The Natural History of Symptomatic Androgen Deficiency in Men: Onset, Progression, and Spontaneous Remission

Abstract

OBJECTIVES-To describe the onset, progression, and remission of symptomatic androgen deficiency (SAD) using longitudinal data from the Massachusetts Male Aging Study (MMAS).DESIGN-A prospective, population-based study of men living in Boston, Massachusetts. Data were collected in three waves: T1 (1987/89), T2 (1995/97), T3 (2002/04). Onset, progression, and remission were defined in terms of transitions in SAD status from one wave to the next. SETTING-In-person, in-home interviews.PARTICIPANTS-Seven hundred sixty-six community-dwelling men aged 40 to 70 at baseline (T1) contributed data from T1 to T2 and 391 from T2 to T3. MEASUREMENTS-SADwas defined in terms of serum total and free testosterone (T) levels and symptoms associated with low circulating androgens. Total T and sex hormone-binding globulin (SHBG) were measured using radioimmunoassay. Free T was calculated from total T and SHBG measurements. RESULTS-At T2 or T3, the likelihood of SAD was markedly greater for subjects who had exhibited SAD at the previous wave (odds ratio = 3.8, 95% confidence interval = 1.9-7.4), overall 55% of subjects who exhibited SAD experienced remission by the next study wave. The probability of SAD was greater with older age and greater body mass index. Multivariate models demonstrated that the likelihood of remission was at least 50% for most subpopulations.CONCLUSION-Over approximately 15 years of follow-up, SAD did not represent a stable health state. The likelihood of SAD would remit exceeded the likelihood that it Keywords aging; men; androgen; population study Gradual decreases in serum testosterone (T) concentrations are generally believed to accompany male aging. 1-8 Low T levels have been shown to contribute to diabetes mellitus, Address correspondence to: Thomas G. Travison, PhD, New England Research Institutes, 9 Galen St., Watertown, MA 02474. ttravison@neriscience.com. HHS Public AccessAuthor manuscript J Am Geriatr Soc. Author manuscript; available in PMC 2017 August 15. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript low bone and muscle mass, impaired sexual function, and frailty, 9-13 so interventions intended to slow or reverse age-related declines in T have attracted a great deal of attention.Whether there exists a threshold at which T levels should be considered "deficient" is still the subject of substantial debate. [14][15][16] Although it is known that comorbidity and health behaviors influence T, 8,17 concurrent changes in health do not appear to account for agerelated declines in T. 8,18 In addition, T levels exhibit substantial random variability over periods of weeks or months. 19,20 The presence or absence of true age-related hypogonadism is therefore difficult to determine. 21 For these reasons, it has been proposed that a composite measure of T levels and seemingly related symptoms, many of them having to do with mood and self-assessed well-being, may represent a more clinically meaningful assessment of male hormonal status. [22][23][24][25][26][27][28] Implicit in thi...

Are declining testosterone levels a major risk factor for ill-health in aging men?

“…138,139 However, even with careful clinical and biochemical evaluation, symptomatic androgen deficiency may not be a stable physical state as up to half of men initially classified as such no longer met the criteria when reassessed after an interval of time. 140 Furthermore, if low testosterone levels are a causative factor contributing to poorer health in aging men, many men with testosterone levels in the low-normal range who do not meet diagnostic criteria might not qualify for treatment and may be at risk of ill-health. An attractive alternative to screening for and treating hypogonadal men would be to develop nonpharmacological interventions potentially applicable on a wide scale to ameliorate or prevent the age-related decline in testosterone levels.…”

Testosterone and glucose metabolism in men: current concepts and controversies

“…Several lines of evidence (Farooqi et al 2002, Zumoff et al 2003, Travison et al 2008, Grossmann 2011, Sartorius et al 2012, Camacho et al 2013, Corona et al 2013a,b, George et al 2013, summarised in Box 1, suggest that the in the majority of men, suppression of the diabesity-associated HPT axis is functional, and may hence be reversible. Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al 2012b) are important contributors to the suppression of the HPT axis.…”

An old emperor finds new clothing: rejuvenation in our time

“…The approach of relating non-specific symptoms to serum testosterone levels originates from clinical studies that defined thresholds for symptoms of androgen deficiency in classical pathologically based hypogonadism using clinic-based, convenience populations 16,17 an approach that was extended to population-based analysis of MMAS data seeking to define symptomatic age-related androgen deficiency among older men. 18,19 An important caveat arising from detailed studies of individual men with authentic androgen deficiency is that, although individuals have highly consistent blood testosterone thresholds for symptoms, neither thresholds nor symptoms are consistent between individuals. 16 Thus grouping individuals according to symptom(s) would encompass a wide range of individual blood testosterone thresholds so that averaged between-individual estimates of threshold would provide only a crude representation of the component, divergent individual thresholds.…”