Serum testosterone levels correlate with haemoglobin in middle-aged and older men (original) (raw)

In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study

European Journal of Endocrinology, 2007

Objective: An age-related decline in serum total and free testosterone concentration may contribute to ill health in men, but limited data are available for men O70 years of age. We sought to determine the distribution and associations of reduced testosterone concentrations in older men. Design: The Health in Men Study is a community-representative prospective cohort investigation of 4263 men aged R70 years. Cross-sectional hormone data from 3645 men were analysed. Methods: Early morning sera were assayed for total testosterone, sex hormone binding globulin (SHBG) and LH. Free testosterone was calculated using the Vermeulen method. Results: Mean (GS.D.) serum total testosterone was 15.4G5.6 nmol/l (444G162 ng/dl), SHBG 42.4G 16.7 nmol/l and free testosterone 278G96 pmol/l (8.01G2.78 ng/dl). Total testosterone correlated with SHBG (Spearman's rZ0.6, P!0.0001). LH and SHBG increased with age (rZ0.2, P!0.0001 for both). Instead of declining, total testosterone increased marginally (rZ0.04, PZ0.007) whilst free testosterone declined with age (rZK0.1, P!0.0001). Free testosterone was inversely correlated with LH (rZK0.1, P!0.0001). In multivariate analyses, increasing age, body mass index (BMI) and LH were associated with lower free testosterone. Conclusions: In men aged 70-89 years, modulation of androgen action may occur via an age-related increase in SHBG and reduction in free testosterone without a decline in total testosterone concentration. Increasing age, BMI and LH are independently associated with lower free testosterone. Further investigation would be required to assess the clinical consequences of low serum free testosterone, particularly in older men in whom total testosterone may be preserved.

Differential associations of testosterone, dihydrotestosterone and oestradiol with physical, metabolic and health-related factors in community-dwelling men aged 17-97 years from the Busselton Health Survey

Clinical Endocrinology, 2014

Objectives Lower testosterone (T) levels are associated with poorer health outcomes in older men, but associations in younger or middle-aged men are uncertain, and data for dihydrotestosterone (DHT) and oestradiol (E2) are limited. We assessed the associations of circulating T, DHT and E2 with physical and healthrelated factors in a cohort comprising men aged 17-97 years. Participants and methods Serum from 2143 communitydwelling men from the 1994/95 Busselton Health Survey was assayed for T, DHT and E2 using liquid chromatography-tandem mass spectrometry. Men receiving hormonal therapy or reporting the use of testosterone, or with prostate cancer or orchidectomy were excluded. Results Of the men, 43% had never smoked, 6Á1% had diabetes and 16Á8% cardiovascular disease (CVD). Mean (AESD) age was 50Á3 AE 17Á0 years. Total T was moderately correlated with DHT (r = 0Á56), E2 (r = 0Á35) and sex hormone-binding globulin (r = 0Á53). In age-, smoking-, body mass index (BMI)-and sex hormone-binding globulin (SHBG)-adjusted analyses, T was inversely associated with metabolic syndrome score, while DHT and E2 were not associated. In multivariable models, higher total T was associated with lower age, BMI and C-reactive protein, and with higher creatinine and haemoglobin, independently of SHBG. Higher DHT was associated with lower age, BMI and glucose level, and higher creatinine and haemoglobin. E2 was positively associated with age, BMI and haemoglobin. Conclusions In men spanning younger, middle and older ages, circulating androgens are more related to age and metabolic factors than CVD or chronic disease. Further investigation is required to clarify whether androgens and oestrogens have contrasting roles as risk predictors for CVD.

Relation of total and free testosterone and sex hormone-binding globulin with cardiovascular risk factors in men aged 24–45 years. The Cardiovascular Risk in Young Finns Study

Atherosclerosis, 2012

Background: Total and free testosterone decrease gradually in men with advancing age but it is not completely known how lower levels of testosterone are related with various cardiovascular risk factors. We studied the levels of total testosterone, calculated free testosterone and sex hormone-binding globulin (SHBG), and their relations with cardiovascular risk factors in young Finnish men. Methods: The study cohort consisted of 24-45-year-old men participating the Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in 2001 (N = 1024) and 2007 (N = 991). Levels of total testosterone, SHBG, lipids, glucose, insulin, blood pressure and anthropometric factors were measured and free testosterone was calculated. Results: In multivariable analyses adjusted for age, body mass index and life-style factors (alcohol consumption, smoking and physical activity), total and calculated free testosterone were inversely correlated with triglycerides (both P < 0.0001), insulin (P = 0.0004 and P = 0.01), systolic blood pressure (P = 0.007 and P = 0.01), and directly with high-density lipoprotein (HDL) cholesterol (P < 0.0001 and P = 0.003). SHBG was inversely correlated with triglycerides and insulin, and directly with HDL-cholesterol (all P < 0.001). In longitudinal analyses, lower levels of testosterone and SHBG were associated with higher levels of triglycerides and insulin six years later (all P < 0.01). Baseline level of SHBG was directly associated with HDL-cholesterol (P < 0.0001). Conclusion: In young and middle-aged men, higher levels of testosterone and SHBG are associated with favourable cardiovascular risk profile characterized by lower levels of triglycerides, insulin and systolic blood pressure, and higher levels of HDL-cholesterol.

Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study

Clinical Endocrinology, 2012

Objective 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. Design Observational, repeated measures study. Participants Men (n = 325) with 40 years and older selfreporting very good or excellent health. Measurements 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. Results Mean serum T did not vary with age (P = 0•76) but obesity (À0•35 nM per body mass index (BMI) unit, P < 0•0001) and ex-smoker status (À1•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 (À0•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). Conclusions Serum T, DHT and E 2 displayed no decrease associated with age among men over 40 years of age who selfreport very good or excellent health although obesity and exsmoking 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.

Prevalence of testosterone deficiency among aging men with and without morbidities

The Aging Male, 2019

In this cross-sectional study 1852 men aged 40-70 years attending primary health care were invited to fill out the aging male symptoms (AMS) scale. Out of these, 1222 men were found positive for the AMS and agreed to provide blood samples for the general blood test, lipid profile, glucose levels, and assessment of both total and free testosterone (T) levels. Men were screened for the following morbidities and syndromes: dyslipidemia, arterial hypertension, obesity, type II diabetes, metabolic syndrome, and chronic obstructive pulmonary disease (COPD). Testosterone deficiency was diagnosed if total T 3.46 ng/mL or free T 72 pg/mL. Among all 1222 men with positive AMS, decreased blood testosterone levels were detected in 669 men (55%). A total of 402 men were found healthy and 820 men were detected with different morbidities. Out of 669 men with testosterone deficiency, only 2.8% had no co-morbidities and 97.2% were men with co-morbidities. Testosterone levels were found significantly higher among healthy men (median 4.7 ng/mL) as compared to the men with morbidities (median 2.55 ng/mL, p<.001), adjusted for age. Testosterone deficiency was detected in significantly lower proportion of 402 men without co-morbidities as compared to the 820 men with co-morbidities: in 19 men (4.7) and in 650 men (79.3%, p<.05), respectively.

Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts

The Journal of Clinical Endocrinology & Metabolism, 2011

Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. Results: In a reference sample of 456 men, mean (SD), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Age-Related Changes in Serum Testosterone and Sex Hormone Binding Globulin in Australian Men: Longitudinal Analyses of Two Geographically Separate Regional Cohorts

The Journal of Clinical Endocrinology & Metabolism, 2007

Background: Cross-sectional studies from different populations show a variable decline in blood testosterone concentrations as men age. Few population representative cohorts have been followed up over time. Objective: The objective of the study was to quantify longitudinally the change in serum testosterone and SHBG concentrations with age in two well-defined, representative but geographically widely separated regional Australian cohorts. Subjects and Setting: The Busselton cohort comprises individuals aged 18–90 yr residing in Western Australia assessed prospectively since 1981. Sera were assayed from 910 men, from whom further samples were available 14 yr later in 480. The Dubbo cohort involves individuals aged 61–90 yr living in Eastern Australia. Baseline sera were collected from 610 men and additional sera on a second (n = 370) and third (n = 200) occasion from 1989 to 2004. Men from both cohorts are community dwelling and of predominately European origin. Results: Longitudinal...

Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study

European Journal of Endocrinology, 2009

Objective: Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by agerelated changes in sex hormone status. We examined whether lower testosterone or sex hormonebinding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity. Design: Cross-sectional analysis of 2470 community-dwelling non-diabetic men aged R70 years. Methods: Age, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR). Results: Total testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P!0.001) and correlated inversely with log HOMA2-IR (rZK0.27, K0.14 and K0.24 respectively, all P!0.001). After adjusting for age, BMI, waist circumference, highdensity lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR (bZ0.05, P!0.001), while SHBG was not. Serum total testosterone !8 nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02-2.73) as was total testosterone R8 and !15 nmol/l (OR 1.29, 95% CI 1.03-1.63). Conclusions: In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.

ANNALS EXPRESS: Estimating Age-Specific Trends in Circulating Testosterone and SHBG in Males and Females Across the Lifespan

Annals of clinical biochemistry, 2015

Age-specific trends of serum testosterone (T) and sex hormone binding globulin (SHBG) across the full lifespan have not been reported. We deduced age-specific trends in serum testosterone and SHBG in males and females between ages 10 and 90 from a large sample of consecutive results from a single large pathology laboratory. Coded results of 110,712 consecutive blood samples requesting serum testosterone over 7 years (2007-13) comprising blood T, SHBG and calculated free T (cFT) together with gender and age were analyzed create smoothed age-specific centiles (2.5%, 5%, 25%, 50%, 75%, 95%, 97.5%) for males and females. These identified the pubertal increases in serum T in males peaking at 20 years of age and remaining stable thereafter until the 8(t) (h) decade. In women circulating T peaked in late adolescence and declined gradually over the next 2 decades but remained stable across menopause and beyond. After early childhood, serum SHBG declines to a nadir in men the age of 20 years...

The association of obesity with sex hormone‐binding globulin is stronger than the association with ageing – implications for the interpretation of total testosterone measurements

Clinical Endocrinology, 2015

Objective-Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG. Design-We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. Patients, Measurements and Analysis-A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed. Results-Obesity was associated with a significantly lower SHBG [β = −1•26 (95% CI −1•14, −1•38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [β = 0•46 (95% CI 0•39, 0•53) nmol/l per year] (P < 0•001 for both effects). The association of obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI >30 kg/m 2) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean ± SD) SHBG: 36 ± 22 vs 50 ± 27 nmol/l and total testosterone: 10•5 ± 5•4 nmol/l vs 14•1 ± 7•4 nmol/l; (P < 0•001 for both comparisons)], but calculated free testosterone concentrations did not differ between obese and nonobese men. Conclusions-We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men.