The metabolic syndrome: when is testosterone treatment warranted

Abstract

With aging a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men [1,2]. This contribution focuses on the relevance of declining serum testosterone levels to the metabolic syndrome.

Four studies have found that a low testosterone level is a predictor of mortality in elderly men [3–6], but another study did not confirm this [7]. While disagreeing on the relationship between plasma testosterone and over-all mortality the latter study demonstrated that a low testosterone level was predictive of mortality from ischemic heart disease and respiratory disease and that research into this relationship may be warranted. It would seem that a low testosterone level is a marker, an indicator of disease, and it is plausible that disease predicts mortality. Obviously, epidemiological studies cannot unravel cause-relationships but the evidence is convincing that the decline in testosterone levels with aging is accounted for rather by (age-related) disease than the calendar age of men. Intervention studies provide potential answers to the causality of the relationship.

Numerous studies have found associations between features of the metabolic syndrome and plasma testosterone [8–13]. So, while it is clear that disease, and in the context of this contribution, in particular the metabolic syndrome can suppress circulating testosterone levels, it has also been documented that low testosterone levels induce the metabolic syndrome [14,15], dramatically demonstrated by findings in men with prostate cancer who undergo androgen ablation therapy [16,17]. A recent study showed convincingly that acute androgen deprivation reduces insulin sensitivity in young men [18].

Very well documented is that androgen deprivation leads to osteoporosis and increases bone fractures [19]. So, it is evident that low testosterone levels are a factor in the etiology of common ailments of elderly men such as the metabolic syndrome and osteoporosis. The question arises then whether testosterone treatment has role to play in the treatment of the metabolic syndrome and its sequels such as diabetes mellitus type 2 and cardiovascular disease. There is increasing evidence of a beneficial effect of testosterone treatment on visceral fat and other elements of the metabolic syndrome [20–22]. Evidently, the justification for testosterone treatment lies in a proper diagnosis of testosterone deficiency.

It has to be kept in mind that changes in lifestyle (diet / exercise) might partially prevent or redress the metabolic syndrome and its associated decline of androgen levels with aging [23–25] and therefore should be part of the treatment strategy.