Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial

OBJECTIVE: To assess the effects of raloxifene, estrogen, and placebo on quality of life in healthy, asymptomatic, postmenopausal women. METHODS: In a multicenter, double-blind, 12-month study, 398 women were assigned randomly to one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100); conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The Women's Health Questionnaire, a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and 3-month intervals. RESULTS: Overall, quality of life from baseline to end point was preserved equally in all treatment groups. Six domains (depressed mood, somatic symptoms, memory/concentration, sexual behavior, sleep problems, and perceived attractiveness) were unchanged in all groups. Three domains (menstrual symptoms, vasomotor symptoms, and anxiety/fears) were statistically significantly different among groups. Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment (P <.05), irrespective of previous hormone replacement therapy, baseline estradiol (E2) levels, or years postmenopause. CONCLUSION: Most quality-of-life domains were not affected by treatment with estrogen or raloxifene. Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved anxiety levels in postmenopausal women.     

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     

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.     

Effects of the selective estrogen receptor modulator, raloxifene, on carotid artery pulsatility index in postmenopausal women

OBJECTIVE: Estrogen replacement therapy after menopause reduces the incidence of arterial disease and cerebrovascular events. The reduced incidence also seems to be due to a positive effect of estrogens on brain blood flow as shown by a decrease in the carotid artery pulsatility index. Raloxifene, a second-generation selective estrogen receptor modulator, has aroused considerable interest because of its tissue-specific agonist-antagonist effect on estrogen receptors. However, there have been no studies on the effect of raloxifene on carotid blood flow after menopause. METHODS: A total of 66 healthy women in postmenopause for more than a year were divided randomly into 2 groups: the first group (n = 33; mean age +/- SD, 53.3 +/- 5.2 years) was treated with raloxifene (one 60-mg capsule per day) for 6 months, and the other group (n = 33; mean age +/- SD, 51.9 +/- 4 years) was untreated. Doppler ultrasonography was used to measure carotid artery pulsatility index (PI) at the beginning of the study and at 2-month intervals. RESULTS: A reduction in carotid artery PI was observed in all patients receiving raloxifene. No significant changes were observed in the control group. The reduction with respect to baseline values was 6.1%(P <.05) after 2 months, 11.2% (P <.05) after 4 months, and 13.2% (P <.05) after 6 months of therapy.The higher the baseline PI, the greater was its reduction after therapy. CONCLUSIONS: After 6 months of therapy, raloxifene induced a reduction in PI similar to that reported after estrogen therapy. The present results further our understanding of the mechanisms by which raloxifene might reduce the incidence of cardiovascular disease in postmenopausal women.     

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.     

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.     

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.     

Climacteric symptom control after the addition of low-dose esterified conjugated estrogens to raloxifene standard doses.

INTRODUCTION: Hormone therapy (HT) is one the best options for climacteric symptom control; however when women are switched to raloxifene, after several years of HT, they restart with symptoms. OBJECTIVE: To evaluate the effect of the addition of low-dose esterified conjugated estrogens to the conventional dose of raloxifene in the control of climacteric symptoms. MATERIALS AND METHODS: 14 healthy postmenopausal patients were studied. Climacteric symptoms were evaluated at baseline and 3 months after the beginning of treatment by the Kupperman's index (KI) and by the sum of the symptom evaluations carried out with an analog visual scale called SUMEVA. In all the anthropometric variables were documented, as well as time since menopause and endometrial thickness. At random they were distributed in some of the following groups: I) Raloxifene 60 mg/day (n=7) and II) Raloxifene 60 mg/day plus esterified conjugated estrogens 0.312 mg/day (n=7). STATISTICAL ANALYSIS: Differences among the groups, as well as those among baseline and those at the end of treatment, were determined by student's t test for independent samples and paired samples respectively. RESULTS: There were no differences in anthropometric variables, nor in the time since menopause. After three months of treatment the libido alterations vertigo and vaginal dryness were significantly greater in group I. In group II a significant decrease in hot flushes, insomnia, nervousness, vaginal dryness, KI, and SUMEVA were found, as was a significant increase in endometrial thickness. CONCLUSION: The treatment that is proposed in this study can constitute a temporary alternative during the period of transition from HT to raloxifene.     

Effect of estrogen replacement therapy on cardiac function in postmenopausal women with and without flushes.

Left ventricular heart function and its response to long-term estrogen replacement therapy was assessed in 30 postmenopausal women, 20 of whom had modest to severe hot flushes and 10 of whom had never had them. Continuous transdermal estradiol was given to women who had surgically induced menopause, and a combination of transdermal estradiol and sequential medroxyprogesterone acetate was given to those who had spontaneous menopause. Left ventricular systolic and diastolic function was evaluated by complete two-dimensional M-mode and pulsed Doppler echocardiography before and after 6 and 12 months of therapy. The parameters assessed were: systolic and diastolic blood pressure, heart rate, cardiac septal and posterior wall dimensions, left ventricular end-systolic and end-diastolic dimensions and volumes, ejection fraction (EF), ejection time, peak left ventricular outflow velocity (PFV), flow velocity integral (FVI), acceleration time (AT), mean acceleration of systolic flow (MA), duration of early and late filling phase, peak velocity of the early (E) and late (A) mitral flow, and A/E velocity ratio. Although no difference in chamber and wall dimensions between flushers and non-flushers was found, women with hot flushes had lower (not significantly) EF, PFV, FVI, MA, blood pressure and heart rate before therapy. Twelve-month estrogen replacement therapy significantly reduced cardiac wall dimensions and improved systolic function in both flushers and non-flushers. However, stroke volume, EF and MA were increased whereas systolic blood pressure and heart rate were decreased more in flushers. Also, the increase in E mitral flow and decrease in A/E were more pronounced in flushers. Thus, although estrogen replacement therapy significantly improves heart function in healthy postmenopausal women, there appears to be some minor differences in response between flushers and non-flushers.     

Endocrine and metabolic effects of simple hysterectomy

A survey of 60 women who had undergone simple hysterectomy with preservation of ovaries revealed a high prevalence of menopausal flushes. Only 5 (8%) had menopausal concentrations of gonadotropins and estradiol. This is similar to the prevalence of natural menopause in population of comparable age. Of the remaining 55 women, 28 (47% of the total) had normal gonadotrophins and estradiol concentrations although they complained of hot flushes; these levels were not significantly different from those in 27 women who did not flush. The "flushers" did, however, have significantly diminished bone mineral index and higher serum uric acid concentrations than the "non-flushers". Flushes disappeared in those women who took estrogen replacement therapy. These data show that although full-blown menopause does not increase in frequency following simple hysterectomy, a subtle diminution in estrogenisation is frequent. This hypo-estrogenisation is sufficient to cause: (a) hot flushes; (b) demineralisation of the skeleton and (c) an elevation in serum uric acid concentrations. There may be a case for estrogen therapy in all women who develop hot flushes following simple hysterectomy.     

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.     

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.     

Effect of raloxifene on the ovarian circulation in women after menopause

OBJECTIVE: We sought to determine whether raloxifene effects the ovarian circulation in women after menopause. STUDY DESIGN: The resistance indices of the ovarian blood flow were assessed in 130 women after menopause who were randomly assigned to receive either 60 mg of raloxifene, a continuous combined estrogen-progestin tablet daily, or neither treatment for 24 months. RESULTS: The women who received raloxifene or hormonal replacement therapy had a significant time-related decrease in the resistance index of the ovarian artery blood flow compared to baseline values (resistance index, 0.91) starting after 12 and 18 months of treatment (resistance index, 0.88 and 0.89, respectively; P <.002 and.001, respectively). Whereas significant increases in the resistance index respective to the prestudy values were observed in the nontreated women at 24 months (resistance index, 0.93; P <.0001). The mean (+/-SD) resistance index of the ovarian blood flow at the end of the study (resistance index, 0.89) was significantly lower in the women who were treated with raloxifene than in the women who were treated with hormone replacement therapy (P <.002). No changes in the ovarian dimensions or appearance were noticed during the entire study. CONCLUSION: Daily therapy with raloxifene has significant ovarian vascular-relaxing effect in women after menopause. This potentially important direct vasculoprotective long-term effect of raloxifene on cardiovascular disease deserves further investigation.     

Comparison of the effect of raloxifene and continuous-combined hormone therapy on mammographic breast density and breast tenderness in postmenopausal women

OBJECTIVE: The objectives were to evaluate mammographic changes in breast density that are associated with raloxifene or hormone therapy and to compare the safety profiles of the two therapies. STUDY DESIGN: Postmenopausal women older than 60 years who had a bone mineral density T-score of < or =-1 were assigned randomly to receive raloxifene hydrochloride 60 mg/day or continuous-combined hormone therapy that consisted of conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day in a 1-year, open-label study. Radiologists who were blinded to the treatment assignment assessed the mammograms according to the American College of Radiology Breast Image Reporting and Data System breast density categories. Breast density changes were analyzed for treatment differences. RESULTS: After 12 months of treatment, 0.9% of the women who received raloxifene had increased mammographic breast density compared with 27.4% of the women who received continuous-combined hormone therapy (P <.001). In the continuous-combined hormone therapy group, 77% of the women reported breast tenderness at any time during the study, compared to 22% of the women in the raloxifene group. CONCLUSION: In postmenopausal women with low bone mass, raloxifene therapy for 12 months does not increase mammographic breast density, whereas continuous-combined hormone therapy substantially increases breast density in a significant number of women.     

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.     

绝经后潮热妇女血浆5-羟色胺前体及代谢产物水平的变化

目的　探讨更年期妇女血浆 5 羟色胺 (5 HT)代谢的变化与潮热之间的关系。方法　采用高效液相色谱 荧光检测器 ,测定 2 0例绝经过渡早期 [年龄 (46± 3 )岁 ]、2 6例绝经过渡后期 (绝经≤1年 )、2 8例绝经 1～ 3年、2 4例绝经 3～ 6年及 12例正常育龄 (2 0～ 3 0岁 )妇女血浆中色氨酸 (TP)、5 羟色氨酸 (5 HTP)、5 HT、5 羟吲哚乙酸 (5 HIAA)及绝经后妇女血浆促黄体生成素 (LH)的水平 ;对绝经后妇女采用Kupperman评分法评分 ,其中潮热次数≤ 5次 /d(轻度潮热 )的有 2 0例 ,>5次 /d(重度潮热 )的有 15例 ,无潮热者 17例 ,分析 5 HT代谢变化与绝经时间、LH水平和潮热之间的关系。结果　 (1)绝经过渡早期妇女血浆 5 HT、绝经过渡后期和绝经 1～ 3年妇女的血浆 5 HT及 5 HIAA水平 ,显著高于育龄妇女 (P <0 0 1) ,绝经 3～ 6年妇女的血浆 5 HTP和 5 HT水平高于育龄妇女 ,而 5 HIAA水平则低于育龄妇女 (P <0 0 5 )。 (2 )绝经后妇女血浆 5 HT水平与LH水平间呈正相关 (r2 =0 5 3 0 7,P<0 0 1)。(3 )绝经后有轻度潮热者的血浆 5 HTP水平、重度潮热者血浆 5 HTP和 5 HT水平均高于无潮热者 (P均 <0 0 5 ) ,重度潮热者 5 HIAA/ 5 HT比值则显著降低 (P <0 0 5 )。结论　绝经后妇女 5 HT     

Hormone replacement therapy and lipid-lipoprotein concentrations.

OBJECTIVE: To evaluate the links between hormone replacement therapy and lipid-lipoprotein concentrations (total cholesterol [T.Ch] triglycerids, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C] and very low density lipoprotein cholesterol [VLDL-C]) in a total of 6416 postmenopausal women. STUDY DESIGN: Open prospective longitudinal study. Of the 2184 surgical postmenopausal women, 1102 received conjugated equine estrogen (CEE), and 1082 transdermal estradiol (TDE2). Of the 4232 natural postmenopausal women: 1073 received CEE+medroxyprogesterone acetate (MPA), 1068 CEE+dydrogesterone (DD), 1044 TDE2+MPA, 1047 TDE2+DD. Lipid-lipoprotein concentrations were evaluated by using a SPSS program at 1,2,3,4,5,6,7 years of therapy and cumulatively. RESULTS: Cumulative evaluation of the data on estrogen only replacement therapy revealed a significant decrease in T.Ch, LDL-C and VLDL-C, and an increase in HDL-C; however, the increase in HDL-C and triglycerids was significantly higher in CEE than TDE2 (P<0.01). Cumulative evaluation of the data on estrogen progestin hormone replacement therapy revealed a significant decrease in T.Ch, LDL-C and an increase in HDL-C for all; however, triglycerides and VLDL levels decreased in TDE2+MPA and TDE2+DD groups (P<0.05). CONCLUSION: Both the natural and surgical menopause patients were found to have more favorable lipid profiles after treatment with estrogen progesterone combined formulations and estrogen only replacement.     

Raloxifene therapy in postmenopausal women is associated with a significant reduction in the concentration of serum vascular endothelial growth factor

OBJECTIVE: To determine whether raloxifene has an effect on serum vascular endothelial growth factor (VEGF) concentration in postmenopausal women. DESIGN: A randomized, placebo-controlled trial. SETTING: University-based obstetrics and gynecology unit. PATIENT(S): Fifty postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study. INTERVENTION(S): The participants were randomly assigned on a one-to-one basis to receive either raloxifene (60 mg daily) or placebo for 36 weeks. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations at baseline and at 12 weeks and 36 weeks after the commencement of intervention. RESULT(S): The serum VEGF concentrations in the raloxifene group were significantly reduced from 247 +/- 16 pg/mL at baseline to 195 +/- 11 pg/mL at 36 weeks after starting raloxifene. The placebo group showed no significant change in the serum VEGF concentrations throughout the intervention period. CONCLUSION(S): Raloxifene therapy in postmenopausal women is associated with a significant reduction in serum VEGF concentration.     

The effect of hormone replacement therapy on the levels of serum lipids, apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal women

Objectives Estrogen replacement therapy alters the lipid profiles favorably for delaying atherosclerosis in postmenopausal women. The effects of estrogen plus progesterone combination therapy on lipids are controversial. This study was designed to evaluate the effect of female sex hormones on lipids and lipoproteins and to clarify the influence of progesterone on the effect of estrogen in postmenopausal women.Methods Of the 60 postmenopausal women admitted to our menopause clinic, 40 had intact uterus and received continuous 0.625 mg conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA), whereas the remaining 20 were hysterectomized and received 0.625 mg CEE daily. To assess the alterations in lipids and lipoproteins during menopause, 45 healthy premenopausal women were investigated. Lipid and lipoprotein levels were assessed in each subject at baseline and at the 6th and 18th months of therapy.Results In menopause, a shift towards more atherogenic lipid and lipoprotein profiles than those of the premenopausal state was found. Following 18 months of treatment, both regimens reduced total cholesterol (TC) levels as compared with the baseline (6.4 vs. 6.9% in the CEE/MPA and CEE groups, respectively). The CEE group had a more pronounced increase in high-density lipoprotein (HDL) cholesterol than the CEE/MPA group (10.3 vs. 8.8%, respectively). Both groups displayed reduced TC, low-density lipoprotein (LDL) cholesterol and apolipoprotein-B (ApoB) concentrations, whereas triglycerides increased, with a greater tendency to increase in the CEE/MPA group at the end of the trial. Also, the lipoprotein (a) [Lp(a)] levels decreased significantly (27.6 vs. 24.5% in the CEE/MPA and CEE groups, respectively). This decrease was more pronounced in subjects with a relatively higher basal Lp(a) concentration.Conclusion Both treatment regimens caused positive alterations in the lipid and lipoprotein profiles. This association might play a pivotal role in the postmenopausal increases in atherosclerotic diseases and cardioprotective effect of estrogen in postmenopausal women.