Abnormal LH pulsatility in women with hyperprolactinaemic amenorrhoea normalizes after bromocriptine treatment: deconvolution-based assessment

OBJECTIVE The present study examines the LH secretory process in hyperprola ctinaemic women before, during and after bromocriptine therapy, using restr ictive clinical selection criteria as well as improved methodological tools . PATIENTS AND DESIGN Six women (aged 20-40 years) with microprolactinomas (m ean +/- SE prolactin, PRL: 2478 +/- 427 mU/l, range: 1370-3800 mU/l) and fo ur age- and sex-matched healthy controls were admitted to the study. After an overnight fast, all patients and controls had blood samples withdrawn at 10 minute intervals for 6 h (during saline infusion) from 0800 h to 1400 h to determine serum LH and PRL concentrations. After baseline evaluation, p atients were treated with bromocriptine, which was started at a daily dose of 1.25 mg for 7 days; the dose was then increased to 2.5 mg daily for the next 7 days and subsequently to 2.5 mg twice daily. PRL levels were evaluat ed at weekly intervals after the beginning of bromocriptine therapy for the duration of the study. The 6 h pulsatility study was repeated on four pati ents during treatment at a time when PRL levels were decreased, although no t normalized (PRL range: 450-1350 mU/l) and, on four patients, with the att ainment of normal serum PRL levels (PRL < 450 mU/l) in the early follicular phase of the menstrual cycle (days 2-5). The LH instantaneous secretion ra te was reconstructed by a nonparametric deconvolution method. In addition t o pulse analysis made using the program DETECT, the evaluation of the secre tion rate yielded the pulse frequency as well as the pulse amplitude distri bution. RESULTS Each time series was submitted to deconvolution analysis using a no nparametric method in order to estimate the instantaneous secretion rate (I SR). Hyperprolactinaemic patients had very few high-amplitude LH pulses abo ve 0.2 IU/(l minutes) before treatment (average frequency: 0.83 +/- 0.40 pu lses/6 h) and at the intermediate evaluation (0.25 +/- 0.25 pulses/6 h). In both cases, the pulse frequency was significantly lower than in controls ( P < 0.05 and P < 0.01, respectively). When PRL was normalized, the number o f high-amplitude LH pulses (4.25 +/- 1.03 pulses/6 h), became statistically different from the pulse number before (P < 0.01) and during (P < 0.01) th erapy; in particular the pulse frequency after therapy rose to a level not statistically different from that in controls. CONCLUSION The present study shows the presence of reduced LH pulsatility i n hyperprolactinaemic women that recovers completely to within the physiolo gical distribution when PRL levels are normalized by bromocriptine therapy.