Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study

Objective There is little consensus on what androgen levels are 'normal' for healthy, ageing men. Using data from the Massachusetts Male Ageing Study (MMAS), we estimated age-specific, normal androgen levels for men aged 40-79 years while accounting for health status and behavioural factors known to influence hormone levels. Design Prospective, observational study. Patients Community-based random sample of men aged 40-79 years: n = 1677 men studied at T1 (1987-1989), n = 1031 at T2 (1995-1997) and n = 631 at T3 (2002-2004), for a total of 3339 observations. The average number of years between the T1 and T2 interviews was 8.8 (range 7.1-10.4 years) and 6.4 (range 5.6-7.9 years) between T2 and T3. Measurements Serum total testosterone (T) and sex hormone-binding globulin (SHBG) were measured on nonfasting blood samples collected within 4 h of subject's awakening. Free and bio-available T were calculated from T and SHBG using the Sodergard equation. Trained interviewers administered an in-home questionnaire of health, medication and lifestyle. Participants were considered apparently healthy if all of the following were met: (i) absence of self-reported chronic disease (diabetes, heart disease, high blood pressure, cancer, ulcer); (ii) not on prescription medication believed to affect hormone levels; (iii) body mass index (BMI) not exceeding 29 kg/m(2); (iv) alcohol consumption less than or equal to six drinks/day; and (v) nonsmoking. Results Chronic disease and high BMI significantly decreased whereas smoking tended to increase total, free and bio-available T concentrations. Apparently healthy men had significantly higher median hormone concentrations at most time points than did not apparently healthy men. Due to the opposite effects of smoking and the other components of the definition, apparently healthy men were compared to nonsmoking, apparently unhealthy men. The former group had significantly higher androgen levels (Wilcoxon rank-sum P-values ranged from 0.01 to 0.0001) for all hormones at all interviews. Ninety-five percent of apparently healthy men in their 40s, 50s, 60s and 70s would be expected to have total T in the range (2.5-97.5th percentile): 8.7-31.7, 7.5-30.4, 6.8-29.8 and 5.4-28.4 nM (251-914, 216-876, 196-859, 156-818 ng/dl), respectively. Age, health and lifestyle factors impact androgen levels and should be accounted for in calculations of normal reference ranges. We propose the following age-specific thresholds, below which a man is considered to have an abnormally low total T: 8.7, 7.5, 6.8 and 5.4 nM (251, 216, 196 and 156 ng/dl) for men in their 40s, 50s, 60s and 70s, respectively. These cutoffs correspond to the 2.5th percentile in our data; thus, approximately 2.5% of men aged 40-79 years would have abnormally low T levels based on hormone levels alone.