Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine

Abstract

Objective: It has recently been shown that increased body weight is associated with prolactinomas and that weight loss occurs with normalization of prolactin levels. On the other hand, decreased dopaminergic tone in humans is well correlated with obesity. The objective of this study was to correlate changes in prolactin levels with leptin and body mass index (BMI) in patients with prolactinomas treated with the long-acting dopamine agonist bromocriptine (BC). Methods: Eleven female and twelve male patients, aged 36:7^2:6 years with BMI in males of 30:41:7 kg=m 2 and in females of 24:4^1:2 kg=m 2 ; were evaluated after 1 and 6 months and 11 patients were further evaluated after 2 years of BC therapy. Plasma prolactin is presented as the mean of four samples taken daily. Serum leptin was determined in the pooled serum from three samples taken at 15-min intervals at 0800 h after an overnight fast. Multivariate linear regression and repeated measures analysis of covariance were used. Results: In males, pretreatment prolactin levels were 71 362^29 912 mU=l while leptin levels were 14:9^1:8 mg=l: In females, pretreatment prolactin levels were 11 395^5839 mU=l and leptin levels were 16:7^2:5 mg=l: The sexual dimorphism of serum leptin levels at initial presentation was preserved after adjusting for BMI and prolactin-induced hypogonadism. After 1 month of therapy, prolactin levels significantly decreased (males: 17 618^8736 mU=l; females: 3686^2231; P , 0:05), BMI did not change (males: 30:2^1:7 kg=m 2 ; females: 24:1^1:2 kg=m 2 ; P . 0:05), while serum leptin levels decreased (males: 12:5^1:5 mg=l; females: 13:6^2:1 mg=l; P , 0:05). After 6 months of treatment, prolactin further decreased (males: 3456^2101 mU=l; females: 677^360 mU=l; P , 0:05) as did BMI (males: 28:6^1:6 kg=m 2 ; females 23:1^1:0 kg=m 2 ; P , 0:05). The difference was more pronounced in male patients. Leptin levels were 12:82 :8 mg=l in males and 12:9^1:8 mg=l in females ðP , 0:05Þ: After 2 years of BC treatment, prolactin levels were near normal (males: 665^439 mU=l; females 447^130 mU=l; P , 0:05) and BMI remained 26:5^1:9 kg=m 2 for males and 23:6^0:8 kg=m 2 for females ðP , 0:05Þ: Leptin levels were 9:5^2:2 mg=l in males and 18:7^3:1 mg=l in females ðP , 0:05Þ: There was a gradual increase in the gender difference in serum leptin levels over time. Changes in serum leptin levels significantly correlated with changes in BMI ðr ¼ 0:844; P , 0:001Þ but did not correlate with changes in plasma prolactin levels after 1 month ðr ¼ 0:166Þ; 6 months ðr ¼ 0:313Þ and 2 years ðr ¼ 0:234; P . 0:05Þ: Conclusion: The long-acting dopamine agonist BC, by increasing dopaminergic tone, may influence body weight and likely body composition by mechanisms in addition to reducing hyperprolactinemia in patients with prolactinomas.

Body weight and prolactinoma: a retrospective study

“…[1][2][3] Subsequent weight loss after treatment with dopamine agonists has also been reported, 3,4 although this has been disputed in one study that showed weight gain after treatment. 5 We therefore undertook a retrospective study of 37 patients with prolactinoma (22 macroprolactinoma and 15 with microprolactinoma, defined by MRI scan of tumour size) and related body weight changes over 24 months to changes in serum and prolactin concentrations.…”

Different Effects of Cabergoline and Bromocriptine on Metabolic and Cardiovascular Risk Factors in Patients with Elevated Prolactin Levels

“…These abnormalities may be alleviated or reversed by dopamine agonists, being the drugs of choice in the treatment of prolactin-secreting tumours and elevated prolactin levels secondary to other disorders [9]. Dopamine agonist-induced normalization of elevated prolactin levels reduced body-weight [7,10] and improved insulin receptor action [4]. The effect of cabergoline on waist circumference, plasma lipids, glycated haemoglobin, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), despite dose dependency, was observed regardless of the degree of reduction in prolactin levels [11].…”

Prolactinoma-associated obesity treated with bupropion and methylphenidate

“…Notably, abnormalities of the circadian rhythm of prolactin secretion rather than the baseline prolactin level has been associated with weight increase [Doknic et al 2002], which might explain some inconsistencies in the literature mentioned above [Greenman et al 1998;Delgrange et al 1999;dos Santos Silva et al 2011]. As the somatotropin levels were normalized at the point of treatment, we did not substitute this hormone.…”

“…However, both standard pharmacological treatments for prolactinoma and cognitive-behavioural treatment often fail to reduce patients' weight [Doknic et al 2002;dos Santos Silva et al 2011]. Overall, there is a considerable need for effective clinical options to address obesity associated with pituitary tumours and to elucidate the relationship between central and peripheral dopamine effects on adipogenesis including the role of prolactin.…”