Resistance to
bromocriptine, defined as the absence of normalization of
prolactin (PRL) levels despite a 15-30 mg daily dose of
bromocriptine during at least 6 months, has been observed in 5-17% of the
prolactinomas according to the literature. The recent availability of a new potent
dopamine agonist,
quinagolide, prompted us to analyze its long-term
therapeutic effects in 28 patients with
prolactinomas resistant to
bromocriptine. Before
bromocriptine, their PRL levels were 520 +/- 185 micrograms/l (mean +/- SEM) and decreased to 291 +/- 154 micrograms/l after a 6-21 month period of
bromocriptine treatment. All the women (N = 20) remained amenorrheic and
hypogonadism was not improved in men (N = 8). Subsequently, after 1 year of 150-300 micrograms/day
quinagolide, 12/28 patients of the present series recovered normal gonadal function and their initial mean baseline PRL value (404 +/- 180 micrograms/l) was 16 +/- 2 micrograms/l after 1 year of treatment. A significant
tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under
quinagolide, a similar good control was achieved in these patients, with the exception of one man presenting with a secondary rise of PRL under
quinagolide. In contrast, 15 other patients (one patient interrupted
quinagolide at 6 months because of poor tolerance) were not normalized under 150-450 micrograms/day
quinagolide. Their initial PRL levels (606 +/- 298 micrograms/l) were reduced to 343 +/- 187 micrograms/l (versus 463 +/- 265 micrograms/l under
bromocriptine after the same
duration of treatment). Despite such a partial inhibitory effect of
quinagolide, 7/12 women resumed menstrual cycles and three pregnancies occurred. In no case was any
tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 years of
quinagolide treatment, with a secondary rise of PRL values associated with a further
tumor growth in two patients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In five women, after
quinagolide withdrawal, the plasma PRL baseline values ranged from 52 to 158 micrograms/l and from 65 to 192 micrograms/l, respectively, at the first trimester and at the end of uneventful pregnancies. In contrast, in two women a rapid increase of PRL (240-400 micrograms/l) correlated with
tumor growth during the first trimester. Such a
tumor progression was blocked by
quinagolide treatment but not by
bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of patients at risk. Finally, in the whole population, long-term control of
hyperprolactinemia by
quinagolide was obtained in 11/28 patients (39%) previously resistant to
bromocriptine, and 15/20 women (75%) resumed normal gonadal function with a
quinagolide daily dose of 300 micrograms in most of them.