ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveWe prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group.DesignTwo hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (± 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (± 3.01) years, with a median of 3.05 years.ResultsHot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P= 0.01), to have received prior ERT (P< 0.001), and to have received no adjuvant tamoxifen (P< 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143;P= 0.85), contralateral breast cancers (10/258 v 9/260;P= 0.99), or systemic metastasis (8/277 v 15/277;P= 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P= 0.03). Overall survival favored the ERT group (P= 0.02).ConclusionsIn these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo compare the long-term effects of oral and transdermal hormone replacement therapy (HRT) on serum homocysteine levels in postmenopausal women.DesignAn open, prospective, controlled study. Seventy-five healthy postmenopausal women were recruited as eligible for the study. Fifty women seeking HRT were randomized to receive continuous 17&bgr;-estradiol, either by oral (2 mg daily;n= 25) or transdermal (50 &mgr;g daily;n= 25) administration, plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle. Twenty-five women unwilling to receive hormone treatment received only calcium supplementation, representing the control group. Fasting blood samples were analyzed at baseline and then after 6, 12, and 24 months to determine plasma homocysteine levels.ResultsFifty-nine women completed the study. After 6 months of therapy, homocysteine concentrations showed a statistically significant reduction in the treated groups versus both baseline and controls, and no further significant variations were found thereafter. The mean reduction in the homocysteine levels throughout the study was 13.6% in the oral and 8.9% in the transdermal group, respectively, without significant difference between the two routes of estradiol administration. Women with the highest baseline levels of homocysteine experienced the greatest reduction. No significant variations in homocysteine concentrations were found in the control group.ConclusionsOral and transdermal estradiol sequentially combined with dydrogesterone shows comparable effectiveness in reducing plasma homocysteine levels in postmenopausal women. Women with the highest pretreatment concentrations of homocysteine benefit the most by the lowering effect of HRT.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe normal ovary produces abundant testosterone in addition to estradiol (E2) and progesterone, but usually only the latter two hormones are “replaced” in the treatment of ovarian failure and menopause. Some clinical and genetic evidence suggests, however, that endogenous androgens normally inhibit estrogen-induced mammary epithelial proliferation (MEP) and thereby may protect against breast cancer.DesignTo investigate the role of endogenous androgen in regulating mammary epithelial proliferation, normal-cycling rhesus monkeys were treated with flutamide, an androgen receptor antagonist. To evaluate the effect of physiological testosterone (T) supplementation of estrogen replacement therapy, ovariectomized monkeys were treated with E2, E2plus progesterone, E2plus T, or vehicle.ResultsWe show that androgen receptor blockade in normal female monkeys results in a more than twofold increase in MEP, indicating that endogenous androgens normally inhibit MEP. Moreover, we show that addition of a small, physiological dose of T to standard estrogen therapy almost completely attenuates estrogen-induced increases in MEP in the ovariectomized monkey, suggesting that the increased breast cancer risk associated with estrogen treatment could be reduced by T supplementation. Testosterone reduces mammary epithelial estrogen receptor (ER) &agr; and increases ER&bgr; expression, resulting in a marked reversal of the ER&agr;/&bgr; ratio found in the estrogen-treated monkey. Moreover, T treatment is associated with a significant reduction in mammary epithelial MYC expression, suggesting that T's antiestrogenic effects at the mammary gland involve alterations in ER signaling to MYC.ConclusionsThese findings suggest that treatment with a balanced formulation including all ovarian hormones may prevent or reduce estrogenic cancer risk in the treatment of girls and women with ovarian failure.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThis comprehensive review examines the safety ofCimicifuga racemosafor the treatment of menopause symptoms, particularly in populations in which conventional menopause treatment regimens, including estrogen replacement, are contraindicated.DesignAn extensive database of information onCimicifuga, which included all published literature pertaining to preclinical and clinical safety of various forms ofCimicifuga, the FDA and World Health Organization adverse-event reporting systems, monographs, compendia, internal unpublished data from a major manufacturer, foreign literature, and historical anecdotal reports, was reviewed, and findings pertaining to the safety ofCimicifugause for menopause treatment were reported.ResultsUncontrolled reports, postmarketing surveillance, and human clinical trials of more than 2,800 patients demonstrate a low incidence of adverse events (5.4%). Of the reported adverse events, 97% were minor and did not result in discontinuation of therapy, and the only severe events were not attributed toCimicifugatreatment.ConclusionsAlthough the effects ofCimicifugamay be dependent on the specific extract preparation, this review clearly supports the safety of specificCimicifugaextracts, particularly isopropanolic preparations, for use in women experiencing menopausal symptoms and as a safe alternative for women in whom estrogen therapy is contraindicated.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveSoy isoflavones, as dietary supplements, may reduce the formation of atherosclerotic lesions that increase in women after menopause. The objectives of this study were to determine whether (1) ovariectomized (ovx) hamsters will develop atherosclerotic lesions and (2) soy isoflavones can dose-dependently prevent the ovariectomy-induced rise in plasma cholesterol and atherosclerotic lesions in hamsters.DesignSeventy-two 6-month-old female Golden Syrian hamsters were randomly assigned to six groups: sham-operated; ovx control; ovx + 17&bgr;-estradiol (E2; 10 &mgr;g E2per kilogram of body weight); and ovx + 9.5 (low-dose), 19 (medium-dose), or 38 (high-dose) mg isoflavones per kilogram diet. Treatments were initiated immediately after surgery and continued for 120 days. Blood was drawn via abdominal aorta for assessment of circulating lipids, and tissues were collected, including the aortic arch for assessment of atherosclerotic lesions.ResultsAll three doses of isoflavones prevented the rise in plasma total cholesterol from ovx; and, as the isoflavone dose increases, the cholesterol-lowering effects of isoflavones become more pronounced (7.8%, 11.8%, and 19.6% reductions in total cholesterol for low-dose, medium-dose, and high-dose, respectively). Ovx hamsters developed atherosclerotic lesions without being on an atherogenic diet. Ninety-two percent of hamsters in the ovx control group had atherosclerotic lesions compared with only 8% in sham, 62% in the E2group, 29% in the low-dose group, 38% in the medium-dose group, and 58% in the high-dose group. The aortic fatty streak area was approximately 20 times higher in ovx hamsters compared with the sham animals. All doses of isoflavones were able to significantly reduce fatty streak area to that of the sham group.ConclusionsSoy isoflavones, independent of the protein source, prevent hypercholesterolemia and the formation of atherosclerotic lesions induced by ovarian hormone deficiency in hamsters. The antiatherogenic mechanisms of isoflavones need further investigation.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveMenopause-induced estrogen deficiency increases the risk of cardiovascular disease, which is related to a shift in regional fat distribution. We tested the hypothesis that estrogen-like isoflavones in soy protein isolate (SPI+) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy (SPI−).DesignPerimenopausal participants (N= 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy or whey protein per day): SPI+ (n= 24), SPI− (n= 24), or whey control (n= 21); each participant had blood drawn in the fasted (12 hours) state, had physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist, hip, and thigh regions.ResultsMean body mass increased (P< 0.01) in each group, but treatment had no effect on gain in overall body mass, fat mass, or lean mass using analysis of variance. In all treatment groups combined, lean mass increased in each region; fat mass increased only in the waist region. Treatment had an effect (P= 0.039) on hip lean mass and a marginal effect (P= 0.077) on thigh fat. Regression analyses revealed that SPI+ diminished the increase in thigh fat (P= 0.018) and heightened the increase in hip lean (P= 0.035) mass. Carbohydrate intake (P= 0.006) and cohort (reflective of season;P= 0.011) contributed to the gain in thigh fat. Total protein intake (P= 0.0012), plasma insulin (P= 0.0034), and physical activity (P= 0.047) contributed to the gain in hip lean mass.ConclusionsGain in hip lean mass was greater (P= 0.014) in SPI+ than other groups, but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveCombination of a statin plus estrogen may reveal benefits on the cardiovascular system in postmenopausal women by additively ameliorating both the lipid profile and vascular function. Long-term therapy with estrogens, however, is associated with an increase of breast cancer risk. In contrast, evidence is accumulating that statins may inhibit carcinogenesis because of their central action on important cellular functions. It is of special clinical interest whether a statin/estrogen combination may reduce the most undesired side effect of estrogen therapy, that is, an increase in breast cancer risk. Therefore, in the present in vitro study, for the first time we have compared the effect of five statins on the proliferation of human breast cancer cells alone and in the presence of stimulatory estradiol (E2).DesignAs cell models, the receptor-positive cell line MCF-7 and the receptor-negative cell line MDA-MB 231 were used. The statins atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin were tested in the concentration range of 1.6 &mgr;m to 50 &mgr;m alone and in the range of 0.01 nm to 10 &mgr;m in combination with E2. Cell proliferation was measured after 4 days by the adenosinetriphosphate-chemosensitivity test.ResultsAll statins except pravastatin were able to significantly inhibit dose dependently the cell proliferation of both cell lines. The inhibitory values were between 10% and 90%, whereby the potency was greater in the case of receptor-negative cancer cells. A significant difference in the efficacy of the statins was observed for MCF-7 cells, in which atorvastatin was less effective than the other statins. In contrast, in the presence of E2, the statins showed similar antiproliferative actions in MCF-7 cells when tested in the concentration range of 0.01 nm to 10 &mgr;m. A reduction of cell proliferation of less than 10% was observed at the lower concentrations and between 15% and 25% at the highest concentration of 10 &mgr;m.ConclusionsThe present data indicate that statins can inhibit the proliferation of receptor-positive and -negative human breast cancer cells but failed to completely abrogate the E2-induced proliferation of receptor-positive breast cancer cells. Clinical trials, however, are necessary to prove this anticarcinogenic action of statins.

ISSN:1072-3714    

出版商:OVID    

年代:2003

数据来源: OVID