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

Aim: The age-specific population profiles in men of circulating testosterone and its two bioactive metabolites dihydrotestosterone (DHT) and estradiol (E 2 ) across the adult lifespan and its determinants are not well described. Objective: Our objective was to deduce smoothed age-specific centiles of circulating testosterone, DHT, and E 2 in men using pooled data from population-based studies in three Australian cities from liquid chromatography-mass spectrometry steroid measurements in a single laboratory. Design, setting, and participants: We pooled data of 10 904 serum samples (serum testosterone, DHT, E 2 , age, height, and weight) from observational population-based studies in three major cities across Australia. Main outcome measures: Age-specific smoothed centiles for serum testosterone, DHT, and E 2 in men aged 35-100 years were deduced by large sample data analysis methods. Results: We found that serum testosterone, DHT, and E 2 decline gradually from ages 35 onwards with a more marked decline after 80 years of age. Higher weight, BMI, and body surface area as well as shorter stature are associated with reduced serum testosterone, DHT, and E 2 . Conclusions: Among Australian men, there is a gradual progressive population-wide decline in androgen status during male aging until the age of 80 years after which there is a more marked decline. Obesity and short stature are associated with reduced androgen status. Research into the age-related decline in androgen status should focus on the progressive accumulation of age-related comorbidities to better inform optimal clinical trial design.

Section: Discussionmentioning

confidence: 97%

Age-specific population centiles for androgen status in men

Handelsman

Yeap

Flicker

et al. 2015

“…Our findings need to be evaluated across a wider age range, as ageing is related to an increase in SHBG concentration, a fall in androgen levels (55,56,57) and a rise in CVD absolute rates (58). It has been suggested that specific genotypes might influence the binding affinity of SHBG with testosterone and thereby affect the calculation of FT based on the law of mass action, as used in the Vermeulen equation (54) (which is essentially the same as statistically adjusting for SHBG in a regression model).…”

Section: Discussionmentioning

confidence: 99%

Serum sex hormone-binding globulin and testosterone in relation to cardiovascular disease risk factors in young men: a population-based study

Canoy

Barber

Pouta

et al. 2014

Objective: Reduced sex hormone-binding globulin (SHBG) concentration predicts insulin resistance and type 2 diabetes, but its association with cardiovascular disease (CVD) risk is unclear. We examined the association between SHBG and cardiovascular risk factors, independently of total testosterone (TT), in young men. Design: Observational, cross-sectional study. Setting: General community. Participants: The study included 2716 men aged 31 years in the Northern Finland Birth Cohort in 1996 with clinical examination data and fasting blood samples. Outcome variables: Blood pressure (BP), lipids and C-reactive protein (CRP) as biological CVD risk markers. Results: SHBG concentration was significantly and inversely related to systolic and diastolic BP, triglycerides and CRP, but positively to HDL cholesterol after adjusting for insulin, BMI, waist circumference, smoking, education and physical activity (all P!0.05). These linearly graded associations persisted with additional adjustment for TT. SHBG was significantly associated with total cholesterol only with adjustment for covariates and TT (P!0.05). The direction and magnitude of associations between TT and risk factors were variable, but further adjustment for insulin, adiposity and SHBG showed positive associations between TT and BP, total and LDL-cholesterol and triglycerides and an inverse association with CRP (all P!0.05), but its relation with HDL-cholesterol was no longer significant. Conclusions: In this cohort of young adult men, higher SHBG concentration was associated with a more favourable CVD risk profile, independently of TT. SHBG concentration modified the associations of TT with CVD risk factors.

“…Total and free, or bioavailable, testosterone levels in men have been shown to decrease with advancing age, even after adjusting for potential confounding factors, such as comorbid conditions, medications, timing of samples, and technical issues related to the methods for hormone assays (21,22,23,24). After age 40, circulating levels of testosterone gradually decline at a rate of 1.6% per year for total testosterone and 2-3% per year for bioavailable testosterone (23).…”

Section: Discussionmentioning

confidence: 99%

“…After age 40, circulating levels of testosterone gradually decline at a rate of 1.6% per year for total testosterone and 2-3% per year for bioavailable testosterone (23). Because there is an age-related increase in SHBG, the magnitude of the decrease in bioavailable testosterone in men is much greater than the decrease in total testosterone levels is (12).…”

Section: Discussionmentioning

confidence: 99%

High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass

Aguirre

Colleluori

Fowler

et al. 2015

Objective: Because the aromatase enzyme catalyzes the conversion of testosterone to estradiol (E 2 ), the activity of this enzyme could be important in the musculoskeletal health of men with low testosterone. The objective of the present study is to determine the influence of aromatase activity on the bone mineral density (BMD) and body composition of patients with hypogonadism. Design: Cross-sectional study. Methods: The baseline data of 90 patients between 40 and 74 years old who participated in a genetic study of response to testosterone therapy in men with low testosterone (i.e., !300 ng/dl) were analyzed. BMD and body composition were measured by dual-energy X-ray absorptiometry. Serum testosterone was measured by automated immunoassay, E 2 was measured by ultrasensitive enzyme immunoassay, and sex hormone-binding globulin was measured by enzyme immunoassay. Results: Men in the highest tertile of E 2 to testosterone ratio (E 2 :T) had the highest spine BMD (P%0.037), highest truncal fat (PZ0.046), and lowest truncal lean body mass (PZ0.045). A similar pattern was observed in the upper extremities; that is, fat mass significantly increased (PZ0.047), whereas lean mass significantly decreased (PZ0.034) with increasing E 2 :T tertiles. Conclusion: The present findings suggest that in men with hypogonadism, aromatase activity could be an important determinant of musculoskeletal health. Men with high aromatase activity are able to maintain a higher BMD despite low circulating testosterone, but they have lower lean and higher truncal fat mass as compared to those with lower aromatase activity.