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 hyperprolactinaemic women before, during and after bromocriptine therapy, using restrictive clinical selection criteria as well as improved methodological tools.


METHODS
Six women (aged 20-40 years) with microprolactinomas (mean +/- SE prolactin, PRL: 2478 +/- 427 mU/l, range: 1370-3800 mU/l) and four 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 After an overnight fast, all patients and controls had blood samples withdrawn at 10 minute intervals for 6 h (during saline infusion) from 0800 h to 1400 h to determine serum LH and PRL concentrations.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, patients 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 evaluated at weekly intervals after the beginning of bromocriptine therapy for the duration of the study. The 6 h pulsatility study was repeated on four patients during treatment at a time when PRL levels were decreased, although not normalized (PRL range: 450-1350 mU/l) and, on four patients, with the attainment 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 rate was reconstructed by a nonparametric deconvolution method. In addition to pulse analysis made using the program DETECT, the evaluation of the secretion rate yielded the pulse frequency as well as the pulse amplitude distribution.


RESULTS
Each time series was submitted to deconvolution analysis using a nonparametric method in order to estimate the instantaneous secretion rate (ISR). Hyperprolactinaemic patients had very few high-amplitude LH pulses above 0.2 IU/(l minutes) before treatment (average frequency: 0.83 +/- 0.40 pulses/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 of 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) therapy; in particular the pulse frequency after therapy rose to a level not statistically different from that in controls.


CONCLUSIONS
The present study shows the presence of reduced LH pulsatility in hyperprolactinaemic women that recovers completely to within the physiological distribution when PRL levels are normalized by bromocriptine therapy.
Sartorio
A
A
Divisione Malattie Metaboliche III; Laboratorio Sperimentale di Ricerche Endocrinologiche, Istituto Auxologico Italiano, Milano. sartorio@auxologico.it
Pizzocaro
A
A
Liberati
D
D
De Nicolao
G
G
Veldhuis
J D
JD
Faglia
G
G
D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001971:Bromocriptine / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D011388:Prolactin / Q000037:antagonists & inhibitors; D015175:Prolactinoma / Q000097:blood / Q000150:complications / Q000188:drug therapy; D012636:Secretory Rate; D018709:Statistics, Nonparametric
D006727:Hormone Antagonists; D001971:Bromocriptine; D011388:Prolactin; D007986:Luteinizing Hormone