Hypogonadism in Rhodesian sleeping sickness: evidence for acute and chronic dysfunction of the hypothalamic-pituitary-gonadal axis

Abstract

To investigate acute and long-term effects of Rhodesian sleeping sickness on the function of the hypothalamic-pituitary-gonadal (HPG) axis in men. An observational, cross-sectional study. Primary health care centers under care of the National Sleeping Sickness Control Program in southeast Uganda. Fifty-two male patients with sleeping sickness at different stages of treatment and 11 clinically healthy male volunteers recruited from health care personnel. Patients and controls were questioned about loss of libido and impotence. All received 100 micrograms GnRH i.v. Blood was drawn before and 30 minutes after GnRH administration. Frequency of loss of libido and impotence. Baseline T and sex hormone-binding globulin baseline and GnRH- stimulated serum LH and FSH concentrations. Loss of libido and/or impotence were present in 39% of men with active disease before therapy, whereas 84% were biochemically hypogonadal. After cure, 45% of men still were symptomatic and 45% were biochemically hypogonadal. Compared with controls (806 +/- 59 pg/mL [conversion factor to SI unit, 0.03467]; mean +/- SEM), T concentrations were decreased substantially in patients before (249 +/- 48 ng/dL), during treatment (429 +/- 56 ng/dL), and after cure (431 +/- 58 ng/dL). Corresponding baseline LH concentrations were inappropriately low and the relative LH response to GnRH was reduced both before and during treatment (794% +/- 131% versus 322% +/- 68%). Follicle-stimulating hormone concentrations increased gradually up to 8.0 +/- 1.3 mIU/mL (conversion factor to SI unit, 1.00) at the end of treatment, returning to 4.2 +/- 0.6 mIU/mL after cure. Rhodesian sleeping sickness causes acute and chronic HPG axis dysfunction. The clinical and biochemical picture suggest a combined central and peripheral hypogonadism. This is only in part reversible after cure and most likely due to direct parasitic infiltration and/or secondary inflammation causing necrosis and/or fibrosis at the pituitary and gonadal levels.