Flavone acetic acid enhances accumulation of IL-2 activated NK cells within established metastases

OBJECTIVE: In 1995, we presented our experience in hysteroscopic resection of hemorrhagic submucous fibroids in 196 patients. The objective of the present work was to analyze functional outcome three years later. PATIENTS: One hundred ninety-six patients with abnormal uterine bleeding were treated between 1987 and 1993. Equipment, techniques, characteristics of the procedures and early results were detailed in the previous article. RESULTS: With a mean follow-up of 73 months (range 50,104), results were: 13.8% of the patients were lost to follow-up; 68.4% had symptomatic improvement and failure was observed in 17.8% (subsequent hysterectomy in 12.7%). Forty-nine patients had repeat resection in this series; 61 became menopausal after surgery, and 21 were taking hormone replacement therapy with good results. CONCLUSION: Developed as an alternative to hysterectomy, operative hysteroscopy has proven to be a safe and effective procedure. This treatment modality appears to give satisfactory long-term results, with a low rate of complications.     

Compliance with hormone replacement therapy in postmenopausal women. A comparative study

OBJECTIVE: To assess compliance with hormone replacement therapy in postmenopausal women. METHOD: Two groups were compared prospectively: 100 women who sought treatment for menopausal symptoms, and 82 women who had undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy and were using estrogen replacement therapy. RESULTS: Compliance rates after 6 months were 81.0% and 84.1% in the two groups, respectively, and after 12 months, 73.0% and 80.5%. CONCLUSIONS: The high rates are attributed to our investment in patient education of the benefits of treatment and repeated and close follow-up.     

Therapeutic approaches to primary and secondary brain tumours

INTRODUCTION: This study examined the long-term effects of hysterectomy, with and without bilateral oophorectomy, and treatment with estrogen replacement on bone mineral density in older hysterectomized women. METHODS: Subjects were 346 women 60-89 years of age, who were participants in the Rancho Bernardo Study and attended a follow-up clinic visit in 1988-1991. Bone density was measured at the ultradistal wrist, midshaft radius, lumbar spine and hip. RESULTS: Of these women, 182 had a hysterectomy with conservation of one or both ovaries and 164 had a hysterectomy with bilateral oophorectomy. Current estrogen users had the highest bone densities; those who never used estrogen replacement had the lowest. Only 9.1% of oophorectomized women, compared to 19.2% of those with ovarian conservation had never used estrogen (P < .01). After adjustment for covariates including estrogen replacement therapy, hysterectomized women with ovarian conservation had marginally higher bone densities at the wrist (P < .09) and spine (P < .06) than oophorectomized women. We found significant differences only among women currently using estrogen (P < .05 for wrist and P < .01 for spine densities, respectively). Bone density did not differ at any site by oophorectomy status among past or never users of estrogen. CONCLUSIONS: Hysterectomized women who use estrogen replacement therapy have better bone density, regardless of a bilateral oophorectomy. In addition, bilateral oophorectomy may not have a long-term negative effect on bone density; hysterectomized women who do not use estrogen appear to have equivalent bone density whether or not they had a bilateral oophorectomy.     

Induction of Th2 cell differentiation in the primary immune response: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4

Rates of hormone replacement therapy (HRT) in women have varied substantially over the last 25 years. Data on the impact of recent recommendations for widespread use to prevent cardiovascular disease and osteoporosis and factors that influence use are needed. We attempted to (1) describe recent trends in HRT use, (2) investigate the relationship between HRT use and prepaid drug benefit, and (3) detail prescribing frequencies by provider specialty. We conducted a cross-sectional analysis of annual HRT pharmacy dispensings from 1986 to 1995 in a large HMO to all female HMO members aged 45 years and older. HRT rates increased among all age categories, although the magnitude of change varied by age. Highest rates of use were found in those 50-59 years old. Although combined estrogen-progestin use increased, 57% of all estrogen users did not receive progestin in 1995. Unopposed estrogen use was largely limited to hysterectomized women. Women of all ages with no prepaid drug benefit as part of their HMO coverage had the lowest HRT rates. Internal medicine, obstetrics/gynecology, and family practice providers prescribed over 90% of HRT, and prescriber specialty varied with user age. HRT use increased in the HMO from 1986 to 1995, especially among younger women. In 1995, about half of women aged 50-64 years received one or more HRT dispensings. As the benefits, risks, and cost effectiveness of HRT depend on the duration of use, additional information on current use duration is needed. Combined estrogen-progestin use increased and appeared appropriate to hysterectomy status. Research is needed to determine if lower HRT use rates among women without a prepaid drug benefit indicate less prophylactic HRT use, particularly among younger women, for whom this lack of coverage was relatively common.     

Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat

OBJECTIVES: This study examined the relation of hysterectomy and oophorectomy to heart disease risk factors. METHODS: Data were collected and analyzed for 1150 women aged 50 through 89. RESULTS: Of these women, 21.8% reported hysterectomy with bilateral oophorectomy; 22.1%, hysterectomy with ovarian conservation. Compared with women without hysterectomy, oophorectomized women, especially those 20 or more years postmenopause, had increased lipids, lipoproteins, glucose, and insulin; blood pressures were increased among current estrogen users. Women with hysterectomies with ovarian conservation had similar or more favorable risk factors than nonhysterectomized women. CONCLUSIONS: Bilateral oophorectomy, but not hysterectomy, may have long-term negative consequences for heart disease risk factors not totally ameliorated by estrogen use.     

Hormone replacement and menopausal symptoms following hysterectomy

Hormone replacement therapy (HRT) is recommended for most women who experience surgical menopause following hysterectomy/oophorectomy for noncancerous conditions; it is also commonly prescribed for postmenopausal women. Beginning in 1992, 1,299 women undergoing hysterectomy in 28 hospitals throughout Maryland were interviewed prior to hysterectomy and were subsequently followed over a 2-year period. Interviews included questions about HRT use and symptoms associated with menopause. The majority of the women (66 percent) were white, 55 percent had a high school education or better, 49 percent were obese (body mass index > or =27.3), and 11 percent were postmenopausal. Over 40 percent of premenopausal women underwent bilateral oophorectomy. At 3 months posthysterectomy, 89 percent of these women were on HRT; this figure dropped to 85 percent at 24 months. Among postmenopausal women, 50 percent were on HRT both at 3 months and at 24 months posthysterectomy. Among premenopausal women who had unilateral oophorectomy, 21 percent were on HRT at 3 months, increasing to 35 percent at 24 months. Among premenopausal women who had no ovaries removed, 5 percent were on HRT at 3 months, increasing to 13 percent at 24 months. There were few within-group differences between HRT users and nonusers, except that among postmenopausal women, HRT users were younger and more likely to be white and had higher income and educational levels. Women who were postmenopausal or who underwent bilateral oophorectomy were less likely to have hot flashes if they were on HRT, but women with 0-1 ovary removed who were on HRT were more likely to have hot flashes than those not on HRT. Black women were significantly more likely to experience hot flashes than were white women, independent of HRT status and weight. Obese women were on HRT at approximately the same rates as nonobese women but were significantly more likely to have hot flashes, even when analyses controlled for HRT and race.     

The effect of postmenopausal estrogen therapy on the risk of non-insulin-dependent diabetes mellitus

OBJECTIVES: This study examined the effect of postmenopausal estrogen replacement therapy on the incidence of non-insulin-dependent diabetes in women. METHODS: Postmenopausal women aged 50 through 70 years (n=848) without diagnosed diabetes at baseline were followed for 10 to 15 years for incident diabestes. RESULTS: Over the average 11.5 year follow-ip, there were 105 new cases of diabetes. The age-adjusted relative-risk for development of diabetes was nonsignificantly lower for women with continuous estrogen replacement therapy use than for never users. After adjustment for major covariates, a nonsignificant linear trend with increasing duration of estrogen replacement therapy was reversed. CONCLUSIONS: This study suggests that previous results showing a reduced risk of diabetes in women using estrogen may have been due to selection bias regarding who is prescribed estrogen, confounding factors, or differential diagnostic efforts.     

Co-purification of a ribonuclease and human chorionic gonadotrophin beta-core protein from human urine and displacement of 125I-human luteinizing hormone from Candida albicans binding sites by ribonucleases

OBJECTIVE: To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss. DESIGN: A 2-year, prospective, open label, randomized study. SETTING: Department of Obstetrics and Gynecology of a university hospital. PARTICIPANTS: Fifty-two postmenopausal or oophorectomized women. INTERVENTION: One of the following regimens was continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg + medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4) control. MEASUREMENTS: Lumbar spine and femoral BMD by dual energy X-ray absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH, calcitonin. A1-p, and osteocalcin. RESULTS: Of the 52 patients enrolled in this study, 49 patients completed the 1 year of therapy and 36 completed the 2- year study. The control group showed a significant decrease in lumbar BMD over the 2 years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 approximately 12.4%), 7.4% (0.60 approximately 14.2%) and 3.20% (0.61 approximately 5.84%), respectively, and were significantly higher than pretreatment values. The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA. HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA. CONCLUSIONS: Continuous hormone replacement therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding.     

Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy with suturing technique

Since December 1992 we have performed laparoscopic-assisted vaginal hysterectomy (LAVH) in 50 women using strict, conventional, basic operative rules, and compared it with open abdominal hysterectomy with respect to operation time, cost, postoperative analgesia requirements, and length of hospital stay. The indications for hysterectomy were uterine myoma in 32 patients, dysfunctional bleeding in 13, and postmenopausal bleeding in 5. The mean operating time was 118 minutes. The mean blood loss was 3.2% for preoperative and postoperative hematocrit values. The complication rate was 15%. The advantages of LAVH include short hospitalization, early recovery, low blood loss, and minimal postoperative discomfort.     

Women's health in midlife: the influence of the menopause, social factors and health in earlier life

OBJECTIVE: To describe the health symptoms of a large representative sample of British women at age 47 years, and to examine the influence of the menopause allowing for social factors and health in earlier adult life. DESIGN: A national prospective birth cohort study. Information on health problems, menstrual cycle, use of hormone replacement therapy and life stress at 47 years was collected using a postal questionnaire. Information on health, smoking behaviour and educational attainment earlier in life had been collected at previous home visits. SETTING: England, Scotland and Wales. POPULATION: A general population sample of 1498 women, 84% of those sent a questionnaire. MAIN OUTCOME MEASURE: Twenty self-reported health symptoms over the previous 12 months. RESULTS: Women who had experienced an early natural menopause had a strongly raised risk of vasomotor symptoms (hot flushes or night sweats), sexual difficulties (vaginal dryness or difficulties with intercourse) and trouble sleeping. However, there was little or no excess risk of other somatic or psychological symptoms. In contrast, all types of symptoms were more common among women who had had a hysterectomy or were users of hormone replacement therapy. Women with the least education, stressful lives, or a previous history of poor physical and psychological health at age 36 also reported more symptoms at 47 years compared with other women, but adjustment for these factors in a logistic regression model did not affect the relations between symptoms and current menopausal status. For vasomotor symptoms, postmenopausal women had an adjusted odds ratio of 4.7 (95% CI 2.6-8.5) and perimenopausal women had an adjusted odds ratio of 2.6 (95% CI 1.9-3.5) compared with premenopausal women. Corresponding adjusted odds ratios for sexual difficulties were 3.9 (95% CI 2.1-7.1) and 2.2 (95% CI 1.4-3.2), and for trouble sleeping were 3.4 (95% CI 1.9-6.2) and 1.5 (95% CI 1.1-2.0). CONCLUSIONS: Specific symptoms were clearly associated with the natural menopause. More general health concerns were common among women in middle life, particularly among those with stressful lives, or those who had had a hysterectomy or started taking hormone replacement therapy before they were postmenopausal. Appropriate advice and support needs to be easily accessible.     

Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities

CONTEXT: Postmenopausal vaginal bleeding is a common clinical problem. Endovaginal ultrasound (EVUS) is a noninvasive diagnostic test that may help determine which women should undergo endometrial biopsy. OBJECTIVE: To determine the accuracy of EVUS in detecting endometrial disease in postmenopausal women with vaginal bleeding according to hormone replacement use. DATA SOURCES: Literature search of English-language and non-English-language articles published from 1966 through November 1996 using MEDLINE and by a manual search of bibliographies of published articles. STUDY SELECTION: Studies were included if they prospectively collected EVUS measurements of endometrial thickness prior to obtaining endometrial tissue for histologic evaluation in postmenopausal women with vaginal bleeding. Of 85 studies that included data on EVUS and endometrial histology, 35 were included in the meta-analysis and included 5892 women. DATA EXTRACTION: Articles were reviewed and independently selected and abstracted by 2 reviewers. Disagreement was resolved by consensus. DATA SYNTHESIS: The overall summary mean weighted estimates of sensitivity and specificity were calculated for thresholds of endometrial thickness from 3 to 10 mm. Using a 5-mm threshold to define abnormal endometrial thickening, 96% (95% confidence interval [CI], 94%-98%) of women with cancer had an abnormal EVUS result, whereas 92% (95% CI, 90%-93%) of women with endometrial disease (cancer, polyp, or atypical hyperplasia) had an abnormal result. This did not vary by hormone replacement use. However, the number of women with normal histology who had an abnormal EVUS result did vary by hormone replacement use. In women who were not using hormone replacement therapy, 593 (8%) with normal histological findings had an abnormal EVUS result (specificity, 92%; 95% CI, 90%-94%), whereas 1544 (23%) using hormone replacement therapy had an abnormal EVUS result (specificity, 77%; 95% CI, 75%-79%). For a postmenopausal woman with vaginal bleeding with a 10% pretest probability of endometrial cancer, her probability of cancer is 1% following a normal EVUS result. CONCLUSION: Endovaginal ultrasound has a high sensitivity for detecting endometrial cancer and other endometrial disease and can reliably identify postmenopausal women with vaginal bleeding who are highly unlikely to have significant endometrial disease so that endometrial sampling may be unnecessary.     

Trends in blood pressure levels and control of hypertension in Finland from 1982 to 1997

OBJECTIVE: To assess the trends in blood pressure levels and hypertension control in Finland from 1982 to 1997. DESIGN: Four independent cross-sectional population surveys conducted in 1982, 1987, 1992 and 1997. SETTING: From 1982 to 1997, the provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in southwestern Finland were surveyed. From 1992 to 1997, the Helsinki-Vantaa region in southern Finland was surveyed. PARTICIPANTS: Men and women aged 25-64 years were selected randomly from the national population register. The total number of participants was 27 623. MAIN OUTCOME MEASURES: We assessed mean systolic and diastolic blood pressure, prevalence of hypertension (subjects with systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or current use of antihypertensive drug treatment) and antihypertensive drug treatment and quality of hypertension care among hypertensive persons. RESULTS: Mean systolic blood pressure and the prevalence of hypertension decreased significantly in all areas except among men in the Helsinki-Vantaa region. The fall in mean diastolic pressure was significant only in eastern Finland. The proportion of hypertensives who were unaware of their condition fell from 45.5 to 24.1% in men and from 27.2 to 15.7% in women. At the same time, the proportion of hypertensives with adequately controlled blood pressure (systolic pressure < 160 mmHg and diastolic pressure < 95 mmHg) increased from 9.4 to 23.5% in men and from 16.0 to 36.7% in women. CONCLUSION: Hypertension care in Finland has improved significantly during the last 15 years. However, the situation is still far from optimal. It is obvious that the biggest problem in hypertension care has shifted from detection to adequate treatment of high blood pressure.     

Oral contraceptive use during the perimenopausal years

Few guidelines exist for the use of estrogen, particularly low-dose oral contraceptives, during the perimenopausal years. Use of low-dose oral contraceptive pills in women over 35 years of age provides protection against unwanted pregnancy, maintains a stable hormonal environment and decreases abnormal menstrual bleeding. Other noncontraceptive health benefits of oral contraceptives include a reduction in bone loss and protection against iron deficiency anemia, dysmenorrhea, benign breast disease, endometrial cancer and epithelial ovarian cancer. This article discusses potential risks of oral contraceptive use in this age group, as well as recommendations about when and how to change from contraceptive therapy to postmenopausal hormone replacement therapy.     

Trends in breast cancer screening in Missouri from 1987 to 1995, and predictions for the years 2000 and 2010

BACKGROUND: Breast cancer is a major cause of morbidity and mortality in the United States (U.S.) and Missouri. In 1992, 3,915 new breast cancer cases were diagnosed and in 1995, 1,006 deaths from breast cancer were reported in Missouri. Although breast cancer incidence has increased in Missouri in the past 20 years, there are indications that early detection has also increased during the same period. Knowledge about which segments of the population have experienced the greatest increase in mammography screening rates helps in planning and implementation of breast cancer control programs at the state level. OBJECTIVES: Examine the prevalence and trends of lifetime mammography and 2-year mammography compliance in Missouri by age, race, and education from 1987 to 1995 and make predictions for the years 2000 and 2010. METHODS: We used data from the Missouri Behavioral Risk Factor Surveillance System (BRFSS), 1987 to 1995, to estimate the prevalence of ever having had a mammogram and compliance with mammography screening guidelines within two years by race, age, and education status among Missouri women over age 18. Using linear models, we regressed breast cancer screening prevalence estimates on time to obtain trends and predictions. RESULTS: Overall, African-American women were more likely to have had a lifetime mammogram than white women. However, we found a steady increase in the prevalence of ever having had a mammogram for all groups of women defined by age and education status, except among African Americans. Increase in the prevalence of ever having had a mammogram was much higher in women age 50 and older and slightly higher among women with a high school education or less. The average prevalence of 2-year mammography screening compliance was about 60% for all groups, a rate which did not significantly change between 1987 and 1995. By the year 2000, white women will have mammography rates equal to or higher than African-American women, and the majority of all women age 50 and older (98.3% to 100%) will have had a lifetime mammogram. CONCLUSION: Missouri target populations are predicted to attain Year 2000 National Health Objectives concerning lifetime mammography. Current efforts should be continued in order to maintain levels of mammography, particularly among African-American women.     

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.     

Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico

PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.     

Prevention of bone loss following oophorectomy in premenopausal women: a retrospective assessment of the effects of oophorectomy and a prospective controlled trial of the effects of mestranol therapy

Prospective studies of bone mass in women following oophorectomy for benign conditions were done by the double-blind technique. Skeletal response to treatment was measured by photon absorption densitometry. Untreated patients were found to lose bone mass rapidly during the first two years after oophorectomy. When estrogen replacement was started within two months of oophorectomy, it was found to be effective in preventing subsequent bone tissue loss. Three years following oophorectomy, untreated women who had already lost bone tissue, and who were then started on estrogen replacement, showed a highly significant increase in their bone mass. The women in whom this treatment was delayed for six years did not respond. No untoward effects were noted in these women, perhaps, in part, because they had undergone hysterectomy. Long-term effects of this treatment are now being evaluated.     

Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?

PURPOSE: To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD: A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS: None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION: In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.