Primary testicular failure in Klinefelter's syndrome: The use of bivariate luteinizing hormone-testosterone reference charts

Background: The diagnosis of androgen deficiency is based on clinical features and confirmatory low serum testosterone levels. In early primary testicular failure, a rise in serum LH levels suggests inadequate androgen action for the individual's physiological requirements despite a serum testosterone level within the normal range. The combined evaluation of serum LH and testosterone levels in the evaluation of testicular failure has not been widely advocated. Patients: Seven hundred and six healthy males and 39 patients with known primary hypogonadism due to Klinefelter's syndrome and SRY-positive 46,XX karyotypes were included in the study. Design: Testosterone, oestradiol and LH serum concentrations were measured in all individuals. Based on the 706 healthy males two-dimensional bivariate LH-testosterone reference charts were constructed. Results: Despite a median serum total and free testosterone and oestradiol levels being reduced (P <0.001) and LH levels elevated (P <0.001) in Klinefelter's syndrome and 46,XX-males, many subjects (69%) had total testosterone within the reference range. However, using the bivariate charts all subjects lay outside the 97.5 percentile. Conclusion: Bivariate LH and testosterone charts are useful in the evaluation of men with known primary testicular failure due to sex chromosomal aneuploidy in whom evaluation based on testosterone measurement in isolation underestimates the prevalence of hypogonadism. It is, however, important to emphasize that isolated use of the bivariate evaluation should not form the basis for androgen substitution therapy. Further studies are needed in order to evaluate the use of bivariate LH and testosterone charts in the assessment of any younger man with possible primary testicular failure.