Receiving Hormone Replacement Therapy Research Articles

Author's response to letter from Ray et al.

Author's response to letter from Ray <i>et al</i>.

Fatty acid composition of serum phospholipid of premenopausal women and postmenopausal women receiving and not receiving hormone replacement therapy

To compare the fatty acid composition of serum phospholipid of premenopausal women with that of postmenopausal women receiving and not receiving hormone replacement therapy (HRT). Women between the ages of 43 and 70 were recruited for two separate case-comparison studies. Participants were grouped as either premenopausal, postmenopausal receiving HRT, or postmenopausal not receiving HRT. All participants were required to complete a 3-day dietary record before providing a 12-h fasting blood sample. Fatty acid composition of phospholipids and lipid concentrations was determined from serum samples. The postmenopausal women receiving HRT had significantly higher concentrations of palmitic acid (16:0), palmitoleic acid (16:1), and di-homo-gamma-linolenic (20:3n-6) and significantly lower levels of docosapentaenoic acid (22:5n-3) than the other groups in both studies. In addition, the postmenopausal women receiving HRT had lower levels of behenic (22:0), lignoceric (24:0), and nervonic acid (24:1) in comparison with the postmenopausal women not receiving HRT. The results of this study indicate that the fatty acid composition of serum phospholipids in women is influenced by menopausal status and hormone use. These results are of interest because high levels of 20:3n-6 and low levels of docosapentaenoic acid have been associated with increased myocardial infarction plus stroke mortality from cardiovascular disease.

Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women

Objective: Estrogen deficiency is associated with increased cardiovascular risk and endothelial dysfunction. Improvements in endothelial function with antioxidants, including vitamin C, have been reported. We aimed to determine the acute effect of vitamin C on endothelial function in healthy women with established menopause. Subjects: Subjects (aged 47-59 years) were at least 1 year postmenopause. Ten (serum estradiol < 50 pmol/l) were not receiving hormone replacement therapy, while eight hysterectomized subjects received subcutaneous estradiol. Design: Forearm blood flow (FBF; strain-gauge plethysmography) responses to intrabrachial artery infusions of incremental doses of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) were determined at baseline, and following 1.5 g vitamin C given intravenously. Results: At baseline, estrogen-treated subjects had a lower index of insulin resistance (homeostasis model assessment, HOMA) and lower fibrinogen than those of estrogendeficient subjects. There was a trend towards higher baseline FBF and larger baseline FBF response to acetylcholine in estrogen-treated subjects. FBF responses to acetylcholine were significantly enhanced after vitamin C in estrogen-deficient subjects (area under the dose-response curve (AUC): estrogen-deficient 9.9 ± 2.6 vs. 15.1 ± 3.2 (mean ± SEM), p = 0.02; estrogen-treated 17.0 ± 2.9 vs. 21.0 ± 3.2, p = 0.07). Resting FBF and response to sodium nitroprusside were unchanged in either group by vitamin C. Plasminogen activator inhibitor-1 levels fell after vitamin C in the estrogen-deficient group (17.0 ± 1.6 vs. 14.7 ± 0.9 IU/ml, p = 0.03). Conclusions: These results indicate that endothelial function may be improved acutely by antioxidant treatment in postmenopausal women with established estrogen deficiency.

The office hysteroscopic evaluation of postmenopausal patients.

The objective was to characterize postmenopausal women with endometrial polyps and to evaluate their significance. The study population included all consecutive postmenopausal patients with a diagnosis of endometrial polyps. Demographic, medical and gynecological data were assessed with regard to the endometrial histologic findings. Of the 181 eligible patients, 34 had endometrial hyperplasia (4 cases of them had endometrial carcinoma). The 144 patients using hormone replacement therapy had significantly higher rate of endometrial hyperplasia than non-hormone users (p<0.006). No differences were observed among the endometrial histological categories for any of the presenting symptoms and signs, ultrasonographic findings, or medical histories. Postmenopausal endometrial polyps is a common, mostly benign entity. However, the relatively high rate of concomitant endometrial hyperplasia, especially in patients receiving hormone replacement therapy, dictates a thorough histological evaluation in all cases.

Effects of estradiol and progesterone on radial maze performance in middle-aged female rats fed a low-calcium diet

There is increasing evidence that ovarian steroids and calcium ions are involved in learning and memory. To examine the effect of ovarian steroids on learning and memory under a low-calcium condition, middle-aged female rats were fed either a low-calcium (0.02% Ca) or a normal-calcium (1.25% Ca) diet. All rats were ovariectomized (OVX), and these animals were divided into eight groups: 1) an OVX group with a normal-calcium diet (OVX-normal-Ca group), 2) an OVX group with 17β-estradiol treatment and a normal-calcium diet (E2 group), 3) an OVX with progesterone treatment and a normal-calcium diet (P4 group), 4) an OVX with 17β-estradiol and progesterone treatments and a normal-calcium diet (E2+P4 group), 5) an OVX group with a low-calcium diet (OVX-low-Ca group), 6) an OVX group with 17β-estradiol treatment and a low-calcium diet (LE2 group), 7) an OVX group with progesterone treatment and a low-calcium diet (LP4 group), and 8) an OVX group with 17β-estradiol and progesterone treatments and a low-calcium diet (LE2+LP4 group). Seventy-seven days after the OVX operation, the learning and memory abilities of the rats were examined by using an eight-arm radial maze task. E2 and E2+P4 groups learned in fewer trials, and performed better in the radial maze and the working memory task than the other groups under the normal-calcium condition. Rats in the LE2 group learned in fewer trials, and performed better in the maze and working memory task than the other low-calcium groups, but in combination with progesterone under the low-calcium condition (LE2+LP4 group), the facilitative effect of estradiol in all the tasks was inhibited. Treatment with progesterone alone did not inhibit the learning and memory task performance. These results suggest the possibility that treatment with estradiol under low-calcium conditions cannot improve impaired learning and memory when progesterone is applied simultaneously, and that the intake of adequate calcium may be necessary and effective for patients with learning and memory hypofunction receiving hormone replacement therapy.

Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: A pilot study

Objective: The purpose of this study was to determine the effect of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy. Study Design: This was a prospective, randomized, double-blind, placebo-controlled study at a university teaching program. Twenty-five postmenopausal women who were ≥75 years old with an intact uterus were assigned randomly to receive conjugated equine estrogens (0.625 mg/d plus medroxyprogesterone acetate 5 mg/d for 13 days every 3 months (n = 13) or placebo (n = 12) for 9 months). At the end of the 9 months, patients in the hormone replacement therapy arm continued therapy for an additional 9 months. Statistical analysis was performed with the Student t test, the χ2 test, and the Fisher exact test. Results: Transvaginal sonography was performed at baseline and at 9 and 18 months. Endometrial biopsy was performed if the endometrial thickness was >4 mm or as clinically indicated at 18 months. Patients in the hormone replacement therapy group demonstrated a significant increase in endometrial thickness between baseline (3.9 + 0.8 mm) and 9 months (8.0 + 4.8 mm). There were no cases of endometrial hyperplasia at the 18-month endometrial biopsy. Conclusion: Trimonthly progestin administration in elderly postmenopausal women who receive hormone replacement therapy may be a reasonable alternative to the monthly administration of progestin in hormone replacement therapy. (Am J Obstet Gynecol 2003;189:11-5.)

Postmenopausal osteoporosis in the dialysis patient.

Osteoporosis is the most prevalent bone disorder in the general population, particularly in the middle and older age groups. Although more than half of the prevalent dialysis population is within these age groups, little concern has been given to the possible role of estrogen deficiency in the pathogenesis of bone disease in end-stage renal disease. The purpose of this review is to summarize the recent published evidence that supports a potential role of the postmenopausal state in the pathogenesis of bone disease in end-stage renal disease and their implications for treatment. Recent studies have shown that although the risk factors for fracture in end-stage renal disease are similar to the general population, the incidence is three to fourfold higher. The high prevalence of older population, the frequently observed premature amenorrhea and early menopause in dialysis patients may play a role. Similarly, the proportion of end-stage renal disease women receiving hormone replacement therapy is at least three times lower than the general population. Recent evidence on the risk of hormone replacement therapy should caution about its use in end-stage renal disease patients. New evidence suggests that selective estrogen receptor modulators may increase bone mass without significant secondary effects. Other alternatives, such as the use of bisphosphonates, should be considered with caution due to the risk of excessive suppression of bone turnover, worsening or favoring the development of adynamic bone disease. Osteoporosis should be recognized as an important entity that may modify the current conception of renal osteodystrophy in postmenopausal patients with end-stage renal disease. Further clinical studies are needed in order to propose strategies that may reduce the impact of postmenopausal osteoporosis in the dialysis population.

Endometrial blood flow mapping using transvaginal power Doppler sonography in women with postmenopausal bleeding and thickened endometrium.

To evaluate the role of transvaginal power Doppler sonography to discriminate between benign and malignant endometrial conditions in women presenting with postmenopausal bleeding and thickened endometrium at baseline sonography. Ninety-one postmenopausal women (median age, 58 years; range, 47-83 years) presenting with uterine bleeding and a thickened endometrium (> or = 5-mm double-layer endometrial thickness) on transvaginal sonography were included in this prospective study. Endometrial blood flow distribution was assessed in all patients by power Doppler immediately after B-mode transvaginal sonography. Three different vascular patterns were defined: Pattern A: multiple-vessel pattern, Pattern B: single-vessel pattern and Pattern C: scattered-vessel pattern. Histological diagnoses were obtained in all cases. No patient taking tamoxifen citrate or receiving hormone replacement therapy was included. Histological diagnoses were as follows: endometrial cancer: 33 (36%), endometrial polyp: 37 (41%), endometrial hyperplasia: 14 (15%), endometrial cystic atrophy: 7 (8%). Blood flow was found in 97%, 92%, 79% and 85% of cases of carcinoma, polyp, hyperplasia and endometrial cystic atrophy, respectively. A total of 81.3% of vascularized endometrial cancers showed Pattern A, 97.1% of vascularized polyps exhibited Pattern B and 72.7% of vascularized hyperplasias showed Pattern C. Sensitivity and specificity for endometrial cancer were 78.8% and 100%. For endometrial polyp these respective values were 89.2% and 87% and for hyperplasia they were 57.1% and 88.3%. Transvaginal power Doppler blood flow mapping is useful to differentiate benign from malignant endometrial pathology in women presenting with postmenopausal bleeding and thickened endometrium at baseline sonography.

Angiotensinogen single nucleotide polymorphisms, elevated blood pressure, and risk of cardiovascular disease.

In this study of 10 690 individuals, associations with elevated blood pressure, ischemic heart disease, and ischemic cerebrovascular disease were determined for two noncoding [A(-20)C, G(-6)A] and two coding (T174M, M235T) single nucleotide polymorphisms, analyzed alone and in combination (haplotypes). Participants from the general population with (n=4950) and without (n=4234) elevated blood pressure were compared (study 1), as were participants from the general population without ischemic heart disease and ischemic cerebrovascular disease (n=7965) and cases with either ischemic heart disease (n=1850, study 2) or ischemic cerebrovascular disease (n=848, study 3). Finally, 22-year follow-up of 9184 individuals from the general population examined risk of ischemic heart disease (study 4) and ischemic cerebrovascular disease (study 5). Individuals with -6AA, 174TT, or 235TT had plasma angiotensinogen levels increased by 80 ng/mL (P=0.01 and 0.05 for women and men) compared with individuals with -6GG, 174TT, or 235 MM. In women, this difference was associated with an odds ratio of elevated blood pressure of 1.25 (1.03 to 1.51), which increased to 1.63 (1.05 to 2.51) in postmenopausal women receiving hormone replacement therapy. The promoter single nucleotide polymorphisms alone or as haplotypes did not predict the continuous variables of systolic, diastolic, or pulse pressure in cross section or the risk of ischemic heart disease or ischemic cerebrovascular disease in either gender in case-control or prospective studies. Individuals with -6AA, 174TT, or 235TT in the angiotensinogen gene have increased plasma angiotensinogen levels and moderately increased risk of elevated blood pressure (women only) but unaltered blood pressure examined as a continuous variable and unaltered risk of ischemic heart disease and ischemic cerebrovascular disease.

Sex steroids and bone: current perspectives.

Although the process of bone remodelling or its control has not yet been fully elucidated there is, at present, sufficient information available to conclude that ovarian steroids (estrogens, androgens, progesterone) play an essential role in skeletal homeostasis. The mechanism of action of sex steroids on the skeleton is still not entirely clear, but it has traditionally included indirect effects on systemic hormones that regulate calcium balance and a direct receptor-mediated action. More recently, changes in cytokine production within the bone marrow, as well as pro-apoptotic and anti-apoptotic effects in the osteoblastic cells, have been proposed as new perspectives on the cellular and molecular mechanisms by which sex steroids influence adult bone homeostasis. Mechanical loading, when combined with estrogens or androgens, results in a greater osteogenic response than either condition separately. Women are especially at risk for osteoporosis if they have had a premature or surgical menopause and have not received hormone replacement therapy (HRT). Other reproductive factors that can help to identify women with osteopenia and emphasize the role of sex steroids in preserving bone mass in premenopausal women include: age at menarche, menstrual history and irregularities (including those associated with excessive exercise), age at menopause, previous hysterectomy, hyperprolactinaemia, anorexia nervosa, scoliosis, ovarian dysgenesis, pregnancy and lactation, and pharmacological ovarian suppression. The prevention of osteoporosis starts with the onset of the menarche. A combination of exercise, appropriate nutrition and a healthy lifestyle all maximize bone mineral accrual and result in optimal peak bone mass; normal ovarian function is essential to this process. Unfortunately, many women actually become aware of the need for osteoporosis prevention much later in life, usually after they have already become menopausal. HRT, however, has important limitations for prevention of fractures in post-menopausal women. Future perspectives for treatment of osteoporosis include androgen therapy and anabolic agents. Specifically, synthetic ligands of the estrogen receptor that can evoke the non-genotrophic but not the genotrophic signal of the receptor may be bone anabolic agents, as opposed to natural estrogens or selective estrogen receptor modulators that are anti-resorptive agents. The same ligands may circumvent the side effects associated with conventional HRT.

Distributions of C-reactive protein measured by high-sensitivity assays in apparently healthy men and women from different populations in Europe.

C-reactive protein (CRP), the classic marker of acute-phase response, is an indicator of a variety of pathologic processes, including infections, tissue damage, and chronic inflammatory diseases (1)(2). The majority of more than 15 well-conducted prospective studies in initially healthy individuals have shown a strong and independent association between concentrations of CRP within the reference interval (<5 mg/L) and future major cardiovascular events (3), although in some of them, no such association could be established (4)(5)(6)(7). The summary estimate of the relative risk in formal metaanalysis was 2.0 (95% confidence interval, 1.6–2.5) (3). Furthermore, CRP has been shown to add to risk prediction beyond and above established cardiovascular risk factors (8). On the basis of data from the Physicians’ Health Study and the Nurses’ Health Study, an algorithm for risk assessment of future coronary events that combines both CRP concentration and the ratio of total cholesterol to HDL-cholesterol has recently been proposed (9). Because atherosclerosis represents a low-grade inflammatory process in the vascular bed, high-sensitivity (hs) assays are needed when using circulating CRP concentrations for risk prediction in cardiovascular diseases. Such assays have been developed and are now commercially available (10)(11). However, before screening of individuals at risk can be recommended, CRP distributions in apparently healthy adults in the general population must be known. Such information is scarce. Furthermore, in previous reports, women using oral contraceptives or receiving hormone replacement therapy (HRT), both of which have been shown to significantly increase CRP concentrations, had not been excluded (12)(13)(14)(15). In this report, we describe the frequency distribution of CRP concentrations in 13 527 adult men and women from different representative populations in Western Europe. Furthermore, for one area [the MONICA (Monitoring Trends and Determinants in …

P1787 Interleukin-6 and flow mediated dilatation as markers of increased vascular inflammation in patients receiving hormone replacement therapy

P1787 Interleukin-6 and flow mediated dilatation as markers of increased vascular inflammation in patients receiving hormone replacement therapy

P1703 Prothrombotic mutations are associated with increased cardiovascular events in postmenopausal women receiving hormone replacement therapy

P1703 Prothrombotic mutations are associated with increased cardiovascular events in postmenopausal women receiving hormone replacement therapy

Bone turnover and body weight relationships differ in normal-weight compared with heavier postmenopausal women.

Low body weight is associated with increased risk for fractures, whereas higher body weight has been shown to be protective against osteoporosis. This study evaluated whether body weight plays a role regulating bone turnover and mass in normal-weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (BMI> or =30 kg/m2) postmenopausal women who were either receiving hormone replacement therapy [HRT(+)] or not [HRT(-)] (total of six groups). Body weight, BMI, total body bone mineral content (TBBMC), and markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline (PYD) and deoxypyridinoline) were retrospectively analyzed in 210 postmenopausal women. The mean age was 67+/-6 years, with mean body weight of 70.8+/-14.2 kg, ranging from 45.0 to 115.5 kg. Body weight was positively correlated with TBBMC ( r=0.50, p<0.0001). There was a lower TBBMC and higher bone formation rate in normal-weight than obese HRT(-) women, but in women taking HRT there were no differences between BMI categories. In addition, in normal-weight HRT(-) women only, PYD and body weight showed a negative correlation (r=-0.39, p=0.01). Among normal-weight, but not overweight or obese subjects, we observed higher TBBMC and lower bone turnover in the HRT(+) compared with the HRT(-) group. Regression models explained 36% of the variance in TBBMC, mainly through body weight. Additional models could only explain 11-15% of the variance in bone turnover. Taken together, these data suggest that among normal-weight but not obese postmenopausal women, higher bone turnover is associated with lower bone mass, and that only normal-weight women show a different bone turnover profile with HRT treatment. Body weight should be considered an important factor in bone metabolism with relevant clinical implications.

Postmenopausal Hormone Replacement Therapy Use Decreases Oxidative Protein Damage

Objectives: The aim of this study is to evaluate oxidative protein damage (OPD) by investigating protein carbonyl (PCO) and nitrotyrosine (NT) levels, oxidative stress by total thiol (T-SH), erythrocyte glutathione (GSH) and nitric oxide (NO) levels in women receiving hormone replacement therapy (HRT). Materials and Methods: To examine the influence of oxidative stress on OPD, we studied 12 postmenopausal women who had received HRT for 6 months, and 13 postmenopausal women who did not receive HRT, as the control group. All subjects were non-smokers. Blood samples were drawn in the fasting state and processed within 1 h of collection. For NT and NO, serum samples were stored at –70°C until analysis; all other parameters were determined on the same day of collection. Results: After 6 months, plasma PCO and T-SH levels were decreased, GSH and NO levels were increased, and NT levels were not changed in 12 postmenopausal women receiving HRT. Except the NT levels, the rest of the parameters did not significantly change in the control group. Interestingly, mean NT levels in the control group increased significantly. Conclusions: A crucial part of the protective effect of HRT on the cardiovascular system arises secondary to the interaction between estrogen and vessel wall. Our results suggest that an important component of the mechanism underlying this interaction may depend on estrogen’s antioxidant effect and its preventive role in OPD.

Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women

Objective: Estrogen deficiency is associated with increased cardiovascular risk and endothelial dysfunction. Improvements in endothelial function with antioxidants, including vitamin C, have beenreported. We aimed to determine the acute effect of vitamin C on endothelial function in healthy women with established menopause.Subjects: Subjects (aged 47-59 years) were at least 1 year postmenopause.Ten (serum estradiol < 50 pmol/l) were not receiving hormone replacement therapy, while eight hysterectomized subjects received subcutaneous estradiol.Design: Forearm blood flow (FBF; strain-gaugeplethysmography) responses to intrabrachial artery infusions of incremental doses of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) weredetermined at baseline, and following 1.5 g vitamin C given intravenously.Results: At baseline, estrogen-treated subjects had a lower index of insulin resistance (homeostasis model assessment,HOMA) and lower fibrinogen than those of estrogendeficient subjects. There was a trend towards higher baseline FBF and larger baseline FBF response to acetylcholine in estrogen-treated subjects. FBF responsesto acetylcholine were significantly enhanced after vitamin C in estrogen-deficient subjects (area under the dose-response curve (AUC): estrogen-deficient 9.9 ± 2.6 vs. 15.1 ± 3.2 (mean ±SEM), p = 0.02; estrogen-treated 17.0 ± 2.9 vs. 21.0 ± 3.2, p = 0.07). Resting FBF and response to sodium nitroprusside were unchanged in either group by vitamin C. Plasminogenactivator inhibitor-1 levels fell after vitamin C in the estrogen-deficient group (17.0 ± 1.6 vs. 14.7 ± 0.9 IU/ml, p = 0.03).Conclusions: These results indicate that endothelialfunction may be improved acutely by antioxidant treatment in postmenopausal women with established estrogen deficiency.

Prevalence of sexual dysfunction in a cohort of middle-aged women: influences of menopause and hormone replacement therapy

In order to determine the prevalence of sexual dysfunction (SD) and related risk factors in a cohort of middle-aged women the Laumann's test (DSM-IV) was passed to 534 healthy women between 40 and 64 years old (mean: 52.4 ± 5.7) attending the Southern Metropolitan Health Service in Santiago de Chile. Of all the women, 82.8% were peri- or postmenopausal, 23% had received hormone replacement therapy (HRT) and 79.2% were sexually active. Among those who were sexually active a total of 51.3% presented SD. The prevalence of SD increased with age (from 22.2% in the 40–44-year age group to 66% in the 60–64-year age group). HRT users and healthy women presented a lower risk of SD (OR: 0.1 CI: 0.0–0.1 and OR: 0.6 CI: 0.3–0.9, respectively). The risk increased after the menopause (OR: 3.3 CI: 1.6–6.9) and with age older than 49 years (OR: 3.4 CI: 1.8–6.4), hysterectomy (OR: 3.7 CI: 1.3–10.6) and when male partners presented erectile dysfunction (OR: 3.2 CI: 1.2–8.6). In conclusion sexual dysfunction affects more than 51% of middle-aged women who are sexually active and increases with age. Ovarian function and HRT significantly influence sexual activity.

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition.

To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women. A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks. Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping. These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.

Intranasal hormone replacement therapy.

Although the optimal route of delivery for hormone replacement therapy has not yet been determined, desirable qualities would include good efficacy, easy administration, minimal side effects, and optimal therapeutic profile. This would potentially serve to improve patient compliance and satisfaction. The intranasal route has been evaluated for the administration of menopausal hormones and seems to fulfill these requirements. The intranasal route would also seem to be a viable alternative for drugs that are poorly absorbed after ingestion by avoiding hepatic first-pass elimination. The intranasal route is, therefore, innovative for the delivery of natural sex steroids in postmenopausal women receiving hormone replacement therapy. Early studies demonstrate that it is safe, effective, and acceptable to postmenopausal women. In addition, the nasal administration of a combination of estradiol and progesterone would seem to be an attractive way to deliver hormones to nonhysterectomized postmenopausal women. Providing alternative routes of administration may also enhance compliance.

Hormone replacement therapy is associated with improved survival in women undergoing coronary artery bypass grafting

Objectives: The effect of hormone replacement therapy on cardiovascular events in postmenopausal women is controversial. We investigated the roles of sex and hormone replacement status in female patients undergoing coronary artery bypass grafting. Methods: We reviewed the records of 4259 consecutive patients aged 55 years or older who underwent primary elective isolated coronary artery bypass at our hospital between May 1996 and September 2001. Results: Female sex with hormone replacement therapy was an independent predictor of decreased mortality, regardless of age. Mortality was 6.7% (61/905) for women not receiving hormone replacement therapy, 2.3% (6/256) for hormone replacement therapy recipients, and 2.7% (82/3098) for men (P <.01 for all comparisons). Of the characteristics examined, multivariate analysis indicated that independent predictors of mortality were advanced age, previous congestive heart failure, class IV angina, and female sex without hormone replacement (P <.005). Independent predictors of survival included use of an internal thoracic artery graft and white ethnicity. There were no significant intergroup differences in the incidence of nonfatal, morbid postoperative events. Conclusions: Postmenopausal women undergoing coronary artery bypass had a significantly improved in-hospital survival if they had been receiving hormone replacement therapy. The improved survival might be related to one or more of the numerous cardiovascular effects of estrogen that are considered beneficial. A prospective randomized trial is needed to validate the observation that hormone replacement therapy is protective in this setting.J Thorac Cardiovasc Surg 2002;124:1255-9