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ABSTRACT: BACKGROUND: Poor vitamin D status and frailty are common in older people and associated with adverse health outcomes. The aim of this study was to examine the associations between serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels and frailty and components of frailty in older Australian men. METHODS: Cross-sectional analysis of the Concord Health and Ageing in Men Project, a large epidemiological study conducted in Sydney, Australia, between January 2005 and May 2007. Participants included 1,659 community-dwelling men. Main outcome measurements were frailty (assessed using the Cardiovascular Health Study), frailty criteria comprising five core components: weight loss; reduced muscular strength/weakness; slow walking speed; exhaustion; and low activity level, and the separate components of frailty. Covariates included serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels measured by radioimmunoassay, age, country of birth, season of blood collection, sun exposure, body mass index, vitamin D supplement use, income, measures of health, parathyroid hormone, estimated glomerular function. RESULTS: Frailty was present in 9.2% of the sample. Low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were independently associated with frailty and with four of the five components of frailty (except weight loss). CONCLUSIONS: 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D levels were independently associated with frailty in older men. This suggests that there might be a number of different biological mechanisms for how low vitamin D status might contribute to the frailty syndrome. In addition, the possibility that improving vitamin D status may specifically influence the incidence and progression of frailty needs to be explored.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2013; · 4.60 Impact Factor
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ABSTRACT: Urine provides a convenient non-invasive alternative to blood sampling for measurement of certain hormones. Urinary luteinizing hormone (LH) measurements have been used for endocrinology research and anti-doping testing. However, the commercially available LH immunoassays are developed and validated for human blood samples but not urine so that LH assays intended for use with urine samples need thorough validation. Therefore, the present study evaluated the measurement of urinary LH immunoreactivity using previously validated immunofluorometric (IF) and immunochemiluminometric (ICL) LH assays after prolonged frozen storage. LH was measured in serial urine samples following administration of a single injection of one of two doses of recombinant human chorionic hormone (rhCG) with assays run at the end of study (2008) and again after four years of frozen (-20 °C) storage where samples were stored without adding preservatives. The ICL assay showed quantitatively reproducible LH measurements after prolonged -20 °C storage. However, the IF immunoassay gave consistently lower LH levels relative to ICL (2008) with a further proportionate reduction after four years of sample storage (2012). Yet, both the assays displayed similar patterns of the time-course of urine LH measurement both before and after four years of frozen storage. In conclusion, we found that both immunoassays are suitable for urinary LH measurements with ICL assay being more robust for quantitative urinary LH measurement such as for anti-doping purposes, whereas the IF could be applicable for research studies where urine LH levels are compared within-study but not in absolute terms. Copyright © 2013 John Wiley & Sons, Ltd.
Drug Testing and Analysis 04/2013; · 2.54 Impact Factor
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Asian Journal of Andrology 03/2013; 15(2):208-11. · 1.52 Impact Factor
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Asian Journal of Andrology 03/2013; 15(2):159-61. · 1.52 Impact Factor
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Danijela Gnjidic,
David G Le Couteur,
Fiona M Blyth,
Tom Travison,
Kris Rogers,
Vasi Naganathan,
Robert G Cumming,
Louise Waite,
Markus J Seibel, David J Handelsman,
Andrew J McLachlan,
Sarah N Hilmer
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ABSTRACT: The aim of this analysis was to investigate the relationship of statins with institutionalisation and death in older men living in the community, accounting for frailty.
Prospective cohort study.
Community-dwelling men participating in the Concord Health and Ageing in Men Project, Sydney, Australia.
Men aged ≥70 years (n=1665).
Data collected during baseline assessments and follow-up (maximum of 6.79 years) were obtained. Information regarding statin use was captured at baseline, between 2005 and 2007. Proportional hazards regression analysis was conducted to estimate the risk of institutionalisation and death according to statin use (exposure, duration and dose) and frailty status, with adjustment for sociodemographics, medical diagnosis and other clinically relevant factors. A secondary analysis used propensity score matching to replicate covariate adjustment in regression models.
At baseline, 43% of participants reported taking statins. Over 6.79 years of follow-up, 132 (7.9%) participants were institutionalised and 358 (21.5%) participants had died. In the adjusted models, baseline statin use was not statistically associated with increased risk of institutionalisation (HR=1.60; 95% CI 0.98 to 2.63) or death (HR=0.88; 95% CI 0.66 to 1.18). There was no significant association between duration and dose of statins used with either outcome. Propensity scoring yielded similar findings. Compared with non-frail participants not prescribed statins, the adjusted HR for institutionalisation for non-frail participants prescribed statins was 1.43 (95% CI 0.81 to 2.51); for frail participants not prescribed statins, it was 2.07 (95% CI 1.11 to 3.86) and for frail participants prescribed statins, it was 4.34 (95% CI 2.02 to 9.33).
These data suggest a lack of significant association between statin use and institutionalisation or death in older men. These findings call for real-world trials specifically designed for frail older people to examine the impact of statins on clinical outcomes.
BMJ open. 01/2013; 3(3).
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ABSTRACT: Sertoli cell (SC) androgen receptor (AR) activity is vital for spermatogenesis. We created a unique gain-of-function transgenic (Tg) mouse model to determine the temporal role of SCAR expression in testicular development. The SC-specific rat Abpa promoter directed human Tg AR [Tg SC-specific AR (TgSCAR)] expression, providing strong premature postnatal AR immunolocalized to SC nuclei. Independent Tg lines revealed that TgSCAR dose dependently reduced postnatal and mature testis size (to 60% normal), whereas androgen-dependent mature seminal vesicle weights and serum testosterone levels remained normal. Total SC numbers were reduced in developing and mature TgSCAR testes, despite normal or higher Fshr mRNA and circulating FSH levels. Postnatal TgSCAR testes exhibited elevated levels of AR-regulated Rhox5 and Spinlw1 transcripts, and precocious SC function was demonstrated by early seminiferous tubular lumen formation and up-regulated expression of crucial SC tight-junction (Cldn11 and Tjp1) and phagocytic (Elmo1) transcripts. Early postnatal Amh expression was elevated but declined to normal levels in peripubertal-pubertal TgSCAR vs. control testes, indicating differential age-related regulation featuring AR-independent Amh down-regulation. TgSCAR induced premature postnatal spermatogenic development, shown by increased levels of meiotic (Dmc1 and Spo11) and postmeiotic (Capza3 and Prm1) germ cell transcripts, elevated meiotic-postmeiotic germ:Sertoli cell ratios, and accelerated spermatid development. Meiotic germ:Sertoli cell ratios were further increased in adult TgSCAR mice, indicating predominant SCAR-mediated control of meiotic development. However, postmeiotic germ:Sertoli cell ratios declined below normal. Our unique TgSCAR paradigm reveals that atypical SC-specific temporal AR expression provides a direct molecular mechanism for induction of precocious testicular development, leading to reduced adult testis size and decreased postmeiotic development.
Molecular Endocrinology 11/2012; · 4.54 Impact Factor
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ABSTRACT: Ovarian granulosa cells display strong androgen receptor (AR) expression suggesting a functional role for direct AR-mediated actions within developing mammalian follicles. By crossing AR floxed and anti-Müllerian hormone (AMH)-Cre recombinase (Cre) mice we generated granulosa cell-specific androgen receptor knockout mice (GCARKO). Cre expression, assessed by lacZ activity, localized to 70-100% of granulosa cells in most preantral to antral follicles, allowing for selected evaluation of granulosa cell AR-dependent actions during follicle development. Relative to wildtype (WT) females, GCARKO females were sub-fertile, producing a 24% reduction in the number of litters (P < 0.05) over 6 months and an age-dependent decrease in total number of pups born, evident from 6 months of age (P < 0.05). Follicle dynamics were altered in GCARKO ovaries at 3 months of age, with a significant reduction in large preantral and small antral follicle numbers compared to WT ovaries (P < 0.05). Global premature follicle depletion was not observed but increased follicular atresia was evident in GCARKO ovaries at 6 months of age with an 81% increase in unhealthy follicles and zona pellucida remnants (P < 0.01). Cumulus cell expansion was decreased (P < 0.01) and oocyte viability was diminished in GCARKO females with a significant reduction in the percentage of oocytes fertilised after natural mating and thus rate of progression to the two-cell embryo stage (P < 0.05). In addition, compared with age-matched WT females, 6 month old GCARKO females exhibited significantly prolonged estrous cycles (P ≤ 0.05) suggesting altered hypothalamic-pituitary-gonadal feedback signalling. In conclusion, our findings revealed that selective loss of granulosa cell AR actions during preantral and antral stages of development leads to a premature reduction in female fecundity, through reduced follicle health and oocyte viability.
Biology of Reproduction 10/2012; · 4.01 Impact Factor
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ABSTRACT: BACKGROUND: Regulation of steroid synthesis within the prostate is not well understood. In this study, we examined androgen synthesis and metabolism in the mouse prostate. METHODS: Using LC-MSMS steroid assays, immunohistochemistry and real-time PCR we examined the role of prostate epithelial AR in regulating 5αR expression and subsequent androgen metabolism by analyzing natural differences in epithelial AR expression between lobes as well as in the prostate epithelial AR knockout (PEARKO) mouse model. Subsequently, the role of intraprostatic androgen metabolism and epithelial AR in the generation and progression of prostate epithelial pathology was examined using long-term exogenous testosterone (T) + estradiol (E2) exposure. RESULTS: Epithelial AR and 5αR2 expression as well as intraprostatic DHT followed the same lobe-specific pattern being lower in anterior than the other lobes (n = 6-8, P < 0.05). Lobe-specific 5αR2 expression was similar in PEARKO and wild-type (WT) prostate. However, PEARKO prostate had higher intraprostatic DHT content with significantly increased 5αR2 expression localized in abnormal epithelium. T + E2 treatment induced epithelial pathology was more common in PEARKO prostate compared to WT (20% vs. 2%), and was associated with increased 5αR2 expression (n = 6, P < 0.001). CONCLUSIONS: We suggest that androgen synthesis via 5αR2 expression is driven by its own product (DHT) acting on adjacent stromal cells in a paracrine loop leading to increased in situ androgen levels in the PEARKO prostate. This may form part of a feed-forward loop that promotes the development of epithelial pathology. Prostate © 2012 Wiley Periodicals, Inc.
The Prostate 09/2012; · 3.48 Impact Factor
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The Medical journal of Australia 09/2012; 197(5):273; author reply 274. · 2.81 Impact Factor
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Asian Journal of Andrology 08/2012; · 1.52 Impact Factor
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Jenni Ilomäki,
Danijela Gnjidic,
Sarah N Hilmer,
David G Le Couteur,
Vasi Naganathan,
Robert G Cumming,
Louise M Waite,
Markus J Seibel,
Fiona M Blyth, David J Handelsman,
J Simon Bell
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ABSTRACT: AIM: To explore the association between psychotropic drug use and alcohol drinking in community-dwelling older Australian men. DESIGN AND METHODS: We conducted a cross-sectional population-based study using baseline data collected between 2005 and 2007 from 1705 participants in the Concord Health and Ageing in Men Project (CHAMP) conducted in Sydney, Australia. All participants were men aged ≥70 years. The prevalence of antidepressant and sedative or anxiolytic drug use was ascertained at clinical examinations and alcohol drinking was self-reported. Logistic regression models were used to compute the unadjusted and adjusted prevalence ratios and 95% confidence intervals for the association between sedative or anxiolytic use and antidepressant use with drinking patterns. RESULTS: In the study sample, 8.0% used an antidepressant, 5.7% used a sedative or anxiolytic, 33.7% were daily drinkers, 13.9% were binge drinkers, 19.2% were heavy drinkers and 11.0% were problem drinkers. Overall, 27.1% of antidepressant users were daily drinkers and 42.7% of sedative or anxiolytic users were daily drinkers. Sedative or anxiolytic use was associated with daily drinking (prevalence ratio = 1.42; 95% confidence intervals 1.09-1.76) but not with other drinking patterns. The associations between antidepressant use and alcohol drinking were not statistically significant. DISCUSSION AND CONCLUSIONS: Potential psychotropic drug-alcohol interactions were common in older Australian men. Users of sedative or anxiolytic drugs were more likely to engage in daily drinking compared with non-users of sedative or anxiolytic drugs. Clinicians should monitor patients prescribed sedative or anxiolytic drugs for possible adverse events arising from concomitant use with alcohol.
Drug and Alcohol Review 08/2012; · 1.55 Impact Factor
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ABSTRACT: The aim of this cross-sectional study was to investigate the association between sedative load and functional outcomes in community-dwelling older Australian men. A total of 1696 males aged ≥ 70 years, enrolled in the Concord Health and Ageing in Men Project, were studied. Participants underwent assessments during 2005-2007. Sedative load was computed using a published model. Outcomes included activities of daily living (ADL), instrumental activities of daily living (IADL), physical performance measures and a clinical diagnosis of cognitive impairment. Of the participants, 15.3% took medications with sedative properties. After adjusting for age, education, depressive symptoms and comorbidities, participants who took one medication with sedation as a prominent side effect (sedative load = 1) had odds ratio (OR) of 2.15 (95% confidence interval, CI: 1.20-3.85) for ADL disability, compared with participants with sedative load = 0. Participants who took at least one primary sedative or two medications with sedation as a prominent side effect (sedative load ≥ 2) had an OR of 1.55 (95% CI: 1.02-2.35) for IADL disability, compared with participants with sedative load = 0. The mean 6-m walking speed (P = 0.001) and grip strength (P = 0.003) were significantly different between sedative load groups in unadjusted models only. No association between sedative load and poorer performance on balance and chair stands tests or cognitive impairment was observed. Participants with sedative load of one were more likely to report ADL disability, whereas participants with sedative load of ≥2 were more likely to report IADL disability. Higher sedative load was not associated with poorer physical performance or cognitive impairment in older Australian men.
Fundamental and Clinical Pharmacology 07/2012; · 1.80 Impact Factor
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ABSTRACT: This study aimed to determine an optimal discriminating number of concomitant medications associated with geriatric syndromes, functional outcomes, and mortality in community-dwelling older men.
Older men aged ≥ 70 years (n=1,705), enrolled in the Concord Health and Aging in Men Project were studied. Receiver operating characteristic curve analysis using the Youden Index and the area under the curve was performed to determine discriminating number of medications in relation to each outcome.
The highest value of the Youden Index for frailty was obtained for a cutoff point of 6.5 medications compared with a cutoff of 5.5 for disability and 3.5 for cognitive impairment. For mortality and incident falls, the highest value of Youden Index was obtained for a cutoff of 4.5 medications. For every one increase in number of medications, the adjusted odds ratios were 1.13 (95% confidence interval [CI]=1.06-1.21) for frailty, 1.08 (95% CI=1.00-1.15) for disability, 1.09 (95% CI=1.04-1.15) for mortality, and 1.07 (95% CI=1.03-1.12) for incident falls. There was no association between increasing number of medications and cognitive impairment.
The study supports the use of five or more medications in the current definition of polypharmacy to estimate the medication-related adverse effects for frailty, disability, mortality, and falls.
Journal of clinical epidemiology 06/2012; 65(9):989-95. · 2.96 Impact Factor
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Gideon Sartorius,
Sasa Spasevska,
Amanda Idan,
Leo Turner,
Elise Forbes,
Anna Zamojska,
Carolyn A Allan,
Lam P Ly,
Ann J Conway,
Robert I McLachlan, David J Handelsman
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ABSTRACT: To determine serum concentrations, intra-individual variability and impact of age-related co-morbidities on serum testosterone (T), dihydrotestosterone (DHT), estradiol (E(2) ) and estrone (E(1) ) in older men.
Observational, repeated measures study.
Men (n = 325) with 40 years and older self-reporting very good or excellent health.
Standardized history, physical examination and collection of nine blood samples at fixed time intervals were measured over 3 months (three at 20 min intervals on days 1 (fasting) and 2 (non-fasting), one at days 7, 30 and 90). Serum T, DHT, E(2) and E(1) (n = 2900, > 99% of scheduled samples) measured by liquid chromatography-tandem mass spectrometry (LC-MS) were analysed by linear mixed model analysis with fasting, age and obesity as covariables.
Mean serum T did not vary with age (P = 0·76) but obesity (-0·35 nm per body mass index (BMI) unit, P < 0·0001) and ex-smoker status (-1·6 nm, P < 0·001) had significant effects. Serum DHT was increased with age (+0·011 nm per year, P = 0·001) but decreased with obesity (-0·05 nm per BMI unit, P < 0·0001). Serum E(2) did not vary with age (P = 0·31) or obesity (P = 0·12). Overnight fasting increased (by 9-16%, all P < 0·001) and reduced variability in morning serum T, DHT, E(2) and E(1.) Non-fasting serum T and DHT were stable over time (day, week, month or 3 months; P > 0·28).
Serum T, DHT and E(2) displayed no decrease associated with age among men over 40 years of age who self-report very good or excellent health although obesity and ex-smoking status were associated with decreased serum androgens (T and DHT) but not E(2) . These findings support the interpretation that the age-related decline in blood T accompanying non-specific symptoms in older men may be due to accumulating age-related co-morbidities rather than a symptomatic androgen deficiency state.
Clinical Endocrinology 05/2012; 77(5):755-63. · 3.17 Impact Factor
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ABSTRACT: To describe values of serum prostate-specific antigen (PSA) in older men without diagnosed prostate cancer, categorised by age and country of birth, and to describe self-reported prostate cancer screening.
A cohort study (the Concord Health and Ageing in Men Project) involving a representative sample of 1434 eligible community-dwelling men with no diagnosis of prostate cancer who were aged 70 years and over and living in a defined geographic area in Sydney, with baseline data collected between 28 January 2005 and 4 June 2007.
Serum PSA levels and self-reported prostate cancer screening.
11% of men (155) had a PSA level of ≥6.5 ng/mL, increasing from 7.5% of men aged 70-74 years to 31.4% of men aged≥90 years. PSA levels varied with ethnicity, with Australian-born men (695) having the highest levels (median, 2.3 ng/mL; 5th-95th percentile, 0.4-10.1 ng/mL), followed by men born in China (n=42; 2.1 ng/mL; 0.4-12.4 ng/mL), United Kingdom and Ireland (n=70; 1.9 ng/mL; 0.3-8.9 ng/mL), Greece (n=59; 1.5 ng/mL; 0.2-6.1 ng/mL), and Italy (n=293; 1.4 ng/mL; 0.3-7.2 ng/mL). A PSA test in the previous 2 years was reported by 48% of participants, and a digital rectal examination (DRE) in the previous 2 years by 37%.
A significant number of men aged over 70 years reported recent prostate cancer tests. The PSA level ranges reported in this cohort will help with interpreting serum PSA level findings in men aged over 70 years.
The Medical journal of Australia 04/2012; 196(6):395-8. · 2.81 Impact Factor
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ABSTRACT: Hormones, notably estrogens, are pivotal in the origins of breast cancer but androgenic effects, while supported by persistence of AR expression in breast cancers, remain controversial. This study determined the role of the androgen actions via androgen receptor (AR) in experimental mammary cancer. Androgen-resistant female and male mice (ARKO) were generated using Cre/loxP technique and featured a global AR inactivation. The effect of AR inactivation and influence of genetic background on 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis was confirmed using two separate ARKO models with different genetic backgrounds. The onset of palpable mammary tumors was significantly faster in ARKO females (median time 22 vs 34 weeks, respectively; (p = 0.0024; multivariate Cox regression) compared to WT and independent of the mouse genetic background. The cumulative incidence at 9 months was 81 ± 10% [mean ± SE] for ARKO compared to 50 ± 13% in WT females. The increased DMBA susceptibility of ARKO females was associated with a higher epithelial proliferation index but not with major structural or receptor (estrogen or progesterone) expression differences between the virgin WT or ARKO female mammary glands. AR inactivation allowed substantial ductal extension in ARKO males while WT males displayed only rudimentary epithelial branches or complete regression of epithelial structures. Yet, DMBA did not induce epithelial mammary tumors in WT or ARKO males, demonstrating that AR inactivation alone is insufficient to promote mammary tumors. These results demonstrate that AR inactivation accelerates mammary carcinogenesis in female mice exposed to the chemical carcinogen DMBA regardless of mouse genetic background but require prior exposure to endogenous ovarian hormones.
Hormones and Cancer 02/2012; 3(3):113-24.
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ABSTRACT: Polycystic ovary syndrome (PCOS) is the most frequent female endocrine disorder, affecting 5%-10% of women, causing infertility due to dysfunctional follicular maturation and ovulation, distinctive multicystic ovaries and hyperandrogenism, together with metabolic abnormalities including obesity, hyperinsulinism, an increased risk of type 2 diabetes, and cardiovascular disease. The etiology of PCOS is unclear, and decisive clinical studies are limited by ethical and logistic constraints. Consequently treatment is palliative rather than curative and focuses on symptomatic approaches. Hence, a suitable animal model could provide a valuable means with which to study the pathogenesis of the characteristic reproductive and metabolic abnormalities and thereby identify novel and more effective treatments. So far there is no consensus on the best experimental animal model, which should ideally reproduce the key features associated with human PCOS. The prenatally androgenized rhesus monkey displays many characteristics of the human condition, including hyperandrogenism, anovulation, polycystic ovaries, increased adiposity, and insulin insensitivity. However, the high cost of nonhuman primate studies limits the practical utility of these large-animal models. Rodent models, on the other hand, are inexpensive, provide well-characterized and stable genetic backgrounds readily accessible for targeted genetic manipulation, and shorter reproductive life spans and generation times. Recent rodent models display both reproductive and metabolic disturbances associated with human PCOS. This review aimed to evaluate the rodent models reported to identify the advantages and disadvantages of the distinct rodent models used to investigate this complex endocrine disorder.
Biology of Reproduction 02/2012; 86(5):149, 1-12. · 4.01 Impact Factor
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ABSTRACT: There is a lack of evidence on the contribution of mild cognitive impairment (MCI) to institutionalization in older adults. This study aimed to evaluate a range of risk factors including MCI of institutionalization in older men.
Men aged ≥70 years (n = 1705), participating in the Concord Health and Ageing in Men Project, Sydney, Australia were studied. Participants completed self-reported questionnaires and underwent comprehensive clinical assessments during 2005-2007. Institutionalization was defined as entry into a nursing home facility or hostel at any time over an average of 5 years of follow-up. Cox regression analysis was conducted to generate hazard ratios (HR) with 95% confidence intervals (CI).
A total of 125 (7.3%) participants were institutionalized. Piecewise Cox proportional models were generated and divided at 3.4 years (1250 days) of follow-up due to violation of the proportional hazards assumption for the association between MCI and institutionalization (χ(2) = 6.44, p = 0.01). Dementia, disability in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL), poor grip strength, few social interactions, being a Non-English speaking immigrant and age were predictive of institutionalization during both time periods, whereas MCI (HR = 4.39, 95%CI 2.17-8.87) only predicted institutionalization in the period beyond 3.4 years of follow-up. Being married (HR = 0.42, 95%CI: 0.24-0.72) was protective only during the period after 3.4 years of follow-up.
In this study, the strongest predictors of institutionalization were dementia, MCI, ADL and IADL disability. MCI was not a predictor of early institutionalization but became a significant predictor beyond 3.4 years of follow-up.
PLoS ONE 01/2012; 7(9):e46061. · 4.09 Impact Factor
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Kerrin Bleicher,
Robert G Cumming,
Vasikaran Naganathan,
Thomas G Travison,
Philip N Sambrook,
Fiona M Blyth, David J Handelsman,
David G Le Couteur,
Louise M Waite,
Helen M Creasey,
Markus J Seibel
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ABSTRACT: Weight loss is associated with bone loss; however, it is unclear whether loss of fat or loss of lean body mass plays the key role in this relationship. The aim of this longitudinal analysis was to clarify the relationship between hip BMD, hip BMC and whole body BMC with changes in fat and lean tissue mass in older men.
The Concord Health and Aging in Men Project (CHAMP) is a population-based study in Sydney, Australia, involving 1705 men aged 70-97 years. Bone mineral density (BMD) of the total hip, and bone mineral content (BMC) of the hip and whole body (WB), lean mass and fat mass were measured with Dual X-ray Absorptiometry (DXA). Multivariate linear regression models were used to assess relationships.
Over 2.2 years of follow-up, 368(33%) men lost at least 2% of their body weight, which included a mean loss of 0.8 kg/year of lean body mass and 0.9 kg/year of fat body mass. Fat loss was strongly associated with BMD loss in men who lost weight. As a group, weight losers lost 1.0% of hip BMD annually compared to 0.2% in men who gained weight, with each kilo of fat loss associated with 0.6%/year hip BMD loss (p<0.0001). Lean mass was not associated with hip BMD loss in weight losers, however, lean mass change was associated with BMD change in men who gained weight (0.3% hip BMD increase per kilo increase of lean mass p<0.01).
Maintaining body weight is important for bone health in elderly men. Body fat plays an important role in this relationship, which may reflect the additional metabolic function of adipose tissue.
Bone 09/2011; 49(6):1299-305. · 4.02 Impact Factor
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ABSTRACT: Androgens influence prostate growth and development, so androgen withdrawal can control progression of prostate diseases. Although estrogen treatment was originally used to induce androgen withdrawal, more recently direct estrogen effects on the prostate have been recognized, but the nature of androgen-estrogen interactions within the prostate remain poorly understood. To characterize androgen effects on estrogen sensitivity in the mouse prostate, we contrasted models of castration-induced androgen withdrawal in the prostate stromal and epithelial compartments with a prostate epithelial androgen receptor (AR) knockout (PEARKO) mouse model of selective epithelial AR inactivation. Castration markedly increased prostate epithelial estrogen receptor (ER)α immunoreactivity compared with very low ERα expression in intact males. Similarly, strong basal and luminal ERα expression was detected in PEARKO prostate of intact males, suggesting that epithelial AR activity regulated epithelial ERα expression. ERβ was strongly expressed in intact, castrated, and PEARKO prostate. However, strong clusters of epithelial ERβ positivity coincided with epithelial stratification in PEARKO prostate. In vivo estrogen sensitivity was increased in PEARKO males, with greater estradiol-induced prostate growth and epithelial proliferation leading to squamous metaplasia, featuring markedly increased epithelial proliferation, thickening, and keratinization compared with littermate controls. Our results suggest that ERα expression in the prostate epithelial cells is regulated by local, epithelia-specific, androgen-dependent mechanisms, and this imbalance in the AR- and ER-mediated signaling sensitizes the mature prostate to exogenous estrogens.
AJP Endocrinology and Metabolism 07/2011; 301(4):E727-35. · 4.75 Impact Factor
