Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Associations of polysomnographic measures of obstructive sleep apnea, and nocturnal oxygen saturation with incident type 2 diabetes mellitus in middle-aged and older men.

Obstructive sleep apnea (OSA) has been associated with incident type 2 diabetes mellitus (T2DM); however, few prospective epidemiological studies have accounted for important T2DM predictors including pre-diabetes status and testosterone. Participants in the longitudinal Men Androgens Inflammation Lifestyles Environment and Stress (MAILES) study, who underwent eight-channel home-based polysomnography (PSG) in 2010-2011 (n = 824) and were free of diabetes at baseline were included in the analysis (n = 682). From 2015 to 2021, 78.6% (n = 536) completed at least one follow-up assessment. Incident T2DM was determined by self-reported doctor diagnosis, diabetes medications, plasma glucose (fasting ≥7.0 mmol/L or random ≥11.0 mmol/L) or glycated haemoglobin ≥6.5%. Conservative hierarchical Poisson regression models adjusted associations of PSG metrics (categorical and continuous) for age, waist circumference, baseline fasting glucose and testosterone concentrations. In all, 52 men (9.7%) developed T2DM over a mean (range) of 8.3 (3.5-10.5) years. Significant age- and waist circumference-adjusted association of incident T2DM with rapid eye movement (REM) sleep apnea-hypopnea index (AHI) ≥20 events/h (incidence rate ratio [IRR] 1.5, 95% confidence interval [CI] 0.8-2.8; p = 0.23] and highest quartile of delta index (IRR 2.1, 95% CI 0.95-4.6; p = 0.066) were attenuated after adjustment for baseline glucose and testosterone, and the association with the lowest quartile of mean oxygen saturation persisted (IRR 4.2, 95% CI 1.7-10.3; p = 0.029). Categorical measures of AHI severity, oxygen desaturation index, and hypoxia burden index (HBI) were not independently associated with incident T2DM. Associations with T2DM were similar when continuous PSG variables were used; however, HBI was significant (IRR 1.015, 95% CI 1.006-1.024; p = 0.007). In a sub-sample with OSA treatment data (n = 479), these significant associations persisted after excluding adequately treated OSA (n = 32). Understanding underlying OSA endotypes generating hypoxaemia may identify opportunities for diabetes prevention.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Associations of baseline obstructive sleep apnea and sleep macroarchitecture with cognitive function after 8 years in middle-aged and older men from a community-based cohort study.

Previous prospective studies examining associations of obstructive sleep apnea and sleep macroarchitecture with future cognitive function recruited older participants, many demonstrating baseline cognitive impairment. This study examined obstructive sleep apnea and sleep macroarchitecture predictors of visual attention, processing speed, and executive function after 8 years among younger community-dwelling men. Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography, with 157 completing Trail-Making Tests A and B and the Mini-Mental State Examination. Associations of obstructive sleep apnea (apnea-hypopnea index, oxygen desaturation index, and hypoxic burden index) and sleep macroarchitecture (sleep stage percentages and total sleep time) parameters with future cognitive function were examined using regression models adjusted for baseline demographic, biomedical, and behavioural factors, and cognitive task performance. The mean (standard deviation) age of the men at baseline was 58.9 (8.9) years, with severe obstructive sleep apnea (apnea-hypopnea index ≥30 events/h) in 9.6%. The median (interquartile range) follow-up was 8.3 (7.9-8.6) years. A minority of men (14.6%) were cognitively impaired at baseline (Mini-Mental State Examination score <28/30). A higher percentage of light sleep was associated with better Trail-Making Test A performance (B = -0.04, 95% confidence interval [CI] -0.06, -0.01; p = 0.003), whereas higher mean oxygen saturation was associated with worse performance (B = 0.11, 95% CI 0.02, 0.19; p = 0.012). While obstructive sleep apnea and sleep macroarchitecture might predict cognitive decline, future studies should consider arousal events and non-routine hypoxaemia measures, which may show associations with cognitive decline.

The bidirectional association between depression and lower urinary tract symptoms (LUTS) in men: A systematic review and meta-analysis of observational studies.

BACKGROUND: Recent evidence from observational studies suggests a bidirectional association between lower urinary tract symptoms (LUTS) and depression in men. We sought to systematically quantify the effect of the presence of LUTS on depression symptoms, compared to those without LUTS, in adult males, and vice versa. METHODS: Electronic databases (MEDLINE, PsycINFO, SCOPUS, Embase) were examined for articles in English before March 2021. Observational studies of men aged over 18 years; reporting an association between LUTS and depression; including a validated scale for LUTS and depression symptoms were eligible for study inclusion. RESULTS: Seventeen studies out of 1787 records identified 163 466 men with reported depression symptoms by LUTS status, while 10 studies reported 72 363 men with LUTS by depression symptoms. Pooled estimates showed a strong effect of LUTS presence on depression risk (OR: 2.89, 95% CI: 2.50-3.33), with a high degree of heterogeneity among the examined studies (I2 = 83%; τ2 = 0,06; p < 0.001). Subgroup analyses demonstrated differences by study region (Q value:13.7, df:4, p = 0.003), setting (7.8(2), p = 0.020), design (7.2(1), p = 0.003), quality (6.2(1), p = 0.013), and LUTS measure (40.9(3), p < 0.001). Pooled estimates also showed a strong effect of depression presence on LUTS risk in men (OR: 3.13, 95% CI: 2.72-3.60), with only moderate heterogeneity between studies (I2 = 58%; τ2 = 0,02; p = 0.001). CONCLUSIONS: The strong relationship observed between LUTS and depression implies shared risk factors that cannot be solely attributed to the prostate. This has immediate implications for future studies and the assessment and management of patients with either condition.

A thematic analysis of men's help-seeking on an Australian health helpline.

AIMS AND OBJECTIVES: The current study aimed to qualitatively explore men's help-seeking behaviours by analysing male callers' talk on an Australian health helpline. Analysis focused on identifying the ways in which men positioned themselves as help-seekers and the extent to which help-seeking behaviours deviated or conformed to the narrative commonly reported on in men's health literature which, generally speaking, positions men as reluctant help-seekers and health service users. METHODS: The present study utilised naturally occurring instances of men's help-seeking during 196 calls to the helpline, Healthdirect Australia. Thematic analysis was used to explore recurrent themes in help-seeking interactions. FINDINGS: The analysis yielded three broad themes, which were formulated as caller archetypes. These themes included the 'reluctant caller', the 'unwell patient' and the 'concerned carer', as well as a number of associated sub-themes within these broad categories. CONCLUSIONS: The findings demonstrated that male callers sought help in a variety of different ways, rather than prescribing to a homogenous pattern of help-seeking. However, it was acknowledged that some data did align with help-seeking behaviour which indicated men's reluctance to engage with their own health. SO WHAT?: The present study contributes to men's health promotion by identifying the various social devices used by men to facilitate help-seeking. The findings highlight the changing and flexible landscape of contemporary masculinity and its impact on health engagement. Recognising the versatility in men's health behaviour is important for ensuring that men have positive experiences during healthcare encounters which, in turn, may facilitate future health service uptake and engagement.

The association between total phthalate concentration and non-communicable diseases and chronic inflammation in South Australian urban dwelling men.

OBJECTIVE: To investigate associations between urinary total phthalate concentration, chronic low-grade inflammation and non-communicable diseases in a cohort of South Australian men. METHODS: 1504 men aged 39-84 years who provided a urinary sample at the follow-up visit of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a randomly-selected group of urban-dwelling, community-based men from Adelaide, Australia (n = 2038; study participation rate: 78.1%). Total phthalate concentration was quantified in fasting morning urine samples. Chronic diseases were assessed through self-report questionnaire or directly measured using standardised clinical and laboratory procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy. Multivariable linear and logistic regression models were applied to determine associations of log-transformed urinary phthalate concentration with inflammation and chronic disease. RESULTS: Total phthalates were detected in 99.6% of urinary samples; geometric mean (95% CI) was 114.1 (109.5-118.9)µg/g creatinine. Higher total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p < 0.05) and TNF-α but not MPO. Urinary total phthalate concentrations were positively associated with cardiovascular disease, type-2-diabetes and hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios were 1.78 (95% CI 1.17 - 2.71, p-trend = 0.001) for cardiovascular disease and 1.84 (95%CI 1.34 - 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI 1.01 - 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and depression were not significantly associated. CONCLUSION: A positive association between total phthalates and cardiovascular disease, type-2-diabetes, hypertension and increased levels of chronic low-grade inflammatory biomarkers was observed in urban-dwelling Australian men.

Co-morbid OSA and insomnia increases depression prevalence and severity in men.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and insomnia coexist in clinical populations but prevalence in the community and risk factors remain largely unknown. We examined the prevalence and profile of previously undiagnosed co-morbid OSA and insomnia symptoms (COMISA) in community-dwelling men. METHODS: Men (n = 700, aged 58.5 ± 11.0 (mean ± SD) years) without a prior diagnosis of OSA completed full at-home unattended polysomnography, the Pittsburgh Sleep Quality Index and 36-item short form (SF-36) survey (2007-2012). Insomnia symptoms included difficulty initiating/maintaining sleep in the presence of daytime fatigue (DIMS-F). Depressive symptoms were assessed using the Beck Depression Inventory-1A, Centre for Epidemiological Studies Depression Scale and Patient Health Questionnaire-9 (PHQ-9) (2007-2010). Univariate (χ2 and analysis of variance (ANOVA)) and multiple linear regressions were used to compare data from four groups of individuals: neither disorder; previously undiagnosed OSA (apnoea-hypopnoea index ≥ 10) or DIMS-F alone; and COMISA. RESULTS: COMISA prevalence was 6.7%. Depression prevalence (COMISA, 42.6%; DIMS-F, 21.6%; OSA, 8.4%, χ2 = 71.6, P < 0.00) and symptom scale scores (e.g. PHQ-9 mean ± SD: 16.1 ± 5.5 c.f. DIMS-F: 14.0 ± 4.9, P < 0.01 and OSA: 11.4 ± 3.0, P = 0.01) were highest in men with COMISA. In COMISA, respiratory and arousal indices were similar to those observed in OSA whilst reductions in subjective sleep and day dysfunction scores were similar to DIMS-F. After adjustment, predicted mean depression scores were all higher in DIMS-F and COMISA using linear regression (e.g. PHQ-9 ß (95% CI): DIMS-F: 2.3 (1.2, 3.5); COMISA: 4.1 (3.0, 5.1)). CONCLUSION: Men with COMISA have a greater prevalence, and severity, of depression than men with only one disorder.

Association of daytime sleepiness with obstructive sleep apnoea and comorbidities varies by sleepiness definition in a population cohort of men.

BACKGROUND AND OBJECTIVE: To determine correlates of excessive daytime sleepiness (EDS) identified with the Epworth Sleepiness Scale (ESS) and a more broad definition, while accounting for obstructive sleep apnoea (OSA) in community dwelling men. METHODS: Participants of the Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) Study (n = 837, ≥ 40 years) without a prior OSA diagnosis, underwent in-home full unattended polysomnography (PSG, Embletta X100), completed the ESS, STOP questionnaire and Pittsburgh Sleep Quality Index in 2010-2011. In 2007-2010, questionnaires and biomedical assessment (in South Australian public hospital-based clinics) identified medical conditions. An alternate EDS definition (EDSAlt ) consisted of ≥ 2 of 3 problems (feeling sleepy sitting quietly; feeling tired/fatigued/sleepy; trouble staying awake). RESULTS: EDSAlt (30.4%, n = 253), but not ESS ≥ 11 (EDSESS , 12.6%, n = 104), increased significantly across OSA severity and body mass index categories. In adjusted analyses, EDSESS was significantly associated with depression: odds ratio (OR), 95%CI: 2.2 (1.3-3.8) and nocturia: 2.0 (1.3-3.2). EDSAlt was associated with depression, financial stress, relationship, work-life balance problems and associations with nocturia and diabetes were borderline. After excluding men with EDSESS , EDSAlt was associated with oxygen desaturation index (3%) ≥ 16 and the highest arousal index quartile but not with comorbidities. CONCLUSION: Sleepiness not necessarily leading to dozing, but not ESS ≥ 11, was related to sleep disordered breathing. Clinicians should be alert to (1) differing perspectives of sleepiness for investigation and treatment of OSA, and (2) the presence of depression and nocturia in men presenting with significant Epworth sleepiness regardless of the presence of OSA.

Undiagnosed obstructive sleep apnea is independently associated with reductions in quality of life in middle-aged, but not elderly men of a population cohort.

PURPOSE: Obstructive sleep apnea (OSA) is now highly prevalent but largely undiagnosed. Quality of life is an indicator of both the impact of undiagnosed OSA and the need for strategies to increase OSA diagnosis. We determined age-related impacts of undiagnosed OSA on health-related quality of life (HRQL) and whether this was independent of sleepiness and comorbidities. METHODS: In 2010-2012, 837 participants from the Men Androgen Inflammation Lifestyle Environment and Stress Study (population cohort n = 1869, ≥40 years, Adelaide, Australia), without a prior OSA diagnosis underwent full in-home polysomnography (Embletta X100) and completed the Epworth Sleepiness Scale and SF-36 questionnaire. The effects of the apnea-hypopnea index (AHI) on SF-36 physical (PCS) and mental (MCS) component summary scores and standardized SF-36 scale z-scores were estimated using multiple linear regression adjusted for major comorbidities and sleepiness, stratified by age. RESULTS: Men ≤69 years demonstrated significant (p < 0.05) decrements/event increase in AHI in PCS score [unstandardized B coefficient (SE) = -0.068 (0.023)], physical functioning, role physical, general health, and vitality z-scores in fully adjusted models. Severe OSA (AHI ≥30) was associated with significant reductions in PCS [B = -4.1 (1.1)] and MCS score [B = -3.6 (1.2)] independent of sleepiness and comorbidities which were attenuated but persisted in men <69 years without depression. In men aged ≥70 years, statistically significant AHI-associated impairments were generally not seen. CONCLUSIONS: Undiagnosed OSA was a major independent contributor to HRQL impairments in men <69 years. Improved strategies to identify undiagnosed OSA are indicated that may require a reduced focus on daytime sleepiness.

Predictors of sexual dysfunction incidence and remission in men.

INTRODUCTION: The progress and determinants of sexual dysfunction in middle-aged and elderly men remain unclear. AIM: To describe the incidence or remission and biopsychosocial predictors of erectile dysfunction (ED) and low sexual desire (SD). MAIN OUTCOME MEASURES: Erectile function (International Index of Erectile Function) and sexual desire (Sexual Desire Inventory 2) were assessed at follow-up. Sociodemographic, lifestyle, and health-related factors were examined in multivariate models of ED and low SD. METHODS: Data were collected from 810 randomly selected men residing in northern and western Adelaide, Australia, and aged 35-80 years at baseline, who made clinic visits 5 years apart. RESULTS: At baseline, 23.2% (n = 123) of men had ED. ED incidence and remission were observed in 31.7% (n = 179) and 29.0% (n = 71) of eligible men, respectively. At baseline, 19.2% (n = 165) had low solitary sexual desire, and 6.0% (n = 50) had low dyadic sexual desire; incidence of low sexual desire occurred in 17.6% (n = 83) (solitary) and 8.3% (n = 51) (dyadic), while remission occurred in 15.4% (n = 68) (solitary) and 22.6% (n = 40) (dyadic) of men. In the final regression models, predictors of incident ED were higher age, lower income, higher abdominal fat mass, low alcohol intake, higher risk of obstructive sleep apnea (OSA) risk, voiding lower urinary tract symptoms (LUTS), depression, and diabetes. Predictors of ED remission were lower age, current employment, and absence of voiding LUTS, angina, diabetes, and dyslipidemia. Predictors of low dyadic SD incidence included higher age, never having been married, widowhood, being unemployed, being retired, insufficient physical activity, and low alcohol intake. Predictors of low dyadic SD remission were being married, not being widowed, higher income, lower abdominal fat mass, lower OSA risk, and higher plasma testosterone. Predictors of low solitary SD included never having been married, being unemployed, low alcohol intake, lower testosterone, storage LUTS, and hypertension. Predictors of low solitary SD remission were being married, being employed, higher income, higher physical activity, moderate alcohol intake, and depression. CONCLUSIONS: Sexual dysfunction in aging men is a dynamic disorder whose incidence and remission are predicted by a range of modifiable risk factors.

Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study.

Purpose: Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men. Patients and Methods: Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010-2011), with 157 completing baseline (2007-2010) and follow-up (2018-2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition. Results: The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p>0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance. Conclusion: In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study.

OBJECTIVES: Previous studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. METHODS: Florey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). RESULTS: In fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = -0.43, 95% confidence interval [-0.74, -0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). CONCLUSIONS: Specific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep microarchitecture parameters determined by quantitative power spectral analysis of electroencephalograms have been proposed as potential brain-specific markers of cognitive dysfunction. However, data from community samples remain limited. This study examined cross-sectional associations between sleep microarchitecture and cognitive dysfunction in community-dwelling men. METHODS: Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography (2010-2011). All-night electroencephalogram recordings were processed using quantitative power spectral analysis following artifact exclusion. Cognitive testing (2007-2010) included the inspection time task, Trail-Making Tests A and B, and Fuld object memory evaluation. Complete case cognition, polysomnography, and covariate data were available in 366 men. Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders determined cross-sectional associations between sleep microarchitecture and cognitive dysfunction overall and by age-stratified subgroups. RESULTS: In the overall sample, worse Trail-Making Test A performance was associated with higher rapid eye movement (REM) theta and alpha and non-REM theta but lower delta power (all P < .05). In men ≥ 65 years, worse Trail-Making Test A performance was associated with lower non-REM delta but higher non-REM and REM theta and alpha power (all P < .05). Furthermore, in men ≥ 65 years, worse Trail-Making Test B performance was associated with lower REM delta but higher theta and alpha power (all P < .05). CONCLUSIONS: Sleep microarchitecture parameters may represent important brain-specific markers of cognitive dysfunction, particularly in older community-dwelling men. Therefore, this study extends the emerging community-based cohort literature on a potentially important link between sleep microarchitecture and cognitive dysfunction. The utility of sleep microarchitecture for predicting prospective cognitive dysfunction and decline warrants further investigation. CITATION: Parker JL, Appleton SL, Melaku YA, et al. The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study. J Clin Sleep Med. 2022;18(6):1593-1608.

The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men. METHODS: Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11-16 Hz), slow density (11-13 Hz), and fast density (13-16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics. RESULTS: In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = -0.003, p = 0.032; TST90, B = -0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = -1.27, p = 0.030) and fast density (B = -4.36, p = 0.028) during N3 sleep. CONCLUSIONS: Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.

Prevalence and factors associated with uncomplicated storage and voiding lower urinary tract symptoms in community-dwelling Australian men.

PURPOSE: To determine the prevalence of, and associated risk factors for, voiding and storage lower urinary tract symptoms (LUTS) in a population-based sample of Australian men. METHODS: Data were collected from 1,103 men randomly selected, community-dwelling men, as part of the Florey Adelaide Male Ageing Study, after exclusion of men with prostate or bladder cancer or prior surgery to either organ. The presence of LUTS was assessed using the International Prostate Symptom Score. Urine flow was measured via flow meter. Demographic, clinical, and bio-psychosocial data were collected by questionnaire. RESULTS: The prevalence of total, storage, and voiding LUTS was 18.1, 28.0 and 12.6%, respectively. The most common storage symptoms were frequency (12.3%), nocturia (9.9%) and urgency (8.1%), and voiding symptoms were weak stream (8.5%), intermittency (5.4%), incomplete emptying (5.1%) and straining (2.4%). There were linear associations between storage LUTS and increased abdominal fat mass, plasma glucose and low HDL cholesterol (components of the metabolic syndrome), obstructive sleep apnoea (OSA) risk, and retirement. Voiding symptoms were associated with a previous diagnosis of benign prostatic enlargement (BPH), mean peak urine flow, total energy intake, elevated risk of OSA, erectile dysfunction, physician-diagnosed thyroid dysfunction and higher household income. CONCLUSIONS: The close association of storage LUTS with the metabolic syndrome, and of both storage and voiding LUTS with OSA, suggest that these conditions should be considered in men presenting with LUTS.

The Association of Obstructive Sleep Apnea and Nocturnal Hypoxemia with Lipid Profiles in a Population-Based Study of Community-Dwelling Australian Men.

OBJECTIVE: To determine the association of obstructive sleep apnea and nocturnal hypoxemia with serum lipid profiles in unselected community-dwelling men. METHODS: Cross-sectional data from participants of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study (n=753) who underwent full in-home polysomnography (Embletta X100) was used. Triglycerides, high- (HDL), low-density lipoprotein (LDL), and total cholesterol were assessed on a fasting morning blood sample. Multivariable linear regression analyses assessed associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index (3%) (ODI), apnea-hypopnea index (AHI), and rapid eye movement sleep apnea-hypopnea index (REM-AHI)), adjusted for chronic conditions, risk behavior and sociodemographic factors. Sensitivity analyses examined the effect of lipid lowering therapies on reported estimates. Effect modification was examined through stratification by waist circumference groups. RESULTS: In 753 participants with mean (SD) age of 60.8 (10.9) years and waist circumference: 99.3 (11.6) cm, the prevalence of OSA (AHI≥10) was 52.6%. Overall, no significant associations between OSA metrics and lipid measures were found. Similarly, sensitivity analysis excluding lipid lowering therapies showed no significant associations. In analysis stratified by waist circumference (<95cm, 95-100cm, >100cm), ODI (3%, unstandardized B: 0.027, 95% CI: 0.015-0.040), AHI (0.023, 0.012-0.033) and AHIREM (0.012, 0.001-0.022) were positively associated with serum triglycerides in participants with a normal waist circumference (<95cm). CONCLUSION: Obstructive sleep apnea metrics were positively associated with serum triglyceride levels in men with a normal waist circumference. Healthy weight individuals with OSA require clinical attention to improve cardiometabolic risk profiles.

Analysis of major fatty acids from matched plasma and serum samples reveals highly comparable absolute and relative levels.

Measuring fatty acid (FA) levels in blood as a risk factor for chronic disease has been studied extensively. Previous research has used either plasma or serum samples to examine these associations. However, whether results from plasma and serum samples can be compared remains unclear, as differences in methodology related to the separation of plasma and serum from whole blood may impact FA levels. This study analyzed the individual FA content of matched plasma and serum samples in both absolute (µg/mL) and relative percent (%) composition. Analyses were performed using archived fasted morning samples from the Florey Adelaide Male Ageing Study (FAMAS). Matched plasma and serum samples were available from 98 male subjects aged 40-85. Total FA were analyzed by gas-liquid chromatography equipped with a flame ionization detector (GLC-FID). Analyses comprised of over 60 FA including major FA such as Palmitic Acid (PA), Palmitoleic acid (POA), Stearic Acid (SA), Oleic Acid (OA), Linoleic Acid (LNA), alpha-linolenic acid (ALA), Eicosapentaenoic acid (EPA), Arachidonic Acid (ARA), and Docosahexaenoic acid (DHA). Differences between groups was determined by t-test. Correlation and Bland-Altman analyses were also performed to examine the relationship between plasma and serum samples. There were no significant differences between major plasma and serum fatty acids expressed in µg/mL and relative % composition. Correlation analysis determined a strong and significantly positive association (r ≥ 0.65, p < 0.05) between major plasma and serum FA in absolute and relative terms. Bland-Altman analysis further supported the strong agreement between plasma and serum values in both absolute and relative terms. These findings demonstrate that studies reporting plasma or serum fatty acid analyzed by GLC-FID can be compared with one another.

Serum testosterone bioassay evaluation in a large male cohort.

OBJECTIVE: To assess if a cell-based readout of androgen action in serum demonstrates a closer association with recognized classical parameters of androgen action in men than current measures of serum testosterone (T). DESIGN: To develop, validate and utilize a mammalian cell-based assay to measure specifically bioactive T and determine if this measure is a physiologically relevant fraction of serum T. MEASUREMENTS AND PARTICIPANTS: We have developed a specific serum T bioassay using human prostate cancer cells. A rapid 5-min exposure to 100% serum followed by serum withdrawal confers specificity of the assay to serum T and provides sufficient sensitivity to measure T in male serum samples. Matrix effects were experimentally discounted as a confounding issue. A total of 960 male serum samples from the Florey Adelaide Male Ageing Study (FAMAS) with previous comprehensive cohort data and serum measurements were utilized. RESULTS: Bioassay T measurement in the 960 FAMAS serum samples returned a median of 10.7 nmol/l (1.7-45.4), and was most closely related to immunoassayed total T, but not immunoassayed bioavailable T or calculated free T. Immunoassayed total T demonstrated a positive association with isometric grip-strength (R(2) = 0.127, P < 0.001), self-reported sexual desire (R(2) = 0.113, P < 0.001) and erectile function (R(2) = 0.085, P < 0.05) while bioassay T did not. CONCLUSIONS: While cellular bioassays offer a rapid and sensitive means of identifying the androgenic potential of complex environmental compounds, the utility of such assays in defining a clinically relevant fraction of serum T distinct from total T needs further investigation.