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Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss.

OBJECTIVE: To evaluate the efficacy of Tofupill/Femarelle (DT56a), a novel phyto-selective estrogen receptor modulator (SERM), in preserving bone mineral density (BMD) in postmenopausal women. DESIGN: The study sample consisted of 98 healthy, postmenopausal women who were randomly allocated, on a double-blind basis, to receive either 644 mg/d DT56a (study group) or 344 mg/d DT56a supplemented with calcium (low-dose group) for 12 months. Each participant was assessed with a comprehensive health questionnaire, a detailed physical, and laboratory and pelvic sonogram examinations at entry and every 3 months thereafter. BMD was assessed by dual-energy x-ray absorptiometry (Lunar) of the lumbar spine and femoral neck before the study began and after 12 months of treatment. RESULTS: After 12 months of treatment, BMD had increased in the study group by 3.6% in the lumbar spine (P = 0.039) and by 2.0% in the femoral neck (NS). In the low-dose group, BMD had decreased in the lumbar spine by 0.6% (NS) and by 0.6% in the femoral neck (NS). Comparison of the change in bone density between the groups yielded a significant difference for the lumbar spine (P = 0.037). Neither group showed a change in endometrial thickness and sex hormone levels nor reported any side effects of treatment. CONCLUSIONS: Tofupill treatment in postmenopausal women increases BMD without unwanted estrogenic effect. Tofupill appears to be a promising phyto-SERM for the prevention of postmenopausal osteoporosis.

Bone Density↗

Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study.

OBJECTIVES: Results from the Women's Health Initiative showed that postmenopausal hormone replacement therapy (HRT) prevents fractures but has an overall unfavorable risk:benefit ratio, leading to the recommendation that HRT be used only for women with troublesome menopause symptoms, and for as short a time as possible. This recommendation has important implications for the timing and duration of HRT and the prevention of osteoporosis. The large number of women participating in the National Osteoporosis Risk Assessment (NORA) program provided the opportunity to evaluate bone mineral density (BMD) and 1-year fracture risk in analyses stratified by duration and recency of HRT. DESIGN: Participants were 170,852 postmenopausal women aged 50 to 104, without known osteoporosis, who were recruited from primary physicians offices across the US. BMD was measured at one of four peripheral sites, and the 1-year risk of osteoporotic fracture was assessed by questionnaire. RESULTS: At baseline, current HRT users had the highest T-scores at every age. Among current hormone users, women who had used HRT longest had the highest BMD levels. Women who had stopped HRT more than 5 years previously, regardless of duration of use, had T-scores similar to never-users. Current but not past hormone use at baseline was associated with a 25% to 29% lower risk of osteoporotic fracture (P < 0.0001) in 1 year, compared with nonusers. These findings were independent of age, ethnicity, body mass index, lifestyle, years postmenopausal, and site of BMD measurement. CONCLUSIONS: We conclude that postmenopausal BMD and fracture are closely associated with current, but not prior, HRT use. Use of HRT for 5 years or less, as proposed for treatment of symptomatic women during menopause transition, is unlikely to preserve bone or significantly reduce fracture risk in later years.

Aged↗

Prevalence of natural health product use in healthy postmenopausal women.

OBJECTIVES: Population studies examining dietary supplement use reveal that users are more likely to be women of older age, yet there are few focused studies among postmenopausal women. The purpose of this study was to determine the prevalence of natural health product (NHP) use, as well as the attitudes and motivations associated with NHP use, among postmenopausal women. DESIGN: Healthy postmenopausal women were recruited from shopping malls and community centers to complete a questionnaire that collected information regarding use of NHPs; attitudes and motivations about NHPs; and demographic, health, and lifestyle characteristics. RESULTS: The prevalence of NHP use among the 204 subjects was 83.3%. There were no significant differences in characteristics between NHP users and non-users, with the exception of a lower body mass index among NHP users (P = 0.01). The most commonly consumed NHP was calcium, followed by multivitamins/minerals, vitamin C, and vitamin E. Almost all NHP users (98.8%) believed that NHPs improved their overall health, and most (70.6%) attributed specific positive effects to their NHPs. Three quarters of NHP users believed that their NHPs could not cause adverse effects, and 64.2% believed that their NHPs could not interact negatively with medications. The most common source of NHP information was magazines/books, and 71.8% of NHP users indicated they did not need further information about their NHPs. CONCLUSIONS: In this study, we found that the prevalence of NHP use among a sample of 204 healthy postmenopausal women was 83.3% and that, apart from body mass index, there were no variables that predicted NHP use.

Aged↗

Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis.

OBJECTIVE: There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer. DESIGN: We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of "current use" of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses. RESULTS: Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18). CONCLUSIONS: Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials.

Breast Neoplasms↗

Postmenopausal oral estrogen therapy and blood pressure in normotensive and hypertensive subjects: the Estrogen in the Prevention of Atherosclerosis Trial.

OBJECTIVE: To determine if 17beta-estradiol increases blood pressure in postmenopausal women. DESIGN: A total of 222 healthy postmenopausal women were randomly assigned to either 1 mg micronized 17beta-estradiol daily or placebo for 2 years. Blood pressure measurements were obtained every other month and common carotid artery intima-media thickness measured every 6 months. Statistical analyses comparing longitudinal changes in systolic and diastolic blood pressure between treatment groups used a mixed general linear model including interaction terms to evaluate variations by age or estradiol level. RESULTS: Both placebo and estradiol groups showed small declines in systolic and diastolic blood pressure during the trial among the normotensive subjects and subjects on antihypertensive medications. However, the decline did not differ significantly between the groups. Treatment effects on systolic blood pressure differed significantly by the age of the subject (interaction P value = 0.04) with younger women on estradiol showing on average a rise in systolic blood pressure, and older women a decline. The association between serum estradiol level and systolic blood pressure showed a similar modification with age (P = 0.03). Changes in systolic blood pressure in women on estradiol were positively correlated with intima-media thickness progression (P = 0.03). CONCLUSIONS: Overall, 17beta-estradiol did not influence changes in blood pressure in normotensive or hypertensive women. The effect of 17beta-estradiol treatment on systolic blood pressure may be influenced by a woman's age. Estradiol may increase systolic blood pressure in younger postmenopausal women, while having the opposite effect in older postmenopausal women.

Age Factors↗

Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene.

OBJECTIVE: Osteoporosis is a significant health problem in postmenopausal women. Consequently, new and effective therapies are being sought to preserve bone mass and prevent osteoporosis in this population of women. The objective of this study was to compare the effects of lasofoxifene with raloxifene and placebo on indices of bone health in postmenopausal women. DESIGN: A randomized, double-blind, placebo- and active treatment-controlled study of 2 years duration was conducted. Women included 410 postmenopausal women aged 47 to 74 years. The four treatment groups were: lasofoxifene 0.25 mg/day, or 1.0 mg/day, raloxifene 60 mg/day, or placebo daily. All women received daily calcium and vitamin D supplements. The primary endpoint was percent change from baseline to 2 years in lumbar spine bone mineral density (BMD) in all women having baseline and at least one follow-up bone density measurement. Total hip BMD, biochemical markers of bone turnover, low-density lipoprotein cholesterol, and safety were also evaluated in all women. RESULTS: Both doses of lasofoxifene significantly increased lumbar spine BMD compared with raloxifene (P < or = 0.05) and with placebo treatment (P < or = 0.05). Least squares mean increases (95% CI) from baseline in lumbar spine BMD, compared with placebo, were 3.6% (1.9, 5.2) for lasofoxifene 0.25 mg/day, 3.9% (2.4, 5.5) for lasofoxifene 1.0 mg/day, and 1.7% (0.3, 3.0) for raloxifene. The two doses of lasofoxifene and raloxifene were equally effective at increasing total hip BMD. Lasofoxifene and raloxifene significantly reduced the levels of biochemical markers of bone turnover compared with placebo. In general, the effects of lasofoxifene were greater than the responses to raloxifene. At 2 years, lasofoxifene significantly (P < or = 0.05) reduced low-density lipoprotein cholesterol levels by 20.6% and 19.7% with 0.25 mg/day and 1 mg/day, respectively, compared with raloxifene (12.1%) and placebo (3.2%). Lasofoxifene and raloxifene had a similar adverse event profile with low rate of discontinuations due to adverse events. CONCLUSIONS: Lasofoxifene may be an effective and well-tolerated treatment option for the prevention of bone loss in postmenopausal women.

Aged↗

Effect of estradiol versus estradiol and testosterone on brain-activation patterns in postmenopausal women.

OBJECTIVE: To determine the effect of estradiol and testosterone on brain-activation patterns in surgically postmenopausal women viewing erotic video clips using functional magnetic resonance imaging. DESIGN: Six women, who had undergone a bilateral oophorectomy and hysterectomy for benign disease, viewed erotic and neutral videos during functional magnetic resonance imaging while not on hormone therapy, while on estradiol therapy, and while on estradiol and testosterone therapy. Five similarly aged premenopausal women viewed the same videos. Areas of brain activation between the functional magnetic resonance imaging scans of both groups of women were compared with determine whether agonadal serum levels of sex hormones and administration of estradiol and testosterone impacted brain patterns of sexual arousal. RESULTS: When compared with premenopausal women, untreated postmenopausal women had significantly decreased areas of brain activation during both erotic and neutral stimulations. Administration of estradiol increased global brain-activation patterns during both visual stimulations, with erotic video viewing causing a limited increase in limbic system activation. Combined estradiol and testosterone therapy was associated with a greater activation of the central nervous system, with more limbic system activated during the erotic video. Brain-activation patterns of the postmenopausal women were similar to the premenopausal group only during the estradiol and testosterone treatment phase. CONCLUSIONS: Agonadal serum hormone levels result in globally decreased brain-activation patterns in postmenopausal women while viewing neutral and erotic videos. Administration of both estradiol and testosterone increase global brain activation, and both sex steroids are independently associated with enhanced limbic system response during erotic visual stimulation.

Adult↗

The importance of continued exercise participation in quality of life and psychological well-being in previously inactive postmenopausal women: a pilot study.

OBJECTIVE: Exercise and physical activity provide a wide range of health benefits for postmenopausal women, although the impact of maintained exercise participation on psychological well-being is unclear. An exploration of continued exercise participation in psychological well-being after a moderate-intensity exercise program in previously inactive postmenopausal women was therefore undertaken. DESIGN: : Twenty-three healthy sedentary postmenopausal women (age 56 +/- 4 years) were randomly assigned to two groups. All participants completed the Short Form-36, Hospital Anxiety and Depression Scale (HADS), and Health Anxiety Questionnaire (HAQ) and then began a 6-week walking program at 50% heart rate reserve defined by (.-)V(O(2)) treadmill testing. Post-intervention, all participants underwent (.-)V(O(2)) treadmill testing and questionnaires. Group 1 was then instructed to continue exercising, whereas group 2 was instructed to desist for an additional 6-week period. On completion of the 6-week follow-up, participants completed a final set of questionnaires. RESULTS: Participants performed 97% of the prescribed 15-hour (900 minute) exercise program (875.1 +/- 177.4 minutes) in an average of 26 +/- 5 sessions. Total HAQ (P = 0.001), health worry (P = 0.001), fear of illness (P = 0.037), reassurance seeking behavior (P = 0.037), SF-36 well-being (P = 0.037), total HADS (P = 0.019), and HADS depression (P = 0.015) improved significantly following the exercise program. At follow-up, group 1 had lower HADS anxiety (P = 0.013), total HADS (P = 0.02), total HAQ (P = 0.03), and HAQ interference with life (P = 0.03) and significantly higher SF-36 energy (P = 0.01) than group 2. CONCLUSIONS: Healthy postmenopausal women gain significant psychological benefit from moderate-intensity exercise. However, exercise participation must continue to maintain improvements in psychological well-being and quality of life.

Depressive Disorder↗

Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.

OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.

Age Factors↗

Effect of isolated isoflavone supplementation on ABCA1-dependent cholesterol efflux potential in postmenopausal women.

OBJECTIVE: Isoflavones may display beneficial health effects in postmenopausal women. We studied in a clinical trial whether isolated isoflavone treatment in postmenopausal women could affect reverse cholesterol transport as evaluated by adenosine triphosphate-binding cassette A1- (ABCA1), dependent cholesterol efflux from macrophages. In addition, various serum lipid and lipoprotein parameters were investigated. Furthermore, we separately assessed equol-producing and non-equol-producing women. DESIGN: Postmenopausal women (n=56) were treated with either isoflavone or placebo tablets for 3 months in a crossover design, separated by a 2-month washout period. Fifteen women were classified as equol producers, and 15 women were classified as non-equol producers. Serum samples were collected before and after each treatment period. [H]-Cholesterol-labeled J774 macrophage cells, with and without ABCA1 up-regulation, were incubated with the samples, and ABCA1-dependent cholesterol efflux and serum lipid and lipoprotein levels were assessed. RESULTS: Serum promoted 3.1%+/-1.1% and 3.2%+/-1.1% cholesterol efflux from macrophages after isoflavone and placebo treatment, respectively. Thus, isoflavone supplementation did not affect ABCA1-dependent cholesterol efflux to serum. However, as a novel finding, isoflavone treatment increased a subclass of high-density lipoprotein, the pre-beta high-density lipoprotein levels by 18% without affecting any other serum lipid concentrations. ABCA1-facilitated cholesterol efflux and lipid parameters did not differ between equol-producing and non-equol-producing women. CONCLUSION: In postmenopausal women, isolated isoflavone treatment does not affect ABCA1-dependent cholesterol efflux potential from macrophages but increases circulating pre-beta high-density lipoprotein level, which could provide beneficial vascular effects.

ATP-Binding Cassette Transporters↗

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women.

OBJECTIVE: To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. DESIGN: Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. RESULTS: Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/- 3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. CONCLUSIONS: Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.

Alleles↗

Early postmenopausal hormone therapy improves postural balance.

OBJECTIVE: Postmenopausal hormone therapy (HT) results in more substantial reductions in the risk of hip fracture when initiated sooner rather than later after menopause. We studied the effects of postmenopausal HT on the postural balance of postmenopausal women, with further assessment according to the time since they achieved menopause. DESIGN: One hundred women with a mean age of 52.5 years (91 evaluable) were randomly and blindly assigned to either a sequential estradiol-norethisterone acetate regimen or placebo for 3 months, after which all participants received open HT for a further 3 months. Postural balance was assessed as sway velocity using a force platform. RESULTS: After 3 months of HT, sway velocity had improved (decreased) from baseline by 7.0% (P = 0.007 vs baseline and P = 0.038 vs placebo). Continued HT for 6 months further improved sway velocity by 12% from baseline (P < 0.0001) to reach values similar to those historically found in younger women or in postmenopausal women after long-term HT. Closer proximity to menopause and more pronounced increases in serum estradiol values were associated with stronger improvements in sway velocity (P = 0.018 for interaction). HT also improved dizziness (P = 0.016 vs baseline and 0.022 vs placebo). (Nonparametric statistics are used throughout, except for analyses of interaction and dizziness.) CONCLUSIONS: Initiation of HT soon after menopause rapidly improved postural balance to levels normally seen in young women. We suggest that improved postural balance can contribute to the protection against fractures associated with HT and explain the more substantial reduction in hip fracture risk after HT initiated sooner, compared with later, after menopause. Further study is required to confirm these results.

Dizziness↗

Type 2 diabetes mellitus is a risk factor for the development of hypertension in postmenopausal women.

OBJECTIVE: Hypertension and type 2 diabetes mellitus are common diseases that are frequently found concomitantly in postmenopausal women. These findings suggest a close and/or synergistic nature in the relationship between the two disease processes; however, no prospective data exist on the incidence rate of hypertension in postmenopausal women with type 2 diabetes mellitus. METHODS: The present study assessed the risk of developing hypertension in 840 postmenopausal women: 102 women (12.1% of the cohort) with type 2 diabetes mellitus and 738 (87.9%) free of diabetes. The mean +/- SD follow-up was 3.2 +/- 0.9 years (range 0.5-6.0 years). RESULTS: The incidence rate (cases of hypertension per 100 person-years) was 1.1 for the group of women without diabetes versus 5.6 in women with diabetes (P < 0.0001). Compared with the non-diabetic group, women with type 2 diabetes mellitus had a statistically significant higher risk of developing hypertension. The relative risks for women with diabetes was 5.09 [crude: 95% confidence interval (CI) = 3.52-7.36; P < 0.0001]; 3.43 (adjusted for body mass index and waist circumference: 95% CI = 2.25-5.14; P < 0.001); and 2.95 (adjusted for all potential confounders: 95% CI = 1.86-4.32; P < 0.01). CONCLUSION: In our prospective study, on the incidence of hypertension, the presence of type 2 diabetes was found to be a potent independent risk determinant. This suggests that postmenopausal women affected by type 2 diabetes mellitus comprise a population at high risk for the subsequent development of hypertension.

Age Factors↗

Associations between psychological traits and endothelial function in postmenopausal women.

OBJECTIVE: The objective of this study was to determine whether psychosocial risk factors for cardiovascular disease (CVD) are associated with impairments in endothelial function and to determine whether use of hormone replacement therapy (HRT) can moderate observed associations among women without prior CVD. METHODS: Flow-mediated dilation was assessed by brachial ultrasound after reactive hyperemia in 193 postmenopausal women enrolled in the prospective Healthy Women Study. Measures of psychosocial characteristics had been completed at study entry, when the women were premenopausal (mean = 13.6 years earlier), and at a separate postmenopausal follow-up exam near the time of the ultrasound (mean = 1.5 years earlier). RESULTS: Factor analyses of the psychosocial characteristics yielded two factors: Type A/anger and anxiety/depression. Anxiety/depression scores at the study entry and follow-up exams and Type A/anger scores at the study entry exam were associated with less vasodilation (p values < 0.05). Type A/anger scores at the follow-up exam were associated with less vasodilation among women not using HRT (p <.05). CONCLUSIONS: Psychosocial risk factors for CVD are associated with impaired brachial artery dilation among postmenopausal women. HRT use may mask some associations between psychosocial risk factors and endothelial dysfunction among postmenopausal women.

Aged↗

Prospective study of saline infusion sonohysterography in evaluation of perimenopausal and postmenopausal women with abnormal uterine bleeding.

AIM: To evaluate saline infusion sonohysterography as an investigative modality in abnormal uterine bleeding in perimenopausal and postmenopausal women. METHODS: Fifty-eight patients, 52 perimenopausal and six postmenopausal women, with abnormal uterine bleeding were selected from the department of Obstetrics and Gynecology of Shrimati Sucheta Kriplani Hospital. After complete work-ups, transvaginal examinations were performed followed by sonohysterographies. The sensitivity, specificity, positive predictive values and negative predictive values were calculated for transvaginal sonography (TVS) and saline infusion sonohysterography as compared with findings of hysteroscopy/hysterectomy. RESULTS: Saline infusion sonohysterography was performed in 56 cases. It could not be done in one perimenopausal and one postmenopausal woman. Cavity was normal in 41 perimenopausal and five postmenopausal women. Ten women displayed abnormalities. Two had submucosal fibroids, two had intramural fibroids, one had fibroid polyp, three had endometrial polyps and two patients had endometrial growths. We found that TVS missed three endometrial polyps and one endometrial growth and led to mislabeling two intramural fibroids as submucosal. On comparing the sonohysterographic findings with those of hysteroscopy or hysterectomy, one endometrial polyp and one endocervical polyp was missed on sonohysterography, and one false positive growth was observed on sonohysterography. The sensitivity, specificity, positive predictive value and the negative predictive value of TVS were 84.8%, 79%, 82.4% and 82%, respectively. The sensitivity, specificity, positive predictive value and the negative predictive value of saline infusion sonohysterography were 94.1%, 88.5%, 91.4% and 92%, respectively. CONCLUSION: Saline infusion sonohysterography is a safe, convenient, time conserving, cost effective, easily accessible and acceptable investigative modality. It definitely enhances the diagnostic potential of TVS in assessment of endometrium and intracavitary pathologies.

Administration, Topical↗

Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II genes.

A number of epidemiological and clinical studies have revealed that excess body weight increases the risk of postmenopausal breast cancer and also adversely affects subsequent malignant progression. To elucidate the molecular mechanisms underlying these observations, we examined mRNA expression of various genes in normal (non-cancerous) mammary gland and cancer tissue of Japanese patients with primary breast cancer, in association with their body mass index (BMI). On the basis of analysis of 106 breast cancer patients, we found that mRNA expression of insulin-like growth factor I receptor (IGF-IR) and insulin-like growth factor II (IGF-II) in the normal mammary gland showed a significant and positive association with increased BMI among postmenopausal patients. Furthermore, the positive association of increased BMI with IGF-IR mRNA expression was also found in postmenopausal breast cancer tissue, while this association was not observed among premenopausal patients. In addition, increased mRNA expression of cyclin D1 and bcl-2 was observed in association with increased mRNA levels of IGF-IR among the patients regardless of menopausal status. These findings suggest that the molecular consequence of the increased BMI is the increased expression of IGF-II and IGF-IR, resulting in development of postmenopausal breast cancer and its progression mediated through modulation of the cell cycle and apoptosis.

Adult↗

Effect of promethazine on lumbar vertebral bone mass in postmenopausal women.

OBJECTIVES: Work in mice suggests that the age-related loss of bone mineral noted in that species is caused by an intrinsic defect in a haematopoietic cell population which results directly or indirectly in increased bone resorption. This age-related loss of bone mineral is prevented or reversed by well-tolerated doses of promethazine HCL. The present study was undertaken to determine if promethazine would retard or reverse bone loss in postmenopausal women. DESIGN: Postmenopausal women whose spine (L2 to L4) bone mineral content (BMC) was two standard deviations below young normal values were assigned randomly to receive calcium or promethazine and calcium daily. Subjects who had been taking oral oestrogen for more than 4 years also were assigned randomly but independently to the calcium or promethazine groups. SETTING: All subjects were seen in the out-patient clinic of the Department of Medicine, School of Medicine, University of California, Los Angeles. SUBJECTS: Healthy, ambulatory postmenopausal females were recruited by word of mouth and by advertisement from the local community. Fifty-four subjects completed the first 6 months of the study and 43 completed 30 months. INTERVENTIONS: The subjects were assigned randomly to receive 1000 mg calcium daily or promethazine 50 mg and calcium 1000 mg daily throughout the period of the study. MAIN OUTCOME MEASURES: Bone mineral content of the lumbar vertebrae (L2 to L4) was determined by dual photon densitometry every 6 months. Dorsolumbar spine X-rays were obtained yearly and at the completion of the study to detect new compression fractures. RESULTS: In the groups not taking oestrogen, BMC decreased at the rate of 1.53% year-1 in the group given only calcium; in contrast, BMC increased at 3.22% year-1 in the group given promethazine and calcium (P < 0.001). Among the women taking oestrogen, increases in mean BMC were noted in both groups, but those taking promethazine and calcium had a greater rate of increase than observed in the group taking only calcium (5.62% vs. 1.97% per year-1, P < 0.001). CONCLUSIONS: These results suggest that promethazine can induce a modest increase in vertebral BMC in postmenopausal women who are not taking oestrogen and greater increases in those who are.

Absorptiometry, Photon↗

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International.

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.

Alendronate↗