Prolactinomas: evolution after menopause

Abstract

Objetive:The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Subjects and methods: Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions: Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.Arch Endocrinol Metab. 2016;60(1):42-6

Are dopamine agonists still the first-choice treatment for prolactinoma in the era of endoscopy? A systematic review and meta-analysis

“…A total of 81 studies [ 4 – 8 , 13 , 68 , 84 , 92 – 97 , 99 – 112 , 114 , 118 , 120 – 123 , 125 , 127 – 133 , 135 – 137 , 139 , 141 – 156 ] comprising 4397 patients who received surgery and 74 studies [ 3 – 6 , 8 , 13 , 17 – 21 , 25 , 26 , 28 – 36 , 38 , 42 – 46 , 48 – 51 , 54 – 58 , 60 , 61 , 65 – 73 , 76 , 79 – 81 , 85 – 87 , 89 , 91 ] comprising 2659 patients who used DAs were included in this part of the research. The pooled prolactin normalization rates were 0.66 (0.62, 0.71) ( I 2 = 93.8%, p = 0.000) in the surgery group and 0.78 (0.75, 0.82) ( I 2 = 89.4%, p = 0.000) in the DAs group, respectively (Fig.…”

“…A total of 8 studies [ 7 , 98 , 124 , 134 , 150 ] comprising 555 patients in the surgery group and 27 studies [ 7 , 31 , 33 , 38 , 40 , 42 – 44 , 46 , 48 , 54 , 55 , 59 , 78 , 81 , 83 , 84 , 90 ] comprising 954 patients in the DAs group were included in this part of research. Based on the pooled results, the mean differences in the prolactin levels between pre- and post-treatment were 396.80 ng/ml (222.33, 571.27) ( I 2 = 99%, p < 0.001) for surgery and 375.26 ng/ml (316.21, 434.31) ( I 2 = 98%, p < 0.001) for DAs (Supplementary Fig.…”

Cabergoline Withdrawal Before and After Menopause: Outcomes in Microprolactinomas

“…Touraine et al [6] described a small group of 4 women with microprolactinoma whose PRL spontaneously reduced off treatment after menopause. Mallea-Gil et al followed 22 patients with microprolactinoma for a period between 4 and 192 months after CBG or bromocriptine suspension and found that only two patients needed to restart treatment for increasing PRL levels; among the remaining 20, a spontaneous reduction of PRL and a high rate of tumor disappearance at MRI were found [8]. In a recently published study from UK [9], Santharam et al found that among 16 postmenopausal women who stopped medical treatment after menopause with normalized prolactin levels, recurrence rate was significantly lower than that in premenopausal ones and comparable with that observed in our study, 31%.…”

“…Pathogenesis, natural history, and ideal treatment, in terms of duration or criteria for drug withdrawal, are not fully understood for this subtype of pituitary tumor. There is evidence that estrogens can stimulate normal and neoplastic lactotrophs' growth in vitro and in vivo animal models [4,5]; however, in humans, evidence is limited to a few studies which have shown a positive effect of the postmenopausal state on the course of disease, with spontaneous and progressive reduction of PRL and adenoma size observed in untreated women, and rare cases of hyperprolactinemia recurrence [6][7][8][9]. However, drawing definitive conclusions is difficult for these studies, because patients included were heterogeneous in regard to the etiology of hyperprolactinemia (microprolactinomas vs. macroprolactinomas vs. idiopathic hyperprolactinemia), to the previously employed treatment (surgery vs. medical treatment vs. no treatment) and to the specific drug administered (CBG vs. bromocriptine vs. other dopamine agonists).…”

Rational Evaluation and Treatment of Prolactinomas: A Concise Review

“…High prolactin levels in postmenopausal women are usually of no clinical significance. 24,25 However, male patients with persistent symptomatic prolactin elevation likely require long-term treatment with DA to prevent the hypogonadism state and its complications. 26,27…”