A comparison of cabergoline and bromocriptine on the risk of valvular heart disease in patients with prolactinomas.

Therapy with dopamine agonists has been associated with valvular heart disease (VHD) in Parkinson's disease, raising concern about the safety of these drugs. In hyperprolactinemic patients, the studies have mainly focused on the cardiac effects of cabergoline (CBG), with little information on bromocriptine (BRC). The aim of the present study was to evaluate the prevalence of VHD in patients with prolactinomas treated with CBG and BRC. The CBG group consisted of 51 patients (37 female; age 42.3 ± 13.5 years) who had been taking CBG for at least 1 year (mean 37.8 ± 21.3 months; cumulative doses 16-1,286.8 mg). The BRC group consisted of 19 patients (14 female; age 41.8 ± 11.5 years) who were on BRC for at least 1 year (mean 54.8 ± 30.2 months; cumulative doses 4,687.5-23,478.8 mg). The controls (CTR) were 59 healthy subjects matched for age, sex, and prevalence of arterial hypertension. Participants were subjected to transthoracic echocardiography and the valvular regurgitation was graduated as absent (grade 0), trace (1), mild (2), moderate (3) or severe (4). Compared to CTR, trace mitral (Mi) regurgitation (49% vs. 27.1%; P = 0.02), trace tricuspid (Tri) regurgitation (45.1% vs. 20.3%; P = 0.0003) and mild Tri regurgitation (7.8% vs. 0%; P = 0.0003) were more prevalent with CBG, while trace Tri regurgitation (73.7% vs. 20.3%; P = 0.0004) were more prevalent with BRC. Mitral tenting area was significantly higher in CBG than in BRC and CTR. None of the valvar abnormalities was associated with symptoms. In conclusion, patients with prolactinomas treated with either CBG or BRC showed higher prevalence of trace and mild Tri or Mi regurgitation, but these findings were not clinically significant.

Estradiol reduces cumulative mercury and associated disturbances in the hypothalamus-pituitary axis of ovariectomized rats.

The aim of this research was to verify the incidence of endocrine dysfunction associated with mercury intoxication in the hypothalamus-pituitary reproductive system of normally cycling or castrated female rats and the possible protective action of estrogen replacement therapy. We found no differences in the frequency of estrus cycle stages (diestrus I, diestrus II, proestrus, and estrus) in normally cycling female rats during 54 days of daily oral administration of 0.004, 0.02, and 1 mg/kg MeHgCl. Conversely, the higher dose (1 mg/kg) induced a significant decrease in content of luteinizing hormone releasing hormone (LHRH) into the medial hypothalamus when administered daily during 3 days in ovariectomized rats. This effect was associated with increased levels of mercury found in the anterior pituitary gland and medial hypothalamus, rather than the anterior and posterior hypothalamus, striatum or cerebellum. A decrease in plasma levels of luteinizing hormone (LH) was also detected after administration of 7.5 mg/kg MeHgCl. These disturbances in LHRH and LH secretion induced by mercury were abolished or superimposed (respectively) by estrogenic replacement therapy (0.025 mg/kg 17beta estradiol cypionate, intramuscular). These effects were associated with a significant reduction in mercury content of the anterior pituitary gland and medial hypothalamus, suggesting a protective estrogenic effect.