The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadotropin-thyrotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteinizing hormone (LH), follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (PRL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with abnormalities of the hypothalamic-pituitary-testicular axis.