Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: a 2-year, double-blind, placebo-controlled study

OBJECTIVE: To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio. DESIGN: A 2-year randomized, double-blind, placebo-controlled study. SETTING: Endocrinology outpatient department. PATIENT(S): Fifty-six postmenopausal, hysterectomized women. INTERVENTION(S): Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years. MAIN OUTCOME MEASURE(S): At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated. RESULT(S): Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was -32.5% (95% CI: -20.1; -44.8%) for CEE; -16.4% (95% CI: -3.6; -29.2%) for raloxifene at 150 mg/day; and -15.4% (95% CI: -1.0; -29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point. CONCLUSION(S): Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.     

Effect of hormone therapy and raloxifene on serum VE-cadherin in postmenopausal women

OBJECTIVE: To investigate the effect of continuous combined hormone therapy and raloxifene on serum VE-cadherin. DESIGN: The study was double blinded, with a placebo run-in period of 28-50 days. SETTING: University menopause clinic. PATIENT(S): Twenty-eight healthy postmenopausal women devoid of climacteric complaints. INTERVENTION(S): Subjects were randomized to 17beta-estradiol (2 mg) + norethisterone acetate (1 mg; E(2)-NETA) or raloxifene hCL (60 mg) for a period of 6 months. MAIN OUTCOME MEASURE(S): Serum VE-cadherin, which was estimated at baseline and at month 6. RESULT(S): Serum VE-cadherin decreased significantly in both E(2)-NETA and raloxifene groups (raloxifene baseline +/- SD: 1.17 +/- 0.44 ng/mL, 6 months: 0.82 +/- 0.29 ng/mL; E(2)-NETA baseline: 1.19 +/- 0.47 ng/mL, 6 months: 0.92 +/- 0.49 ng/mL). Percentage changes from baseline were -21.7 +/- 24.3 for E(2)-NETA and -26.0 +/- 20.6 for raloxifene. CONCLUSION(S): The effect of E(2)-NETA and raloxifene suggests that these drugs may preserve interendothelial junction integrity and control vascular permeability. Although this effect may influence the progress of the atheromatous lesion, its clinical impact on coronary artery disease (CAD) remains uncertain.     

Glycosaminoglycan profile in bladder and urethra of castrated rats treated with estrogen, progestogen, and raloxifene

OBJECTIVE: This study was undertaken to evaluate the action of conjugated equine estrogens alone, medroxyprogesterone, the combination of these estrogens with progestogens, and of raloxifene on the glycosaminoglycan profile in the bladder and urethra of adult oophorectomized rats in comparison with noncastrated rats. STUDY DESIGN: Sixty adult rats, of which 50 were submitted to bilateral oophorectomy, were studied. After 4 days, the latter were assigned to five groups of 10 animals each. For 30 consecutive days the following treatments were given: group 1, conjugated equine estrogens; group 2, conjugated equine estrogens combined with medroxyprogesterone acetate; group 3, medroxyprogesterone; group 4, raloxifene; and group 5, placebo. Thereafter the bladders and urethras of the animals were removed, processed to yield a dry powder of which the sulfated glycosaminoglycan content was determined by densitometry after agarose gel electrophoresis and that of hyaluronic acid by a fluorimetric assay. RESULTS: Glycosaminoglycans found in the bladder and urethra were dermatan sulfate, heparan sulfate, and hyaluronic acid. In the bladder, hypoestrogenism or replacement with estrogens led to a lower sulfated glycosaminoglycan content. Replacement with estrogens and/or medroxyprogesterone reverted this effect. Hypoestrogenism decreased the dermatan sulfate/heparan sulfate ratio and reduced hyaluronic acid content. Estrogen therapy reverted this alteration and medroxyprogesterone addition annulled the estrogenic effect. In the urethra, castration did not alter hyaluronic acid content and sulfated glycosaminoglycan content, but raloxifene decreased the latter. CONCLUSION: Castrated rats had a decrease in sulfated glycosaminoglycans and hyaluronic acid content in the bladder. Hormonal replacement altered the quantity and quality of glycosaminoglycans. In the urethra, raloxifene reduced sulfated glycosaminoglycans.     

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in postmenopausal women: a randomized clinical trial in Beijing

Withdiminishedovarianfunctionanddecreasedestrogenlevels,postmenopausalwomenareatriskforosteoporosis ,whichleadstopossibleseriousanddebilitatingfractures Estrogen ,combinedwithprogestininhormonereplacementtherapy (HRT) ,iscommonlyprescribedtowomentoalleviatepostmenopausalvasomotorsymptomsandprotectagainstthedevelopmentofosteoporosis 1,2 　However ,thelong termuseofestrogenisrequiredtopotentiallyrealizethattheseclinicalbenefitsalsoincreasestherisksofendometrialcancerandbreastcancer 2 4 　Thein…     

Raloxifene

Raloxifene is a selective estrogen receptor modulator, a compound that has estrogen agonist activity at some sites and antagonist activity at others. In investigations in animals and in rigorously conducted trials in humans, raloxifene treatment is associated with a 30%–40% reduction in risk of one or more spine fractures using the 60 mg dose. This reduction in risk is found in women with or without baseline fractures, in women with bone mineral density (BMD) in the lower, middle, or upper third of the low range (all had BMD reduced by more than 2.5 SD) and in women aged less than 65 years, between 65–70 years, and greater than 70 years. A reduction in ankle fractures, but not hip or wrist fractures, was found. Raloxifene treatment also is associated with a 60%–70% reduction in risk for breast cancer and is associated with reduced total and LDL cholesterol, lower fibrinogen, and no rise in triglyceride. Reduced aortic wall cholesterol content is reported in animal studies. These are surrogate endpoints of cardioprotection. There is no evidence that raloxifene reduces the incidence of myocardial or cerebrovascular events. Raloxifene does not induce breast tenderness, endometrial hyperplasia, menstrual bleeding, or endometrial cancer, but may be associated with an increased risk of thromboembolic disease (1/1000 cases per year), leg cramps in 2%–4% of cases and hot flushes in 4%–6% of cases, usually in first 6 months. Received: September 6, 2000     

雷洛昔芬对去卵巢大鼠骨组织雌激素受体亚型表达的影响

目的 探讨雌激素受体在骨质疏松中的作用及雷洛昔芬对其调整作用.方法 选择3月龄Sprague-Dawley雌性大鼠48只,随机分为假手术组、去卵巢组、雌激素组及雷洛昔芬组,每组12只,给药3个月后处死大鼠.分离获取股骨,应用RT-PCR技术检测骨细胞中ER mRNA表达水平.结果 雷洛昔芬使去卵巢大鼠骨密度增加,提高ERα mRNA,对ERβ mRNA的表达无明显的影响作用.结论 雷洛昔芬可能通过对ER基因表达的影响而起到治疗骨质疏松的作用.     

The use of raloxifene in osteoporosis treatment

Management of the menopause is a rapidly growing concern due to the ageing human population. The overall female lifespan has increased over the last century and up to a third of a woman’s life is now spent in menopause. To that end, significant attention has been placed on maximising the quantity and quality of life in the menopausal years. The optimal management strategies are ones that are highly flexible and sensitive to an individual’s expectations and concerns. Thus, while traditional oestrogen replacement therapy has been in place for > 20 years, there is now a greater interest in alternatives to this modality for those women who cannot or will not use it. This article reviews some of the alternative therapies that are being incorporated both in the allopathic and complementary medicine arenas.     

Effects of raloxifene on the renin–angiotensin–aldosterone system and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women

Aim:   An increase in blood pressure after menopause has been documented. The renin–angiotensin–aldosterone system (RAAS) plays a central role in the regulation of blood pressure and in the pathophysiology of hypertension. This study investigated the effects of raloxifene, a selective estrogen receptor modulator, on components of the RAAS and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.
Methods:   A total of 41 hypertensive or normotensive postmenopausal women with osteoporosis or osteopenia were divided into four groups. Eleven hypertensive and eight normotensive women received raloxifene hydrochloride (60 mg/day) p.o. for 6 months, and 12 hypertensive and 10 normotensive women did not receive raloxifene hydrochloride for 6 months. In all of the hypertensive women, blood pressure had been controlled prior to the start of the study using a variety of antihypertensive drugs other than angiotensin-converting enzyme (ACE) inhibitors, angiotensin (Ang)II type 1 receptor antagonists or diuretics. Plasma renin activity (PRA), serum ACE activity, plasma AngI, AngII and aldosterone concentrations, and blood pressure were measured before and 6 months after the start of the study.
Results:   No significant changes in PRA, ACE activity, or the AngI, AngII or aldosterone levels were observed in any of the groups. In all the groups, blood pressure remained unchanged.
Conclusion:   Raloxifene may have no significant effect on the RAAS or blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.