Anti-proliferative effects of high doses cabergoline in patients with organic hyperprolactinemia

Abstract

The aim of the study – to inestigate the antiproliferative effect of cabergoline (CAB) which was used in different regimes of suppressive therapy during 12 months in patients with prolactinomas.Materials and methods. It was examined and underwent a 12 month course of treatment by selective dopamine agonist (AgDof) CAB 61 patients with prolactinoma (PROL) (52 women and 9 men) aged 16–66 years. The total duration of the disease ranged from 1 to 60 months, average (12,3±10,1) months. Among the women, treated with CAB, it was mikroPROL 40, macro&giant PROL-12. Among men it 2 was microadenoma, 7 macroadenoma. PROL was verified using magnetic resonance imaging (MRI). Pituitary volume was calculated by the formula Di Chiro-Nelson using the correction coefficient. Were estimated total and partial secretory activity (PSA) in PROL for VS Pronin. PRL blood levels (ng/mL) were determined by commercial reagent kit ELISA (DRG Diagnostics, USA) on automated analyzer Stat Fax 2100 (Awareness Technology, USA). Applied two modes of therapy: 1 – the mode of gradual increase of a CAB dose, since 0,5 mg a week with the subsequent control of the PRL blood level in each 4 weeks and titration CAB dose if necessary (increase in a week dose by 0,25–0,5 mg); 2 – the mode of high starting doses from calculation: the quantity of tablets CAB (0,5 mg) corresponded to frequency rate of increase of the PRL blood level in relation to the upper limit of age norm, but no more than 4 mg (8 tablets) a week. The statistical data analysis was carried out with the certified program package Statgraphics Plus for Windows 3.0 (Manugistic Inc. USA).Results and discussion. At purpose of high starting doses of CAB after 1 month of treatment PRL level in 58.1% of patients decreased to the reference values, including in patients with macroPROL after 1 month at 26.3% of patients had achieved target levels, after 3 months – at 84.2%, and by 6 months of treatment – at 100% patients. In all patients it was a statistically significant decreasing the pituitary volum after 12 months of treatment (p<0,001), but only in patients who were treated high starting high dose CAB recorded decrease in the size of adenoma by 50% or more of the basal volume: at 9 microPROL and 4 macroPROL. It was a positive correlation between the total and the average cumulative therapeutic CAB dose during the treatment period with the volume of the pituitary gland and PSA indicates whether the use of high starting doses in patients with both micro- and macro&giant PROL.Conclusions. The most expressed anti-proliferative effect is noted at application of high starting doses of CAB. Optimum therapeutic average and cumulative doses of CAB for achievement of the maximum therapeutic effect at patients with microPROL are doses of 0,8 mg/week and 33,8 mg/year, respectively; for patients with macro&giant PROL – 1,3 mg/week and 67,6 mg/year, respectively. At patients with microPROL the positive therapeutic effect is reached on a smaller cumulative CAB dose which is associated with a lower risk of complications in the long term period.