Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. METHODS: Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. RESULTS: After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). CONCLUSIONS: In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Predictors of hot flushes in postmenopausal women who receive raloxifene therapy

OBJECTIVE: In a previous report, we described the results of a randomized, controlled trial that evaluated the potential of raloxifene to induce or exacerbate hot flushes. Here, we provide additional analyses that were undertaken to identify potential predictors of hot flushes and to assess the clinical usefulness of various therapeutic strategies for the reduction of hot flushes in postmenopausal women who receive raloxifene therapy. STUDY DESIGN: In this randomized, double-blind, placebo-controlled study, 487 unselected postmenopausal women were assigned randomly to receive treatment for 8 months with raloxifene, which was administered either at a dose of 60 mg/d every other day for 2 months followed by 60 mg/d (slow-dose escalation) or 60 mg/d throughout (raloxifene), or placebo. Data on the number, duration, intensity, and severity of hot flushes and awakenings because of night sweats were collected. Logistic regression models were used to examine the predictive value of various demographic and menopausal factors on the development or worsening of hot flushes. RESULTS: At baseline, 40.4% of all randomly assigned patients had hot flushes. The mean number of hot flushes (3-5 per week) was low. Fewer years postmenopause, surgical menopause, and previous estrogen or estrogen/progestin therapy were significant predictors of hot flushes at baseline but were not predictive of incident hot flushes during treatment with raloxifene. Of the women who received raloxifene therapy who had pre-existing hot flushes at baseline, 36% women had none at the end point. Early postmenopause and surgical menopause were significant predictors of a biologically relevant increase in hot flushes (>/=14 flushes/week). Early postmenopause, previous estrogen/progestin therapy, high body mass index, and greater duration of hot flushes at baseline were significant predictors of the need for symptomatic treatment. After 2 months of treatment, women in early postmenopause had significantly more hot flushes with raloxifene therapy than with slow-dose escalation ( P = .042), whereas there was no significant difference between raloxifene therapy and slow-dose escalation among women in later postmenopause. In the 50 patients who requested symptomatic treatment during the study, phytohormones or veralipride did not reduce the number of hot flushes markedly. CONCLUSION: A shorter time since menopause and surgical menopause are important predictors of hot flushes both before and during treatment with raloxifene. Previous estrogen/progestin therapy also increases the risk of hot flushes at baseline. For women in early postmenopause, slow-dose escalation of raloxifene therapy may be a suitable therapeutic strategy for the reduction of the risk of hot flushes.     

Veralipride administered in combination with raloxifene decreases hot flushes and improves bone density in early postmenopausal women.

We evaluated the administration of raloxifene and veralipride in postmenopausal women with high osteoporosis risk and hot flushes in whom hormone replacement therapy (HRT) was contraindicated. A group of early postmenopausal women (n = 29) (mean age 51.8 +/- 4.1), complaining of severe vasomotor symptoms and with a bone mineral density (BMD) T-score between -1.5 and -2.5 were evaluated. They were randomly assigned to two treatment groups: raloxfene (60 mg/day) continuously in association with veralipride (100 mg/day) on alternate days (n = 17); or on alternate months (n = 12). BMD, serum prolactin concentration and endometrial thickness were assessed at baseline and after 6 months of therapy. Kupperman Index and hot flushes were assessed before and after 3 and 6 months of therapy. BMD was significantly higher at the end of therapy with an increase of 1.1%. Kupperman Index was significantly reduced after 3 months and a further decrease at 6 months was observed with both protocols. Both treatments led to a significant reduction of hot flushes after 3 and 6 months. No signifcant changes of prolactin levels were observed in either protocol. We found that the combined raloxifene-veralipride treatment, both every other day and every other month, led to a significant improvement in bone density and was effective in hot flushes and other menopause-associated symptoms. These protocols could represent a new way to administer raloxifene in early postmenopausal women at high osteoporosis risk with HRT contraindication.     

Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women

OBJECTIVE(S): Raloxifene, a selective estrogen receptor modulator, has beneficial estrogen agonist effects on bone and cardiovascular risk factors and estrogen antagonist effects on the breast and uterus. Limited clinical data have shown a sustained decrease in total cholesterol, low-density lipoprotein cholesterol, and homocysteine levels; an elevated homocysteine level is an independent risk factor for atherosclerosis. All of these studies were conducted in relatively young populations of women (mean age, 52-54 years). Raloxifene does not affect hot flushes, a major immediate symptom of menopause. This drug may therefore be useful in older women to prevent osteoporosis and cardiovascular disease. The aim of this clinical study was to evaluate the effects of raloxifene on plasma lipids and homocysteine in older women. STUDY DESIGN: The subjects were 45 healthy postmenopausal women, aged 60 to 70 years. The women were randomly assigned to therapy with raloxifene or placebo, 60 mg/d for 1 year. Twenty-six women received raloxifene and 19 received placebo. Checkups were performed every 3 months. At baseline and after 3, 6, 9, and 12 months of treatment we measured homocysteine, total serum cholesterol, triglycerides, and both high-density lipoprotein and low-density lipoprotein cholesterol. RESULTS: An effect on lipids was evident by 3 months with no significant additional modification at 12 months. Mean low-density lipoprotein cholesterol levels were lowered by 15% and total cholesterol was lowered by 8.5%. No reduction in high-density lipoprotein cholesterol or triglycerides was observed. After 3 months of therapy, homocysteine was significantly lower than at baseline (9.9 +/- 1.6 vs 11 +/- 2.1 micromol/L; P < .05). The greatest reduction with respect to baseline was reached after 6 months of therapy (-19.5% +/- 3%; P < .05). CONCLUSION(S): The results of our study show that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density lipoprotein cholesterol and total cholesterol in healthy older women. Our study shows that in older women raloxifene leads to a 19.5% +/- 3% reduction in fasting homocysteine levels. Raloxifene may have a favorable effect on the incidence of cardiovascular disease in older women.     

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis

Objective. The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis.

Methods. Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months.

Results. After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (?53% and ?47%, respectively) was significantly greater than for the raloxifene group (?23% and ?27%, respectively; both p < 0.01).

Conclusions. In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Raloxifene in postmenopausal women

Since the diffusion of the WHI's trial and MWS results, which reported a negative risk/benefit balance of hormone therapy, the management of postmenopausal women has deeply changed over the last 2-3 years. In particular, for the prevention of osteoporosis, the use of other efficient agents tends now to be more widely recommended rather than estrogens. The SERMs with raloxifene are new molecules that have estrogen agonist effects on bone and estrogen antagonist or neutral effects on endometrial and breast tissue. The efficacy of raloxifene to inhibit postmenopausal bone loss as well as to reduce the incidence of vertebral fractures has been demonstrated in women at high risk for osteoporosis through a large randomized placebo-controlled trial involving several thousands of postmenopausal women (MORE trial). Furthermore, the extraskeletal effects of raloxifene might represent an advantage for a global management approach of postmenopausal women, although to date, its exclusive indication is namely the prevention of osteoporosis. However, the estrogen antagonist effects of raloxifene on breast tissue as well as its good safety profile with regard to both the endometrium and the risk of heart diseases are likely to make raloxifene of particular interest for women around the age of 60 years old. Adverse events associated with raloxifene only included an increase in the absolute risk of venous thromboembolism in a comparable manner as with estrogen therapy. Also, its lack of efficacy in reducing hot flushes or preventing vaginal dryness may limit its use in young symptomatic postmenopausal women. Also, its lack of reimbursement in women with no prior fragility fracture must be taken into account.     

A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group.

OBJECTIVE: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. METHODS: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured. RESULTS: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms. CONCLUSION: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.     

Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study

OBJECTIVE: Selective estrogen receptor modulators are novel compounds that bind to the estrogen receptor and have mixed agonistic and antagonistic activities. Recently, an increase in urinary incontinence has been reported with hormone replacement therapy use. A decrease in surgical procedures for pelvic floor relaxation has been recently reported with raloxifene, a selective estrogen receptor modulator that is not uterotropic. Levormeloxifene is a selective estrogen receptor modulator that was developed for the purpose of the treatment and prevention of postmenopausal osteoporosis. STUDY DESIGN: This was a multicentered prospective study of healthy women aged >or=65 years with osteoporosis who were randomized to blindly receive placebo or levormeloxifene 0.5 mg or 1.25 mg daily as part of a planned 3-year osteoporosis treatment study. Multiple medical and gynecologic evaluations were performed. Adverse events were reported to investigators and coded with the use of World Health Organization terminology. This study was halted after 10 months because of the large number of gynecologic and other adverse events. RESULTS: Among 2924 women who were studied, those women who were treated with levormeloxifene had a marked increase compared with placebo in leukorrhea (30% vs 3%), increased endometrial thickness on ultrasound scan (19% vs 1%), enlarged uterus (17% vs 3%), uterovaginal prolapse (7% vs 2%), urinary incontinence (17% vs 4%), increased micturition frequency (9% vs 4%), lower abdominal pain (17% vs 6%), hot flushes (10% vs 3%), and leg cramps (6% vs 0.8%). All of these differences were highly statistically significant with a probability value of.0001 for each. CONCLUSION: Levormeloxifene results in multiple adverse gynecologic and other events in postmenopausal women with osteoporosis.     

雷洛昔芬对绝经后妇女骨密度、骨代谢生化指标和血脂影响的随机对照研究

目的　确定盐酸雷洛昔芬 (RLX)对中国绝经后妇女骨密度、骨代谢生化指标及血脂的影响。方法　将来自 3所医院的 2 0 4例绝经后妇女 [平均年龄 (6 0± 5 )岁 ,平均体重 (6 3± 9)kg]随机分组 ,进行双盲安慰剂对照的临床研究 ,受试者每天接受RLX 6 0mg(n =10 2 ,RLX组 )或安慰剂 (n =10 2 ,安慰剂组 )治疗 12个月 ,并于服药前及服药 12个月后各进行一次骨密度、骨代谢生化指标及血脂的测定。结果　与安慰剂相比 ,RLX使腰椎和髋部骨密度显著升高 ,RLX组腰椎的骨密度增加2 30 % ,而安慰剂组降低 0 0 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1) ;RLX组髋部骨密度增加2 4 6 % ,安慰剂组增加 1 0 7% ,两组比较 ,差异有显著性 (P <0 0 5 )。RLX组骨代谢生化指标血清骨钙素和血清C端交联肽分别降低 2 7 6 %和 2 4 0 % ,而安慰剂组则分别降低 10 6 %和升高 15 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。RLX组总胆固醇和低密度脂蛋白胆固醇分别降低 6 4 %和34 6 % ,而安慰剂组则分别升高 1 4 %和降低 19 1% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。两组间高密度脂蛋白胆固醇和甘油三酯水平未见差异。仅有 5例因不良事件而提前退出研究 (RLX组 3例 ,安慰剂组 2例 )。结论　RLX能增加绝经后中国妇女     

Transition from estrogen-progestin to raloxifene in postmenopausal women: effect on vasomotor symptoms

OBJECTIVE: To compare vasomotor symptoms after transition from estrogen-progestin therapy to raloxifene 60 mg/d with and without a placebo washout. METHODS: Postmenopausal women currently taking continuous combined estrogen-progestin therapy (conjugated equine estrogen, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg) daily for 5 or more months were enrolled. Women were randomized to 1 of 4 blinded regimens: 1) 12 weeks estrogen-progestin; 2) 12 weeks placebo; 3) 4 weeks placebo, then 8 weeks raloxifene; or 4) 12 weeks raloxifene. For the final 36 weeks, all subjects received raloxifene. Vasomotor symptoms were assessed by patient diaries. RESULTS: A total of 266 women (mean age 57.5) were enrolled. Mean hot flush frequency at baseline was approximately 1 per week in the entire population, with 16% of women reporting hot flushes. Mean frequency and severity of hot flushes during the first 12 weeks of the study were statistically greater in the 3 groups transitioned off estrogen-progestin (range of hot flushes per week: 4 weeks, 11-12; 8 weeks, 18-24; 12 weeks, 13-16), as compared with those continuing estrogen-progestin, with no difference between these 3 groups (P> or =.1). Approximately 50-70% of these women reported hot flushes, generally rated as mild to moderate by participants, after estrogen-progestin discontinuation. CONCLUSION: A large proportion of women discontinuing estrogen-progestin experience hot flushes. Raloxifene does not appear to increase the frequency or severity of vasomotor symptoms in women discontinuing estrogen-progestin more than that observed with placebo treatment after estrogen-progestin discontinuation. Transition from estrogen-progestin to raloxifene with no washout period therefore may be acceptable. LEVEL OF EVIDENCE: I     

Effects of a low-dose oral estrogen only treatment on bone mineral density and quantitative ultrasonometry in postmenopausal women

Introduction: The aim of this study was to evaluate an oral low-dose estrogen therapy on bone mineral density (BMD) and quantitative ultrasonometry (QUS) in osteopenic postmenopausal women. Material and methods: This prospective, open-label cohort study investigated 120 postmenopausal hysterectomized women. Forty-seven women had been treated with 0.3?mg conjugated equine estrogen daily (ET). Primary end point was the change in BMD at the spine after 24 months. Secondary end points were among other changes in QUS at the os calcis and phalanges. Results: After matching 42 participants in the ET group, 42 controls were analyzed. The change in BMD differed significantly after 24 months (p = 0.019). Women on ET showed significant increase of spine and hip Z-score, whereas controls showed significant decreases in spine and total hip BMD. In QUS of the os calcis and the phalanges, a number of variables showed a significant improvements with ET. Conclusion: Our results comprised a positive effect of an oral low-dose estrogen therapy on BMD. Limitations of the study are the small sample size and the open-label, non-randomized cohort study design. The findings are in accordance to the common literature and support the use of ET in the primary prevention of postmenopausal bone loss.     

Effect of raloxifene on sexual function in older postmenopausal women with osteoporosis

OBJECTIVE: To assess the effect of raloxifene compared with placebo on sexual function in older postmenopausal women undergoing therapy for the treatment of osteoporosis. METHODS: A subset (12%) of English-speaking women in the United States and Canada participating in the Multiple Outcomes of Raloxifene Evaluation Trial were asked to complete a sexual function questionnaire at baseline and after 36 months of treatment. The Multiple Outcomes of Raloxifene Evaluation Trial is a multicenter, randomized, blinded, placebo-controlled clinical trial, in which 7,705 postmenopausal women with osteoporosis were randomly assigned to one of three groups: raloxifene hydrochloride 60 mg per day or 120 mg per day or placebo. In this substudy, 943 women completed the sexual function questionnaire at both visits. Because preliminary analyses showed no differences by raloxifene dose (n = 302 for 60 mg per day; n = 322 for 120 mg/day), the two groups were combined and compared with the placebo group (n = 319). For the given sample size, we had 80% power (alpha =.05, two-sided, ratio of raloxifene to placebo = 2:1) to detect a 10%-16% difference in the proportion of women experiencing no change in sexual function between placebo and treatment groups. RESULTS: Overall, sexual function and changes in sexual function from baseline to study end between the raloxifene and placebo groups did not differ. In particular, there were no differences in sexual desire or frequency of sexual activity between the groups. Among sexually active women, there were no differences in enjoyment, satisfaction, orgasm, or reported sexual problems. CONCLUSION: Sexual function in older postmenopausal women with osteoporosis is not affected by treatment with raloxifene.     

Bone metabolism and the perimenopause overview,risk factors,screening, and osteoporosis preventive measures

In summary, FDA-approved therapies for prevention and treatment of osteoporosis are all antiresorptive agents. There are no approved therapies at this time that stimulate bone formation, although one such agent (PTH) is awaiting approval. Screening perimenopausal women at risk should identify osteopenic women early in the menopause before the accelerated bone loss of estrogen deficiency causes further irreversible erosion in bone density. The National Osteoporosis Foundation advocates initiating therapy to reduce fracture risk in postmenopausal women with T scores below -2 in the absence or factors and with T scores below -1.5 if other risk factors are present. Estrogen, alendronate, residronate, and raloxifene have all been shown to reduce the incidence of radiographic vertebral fractures in women at risk. Only alendronate and residronate have been shown in large randomized trials to reduce the incidence of nonvertebral fractures including hip fractures in women with postmenopausal osteoporosis. These antiresorptive therapies provide benefits above and beyond those of calcium and vitamin D alone. There is insufficient published evidence from randomized controlled trials convincingly to support a role for soy products, androgens, calcitonin, or fluoride in prevention of postmenopausal osteoporosis or reduction of fracture rates in women at risk.     

Statins have additive effects to vertebral bone mineral density in combination with risedronate in hypercholesterolemic postmenopausal women

BACKGROUND: Recent data suggest that statins used in the treatment of hypercholesterolaemia decrease fracture risk. In this study, we aimed to investigate prospectively whether statins have an additive effect to bisphosphonates (risedronate) according to the primary hypothesis that the addition of atorvastatin to risedronate would produce an increase, from baseline, in lumbar vertebrae and total hip BMD that was greater than that observed with risedronate alone. METHODS: A total of 120 hypercholesterolaemic postmenopausal women with osteoporosis or osteopenia were randomized to receive risedronate (5 mg/day) or risedronate (5 mg/day) plus atorvastatin (20 mg/day). Changes in bone mineral density in the lumbar spine and hip, and serum lipid and glucose metabolism changes were assessed. RESULTS: Compared with risedronate alone, at 6 months, risedronate plus atorvastatin produced significantly greater increases in the bone mineral density of the lumbar spine (1.58% versus 0.75%, p < 0.05). We found no difference after therapy in BMD of the total hip (1.2% versus 1.1%). Risedronate plus atorvastatin therapy had favorable effects on the serum lipid profile: LDL and total cholesterol. Serum fasting glucose and HbA1c levels were not affected during the treatments. CONCLUSION: Statins have modest additive effects to bisphosphonates in improving lumbar spine bone mineral density in hypercholesterolaemic postmenopausal women with established osteoporosis-osteopenia. A long-term study with adequate sample size is necessary to assess the effects of statins -- in combination or alone -- on the bones and prevention of fractures.     

Risk of fracture and treatment to prevent osteoporosis-related fracture in postmenopausal women. A review

OBJECTIVE: To review the antifracture efficacy of pharmacologic therapy approved by the U.S. Food and Drug Administration for the treatment of postmenopausal osteoporosis. STUDY DESIGN: For this literature review, published trials of antiresorptive therapy with the bisphosphonates risedronate and alendronate, the selective estrogen receptor modulator raloxifene and calcitonin were reviewed; hormone replacement therapy was not included as this modality is not indicated for treatment of osteoporosis. RESULTS: In controlled trials of postmenopausal women with osteoporosis, risedronate reduced the incidence of clinically evident vertebral fracture after 6 months of therapy and radiographically detected vertebral and nonvertebral fracture after 1 year. In similar trials, alendronate also reduced the risk of clinical vertebral fractures in 1 year. Risedronate and alendronate were both well tolerated, but some trials of alendronate were closed to women with recent upper gastrointestinal disease. In a large, controlled trial, raloxifene demonstrated a significant reduction in the risk of clinical vertebral fracture but not in the risk of nonvertebral fracture. Raloxifene is also associated with a 3-fold increased risk of thromboembolism. Calcitonin reduced the incidence of vertebral fracture, but there are no conclusive data on prevention of nonvertebral fracture. CONCLUSION: Antiresorptive therapy can reduce the risk of osteoporotic vertebral fracture. The bisphosphonates are also effective in reducing the risk of hip fracture in women with osteoporosis.     

Raloxifene effects on vasomotor and other climacteric symptoms in postmenopausal women

Introduction and Objectives: Raloxifene, a novel selective estrogen receptor modulator (SERM), is under investigation for the prevention of osteoporosis in postmenopausal women. Like traditional estrogen replacement therapy, raloxifene has beneficial effects on bone and on serum lipids whereas, in contrast to estrogen’s adverse effects in the breast and uterus, raloxifene is an estrogen antagonist in the breast and is nonstimulatory in the uterus. This study examines the effects of raloxifene 60 mg/day compared with placebo on: 1) the incidence of vasomotor symptoms: hot flashes (flushing) and sweating (including night sweats), 2) the severity and time course of hot flashes, and 3) the relation of hot flashes to baseline subject characteristics and study discontinuations. Additionally, the study explores the effects of raloxifene 60 mg/day compared with placebo on other climacteric symptoms that affect the quality of life of postmenopausal women, such as depression, insomnia, mood lability and genitourinary complaints.Methods: Integrated data from five randomized, placebo-controlled studies involving 1,165 healthy, postmenopausal women, with up to 30 months of study drug exposure, were analyzed. The incidence and severity of hot flashes and other climacteric symptoms were compared in patients treated with placebo or raloxifene (60 mg/day) via open-ended, non-directed subject self-assessment questionnaires. Data were analyzed for subgroup-by-therapy interactions using many baseline subject characteristics such as age, body mass index, smoking, alcohol, and years post-menopause, as well as preexisting conditions such as hot flashes, sweating, insomnia, depression, and history of hysterectomy. The overall incidence of other climacteric symptoms were reported as adverse events.Results: The increase in overall incidence of hot flashes in raloxifene-treated (24.6%) and placebo-treated (18.3%) subjects was modest, but statistically significant. However, this difference was significant only during the first 6 months of therapy, raloxifene (20.1%) compared with placebo (14.4%). After 6 months of treatment, there was no statistically significant difference in the incidence of hot flashes between the two treatment groups. The majority of hot flashes in raloxifene-treated subjects were subject-assessed as “mild-to-moderate” in severity (89%). The incidence of hot flashes reported as “severe” did not differ significantly in raloxifene- or placebo-treated subjects. Subgroup analyses revealed the overall incidence of hot flashes to be highest for both raloxifene and placebo-treated subjects, in younger (age < 55 years) women (P = .004), in women who had previously experienced hot flashes (P = .031), and in women having had hysterectomies (P < .001). Within each of these subgroups, there was no statistical difference in the incidence of hot flashes between the raloxifene and placebo groups. Between the two treatment groups, there was no difference in the overall incidence of subject discontinuations from study due to hot flashes. The occurrence of the other common vasomotor symptom, sweating (which includes night sweats), was not statistically different for the raloxifene- or placebo-treated subjects.Genitourinary complaints are often symptoms related to vaginal dryness, such as dyspareunia and decreased libido, as well as other symptoms of vaginitis and leukorrhea. No statistically significant differences occurred for raloxifene- or placebo-treated subjects in reports of these genitourinary symptoms. Similarly, for the other common climacteric symptoms; depression, insomnia, and mood lability, no significant differences in incidence between the raloxifene and placebo treatment groups were observed.Conclusions: Raloxifene (60 mg/day) treatment modestly increased the incidence of hot flashes compared with placebo, however, this difference was only statistically significant during the first 6 months of treatment. There were no differences in the severity of hot flashes between treatment groups, and this symptom did not adversely affect subjects’ study participation. In both the raloxifene and placebo treatment groups, young postmenopausal women (age < 55), those with baseline hot flashes, and those with histories of hysterectomy were most likely to experience hot flashes. Raloxifene therapy did not affect the occurrence of other climacteric symptoms commonly affecting the quality of life of women after menopause.     

Raloxifene effect on frequency of surgery for pelvic floor relaxation.

OBJECTIVE: To assess the effects of raloxifene therapy on the frequency of surgery for pelvic floor relaxation in postmenopausal women. METHODS: This analysis used safety data through 3 years of treatment from three double-masked, placebo-controlled, randomized trials of raloxifene, which included 6926 postmenopausal women with uteri at entry. Studies 1 and 2 enrolled 969 nonosteoporotic, postmenopausal women who were assigned to 30, 60, or 150 mg per day raloxifene or placebo. Study 3 enrolled 5957 osteoporotic, postmenopausal women randomized to raloxifene 60 or 120 mg per day or placebo. Indications for any reported pelvic operations were identified, including procedures performed for pelvic organ prolapse or urinary incontinence. RESULTS: A total of 34 (1.51%) women in the placebo group and 35 (0.75%) raloxifene-treated women underwent surgical procedures for pelvic floor relaxation. The odds ratio (and 95% confidence interval) for pelvic floor repair in women assigned to raloxifene was 0.50 (0.31, 0.81). Thus, raloxifene therapy was associated with a significantly reduced risk for pelvic floor surgery (P <.005). CONCLUSION: Raloxifene does not increase pelvic floor relaxation. An apparent protective effect on pelvic floor function warrants further investigation.     

Effect of specific exercise training on bone mineral density in women with postmenopausal osteopenia or osteoporosis

Aim.?To analyse the effect of a specific program of weight training exercise with closed kinetic chain in bone mineral density in postmenopausal women with osteopenia or osteoporosis.

Methods.?A total of 59 postmenopausal women with osteoporosis or osteopenia were included in this prospective study. Subjects were divided into two groups: the study group (SG, n = 30; 57.5 ± 5.1 years) and the control group (CG, n = 29; 56.6 ± 4.6 years). In the study group was applied a weight exercise protocol (longitudinal forces in closed kinetic chain) during 12 months, whereas in the control group no weight exercise protocol was applied. Bone mineral density at the lumbar spine and hip was assessed at baseline and at the end of follow-up by dual energy X-ray absorptiometry.

Results.?Although no significant intragroup differences were found, patients in SG showed a 1.17% increase in the lumbar spine whereas in CG a 2.26% decrease in bone density was detected.

Conclusion.?This protocol of weight training exercise did not significantly improve bone mineral density in postmenopausal women with osteopenia or osteoporosis, but in comparison to the control group, the results showed the importance of practising the specific exercise program for maintenance of bone health in postmenopausal women.     

Association between P1NP and bone strength in postmenopausal women treated with teriparatide

ObjectiveTo evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide.Materials and MethodsThis prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months.ResultsWith teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months.ConclusionP1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.