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Medicina (Kaunas, Lithuania) Aug 2022Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have... (Review)
Review
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma; Treatment Outcome
PubMed: 36013562
DOI: 10.3390/medicina58081095 -
Endocrine, Metabolic & Immune Disorders... 2023This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.
INTRODUCTION
This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.
METHODS
This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations.
RESULTS
The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide.
CONCLUSION
The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.
Topics: Adult; Humans; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 37171003
DOI: 10.2174/1871530323666230511104045 -
Frontiers in Endocrinology 2023Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing...
OBJECTIVE
Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing to the treatment effect is however unknown. The purpose of this study was to explore the effect of bromocriptine on the proliferation and migration properties of the endometrium in women with adenomyosis, by assessing cellular and molecular changes after six months of vaginal bromocriptine treatment.
METHODS
Endometrial specimens were collected during the proliferative phase from women with adenomyosis (n=6) before (baseline) and after six months of treatment with vaginal bromocriptine. Immunohistochemistry was used to determine changes in the protein expression of Ki67 in the endometrium of women with adenomyosis. Primary endometrial stromal cells isolated at baseline were expanded and exposed to different doses of bromocriptine to determine the optimal half-maximum inhibitory concentration (IC50) using CellTiter-Blue Cell Viability Assay. Cell proliferation was assessed by bromodeoxyuridine ELISA assay and Ki67 gene expression was checked by real-time PCR. The migratory ability of endometrial stromal cells was determined by wound healing and transwell migration assays. Small RNA sequencing was applied on tissues collected from women with adenomyosis before and after bromocriptine treatment to identify differentially expressed microRNAs (miRNAs) after bromocriptine treatment. Bioinformatic methods were used for target gene prediction and the identification of biological pathways by enrichment procedures.
RESULTS
Vaginal bromocriptine treatment reduced the Ki67 protein expression in the endometrium of women with adenomyosis and did not change the prolactin mRNA expression and protein concentration of prolactin in endometrial tissues. Bromocriptine significantly inhibited the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis . Moreover, small RNA sequencing revealed 27 differentially expressed miRNAs between the endometrium of women with adenomyosis before and after six months of vaginal bromocriptine treatment. KEGG pathway analysis on targeted genes of 27 miRNAs showed that several signaling pathways associated with cell proliferation and apoptosis were enriched after bromocriptine treatment.
CONCLUSION
Bromocriptine treatment exhibits an anti-proliferative effect in the endometrium of women with adenomyosis and . Bromocriptine might inhibit the proliferation of endometrial tissue in adenomyosis in part through the regulation of dysregulated microRNAs and proliferation-associated signaling pathways.
Topics: Humans; Female; Adenomyosis; Bromocriptine; Ki-67 Antigen; Prolactin; Endometrium; MicroRNAs; Cell Proliferation
PubMed: 36967761
DOI: 10.3389/fendo.2023.1026168 -
British Medical Journal May 1978A review of the effects of using bromocriptine in Parkinson's disease showed that it rarely helps patients not primarily improved by levodopa. Patients who show late... (Review)
Review
A review of the effects of using bromocriptine in Parkinson's disease showed that it rarely helps patients not primarily improved by levodopa. Patients who show late failure with levadopa and whose response to treatment is declining are helped by combining the two drugs. High cost and severe psychosis are the main disadvantages of bromocriptine, and, although it is not recommended for patients who are doing well on levodopa, it is the best available drug for hospital use in patients who show late failure with levodopa.
Topics: Bromocriptine; Drug Evaluation; Drug Therapy, Combination; Humans; Levodopa; Parkinson Disease; Psychoses, Substance-Induced
PubMed: 348261
DOI: 10.1136/bmj.1.6124.1402 -
British Medical Journal (Clinical... Jan 1985
Review
Topics: Bromocriptine; Female; Humans; Male; Pituitary Neoplasms; Prolactin
PubMed: 3917745
DOI: 10.1136/bmj.290.6463.182 -
Neuroendocrinology 2019Dopamine agonists are usually very effective in the treatment of prolactinomas. Nonetheless, a subset of individuals does not respond satisfactorily to these agents, and... (Review)
Review
Dopamine agonists are usually very effective in the treatment of prolactinomas. Nonetheless, a subset of individuals does not respond satisfactorily to these agents, and this resistance is characterized by failure to achieve normoprolactinemia and a 30% or more reduction in maximal tumor diameter (in the case of macroprolactinoma) under maximally tolerated doses. The overall prevalence of dopamine agonist resistance is 20-30% for bromocriptine (BRC) and around 10% for cabergoline (CAB). The 2 main predictive factors are male gender and tumor invasiveness. The management of drug-resistant prolactinomas includes several options. Any BRC-resistant patient should be switched to CAB which will normalize prolactin in 80% of patients. As long as adverse effects do not develop, dose escalation of CAB is reasonable, with the expectation that subsequent dose reduction will be possible. Echocardiographic monitoring is advised in such patients because of the potential association with cardiac valvular fibrosis. Also, maintaining maximal CAB doses at 3.5 mg/week may lead to progressive hormonal control in a significant proportion of patients. Complete resistance to CAB is infrequent. In a study of 122 patients with a macroprolactinoma, only 7 (6%) could not achieve control despite maximal CAB doses for > 12 months. A large resistant prolactinoma is also an indication for transsphenoidal neurosurgery, aiming at a debulking which may improve postoperative medical control. For patients who harbor aggressive prolactinomas, radiotherapy may be considered. However, normal prolactinemia will eventually occur in only one-third of patients after many years. Finally, temozolomide may be a therapeutic option in malignant/aggressive prolactinomas.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Humans; Pituitary Neoplasms; Prolactinoma
PubMed: 30481756
DOI: 10.1159/000495775 -
European Journal of Pharmacology Sep 2023Compared with levodopa, dopamine agonists (DAs) as initial treatment are associated with lower incidences of motor complications in early Parkinson's disease (PD). There... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Compared with levodopa, dopamine agonists (DAs) as initial treatment are associated with lower incidences of motor complications in early Parkinson's disease (PD). There is no strong evidence that a given DA is more potent in lower incidences of motor complications than another.
OBJECTIVE
We performed a network meta-analysis of levodopa versus DAs as monotherapy in early PD to access the risk of motor complications.
METHODS
Databases were searched up to June 2022 for eligible RCTs. Levodopa and four DAs (pramipexole, ropinirole, bromocriptine and pergolide) were investigated. The incidences of motor complications and efficacy, tolerability and safety outcomes were analyzed.
RESULTS
Nine RCTs (2112 patients) were included in the current study. The surface under the cumulative ranking curve (SUCRA) indicated that levodopa ranked first in the incidence of dyskinesia (0.988), followed by pergolide, pramipexole, ropinirole, and bromocriptine (0.704, 0.408, 0.240, 0.160). Pramipexole was least prone to wearing-off (0.109) and on-off fluctuation (0.041). Levodopa performed best in improvements of UPDRS-II, UPDRS-III, and UPDRS-II + III (0.925, 0.952, 0.934). Bromocriptine ranked first in total withdrawals and withdrawals due to adverse events (0.736, 0.751). Four DAs showed different adverse events profiles.
CONCLUSION
In the two non-ergot DAs, ropinirole is associated with a lower risk of dyskinesia while pramipexole is associated with lower risks of wearing-off and on-off fluctuations. Our research may facilitate head-to-head research, larger sample sizes, long following-up time RCTs to confirm the findings of this network meta-analysis.
Topics: Humans; Levodopa; Dopamine Agonists; Bromocriptine; Antiparkinson Agents; Parkinson Disease; Pramipexole; Pergolide; Network Meta-Analysis; Dyskinesias
PubMed: 37385577
DOI: 10.1016/j.ejphar.2023.175884 -
Psychopharmacology Apr 2018The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility.
OBJECTIVE
We assessed these hypotheses by administering tolcapone, bromocriptine, and a placebo to healthy subjects who performed a saccadic eye movement task requiring stability and flexibility.
METHODS
We used a randomized, double-blind, within-subject design that was counterbalanced across drug administration sessions. In each session, subjects were cued to prepare for a pro-saccade (look towards a visual stimulus) or anti-saccade (look away) on every trial. On 60% of the trials, subjects were instructed to switch the response already in preparation. We hypothesized that flexibility would be required on switch trials, whereas stability would be required on non-switch trials. The primary measure of performance was efficiency (the percentage correct divided by reaction time for each trial type).
RESULTS
Subjects were significantly less efficient across all trial types under tolcapone, and there were no significant effects of bromocriptine. After grouping subjects based on Val158Met COMT polymorphism, we found that Met/Met and Val/Met subjects (greater PFC dopamine) were less efficient compared to Val/Val subjects.
CONCLUSIONS
Optimal behavior was based on obeying the environmental stimuli, and we found reduced efficiency with greater PFC dopamine tone. We suggest that greater PFC dopamine interfered with the ability to flexibly follow the environment.
Topics: Adult; Attention; Bromocriptine; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Cognition; Dopamine Agonists; Double-Blind Method; Female; Humans; Male; Prefrontal Cortex; Reaction Time; Saccades; Tolcapone; Young Adult
PubMed: 29427081
DOI: 10.1007/s00213-018-4845-4 -
Nature Metabolism Aug 2019Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is...
Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance.
Topics: Adipose Tissue, Brown; Animals; Bromocriptine; Dopamine; Female; Humans; Hypothalamus; Injections, Intraventricular; Male; Rats; Signal Transduction; Thermogenesis
PubMed: 31579887
DOI: 10.1038/s42255-019-0099-7 -
JPMA. the Journal of the Pakistan... Sep 2022Diabetes is a multi-faceted syndrome on which the brain is an etiopathogenetic factor, as well as a target organ for damage. Drugs which act on the brain, such as...
Diabetes is a multi-faceted syndrome on which the brain is an etiopathogenetic factor, as well as a target organ for damage. Drugs which act on the brain, such as bromocriptine and antipsychotic drugs, are known to influence glycaemic control. This article describes lemborexant, a dual oxexin receptor antagonist (DORA), and hypothesizes that it may be used as an adjuvant in difficult-to-control diabetes. Its utility should be explored in persons with insomnia and high fasting glucose, unregulated appetite, and diabetes distress.
Topics: Humans; Orexin Receptor Antagonists; Antipsychotic Agents; Bromocriptine; Sleep Initiation and Maintenance Disorders; Adjuvants, Immunologic; Diabetes Mellitus; Glucose
PubMed: 36280998
DOI: 10.47391/JPMA.22-93