Pharmaceutical Industry Funding of Health Consumer Groups in Australia: A Cross-sectional Analysis.

Relationships between consumer organizations and pharmaceutical manufacturers are the focus of transparency efforts in some jurisdictions, including Australia. This study describes the frequency and nature of industry sponsorship of Australian health consumer organizations and examines the link between sponsorship of the most highly funded organizations and manufacturers' requests for public reimbursement of products for related health conditions. We downloaded 130 transparency reports covering the period January 2013 to December 2016 from the website of Medicines Australia and carried out a descriptive analysis. For the most heavily funded organizations and their sponsors, we examined Public Summary Documents of the Pharmaceutical Benefits Advisory Committee to identify relevant products under consideration for public reimbursement over the study period. Thirty-four pharmaceutical companies provided 1,482 sponsorships to 230 organizations, spending a total of AU$34,507,810. The top clinical areas in terms of amount of funding received were cancer, eye health, and nervous system disorders. The sponsors of the most highly funded groups were companies that in most cases had drugs under review for public reimbursement for conditions covered by these organizations. Interactions between the pharmaceutical industry and consumer organizations are common and require careful management to prevent biases that may favor sponsors' interests above those of patients and the public.

Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

BACKGROUND: Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. METHODS: We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. RESULTS: At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. CONCLUSIONS: In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.

Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study.

CONTEXT: As men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors. OBJECTIVE: The aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status. DESIGN AND SETTING: The Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers. PARTICIPANTS: A total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later. MAIN OUTCOME MEASURE: Proportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods. RESULTS: In cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment. CONCLUSIONS: Low levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.

Effects of lifestyle and diet on bone health in young adult Chinese women living in Hong Kong and Beijing.

BACKGROUND: Dietary and lifestyle variations may be too small to detect possible associations with bone mineral density (BMD) within a community. Pooled data from communities with different diets and lifestyle but of the same ethnicity may help explore these associations. OBJECTIVE: To examine the effects of dietary and lifestyle factors on BMD in young Chinese women. METHODS: Baseline data were analyzed from 441 women aged 20 to 35 years in Hong Kong and Beijing who were participating in a longitudinal study evaluating the effect of milk supplementation on bone health. Data on demographic characteristics, lifestyle, use of oral contraceptives, diet, physical activity, and BMD of total hip, femoral neck, and total spine measured by dual-energy x-ray absorptiometry were pooled for analysis. RESULTS: Hong Kong subjects had significantly lower BMD and higher body-size-adjusted dietary intakes of protein, fat, fiber, vitamins, potassium, sodium, and selenium than Beijing subjects. Multivariate regression of pooled data showed that body mass index was the most important determinant of BMD at all sites. Age was negatively associated and use of oral contraceptives was positively associated with femoral neck BMD. Carbohydrate intake was positively associated with total hip BMD. Fiber intake was negatively associated with BMD at total hip and total spine. Increased vitamin E intake was associated with greater total spine BMD. None of the nutrients were associated with BMD at the femoral neck. CONCLUSIONS: Diet, lifestyle, and BMD differed greatly between young women from Hong Kong and Beijing. Body mass index was the most important determinant of BMD in young Chinese women, whereas age, use of oral contraceptives, and diet had less pronounced effects.

Associated factors and health impact of sarcopenia in older chinese men and women: a cross-sectional study.

BACKGROUND: Sarcopenia is increasingly being recognized as a feature of frailty in old age and is associated with unfavorable health outcomes in Western populations. Little is known about sarcopenia among Asian elderly populations. OBJECTIVES: The study was undertaken to study the association between sarcopenia and common chronic illnesses, lifestyle factors, psychosocial well-being and physical performance. METHODS: 4,000 community-dwelling Chinese elderly >/=65 years were recruited. Medical illnesses, cigarette smoking, alcohol consumption, physical activity level and psychosocial well-being scores were recorded. Physical performance measured included grip strength, timed chair-stands, stride length and a timed 6-meter walk. Muscle mass was measured using dual-energy X-ray absorptiometry. Relationships between appendicular skeletal muscle mass (ASM/ht(2)) and multiple variables were analyzed using uni- and multivariate analyses. RESULTS: Mean ASM/ht(2) was 7.19 and 6.05 kg/m(2) in men and women respectively. Older age, cigarette smoking, chronic lung disease, atherosclerosis, underweight, and physical inactivity were associated with low adjusted ASM, which was in turn associated with poorer physical well-being in men. After adjustment to age, lower appendicular muscle mass was associated with weaker grip strength in both sexes. In men, lower limb tests (chair-stands, walking speed and step length) were not related to ASM, while in women, lower muscle mass was not associated with poorer lower limb muscle performance. CONCLUSIONS: Sarcopenia in community-dwelling older Chinese men and women was associated with cigarette smoking, chronic illnesses, underweight, physical inactivity, poorer well-being and upper limb physical performance.

A randomised controlled trial of Tai Chi and resistance exercise on bone health, muscle strength and balance in community-living elderly people.

BACKGROUND: The beneficial role of exercise in improving bone mineral density, muscle strength and balance, has been documented predominantly in younger populations. These findings may not apply to elderly populations with limited ability to perform exercises of high intensity. OBJECTIVE: To examine the effects of Tai Chi (TC) and resistance exercise (RTE) on bone mineral density (BMD), muscle strength, balance and flexibility in community living elderly people. DESIGN: Randomised controlled trial, using blocked randomization with stratification by sex. SETTING: A community in the New Territories Region of Hong Kong, China. SUBJECTS: One hundred eighty subjects (90 men, 90 women) aged 65-74, were recruited through advertisements in community centres. METHODS: Subjects were assigned to participate in TC, RTE three times a week, or no intervention (C) for 12 months. Measurements were carried out at baseline, 6 and 12 months. Analyses of covariance (ANCOVA) adjusted for age, and baseline values of variables that were significantly different between groups: i.e. smoking and flexibility for men; quadriceps strength for women. RESULTS: Compliance was high (TC 81%, RTE 76%). In women, both TC and RTE groups had less BMD loss at total hip compared with controls. No effect was observed in men. No difference in either balance, flexibility or the number of falls was observed between either intervention or controls after 12 months. CONCLUSION: The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes.

Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy.

PURPOSE: To prospectively use hydrogen 1 (1H) magnetic resonance (MR) spectroscopy and dynamic contrast material-enhanced MR imaging to measure vertebral body marrow fat content and bone marrow perfusion in older men with varying bone mineral densities as documented with dual x-ray absorptiometry (DXA). MATERIALS AND METHODS: This study had institutional review board approval, and all participants provided informed consent. DXA, 1H MR spectroscopy, and dynamic contrast-enhanced MR imaging of the lumbar spine were performed in 90 men (mean age, 73 years; range, 67-101 years). Vertebral marrow fat content and perfusion (maximum enhancement and enhancement slope) were compared for subject groups with differing bone densities (normal, osteopenic, and osteoporotic). The t test was used for comparisons between groups, and the Pearson test was used to determine correlation between marrow fat content and perfusion indexes. RESULTS: Eight subjects were excluded, yielding a final cohort of 82 subjects (mean age, 73 years; range, 67-101 years) that included 42 subjects with normal bone density (mean T score, 0.8 +/- 1.1 [standard deviation]), 23 subjects with osteopenia (mean T score, -1.6 +/- 0.4), and 17 subjects with osteoporosis (mean T score, -3.2 +/- 0.5). Vertebral marrow fat content was significantly increased in subjects with osteoporosis (mean fat content, 58.23% +/- 7.8) (P = .002) or osteopenia (mean fat content, 55.68% +/- 10.2) (P = .034) compared with that in subjects with normal bone density (50.45% +/- 8.7). Vertebral marrow perfusion indexes were significantly decreased in osteoporotic subjects (mean enhancement slope, 0.78%/sec +/- 0.3) compared with those in osteopenic subjects (mean enhancement slope, 1.15%/sec +/- 0.6) (P = .007) and those in subjects with normal bone density (mean enhancement slope, 1.48%/sec +/- 0.7) (P < .001). CONCLUSION: Subjects with osteoporosis have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with osteopenia. Similarly, subjects with osteopenia have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with normal bone density.

Factors associated with the lumbar spine and proximal femur bone mineral density in older men.

Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.

Prevalence of and risk factors for sarcopenia in elderly Chinese men and women.

BACKGROUND: Several studies have documented the substantial health and economic burdens associated with sarcopenia among the elderly, but there has been no systematic study among Asians. A cross-sectional survey of elderly community-dwelling Chinese volunteers (262 men and 265 women), aged 70 years and older, was undertaken in Hong Kong. The purposes of this study were to evaluate the prevalence of and risk factors for sarcopenia in elderly Chinese, and to compare these observations with those in white persons. METHODS: Muscle mass was estimated by dual-energy X-ray absorptiometry. In this study, sarcopenia was defined as a total adjusted skeletal muscle mass two standard deviations or more below the normal mean for young Asian men and women in this study. The relationship between risk factors (alcohol consumption, cigarette smoking, regular exercise, body mass index, medical conditions) and sarcopenia was studied by multiple logistic regression. RESULTS: The prevalence of sarcopenia was 12.3% in Chinese men and 7.6% in Chinese women aged 70 years and older, which was slightly lower than figures observed in white persons. Being underweight was a significant risk factor in both men (odds ratio, 39.1; 95% confidence interval, 11.3 to 134.6) and women (odds ratio, 9.7; 95% confidence interval, 2.8 to 33.8). No other risk factors were found in Chinese men or women. CONCLUSIONS: Sarcopenia exists among elderly Chinese men and women, albeit at a lower rate than in white persons. This may be due to the lower muscle mass among young men and women or to an attenuated rate of loss in muscle mass with aging in the Chinese elderly. Being underweight is a major risk factor for sarcopenia in both sexes.

Dose effects of progesterone in add-back therapy during GnRHa treatment.

OBJECTIVE: To compare 1 mg norethisterone acetate with 5 mg norethindrone when used in conjunction with 2 mg estradiol given as add-back therapy during treatment with a gonadotropin-releasing hormone agonist (GnRHa). STUDY DESIGN: A prospective, double-blind, randomized study was conducted in a university-based teaching hospital. Forty-seven patients with pelvic endometriosis were recruited. Subcutaneous GnRHa was administered at 6-week intervals, and add-back therapy was commenced with the second dose of GnRHa. Group A patients received 2 mg estradiol and 1 mg norethisterone acetate, while group B patients received 2 mg estradiol and 5 mg norethindrone daily. Changes in bone mineral density, menopausal symptoms, lipid profile and occurrence of breakthrough bleeding were assessed before and after treatment. RESULTS: Patients in group A had no significant bone loss and satisfactory control of menopausal symptoms. The additional dose of progestogen in group B had a deleterious effect on the lipid profile and increased the frequency of breakthrough bleeding. CONCLUSION: In this study, the benefits of add-back therapy during GnRHa treatment were not enhanced, and a deleterious effect upon the lipid profile was seen when using a constant dosage of 2 mg estradiol and 5 mg norethindrone as compared to 1 mg norethisterone acetate.

Depression and bone mineral density: is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong).

Previous epidemiological study has suggested that depression might be associated with low bone mass in Caucasian women. This has not been studied in Asian men. Mr. Os (Hong Kong) is the first, large, cohort study on osteoporosis in Asian men, and the current analysis deals with the association between depression and bone mass in this group. Data from the baseline examination of Mr. Os (Hong Kong) were used. Two thousand Hong Kong men aged 65 to 92 years were recruited from the community. Depression was diagnosed by face-to-face interview, using a validated Chinese version of the Geriatric Depression Scale (GDS), with depression being defined as a cut-off score of 8 or more. Bone mineral density (BMD) of the lumbar spine, total hip and total body was measured by dual X-ray densitometry (DEXA) using the Hologic QDR-4500 W densitometer. Multiple regression was used to compare BMD in depressed and non-depressed subjects, controlling for confounding variables. In the study sample 8.5% of men were found to be depressed, and the BMD at the total hip in these subjects was 2.1% lower than in non-depressed subjects (95% CI -0.13 to -4.1), after adjustment for age, body weight, medical history, alcohol consumption, cigarette smoking, calcium intake, physical activity and antidepressant use. Depression was associated with a 1.4-fold (95% CI 1.00 to 2.08) relative risk (RR) of being diagnosed with a T-score equal to or less than -1.0 (low bone mass). We conclude that depression is associated with lower BMD; however, to determine whether depression causes lower BMD or vice versa, we will need to await findings from future prospective studies.

Bone marrow diffusion in osteoporosis: evaluation with quantitative MR diffusion imaging.

PURPOSE: To determine the diffusion of vertebral body marrow with quantitative MR diffusion imaging and to examine whether differences exist between subjects with postmenopausal osteoporosis and premenopausal control subjects. MATERIALS AND METHODS: A total of 44 consecutive women (mean age, 70 years) with documented bone mineral density (BMD) measured by dual energy x-ray absorptiometry (T-score) and 20 normal subjects (mean age, 28 years) were examined with echo-planar diffusion imaging at 1.5 T using b values of 0, 20, 40, 60, 80, 100, 200, 300, 400, and 500 seconds/mm2. Extravascular diffusion (D) and apparent diffusion coefficient (ADC) were calculated and results from both groups compared. RESULTS: Both D and ADC values tended to decrease with decreasing BMD. Mean D values were significantly lower in postmenopausal women with reduced BMD (0.42 +/- 0.12 x 10(-3) mm2/second) than normal premenopausal women (0.50 +/- 0.09 x 10(-3) mm2/second). Mean ADC values were significantly lower both in subjects with reduced BMD (0.41 +/- 0.10 x 10(-3) mm2/second) and normal BMD (0.43 +/- 0.08 x 10(-3) mm2/second) compared to normal controls (0.49 +/- 0.07 x 10(-3) mm2/second). CONCLUSION: Accumulation of fatty bone marrow associated with osteoporosis is reflected by a decrease in D and ADC. Diffusion imaging may prove useful in the study of osteoporosis.

Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.

OBJECTIVE: Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. DESIGN: To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. RESULTS: Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. CONCLUSIONS: This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.

A prospective, randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women.

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.

A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women.

OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.