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Abstract
The aim of this study was to analyze the circadian profiles of central and peripheral circulating hormones in patients with unoperated primary localized prostate cancer and to test whether any specific endocrine disturbances occur in the presence and/or during the growthf these tumors. The hormones analyzed in serum included melatonin, total testosterone, luteinizing hormone (LH), prolactin, Cortisol, total thyroxine, and thyroid stimulating hormone (TSH). Blood was collected at 4-hourly intervals over one complete 24-h cycle from 18 patients with prostate cancer, from 20 patients with unoperated benign prostatic hyperplasia (BPH) serving as age-matched controls, and from 18 young men. The single cosinor method was used for the mathematical analysis of circadian rhythmicity. The most obvious result was that the circadian amplitude of melatonin was drastically depleted in prostate cancer patients compared to those with BPH (-71%). Prostate cancer patients with primary tumors staged as T2 and higher showed extremely low melatonin levels, leading to the loss of detectable circadian rhythms. A similar trend was observed for prolactin in prostate cancer patients. A further prominent finding was that the MESOR (rhythm-adjusted 24-h mean) of TSH was clearly depleted in prostate cancer patients compared to those with BPH (-46%), showing very low values in patients with T2 and T3/T4 tumors in spite of normal total thyroxine concentrations. The circadian profiles of total testosterone, LH and Cortisol did not exhibit any marked cancer-specific changes, indicating that neither the pituitary-gonadal nor the pituitary-adrenal axis was affected by malignant growth. The observed circadian endocrine disturbances in prostate cancer patients thus show clear central endocrine disturbances. It is at present unclear whether these changes may bear any direct functional significance for the progression and prognosis of prostate cancer. It is, furthermore, unknown how these changes are generated and whether the depression of pineal melatonin secretion may be functionally involved in the observed disturbed circadian secretion of prolactin and TSH.