A gender-related bias in survival rates has been demonstrated in rodent models of critical illness. Sex steroids have differential effects on metabolic, immune and cardiovascular end points which may underlie these observations. The hypothalamo-pituitary-gonadal (HPG) axis response to critical illness in humans is poorly characterised. We have conducted a prospective study to characterise this response in the context of heterogeneous disease severity and disturbances in overall endocrine function.
The study population was taken randomly from admissions to the adult ICU over one calendar month. A severity of illness score (Acute Physiology Score - APS) and endocrine data were measured at admission and at 3-daily intervals thereafter. The following patients were excluded: those on sex steroids; a history of gonadal, adrenal or pituitary disease; pre-menopausal women (to control for variations in menstrual cycle). Male and female groups were matched for age and illness severity. These studies were approved by the Joint Newcastle Ethics Committee.
6 men (median age 61 years, range 45-79) and 5 women (median age 68, range 52-89) were included. One man had testosterone in the normal range (10.8 nm/L); 5/6 were hypogonadal (mean 2.9 nm/L, range 0- 7.4). Gonadotrophin responses were non-uniform: 4 demonstrating hypo- and 1 hyper-gonadotrophic hypogonadism. All women had supra-physiological oestradiol levels (mean 661nm/L, range 82-1323), with suppressed gonadotrophins in 4/5. Increased oestradiol levels correlated positively with severity of illness (r 0.95; p 0.013).
These data highlight a sexual dimorphism in the HPG axis response to critical illness. In men, hypogonadism is common and may be of mixed type. Post-menopausal women demonstrate variable gonadotrophin-independent increases in sex-steroids, suggestive of peripheral aromatisation of adrenal androgens. These data highlight the need for further studies into the mechanism(s) of this dimorphism, and to investigate its role in the differential responses to critical illness.
08 - 11 Apr 2002
British Endocrine Societies