A Population-Level Decline in Serum Testosterone Levels in American Men (original) (raw)

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study

2000

We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40 -70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, sim-ilarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally.

Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men

The Journal of Clinical Endocrinology and Metabolism, 2001

Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, ageinvariant, longitudinal effects of age on both T and free T index (free T index ϭ T/SHBG), with an average change of Ϫ0.124 nmol/L⅐yr and Ϫ0.0049 nmol T/nmol SHBG⅐yr. T, but not free T index, also decreased with increasing body mass index. Use of ␤Ϫblocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.

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.

Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA

European Urology Focus, 2020

Testosterone deficiency has a prevalence of up to 20% among adolescent and young adult (AYA) males, defined as men aged 15-39 yr according to the National Cancer Institute [1,2]. Prior decades have shown a decline in serum total testosterone (TT) levels in the male population but it remains unclear whether this phenomenon is real and if this trend has been pervasive in recent decades [3]. Moreover, this time-dependent pattern of TT decline has not yet been investigated in the AYA population. We sought to analyze serum TT levels among AYA males using the National Health and Nutrition Examination Surveys (NHANES) database with the hypothesis that mean TT levels among AYA men in the USA declined between 1999 and 2016. NHANES are cross-sectional surveys conducted by the

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.

Healthier lifestyle predicts higher circulating testosterone in older men: the Health In Men Study

Clinical Endocrinology, 2009

Objective Circulating testosterone declines during male ageing, and low testosterone may predispose to ill health. We sought to determine whether greater participation in healthy behaviours predicted reduced risk of subsequent lower circulating testosterone in older men. Design Cross-sectional analysis of a population-based follow-up study. Participants A total of 3453 men aged 65-83 years. Measurements Lifestyle score, a tally of eight prudent health-related behaviours, was determined during 1996-99. Early morning sera collected in 2001-04 were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Results Mean (± SD) time between collection of lifestyle data and blood sampling was 5·7 ± 0·9 years. Lifestyle score correlated with subsequent total testosterone ( r = 0·06, P < 0·001) and SHBG ( r = 0·07, P < 0·001), but not free testosterone ( r = 0·03, P = 0·08) or LH ( r = -0·03, P = 0·12). In multivariate analyses, higher lifestyle scores (4 and above) predicted reduced risk of total testosterone and SHBG in the lowest quartile of values. For the highest category ( ≥ 7), odds ratio (95% CI) for total testosterone and SHBG in the lowest quartile were 0·37 (0·18-0·77) and 0·26 (0·13-0·54), respectively. Lower lifestyle scores including and excluding body mass index predicted higher risk of total testosterone and SHBG in the lowest quartiles. Conclusions In men > 65 years old, higher lifestyle score reflecting greater engagement in healthy behaviours predicts higher subsequent total testosterone and SHBG levels. This relationship appears cumulative and may reflect interaction between lifestyle and insulin sensitivity. Successfully promoting healthy behaviours in older men could ameliorate the age-related decline in circulating testosterone.

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.