Revisiting the metabolic syndrome

To the Editor: I read with interest the excellent review article on the metabolic syndrome by Chew et al in the 16 October 2006 issue of the Journal.1 In their article the authors claim there is a lack of data about the relationship between hyperinsulinaemia and changes in free testosterone levels.

As part of the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study, an ongoing prospective epidemiological study of 2682 middle-aged Finnish men investigating risk factors for chronic disease, our research group has shown an association between the presence of metabolic syndrome at baseline and a change in sex hormone levels at follow-up after 11 years.2 In our study, men who met the World Health Organization criteria for metabolic syndrome both at baseline and at 11-year follow-up were at 2.6-fold increased risk of developing hypogonadism (serum total testosterone concentration < 11 nmol/L) during the study period compared with men who did not have metabolic syndrome. There was also a non-significant trend for men with metabolic syndrome to develop hypogonadism as defined by calculated free testosterone levels of < 225 pmol/L at 11-year follow-up.2

In the same cohort, we also reported a reverse association — that is, hypogonadism predicting metabolic syndrome.3,4 However, as the question posed by Chew et al was whether hyperinsulinaemia affects free testosterone levels, I examined the KIHD data further for evidence of such an association. I found that subjects grouped in ascending baseline fasting serum insulin quartiles had baseline mean free testosterone levels of 316 pmol/L (SD, 72 pmol/L), 312 pmol/L (SD, 77 pmol/L), 299 pmol/L (SD, 74 pmol/L) and 271 pmol/L (SD, 79 pmol/L), respectively (P < 0.001 for trend). At 11-year follow-up, mean free testosterone levels for subjects in each quartile were 248 pmol/L (SD, 64 pmol/L), 242 pmol/L (SD, 68 pmol/L), 229 pmol/L (SD, 70 pmol/L) and 216 pmol/L (SD, 67 pmol/L), respectively (P < 0.001 for trend).

The proportional drop in free testosterone levels over 11 years was approximately the same in each quartile, ranging from 20% to 23%. On the basis of these data, it seems that hyperinsulinaemia is associated not only with a fall in serum total testosterone levels but also with a fall in free testosterone levels in a general population.