Evaluation of the sexual function and quality of life in raloxifene treated postmenopausal women

Objective  To evaluate the net effect of raloxifene on overall quality of life and sexual function in postmenopausal women. Methods  The study was performed in the Gynecology and Obstetrics outpatient clinic of Gazi University Faculty of Medicine between January 2002 and February 2005. Fifty postmenopausal women, in whom raloxifene was indicated for prevention and treatment of osteoporosis, were considered the study group. Fifty postmenopausal women who were not osteoporotic were enrolled as the control group. Participants completed a questionnaire composed of several parts (GRISS, BDI and ISI), at the beginning and end of the 12-month treatment period. Results  Two groups were similar to each other with respect to total GRISS scores at the beginning and at the end of the study (P = 0.929 and P = 0.508; respectively). Raloxifene was associated with a significant improvement from baseline in the total scores of BDI (P = 0.0001), whereas this improvement was not significantly different from the control group (P = 0.216). With regard to ISI scores, there were no differences between groups in total scores. Raloxifene use did not seem to affect subscores of ISI either. Conclusions  This study failed to prove any deleterious effect of raloxifene on quality of life and sexual functions.     

Effect of raloxifene on the vaginal epithelium of postmenopausal women

OBJECTIVE: The objective was to analyze the effect of raloxifene on the vaginal epithelium of postmenopausal women. STUDY DESIGN: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted a non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection in the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis. RESULTS: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p>0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups. CONCLUSION: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium in postmenopausal women with osteoporosis.     

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.     

Clinical efficacy of raloxifene in postmenopausal women.

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.     

Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women.

Raloxifene is a selective estrogen modulator able to exert an estrogen-like action on some target tissues and a specific antiestrogenic action on the uterus and breast. In ovariectomized rats, it has been shown to stimulate the beta-endorphin and allopregnanolone concentrations of the anterior and neurointermediate pituitary lobes, the hypothalamus and the hippocampus. The present study aimed to evaluate, in 12 healthy postmenopausal women, the effect of 60 mg/day raloxifene hydrochloride administration for 6 months on plasma beta-endorphin and allopregnanolone levels, and on the dynamic changes of both beta-endorphin and allopregnanolone secretion after the administration of: (1) clonidine, an alpha 2-presynaptic adrenergic agonist; (2) naloxone, an opioid receptor antagonist; and (3) fluoxetine, a serotonin selective reuptake inhibitor. The administration of raloxifene significantly increased both circulating beta-endorphin and allopregnanolone concentrations, at both the third and sixth months of treatment (p < 0.01). Clonidine, fluoxetine and naloxone administration before therapy was not able to stimulate the release of beta-endorphin, but the response was completely restored after raloxifene administration. Before therapy, clonidine and naloxone tests were accompanied by a significant rise in allopregnanolone secretion; the same changes were observed after raloxifene administration, but with significantly higher allopregnanolone concentrations at each time considered. While the fluoxetine test before therapy failed to increase the release of allopregnanolone, the same test after 6 months of raloxifene administration was characterized by a significant release of allopregnanolone at 60 and 90 minutes. The present data indicate that raloxifene has an estrogen-like effect on neuroendocrine pathways in postmenopausal women.     

Adverse events reported by postmenopausal women in controlled trials with raloxifene

OBJECTIVE: To assess the incidence of adverse events in postmenopausal women treated with raloxifene compared with placebo, hormone replacement therapy (HRT), or unopposed estrogen. METHODS: Common treatment groups were pooled across eight randomized, parallel clinical trials (6-30 months' duration) of raloxifene to create the following three databases: placebo-controlled, HRT-controlled, and estrogen-controlled databases. Incidence and severity of all treatment-emergent adverse events, defined as events that first occurred or worsened during treatment, were compared among groups in each of the databases. RESULTS: Discontinuation rates overall, and those related to adverse events, were not significantly different between treatment groups in any database. There was no significant difference in incidence of vaginal bleeding or breast discomfort between women treated with raloxifene (60 mg/d) or placebo. Both of these events were reported more frequently in women receiving HRT or estrogen. Vaginal bleeding was responsible for significantly more discontinuations from the HRT groups compared with the raloxifene group. Hot flashes was the only event common to all three databases that was significantly increased in the raloxifene group, but this event did not increase the discontinuation rates. The incidence of leg cramps was greater in raloxifene-treated women compared with placebo-treated women in the placebo-controlled database, but did not cause any discontinuations of therapy. Raloxifene had no effect on the incidence of vaginal symptoms or central nervous system events. CONCLUSION: Raloxifene had an adverse event profile distinct from HRT and unopposed estrogen and was well tolerated by postmenopausal women.     

Effects of raloxifene hydrochloride on the endometrium of postmenopausal women

OBJECTIVE: We evaluated subtle endometrial morphologic changes in postmenopausal women assigned to placebo, raloxifene hydrochloride 200 or 600 mg/day, or conjugated estrogens (Premarin 0.625 mg/day) according to a new estrogenicity scoring system. Raloxifene, a new selective estrogen receptor modulator, was not expected to stimulate the endometrium. STUDY DESIGN: Baseline and end point endometrial biopsies were performed during this double-blind, placebo-controlled 8-week study. A scoring system that was based on standard glandular and stromal morphologic criteria was used to quantitate estrogen-induced effects. Baseline, end point, and baseline–to–end point changes were analyzed for treatment differences. RESULTS: Treatment groups were similar at baseline with most women showing no estrogenic effects. At end point, statistically significant moderate and marked estrogenic effects were noted in 77% of estrogen-treated women versus 15% of placebo-treated women versus 0% of raloxifene-treated women. CONCLUSIONS: As expected, estrogen treatment stimulated postmenopausal endometrium. In contrast, raloxifene did not induce histopathologic evidence of endometrial stimulation in healthy postmenopausal women.(Am J Obstet Gynecol 1997;177:64)     

Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women.

OBJECTIVE: To evaluate the effects of raloxifene administration on uterine and uterine leiomyoma sizes in postmenopausal women. DESIGN: Prospective randomized, double-blind, placebo-controlled clinical trial. SETTING: Department of Gynecology, Obstetrics, and Pathophysiology of Human Reproduction, University of Naples "Federico II", Italy. PATIENT(S): Seventy spontaneous postmenopausal women affected by uterine leiomyomas. INTERVENTION(S): Twelve cycles (of 28 days each) of treatment with raloxifene (60 mg daily per os) or placebo. MAIN OUTCOME MEASURE(S): At entry and at every 3 cycles, uterine and uterine leiomyoma dimensions were measured by means of transvaginal ultrasound. The difference between uterine and leiomyoma volumes (Delta size) was calculated in all subjects. The characteristics of uterine bleeding and the side effects of the treatments were assessed using a daily diary. RESULT(S): After 6, 9, and 12 cycles of therapy, in subjects treated with raloxifene, the mean uterine and uterine leiomyoma size were significantly decreased, and the mean Delta size significantly increased in comparison with basal values and the placebo group. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S): In postmenopausal women raloxifene appears to act selectively on uterine leiomyomas, reducing their size.     

Effect of risedronate on biochemical marker of bone resorption in postmenopausal women with osteoporosis or osteopenia

Objective.?The primary objective of the present study was to evaluate the effectiveness and adverse events of risedronate use in postmenopausal woman by measuring its effects on urinary crosslinked C-terminal telopeptides of type I collagen (CTx), a biochemical marker of bone resorption.

Methods.?One hundred osteoporotic (control and treatment) and 111 osteopenic (control and treatment) postmenopausal women, selected according to World Health Organization criteria, were included in the study. The treatment groups (osteopenic and osteoporotic) were given risedronate 35 mg once a week. The primary endpoint was mean percentage change in CTx from baseline to 6 months. The secondary endpoints included evaluation of the incidence of clinical or laboratory adverse events occurring during the 6-month study period. The least significant change (LSC), calculated from the within-subject variability in the two control groups, was used to define response.

Results.?Of the 211 women enrolled, 157 (74.4%) completed the study. After 6 months, urinary CTx levels were ?54.7% (range ?67% to ?48%) below baseline in the osteoporotic treatment group and ?66.7% (range ?74% to ?59%) below baseline in the osteopenic treatment group. Analysis of LSC showed that 89% of risedronate treatment groups were categorized as responders after 6 months of treatment.

Conclusion.?The study shows that osteoporotic and osteopenic women on risedronate treatment have statistically significant suppressed bone turnover and CTx can be useful to confirm this observation. The low withdrawal rate and adverse effects rate show that risedronate was well tolerated by the study population.     

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.     

Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women

OBJECTIVE: We sought to compare the uterine effects of raloxifene with those of continuous-combined hormone replacement therapy. STUDY DESIGN: This randomized, double-blind 24-month study involved 136 postmenopausal women who received raloxifene 150 mg/d or conjugated equine estrogens 0.625 mg/d with medroxyprogesterone acetate 2.5 mg/d. After baseline evaluations, endometrial biopsy specimens were obtained, and endometrial thickness was measured annually by means of transvaginal ultrasonography. Statistical analyses were performed with an intention-to-treat approach. RESULTS: In the raloxifene group at the end point of the study 94.4% of biopsy specimens showed normal benign postmenopausal endometrium and 5.6% were classified as benign stimulatory endometrium. In the continuous-combined hormone replacement therapy group at the end point of the study 78.7% of biopsy specimens showed normal benign postmenopausal endometrium, 19. 1% were classified as benign stimulatory endometrium, and 2.1% showed benign abnormal postmenopausal endometrium. Mean endometrial thickness was unchanged from baseline with raloxifene and was increased significantly by 0.5 mm at 12 months with continuous-combined hormone replacement therapy. CONCLUSION: Raloxifene 150 mg/d did not increase endometrial thickness or cause endometrial proliferation in healthy postmenopausal women.     

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.