The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention

Hormone replacement therapy (HRT) has been reported to exert a positive effect on preserving muscle strength following the menopause, however, the mechanism of action remains unclear. We examined whether the mechanism involved preservation of muscle composition as determined by skeletal muscle attenuation. Eighty women aged 50-57 years were randomly assigned to either: HRT, exercise (Ex), HRT + exercise (ExHRT), and control (Co) for 1 year. The study was double-blinded with subjects receiving oestradiol and norethisterone acetate (Kliogest) or placebo. Exercise included progressive high-impact training for the lower limbs. Skeletal muscle attenuation in Hounsfield units (HU) was determined by computed tomography of the mid-thigh. Areas examined were the quadriceps compartment (includes intermuscular adipose tissue), quadriceps muscles, the posterior compartment and posterior muscles. Muscle performance was determined by knee extensor strength, vertical jump height, and running speed over 20 m. Fifty-one women completed the intervention. Vertical jump height and running speed improved in the HRT and ExHRT groups compared with Co (interaction, P < 0.01). For both the quadriceps compartment and quadriceps muscles, HU significantly increased (interaction, P <= 0.005) for HRT, Ex, and ExHRT compared with Co. For the posterior compartment, HU for the HRT and ExHRT were significantly increased compared with Co, while for posterior muscles, ExHRT was significantly greater than Co. Although the effects were modest, the results indicate that HRT, either alone or combined with exercise, may play a role in preserving/improving skeletal muscle attenuation in early postmenopausal women and thereby exert a positive effect on muscle performance.

Hormone replacement therapy and everyday memory in mid-aged New Zealand women

While empirical research to date has generally supported positive effects of estrogen on verbal memory performance in women, the literature examining specific effects of Hormone Replacement Therapy (HRT) on cognitive functioning in mid-life women is more equivocal. The Rivermead Behavioural Memory Test-Extended Version (RBMT-E), a measure of everyday memory functioning in adults within an average range of cognitive functioning, was administered to a sample of 104 New Zealand women aged 40 to 60 years who had self-selected to either use or not use HRT (53 HRT users and 51 non-users). Self-report. measures of mood, stress, general health and menopausal symptoms were also administered. These variables, along with age and education level, were used in analyses of group differences on the everyday memory measures. Results showed significant differences between the groups for three sub-tests of the RBMT-E:'Story Immediate', 'Story Delayed', and 'Message Delayed'. Women who use HRT scored higher on these subtests than those who do not use HRT. After calculation of a total profile score (adjusting for age and IQ), HRT users score higher than HRT non-users on the RBMT-E overall measure of Everyday Memory. These pilot results suggest that HRT use in this sample-is related to enhanced verbal memory in everyday memory tasks and that the RBMT-E may be a useful tool for further work in this area of research.

The muscle strength and bone density relationship in young women: dependence on exercise status

Aim. Numerous studies report an association between muscle strength and bone mineral density (BMD) in young and older women. However, the participants are generally non-athletes, thus it is unclear if the relationship varies by exercise status. Therefore, the purpose was to examine the relationships between BMD and muscle strength in young women with markedly different exercise levels. Methods. Experimental design: cross-sectional. Setting: a University research laboratory. Participants: 18 collegiate gymnasts and 22 age- and weight-matched recreationally active control women. Measures: lumbar spine, femoral neck, arm, leg and whole body BMD (g/cm(2)) were assessed by dual X-ray absorptiometry. In addition, lumbar spine and femoral neck bone mineral apparent density (BMAD, g/cm(3)) was calculated. Handgrip strength and knee extensor and flexor torque (60degrees/s) were determined by dynamometry, and bench press and leg press strength (1-RM) using isotonic equipment. Results. BMD at all sites and bench press, leg press and knee flexor strength were greater in gymnasts than controls (p

Contribution of the collagen I alpha 1 and vitamin D receptor genes to the risk of hip fracture in elderly women

Context and Objective: Hip fracture is partially genetically determined. The present study was designed to examine the contributions of vitamin D receptor (VDR) and collagen I alpha 1 (COLIA1) genotypes to the liability to hip fracture in postmenopausal women. Design: The study was designed as a prospective population-based cohort investigation. Subjects: Six hundred seventy-seven postmenopausal women of Caucasian background, aged 70 +/- 7 yr (mean +/- SD), have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period. Main Outcome: Atraumatic hip fractures were prospectively identified through radiologists' reports. Bone mineral density (BMD) at the hip and lumbar spine was measured by dual-energy x-ray absorptiometry. Genotypes: The TaqI and SpI COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using the Single Nucleotide Polymorphism database, VDR TT, Tt, and tt genotypes were coded as TT, TC, and CC, whereas COLIA1 SS, Ss, and ss were coded as GG, GT, and TT. Results: Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture [odds ratio (OR) associated with CC, 2.6; 95% confidence interval (CI), 1.2-5.3; OR associated with TT, 3.8; 95% CI, 1.3-10.8] after adjustment for femoral neck BMD (OR, 3.4 per SD; 95% CI, 2.3-5.0) and age (OR, 1.4 per 5 yr; 95% CI, 1.1-1.7). Approximately 20 and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively. Conclusion: The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women, and this association was independent of BMD and age.

Hormones down under: Hormone therapy use after the women's health initiative

Aims: The primary objective was to describe the usage pattern of hormone therapy (HT) in a sample of urban Australian women in 2001 and to assess the characteristics of users vs. non-users. The second objective was to determine whether there had been any change in usage since the publication of the results of the combined oestrogen plus progestagen arm of the Women's Health Initiative (WHI) in 2002. Methods: A cohort of 374 postmenopausal women aged 50-80 years participated in this substudy of the LAW (Longitudinal Assessment of Ageing in Women) project: a 5-year multidisciplinary, observational study. Participants completed an annual medical assessment including details of the use of HT and the reasons for use, as well as demographic and psychosocial data. Results: In December 2001, 30.8% of the participants were using HT, whereas 55.4% were ever users. The management of vasomotor symptoms and mood disturbance were the primary reasons for use. Of those who had been using HT in December 2001 (24.4%) women ceased using HT in the 3 months following publication of the WHI results. The percentage of women using HT in December 2003 (13.9%) was less than half of that of December 2001. Conclusion: The rate of HT use and the reasons for use, in 2001 in Brisbane was similar to that of other Australian regions. Usage of HT decreased since the publication of the WHI results in 2002 which may reflect changing attitudes by patients and practitioners regarding HT.

HRT and everyday memory at menopause: A comparison of two samples of mid-aged women

Research on the effect of hormone replacement therapy (HRT) on memory in mid-aged women is equivocal although findings indicate that oestrogen may enhance verbal memory. Mood may mediate the relationship between HRT and memory. This study examined the effect of HRT on mood and everyday memory in two samples of women between ages 40 and 60 years. In the cross-sectional comparison (N = 124), HRT users performed significantly better on tests of everyday and verbal memory. A within-woman comparison of 17 women showed that everyday memory, working memory, and delayed verbal memory improved after 3 months of HRT use. The improvement in memory was not mediated by mood. These results suggest that any effect of HRT on mood may be short-term but that some aspects of everyday memory are enhanced, particularly verbal memory. The development of the everyday memory construct and future investigation are discussed.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The health, aging, and body composition study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index < 0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10-1.63; ORtrabecular = 1.25, 95% CI 1.02-1.53; ORcortical = 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Greene Climacteric Scale: norms in an Australian population in relation to age and menopausal status

Objectives The aim of this study was two-fold: to assess climacteric symptoms and provide normative data for the Greene Climacteric Scale during the menopause transition, and to investigate the prevalence of climacteric symptoms in a representative sample of postmenopausal Australian women. Method A cohort of 500 premenopausal, perimenopausal and postmenopausal women aged 40-80 years participated in the Longitudinal Study of Ageing in Women (LAW study) at the Royal Brisbane and Women's Hospital, Brisbane, Australia. In year 1 of the study (2001), all participants completed the Greene Climacteric Scale and information regarding their menopausal status and the use of hormone therapy (HT) was obtained through a clinical interview with a qualified medical practitioner. Results The 50-59-year age group achieved the highest scores on the vasomotor and the depression scales in comparison to other age groups. Significant differences were also evident on the vasomotor and the depression scales on the basis of menopausal status, especially in perimenopausal women. Approximately 10% of women in the 60-79-year age group continued to experience vasomotor symptoms. Conclusion Vasomotor symptoms, as assessed by the Greene Climacteric Scale, are common during the menopause transition and remain elevated for some years in a minority of older postmenopausal women. The norms presented in this study are appropriate for use in an Australian population.

Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet

Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring (ESTring) to that of a vaginal estradiol tablet (Vagifem®) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency. Quality of life and acceptability of treatment delivery were also assessed. Study design A prospective, randomized study in which women were assigned in a 2: 1 ratio to ESTring and Vagifem and followed for 12 months. The primary endpoint was endometrial safety, based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48. Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3, 12, 24, 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline, 12 and 48 weeks. In addition, pelvic floor strength, vaginal cytological evaluation and pH, bacteruria and patient acceptability were assessed. Quality of life was assessed using a menopause-specific quality-of-life questionnire and a 2-day bladder diary at baseline and 12 and 48 weeks. The comparability of the two groups was assessed using ANOVA, χ(2) or Fisher's exact tests. Results A total of 126 women were randomized to ESTring and 59 to Vagifem. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency. Maturation indices increased in both groups, from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks. After 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. A statistically smaller proportion of bleeding/spotting occurred in the ESTring group (n = 0) compared to the Vagifem users (n = 4). Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range. General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups. Bladder diary variables showed no differences between treatment groups. Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.

Estrogen replacement, muscle composition, and physical function: The health ABC study

Purpose: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to determine whether estrogen use is associated with enhanced muscle composition and, if so, whether this translates into improved strength and physical function. Methods: Cross-sectional analysis of 840 well-functioning community-dwelling white women (current estrogen replacement therapy (ERT) users = 259, nonusers = 581) aged 70-79 yr participating in the Health, Aging and Body Composition Study. Muscle composition of the midthigh by computed tomography included cross-sectional area (CSA) of the quadriceps, hamstrings, intermuscular fat and subcutaneous fat, and muscle attenuation in Hounsfield units (HU) as a measure of muscle density. Isometric hand grip and isokinetic knee extensor strength were assessed by dynamometry. Physical function was assessed using a summary scale that included usual 6-m walk and narrow walk speed, repeated chair stands, and standing balance. Results: In analyses of covariance adjusted for relevant confounders. quadriceps muscle CSA and HU were greater in Current ERT than non-ERT women (P < 0.05). Grip strength was also greater (P < 0.05) in women taking ERT while knee extensor strength approached significance (P < 0.10). However, differences in muscle composition and strength were modest at <= 3.3%. There was no difference by ERT status for the hamstring, muscles. fat CSA. or for physical function. Conclusion: The associations between ERT and muscle composition and strength were minor and did not translate into improved physical function. Initiation of ERT for preservation of muscle composition and function may not be indicated.

Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice

Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment.