Sexual dimorphism of cortisol metabolism is maintained in elderly subjectsand is not oestrogen dependent

OBJECTIVE The net interconversion of inactive cortisone to active cortisol by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol met abolism exhibits a sexual dimorphism with an apparently lower activity of 1 1 beta HSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the se xual dimorphism of cortisol metabolism persists between post-menopausal, oe strogen-deficient women and elderly men. PATIENTS Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, ag ed 62.4-87.5 years, were studied. None of the subjects was receiving steroi d medication at the time of the study. All the women were post-menopausal a nd none was receiving sex steroid replacement therapy. MEASUREMENTS 24-h urine collections were taken from each patient and assaye d for steroid metabolites by gas chromatography. Body composition was deter mined by dual energy X-ray absorptiometry. Blood was drawn, after an overni ght fast, for the determination of serum IGF-I and IGFBP1 levels. RESULTS The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol met abolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55- 1.86) vs. 0.67 (0.46-0.98) (P < 0.02), as was the ratio of allo-tetrahydroc ortisol (5 alpha-THF) + tetrahydrocortisol (THF)/tetrahydrocortisone (THE), 0.74 (0.37-2.08) vs. 0.40 (0.22-1.10) (P < 0.047). In the group as a whole there was a negative correlation between Fm/Em and percent body fat, r = - 0.43 (P < 0.05), and the negative relationship between cortisol and cortis one metabolite (Fm/Em) and total fat mass approached significance, r = - 0. 39 (P = 0.07). These relationships were not apparent in the women when cons idered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 w hich approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant cor relation between IGFBP-1 and Fm/Em in the men, r = 0.84 (P < 0.0001) which persisted when total body fat mass, r = 0.85 (P < 0.0001) and trunk fat mas s, r = 0.83 (P < 0.0001), were controlled for. This relationship was not ev ident among the women. CONCLUSION This study demonstrates that the previously described sexual dim orphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11 beta-H SD1 gene expression during the pre-menopausal period cannot be excluded. Th e findings confirm the primary importance of body fat as a determinant of c ortisol-cortisone conversion.