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

Thomas G. Travison, PhD; Rebecca Shackelton, ScM; Andre B. Araujo, PhD; Susan A. Hall, PhD; Rachel E. Williams, PhD; Richard V. Clark, MD, PhD; Amy B. O'Donnell, MPH; John B. McKinlay, PhD


J Am Geriatr Soc. 2008;56(5):831-839. 

In This Article

Abstract and Introduction

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.
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: SAD was 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 would not, particularly among younger and leaner men.

Gradual decreases in serum testosterone (T) concentrations are generally believed to accompany male aging.[1,2,3,4,5,6,7,8] Low T levels have been shown to contribute to diabetes mellitus, low bone and muscle mass, impaired sexual function, and frailty,[9,10,11,12,13] 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 age-related 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 this claim is the idea that such a composite, which we refer to as apparent symptomatic androgen deficiency (SAD), should represent a more temporally stable description of androgen status than measurements of T alone. No longitudinal analyses have yet been performed to support this contention, and the lack of consistent associations between T and ostensibly related symptoms may call it into question.[29]

To address this issue, data from 762 men enrolled in the longitudinal Massachusetts Male Aging Study (MMAS), a population-based study of men aged 40 to 70 at baseline, with three data collection waves between 1987 and 2004, were examined. The overarching goal of the analysis was to establish the proportion of men whose SAD status changed between study visits. It was hypothesized that, over time, a substantial proportion of men would exhibit SAD who had not previously done so (would experience SAD onset). It was further hypothesized that, consistent with the notion that SAD is stable or reliable, subjects who exhibited SAD would continue to do so (that few subjects would experience remission) and that the likelihood of SAD onset or remission would vary substantially as a function of age and body mass index (BMI). Finally, it was speculated that the age-specific probability of SAD would increase as a function of calendar time, consistent with previous observations of substantial secular decreases in serum T levels.[30]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.