetate, for which prescriptions of sequential and continuous-combined regimens decreased by 20.7% and 22.7%, respectively. In contrast, the prescription rate for tibolone increased by 3.6%. Approximately 30% of physicians changed from standard to low doses, and 67.8% shortened the duration of HT. After publication of the WHI report, the main reasons for not prescribing or discontinuing HT were patient refusal and increased risk of cardiovascular disease, rather than breast cancer risk. After publication of the WHI report, the number of physicians who prescribed alternative or complementary medicines increased, the rate of HT prescription for the prevention of osteoporosis decreased, and the number of postmenopausal outpatients decreased. CONCLUSIONS: Despite the results of the WHI report, most Korean physicians who participated in this study continued prescribing HT; however, approximately half of those who continued prescribing HT changed their prescriptions. The greatest change occurred in regimens using conjugated equine estrogens and medroxyprogesterone acetate.

Quality of life assessment in a chemoprevention trial: fenretinide and oral or transdermal HRT.

BACKGROUND: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) relief menopause symptoms, but may increase breast cancer risk, while the effects of transdermal estradiol (E2) and MPA are less known. In previous studies, fenretinide decreased second breast malignancies in premenopausal but not in postmenopausal women, suggesting a hormone-sensitizing effect. We have evaluated the quality of life through a self-administered questionnaire during a randomized study of oral CEE or transdermal E2 and fenretinide or placebo. METHODS: A total of 226 postmenopausal women were randomly assigned to either CEE 0.625mg/day and placebo (n=55), or CEE and fenretinide 100mg/bid (n=56), or E2, 50microg/day and placebo (n=59), or E2 and fenretinide (n=56) for 12 months. Sequential MPA 10mg/day was added in all groups. Treatment effects were investigated using a validated questionnaire, the Menopause Quality of Life questionnaire (MENQOL). RESULTS: Oral CEE and transdermal E2 have a comparable activity in reducing menopausal symptoms (p=ns). Both routes ameliorate significantly the symptoms after 1 year of treatment (p<0.0001). Fenretinide does not modify the effects of hormonal replacement therapy. CONCLUSIONS: Oral CEE and transdermal E2 have similar effect on menopausal symptoms relief. The choice of the best estrogen replacement therapy (ERT) route should be decided based on a careful analysis of all the clinical aspects of every subject, considering that transdermal therapy may have a safer effect on the cardiovascular system.

A cost-utility analysis of low-dose hormone replacement therapy in postmenopausal women with an intact uterus.

OBJECTIVE: The objective of this study was to evaluate the cost utility of one year's treatment with a low-dose conjugated estrogen/medroxyprogesterone acetate (CE/MPA low dose) preparation (Premique Low Dose [Wyeth Pharmaceuticals, Maidenhead, UK]), compared with a higher-dose preparation (Premique; CE/MPA [Wyeth Pharmaceuticals, Maidenhead, UK]), in postmenopausal women with an intact uterus. The evaluation captured the resource implications associated with the difference in treatment discontinuation and adverse event driven consultations in patients receiving either the low- or higher-dose preparation. This economic evaluation was conducted from the perspective of the NHS. RESEARCH DESIGN AND METHODS: A health economic model was developed to calculate the incremental cost per quality-adjusted life year (QALY) gained from treatment with a lower-dose CE/MPA combination, compared with a higher-dose CE/MPA preparation. Cohorts of 100 patients were assumed to receive either CE/MPA low dose or CE/MPA for one year. A probabilistic sensitivity analysis was used to explore whether the base case model was robust to the assumptions employed. Neither costs nor consequences were discounted because of the one year timeframe. RESULTS: In the base case, CE/MPA low dose dominates, i.e. it showed a greater health gain at a reduced cost, in both mild and severe symptom populations. These results were repeated in the sensitivity analysis, with the cost-effectiveness planes for both mild and severe symptom populations showing a greater utility at a reduced cost. CONCLUSIONS: CE/MPA low dose has been demonstrated to be a cost-effective treatment of estrogen-deficiency symptoms in postmenopausal women with an intact uterus. It has great potential for increasing the number of patients benefiting from relief of menopausal symptoms while also reducing the resource utilisation associated with managing the adverse effects associated with higher-dose HRT.

Assessment of DNA damage in postmenopausal women under hormone replacement therapy.

OBJECTIVE: To evaluate the possible DNA damage in peripheral blood leukocytes of postmenopausal women under different hormone replacement therapies (HRT), comet assay, a standard method for assessing genotoxicity has been used. METHOD: 46 women were categorized in three groups-Group A: 15 surgical menopausal women who underwent surgery for benign conditions, receiving conjugated equine estrogen, 0.625 mg/day (CEE) for 2.3 +/- 1.5 years, Group B: 16 spontaneous menopausal women receiving conjugated equine estrogen, 0.625 mg/day plus medroxyprogesteron acetate, 5mg/day (CEE + MPA) for 2.4 +/- 1.0 years and Group C: 15 spontaneous menopausal women receiving tibolone, 2.5mg/day for 2.4 +/- 1.3 years. Control group consisted of 15 spontaneous menopausal women who never had HRT. RESULTS: Significant differences in terms of DNA damage were observed between Group A and B with controls as mean total comet scores 23.93 +/- 5.84, 19.44 +/- 6.19 and 10.07 +/- 2.40, but no significance (P > 0.05) were detected between Group C and controls as mean total comet scores 12.07 +/- 3.65 and 10.07 +/- 2.40, respectively. CONCLUSION: Reduced DNA damage were observed with tibolone compared to CEE or CEE + MPA therapy. Studies of this approach are needed.

A cost-effectiveness evaluation of two continuous-combined hormone therapies for the management of moderate-to-severe vasomotor symptoms.

OBJECTIVES: After the release of the results of the Women's Health Initiative, an emerging consensus suggests that continuous-combined hormone therapy (CCHT) should be limited to short-term management of moderate-to-severe vasomotor symptoms. This, in turn, raises the important question of the economic value, if any, of short-term CCHT for this indication. We conducted a cost-effectiveness analysis comparing a 1-year treatment course with 1 mg of norethindrone acetate/5 microg of ethinyl estradiol (1/5 NA/EE) or 0.625 mg/day of conjugated estrogens plus 2.5 mg of medroxyprogesterone (0.625/2.5 CEE/MPA) compared with no therapy for the management of moderate-to-severe vasomotor symptoms. DESIGN: A literature-based Markov model was developed to compare these three options' cost and quality-of-life (QOL) benefits. The impact of therapy on vasomotor symptoms and breakthrough bleeding/spotting on the direct costs of care and QOL were considered. RESULTS: Compared with no therapy, CCHTs resulted in net increases in quality-adjusted life-years (QALYs) gained (0.110 for 1/5 NA/NE v 0.104 for 0.625/2.5 CEE/MPA). Net costs (v no therapy) were $167 lower for 1/5 NA/NE compared with 0.625/2.5 CEE/MPA. Cost per QALY gained (compared with no therapy) were $6,200 and $8,200, respectively. Cost-effectiveness was most favorable for individuals with more severe symptoms who were less bothered by breakthrough bleeding/spotting. CONCLUSIONS: A short-term course of CCHT for the sole purpose of managing moderate-to-severe vasomotor symptoms is cost-effective. However, 1/5 NA/NE seemed to be more cost-effective than 0.625/2.5 CEE/MPA. These findings can be used to further refine the role of CCHT and to improve formulary decisions.

The impact of the Women's Health Initiative on hormone replacement therapy in a Medicaid program.

BACKGROUND: Observational studies suggest that hormone replacement therapy (HRT) reduces women's risk of cardiovascular disease (CVD). However the Women's Health Initiative (WHI) HRT arm was stopped early because of increased risk of CVD, stroke, pulmonary embolism, and breast cancer. Evaluating HRT-prescribing patterns in relation to the release of the WHI will help determine if these study results have influenced the use of HRT. METHODS: This is a descriptive time series analysis to primarily evaluate utilization trends of HRT in women > or =50 years enrolled in the Pennsylvania Medicaid Program. HRT was categorized as follows: conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA), CEE only, and other estrogens/progesterone combinations. RESULTS: The overall prevalence of HRT decreased significantly post-WHI study release for all age and racial groups. The prevalence of CEE plus MPA decreased throughout the study; however, the prevalence of HRT declined at a faster rate after the WHI study release among women in their 50s and 60s compared with women in their 70s and 80s. There was a statistically significant reduction in all types of HRT use. CONCLUSIONS: The WHI influenced all types of HRT use among postmenopausal women in a Medicaid program. Administrative claims data can be a useful tool for monitoring an immediate impact of national guidelines or a national level outcomes trial.

Vaginal dryness assessment in postmenopausal women using pH test strip.

OBJECTIVE: To objectively analyze vaginal dryness in postmenopausal women. METHODS: Forty healthy postmenopausal women, were divided in three groups according to the treatment they received. Group I, conjugated equine estrogens (CEE) 0.625 mg/day (n=20), group II, CEE 0.625 mg/day plus chlormadinone 1 mg/day (n=13), and group III, CEE 0.625 mg/day plus medroxyprogesterone 2.5 mg/day (n=7). Vaginal dryness intensity was analyzed using an analog visual scale, and vaginal humidity measuring the moistening in mm of a pH test strip. Both were evaluated at baseline and 3 months after the beginning of treatment. The comparison among groups and between the baseline and final results was done with Student's t-test for paired and independent samples, respectively. Pearson correlation analysis was carried out between final vaginal dryness intensity and the final moistening of the pH test strip. RESULTS: No statistically significant differences were found in age neither in somatometric variables among the groups. In the three groups, vaginal dryness intensity significantly decreased and the pH test strip moistening significantly increased. A significant negative correlation was only found in group II (-0.690 P<0.009). CONCLUSIONS: Vaginal dryness evaluation assessing the pH test strip moistening is an objective method to evaluate this symptom in postmenopausal women, and the results are independent of the hormone replacement therapy schedule.

Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration.

BACKGROUND: Estrogen improves endothelial function in the coronary conduit vessels of animals; however, its effects on the coronary microcirculation have not been studied completely in humans. METHODS AND RESULTS: We measured myocardial blood flow (MBF) with a PET scan at rest, during cold pressor testing (CPT), and during dipyridamole hyperemia in 54 postmenopausal women without coronary artery disease. Of these, 23 were not and 31 women were taking long-term hormone replacement therapy (HRT) using estrogen either alone or with a progestogen. Each group was subdivided by coronary risk factors (RFs). Twelve young healthy women served as controls. In women not taking HRT, MBF measurements were repeated after 25 mg of conjugated equine estrogens IV. Neither short estrogen nor long-term HRT affected MBF at rest in women with and without RFs. Dipyridamole MBF was attenuated only in the women with RF who were not taking HRT. Short-term estrogen and long-term HRT did not reverse the abnormal response. MBF responses to CPT were abnormal in women not taking HRT, regardless of RFs (20+/-15% versus 32+/-21%) and remained unchanged after short-term estrogen administration. Long-term HRT normalized the response to CPT only in women without RF (53+/-22% versus 59+/-36% in the young women; NS). MBFs were similar for women on estrogen alone or estrogen plus a progestogen, regardless of presence or absence of RFs. CONCLUSION: Menopause is associated with abnormal CPT (an indirect measure of endothelial function), which can be reversed by long-term HRT only when RFs are absent. Progestogens do not antagonize this effect. Long-term HRT may therefore be useful in the primary prevention of coronary artery disease in women without RFs.

Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events.

BACKGROUND: Adverse drug events (ADEs) are a major cause of morbidity and mortality, and even minor ADEs may adversely affect patients' compliance with treatment. Because most ADEs are dose-related phenomena, adjusting drug dosages to account for individual patients' needs and tolerances is fundamental to good therapeutics. OBJECTIVE: To determine whether the Physicians' Desk Reference (PDR), the leading source of drug information for physicians, provides the full range of effective drug doses, especially the lowest, least ADE-prone doses of medications, for physicians to consider in treating patients. METHODS: Review of dosage guidelines and dose-response information in the PDR. Comparison with dose-response data obtained from articles listed in MEDLINE from 1966 to 2000. RESULTS: For many types of medications, physicians are frequently advised to use the lowest effective doses of drugs, especially initially. Yet, effective low doses determined in prerelease studies or in postrelease work are often omitted from the PDR, even when they have been recommended by expert panels. CONCLUSIONS: Optimal therapeutics depends on the availability of comprehensive information. However, the PDR contains only the limited dose information from package inserts. Because the PDR was originally developed as a promotional device, there is no mechanism by which all clinically relevant dose-response data or important postrelease discoveries are regularly and rapidly incorporated into it. Thus, a gap exists in the availability of current and comprehensive dose information for physicians. This article provides information on lower, effective doses for 48 major medications, with an extensive reference list-a compilation of low-dose information not previously published, to our knowledge, in the medical literature. Physicians must have a readily accessible source of current and complete dose-response information to individualize drug therapy and minimize the risks of ADEs.

Recruitment of participants for the Estrogen Replacement and Atherosclerosis (ERA) trial. a comparison of costs, yields, and participant characteristics from community- and hospital-based recruitment strategies.

This paper documents recruitment for the Estrogen Replacement and Atherosclerosis trial, a multicenter, placebo-controlled, double-blind angiographic trial of the effects of opposed and unopposed estrogen on coronary atherosclerosis in postmenopausal women (average scheduled duration of follow-up 3.2 years). We compare costs, yields, and participant characteristics between community-based and hospital-based recruitment strategies. We further compare community-based enriched sources (i.e., those that allowed self-selection or targeted women with known health characteristics) and nonenriched sources. Data gathered on potential participants include method of contact, clinical site, eligibility, completion of screening visits, and randomization rates. Demographic data on participants include age, race, education, marital status, and income. Self-reported health status, smoking status, lipid level, ejection fraction as well as history of chest pain, hypertension, and diabetes were recorded at baseline. Recruitment costs were estimated from employee salaries and costs of screening tests and procedures. Yields were compared by clinical site and by method of contact. Enriched sources of recruitment yielded higher percentages of enrolled participants than nonenriched sources. Both types of source resulted in demographically similar participants. Costs of community-based recruitment were less than hospital-based recruitment; however, screening costs were higher. Overall, screening and recruitment averaged $2508 per randomized participant. Control Clin Trials 2001;22:13-25

Correcting prolonged bleeding during renal transplantation with estrogen or plasma.

OBJECTIVE: To determine the efficacy and relative effectiveness of conjugated entrogens (CE) and fresh-frozen plasma (FFP) in normalizing prolonged preoperative bleeding times during renal transplantation. DESIGN: Prospective, randomized trial. SETTING: A university regional referral center for transplantation. PATIENTS: Patients scheduled for renal transplantation with preoperative bleeding times greater than 10 minutes (normal, < 7 minutes) following informed consent were asked to participate in the randomized protocol. Those with bleeding times of 8 to 9.5 minutes were asked, following informed consent, to be a control group receiving neither CE nor FFP. INTERVENTIONS: Following induction of anesthesia and drawing of baseline laboratory tests, patients were administered randomly, using a table of random numbers, either 50 mg of CE or 2 U of FFP. MAIN OUTCOME MEASURES: Bleeding time measurements and other laboratory tests were repeated at the end of surgery as well as at 24 and 48 hours postoperatively. RESULTS: Treatment with CE and FFP decreased the patients' bleeding times from 16.68 +/- 0.8 (SEM) and 17.13 +/- 0.85 minutes to 7.67 +/- 0.79 (P < .001) and 10.50 +/- 1.27 minutes (P < .001), respectively, by the end of surgery. At 24 and 48 hours postoperatively, the CE group had bleeding times of 9.77 +/- 0.99 and 9.81 +/- 1.24 minutes (P < .001 for both), respectively, whereas the FFP group bleeding times were 12.76 +/- 1.57 (P = .003) and 12.14 +/- 1.56 minutes (P = .001), respectively. There were no statistical differences for the control group compared with baseline either at the end of surgery or at 24 hours. CONCLUSIONS: Although both CE and FFP significantly decreased prolonged preoperative bleeding times during renal transplantation, CE might be preferred because of lower risk and cost, as well as a longer duration of action.