Effects Of Dopamine Agonists Research Articles

Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma.

Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy-a patient-focused, multidisciplinary approach- we aim to improve the management of prolactinoma patients.

Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.

Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal depalmitoylation enzyme that mediates protein posttranslational modifications. Loss-of-function mutation of PPT1 causes a failure of the lysosomal degradation of palmitoylated proteins and results in a congenital disease characterized by progressive neuronal degeneration referred to as infantile neuronal ceroid lipofuscinosis (INCL). A mouse knock-in model of PPT1 (PPT1-KI) was established by introducing the R151X mutation into exon 5 of the PPT1 gene, which exhibited INCL-like pathological lesions. We previously reported that hippocampal γ oscillations were impaired in PPT1 mice. Hippocampal γ oscillations can be enhanced by selective activation of the dopamine D4 receptor (DR4), a dopamine D2-like receptor. In this study, we investigated the changes in DR expression and the effects of dopamine and various DR agonists on neural network activity, cognition and motor function in PPT1KI mice. Cognition and motor defects were evaluated via Y-maze, novel object recognition and rotarod tests. Extracellular field potentials were elicited in hippocampal slices, and neuronal network oscillations in the gamma frequency band (γ oscillations) were induced by perfusion with kainic acid (200 nM). PPT1KI mice displayed progressive impairments in γ oscillations and hippocampus-related memory, as well as abnormal expression profiles of dopamine receptors with preserved expression of DR1 and 3, increased membrane expression of DR4 and decreased DR2 levels. The immunocytochemistry analysis revealed the colocalization of PPT1 with DR4 or DR2 in the soma and large dendrites of both WT and PPT1KI mice. Immunoprecipitation confirmed the interaction between PPT1 and DR4 or DR2. The impaired γ oscillations and cognitive functions were largely restored by the application of exogenous dopamine, the selective DR2 agonist quinpirole or the DR4 agonist A412997. Furthermore, the administration of A412997 (0.5 mg/kg, i.p.) significantly upregulated the activity of CaMKII in the hippocampus of 5-month-old PPT1KI mice. Collectively, these results suggest that the activation of D2-like dopamine receptors improves cognition and network activity in PPT1KI mice and that specific DR subunits may be potential targets for the intervention of neurodegenerative disorders, such as INCL.

The activation of D2-like dopamine receptors increases NMDA currents in the dorsal raphe serotonergic neurons

The dorsal raphe nucleus (DRN) receives dopaminergic inputs from the ventral tegmental area (VTA). Also, the DRN contains a small population of cells that express dopamine (DRNDA neurons). However, the physiological role of dopamine (DA) in the DRN and its interaction with serotonergic (5-HT) neurons is poorly understood. Several works have reported moderate levels of D1, D2, and D3 DA receptors in the DRN. Furthermore, it was found that the activation of D2 receptors increased the firing of putative 5-HT neurons. Other studies have reported that D1 and D2 dopamine receptors can interact with glutamate NMDA receptors, modulating the excitability of different cell types. In the present work, we used immunocytochemical techniques to determine the kind of DA receptors in the DRN. Additionally, we performed electrophysiological experiments in brainstem slices to study the effect of DA agonists on NMDA-elicited currents recorded from identified 5-HT DRN neurons. We found that D2 and D3 but not D1 receptors are present in this nucleus. Also, we demonstrated that the activation of D2-like receptors increases NMDA-elicited currents in 5-HT neurons through a mechanism involving phospholipase C (PLC) and protein kinase C (PKC) enzymes. Possible physiological implications related to the sleep-wake cycle are discussed.

Synthetic aporphine alkaloids are potential therapeutics for Leigh syndrome

Mitochondrial diseases are mainly caused by dysfunction of mitochondrial respiratory chain complexes and have a variety of genetic variants or phenotypes. There are only a few approved treatments, and fundamental therapies are yet to be developed. Leigh syndrome (LS) is the most severe type of progressive encephalopathy. We previously reported that apomorphine, an anti- “off” agent for Parkinson’s disease, has cell-protective activity in patient-derived skin fibroblasts in addition to strong dopamine agonist effect. We obtained 26 apomorphine analogs, synthesized 20 apomorphine derivatives, and determined their anti-cell death effect, dopamine agonist activity, and effects on the mitochondrial function. We found three novel apomorphine derivatives with an active hydroxy group at position 11 of the aporphine framework, with a high anti-cell death effect without emetic dopamine agonist activity. These synthetic aporphine alkaloids are potent therapeutics for mitochondrial diseases without emetic side effects and have the potential to overcome the low bioavailability of apomorphine. Moreover, they have high anti-ferroptotic activity and therefore have potential as a therapeutic agent for diseases related to ferroptosis.

Sleep disorders in Parkinson’s disease, an early and multiple problem

In Parkinson’s disease (PD), it remains unclear whether sleep disorders including insomnia, REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), restless legs syndrome (RLS) and sleep-disordered breathing (SDB), are isolated or combined, interact with each other and are associated with clinical factors. We sought to determine the prevalence and combinations of the main sleep disorders, and their clinical and polysomnographic associations in early stage PD. Sleep disorders were systematically diagnosed after medical interview and video-polysomnography in 162 participants with early stage PD and 58 healthy controls from the baseline of the longitudinal ICEBERG cohort. Demographic, clinical (motor, cognitive, autonomic, psychological and sensory tests), therapeutic and polysomnographic associations of sleep disorders were investigated. Sleep disorders were frequent (71%) and combined in half of the patients. The number of sleep disorders increased with disease duration and dysautonomia. Insomnia was the most common (41%), followed by definite RBD (25%), EDS (25%), and RLS (16%). These disorders were more frequent than in controls whereas SDB was rare, moderate and similar in both groups. In patients, insomnia (mainly difficulties maintaining sleep) was associated with female gender, shorter sleep time and RLS, but not with motor or psychological symptoms. RBD was associated with dysautonomia and advanced age, but not with motor and cognitive measures. EDS was associated with psychiatric and motor symptoms as well as the sedative effects of dopamine agonists but not with other sleep disturbances. Sleep disturbances are frequent and combined in early patients with PD. Their determinants and markers are more organic than psychological.

Effectiveness of Dopamine Agonists in managing Non-Functioning Pituitary Adenomas- a United Kingdom single centre retrospective review

Effectiveness of Dopamine Agonists in managing Non-Functioning Pituitary Adenomas- a United Kingdom single centre retrospective review

FRI305 Impulse Control Disorders In Patients With Prolactinomas And Non-Functioning Pituitary Adenomas Treated With Dopamine Agonists

Abstract Disclosure: T. Kolitz: None. E. Shemesh: None. A. Nathan: None. R. Eldor: None. E. Izkhakov: None. Y. Greenman: None. Objective Impulse control disorder (ICD) is a well-recognized side effect of dopamine agonist (DA) treatment in patients with Parkinson’s disease and restless leg syndrome. The available data on the incidence of ICD in patients treated with DA for pituitary tumors are sparse. This study aimed to assess the occurrence of ICD among patients with prolactinomas or NFPA treated with DA compared to patients with prolactinomas or NFPA not treated with DA and to patients with non-pituitary endocrine disorders. Methods Patients attending the general endocrine and pituitary clinics at the Institute of Endocrinology in our medical center were invited to fill in an anonymous validated questionnaire on hypersexuality, pathologic gambling, compulsive shopping, and punding. Associated relevant clinical information was also obtained. Results In total, 174 patients consented to participate. Those with pituitary disorders other than prolactinomas and NFPA were excluded. The final study cohort consisted of 67 patients with NFPA (31 DA-treated) and 40 with prolactinomas (35 DA-treated). The control group consisted of 67 non-DA-treated subjects with other endocrine disorders. The entire cohort was comprised of 77 men and 97 women (mean age 56±17 years). ICDs were reported by 19/66 (29%) DA-treated patients with prolactinomas or NFPA, 3/41 (7%) non-DA-treated patients with prolactinomas or NFPA and 8/108 (7.5%) non-DA-treated patients with prolactinomas, NFPA or other endocrine disorders (p<0.001). There were no significant differences in ICD rates between DA-treated patients with prolactinomas compared to those with DA-treated NFPA, or between non-DA-treated patients with either prolactinomas or NFPA and controls. The ICD rate among DA-treated women was significantly higher than that of non-DA-treated women (34.5% and 7.5%, respectively. p<0.001). No comparable differences were observed in DA-treated versus non-DA-treated men or between all participating men and women. Conclusion ICD rates are significantly higher among patients treated with DA for prolactinomas or NFPA compared to non-DA-treated patients with prolactinomas, NFPA or other non-pituitary endocrine disorders. Patients being treated with DA for any pituitary lesion should be informed of the greater risk of associated ICD. Presentation: Friday, June 16, 2023

Dopamine in the nucleus accumbens shell controls systemic glucose metabolism via the lateral hypothalamus and hepatic vagal innervation in rodents

BackgroundGrowing evidence demonstrates the role of the striatal dopamine system in the regulation of glucose metabolism. Treatment with dopamine antagonists is associated with insulin resistance and hyperglycemia, while dopamine agonists are used in treatment of type 2 diabetes. The mechanism underlying striatal dopamine effects in glucose metabolism, however is not fully understood. Here, we provide mechanistic insights into the role of nucleus accumbens shell (sNAc) dopaminergic signaling in systemic glucose metabolism. MethodsEndogenous glucose production (EGP), blood glucose and mRNA expression in the lateral hypothalamic area (LHA) in male Wistar rats were measured following infusion of vanoxerine (VNX, dopamine reuptake inhibitor) in the sNAc. Thereafter, we analyzed projections from sNAc Drd1-expressing neurons to LHA using D1-Cre male Long-Evans rats, Cre-dependent viral tracers and fluorescence immunohistochemistry. Brain slice electrophysiology in adult mice was used to study spontaneous excitatory postsynaptic currents of sNAc Drd1-expressing neurons following VNX application. Finally, we assessed whether GABAergic LHA activity and hepatic vagal innervation were required for the effect of sNAc-VNX on glucose metabolism by combining infusion of sNAc-VNX with LHA-bicuculline, performing vagal recordings and combining infusion of sNAc-VNX with hepatic vagal denervation. ResultsVNX infusion in the sNAc strongly decreased endogenous glucose production, prevented glucose increases over time, reduced Slc17A6 and Hcrt mRNA in LHA, and increased vagal activity. Furthermore, sNAc Drd1-expressing neurons increased spontaneous firing following VNX application, and viral tracing of sNAc Drd1-expressing neurons revealed direct projections to LHA with on average 67 % of orexin cells directly targeted by sNAc Drd1-expressing neurons. Importantly, the sNAc-VNX-induced effect on glucose metabolism was dependent on GABAergic signaling in the LHA and on intact hepatic vagal innervation. ConclusionsWe show that sNAc dopaminergic signaling modulates hepatic glucose metabolism through GABAergic inputs to glutamatergic LHA cells and hepatic vagal innervation. This demonstrates that striatal control of glucose metabolism involves a dopaminergic sNAc-LHA-liver axis and provides a potential explanation for the effects of dopamine agonists and antagonists on glucose metabolism.

Current and Perspective Approaches to the Treatment of Prolactinomas.

Along with the presence of the 2011 Endocrine Society Clinical Practice Guidelines and numerous large-scale studies on the treatment of hyperprolactinemia of different origin, there are some unresolved questions, ambiguous and sometimes contradictory points of view regarding the management of patients with prolactinomas. This overview is devoted to the analysis of the results of modern clinical studies and the approaches towards the management of hyperprolactinemia caused by prolactinoma. A systematic research of the literature for the appropriate keywords published mainly for the last 10 years was done; also, a reference list of each selected article was analysed. We included to our review the articles reporting controversial issues or new data on the treatment of hyperprolactinemia. The review describes various problems arising during the treatment of prolactinoma. The presence of primary and secondary dopamine agonist resistance in each case requires an individual approach, and sometimes may include the use of the antineoplastic agent t emozolomide. The side effects of dopamine agonists are discussed, with quite rare ones, including valvulopathy, pathological psychological conditions and cerebrospinal rhinorrhea. The controversial issue of the duration and doses of the drug used to achieve a lasting effect in the treatment of prolactinomas is considered. There are some points connected with the frequency of relapses. Thus, recurrence is correlated to the duration of treatment with dopamine agonists, prolactin levels at diagnosis, and the initial tumor size. Metformin, somatostatin analogues, selective estrogen receptor modulators, tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, epidermal growth factor receptor antagonists are investigated nowadays as potential alternative methods of drug treatment of prolactinomas. Drug therapy with dopamine agonists makes it possible to achieve the desired results in the vast majority of patients. However, despite the proven safety of this group of medicines, the risk of side effects should still be taken into account. The therapy regimen should be determined by the clinical course of prolactinoma and the patient's response to treatment. Other options of treatment should be considered in patients intolerant to medical therapy, with contraindication or resistance to dopamine agonists, in the case of a malignant tumor. The presence of refractory to any of the applied methods of treatment and aggressive prolactinomas leads to the search for new drugs.

Dopamine D1-like receptor activation decreases nicotine intake in rats with short or long access to nicotine.

The use of nicotine and tobacco products is highly addictive. The dopaminergic system plays a key role in the initiation and maintenance of nicotine intake. Dopamine D1-like receptor blockade diminishes nicotine intake in rats with daily short (1h) access to nicotine, but little is known about the effects of dopamine receptor antagonists or agonists on nicotine intake in rats with intermittent long (23 h) access. Because of the extended access conditions and high nicotine intake, the intermittent long access procedure might model smoking and vaping better than short access models. We investigated the effects of the dopamine D1-like receptor antagonist SCH 23390 and the D1-like receptor agonist A77636 on nicotine intake in male rats with intermittent short or long access to nicotine. The rats self-administered nicotine for 5days (1h/day) and were then given 15 intermittent short (1h/day) or long (23 h/day) access sessions (3 sessions/week, 0.06 mg/kg/inf). The D1-like receptor antagonist SCH 23390 decreased nicotine intake to a similar degree in rats with short or long access to nicotine. The D1-like receptor agonist A77636 induced a greater decrease in nicotine intake in the rats with long access to nicotine than in rats with short access. Treatment with A77636 induced a prolonged decrease in nicotine intake that lasted throughout the dark and light phase in the long access rats. These findings indicate that blockade and stimulation of D1-like receptors decrease nicotine intake in an intermittent long access animal model that closely models human smoking and vaping.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Role of dopamine agonists in Parkinson's disease therapy.

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists.

Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study

BackgroundRestless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia remains unclear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia.MethodsThis was a retrospective cohort study using the Korean National Health Insurance Service-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the International Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of dopamine agonists on the risk of dementia among RLS patients was also explored.ResultsThe baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24–1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30–2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11–1.72). The use of dopamine agonists was not associated with the risk of subsequent dementia among patients with RLS (aHR 1.00, 95% CI 0.76–1.32).ConclusionsThis retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires confirmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.

Metabolic effects of prolactin and the role of dopamine agonists: A review.

Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.

The Acute Pharmacological Manipulation of Dopamine Receptors Modulates Judgment Bias in Japanese Quail.

We have studied the effects of dopamine antagonists and agonists on Japanese quail behavior in the spatial judgment task. Twenty-four Japanese quail hens were trained in the spatial discrimination task to approach the feeder placed in the rewarded location (Go response, feeder containing mealworms) and to not approach the punished location (No-Go response, empty feeder plus aversive sound). In a subsequent spatial judgment task, the proportion of Go responses as well as approach latencies to rewarded, punished, and three ambiguous locations (near-positive, middle, near-negative, all neither rewarded nor punished) were assessed in 20 quail hens that successfully mastered the discrimination task. In Experiment 1, each bird received five treatments (0.1 and 1.0 mg/kg of dopamine D1 receptor antagonist SCH 23390, 0.05 and 0.5 mg/kg of dopamine D2 receptor antagonist haloperidol, and saline control) in a different order, according to a Latin square design. All drugs were administered intramuscularly 15 min before the spatial judgment test, with 2 days break between the treatments. Both antagonists caused a significant dose-dependent increase in the approach latencies as well as a decrease in the proportion of Go responses. In Experiment 2, with the design analogous to Experiment 1, the hens received again five treatments (1.0 and 10.0 mg/kg of dopamine D1 receptor agonist SKF 38393, 1.0 and 10.0 mg/kg of dopamine D2 receptor agonist bromocriptine, and saline control), applied intramuscularly 2 h before the test. The agonists did not have any significant effect on approach latencies and the proportion of Go responses in the spatial judgment task, as compared to the saline control, except for 10.0 mg/kg SKF 38393, which caused a decrease in the proportion of Go responses. The approach latency and the proportion of Go responses were affected by the cue location in both experiments. Our data suggest that the dopamine D1 and D2 receptor blockade leads to a decrease in the reward expectation and the negative judgment of stimuli. The effect of dopamine receptor activation is less clear. The results reveal that dopamine receptor manipulation alters the evaluation of the reward and punishment in the spatial judgment task.

Apomorphine infusion for improving sleep in Parkinson's disease

Apomorphine infusion for improving sleep in Parkinson's disease

Dopaminergic signaling regulates zebrafish larvae's response to electricity.

Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We recently showed zebrafish's response to electricity. Here, we hypothesized that this response is affected by the dopaminergic signaling pathways. The effects of multiple dopamine agonists and antagonists on the electric response of 6 days-postfertilization zebrafish larvae were investigated using a microfluidic device with enhanced control of experimentation and throughput. All dopamine antagonists decreased locomotor activities, while dopamine agonists did not induce similar behaviors. The D2-selective dopamine agonist quinpirole enhanced the movement. Exposure to nonselective and D1-selective dopamine agonists apomorphine and SKF-81297 caused no significant change in the electric response. Exposing larvae that were pretreated with nonselective and D2-selective dopamine antagonists butaclamol and haloperidol to apomorphine and quinpirole, respectively, restored the electric locomotion. These results reveal a correlation between electric response and dopamine signaling pathway. Furthermore, they demonstrate that electric-induced zebrafish larvae locomotion can be conditioned by modulating dopamine receptor functions. Our electrofluidic assay has profound application potential for fundamental electric-induced response research and brain disorder studies especially those related to the dopamine imbalance and as a chemical screening method when investigating biological pathways and behaviors.

Sexual function and depressive symptoms in men with hypoprolactinaemia secondary to overtreatment of prolactin excess: A pilot study

BackgroundLow prolactin levels have been found to impair libido and arousal, as well as to reduce wellbeing in young women. ObjectiveThe aim of this study was to investigate whether drug-induced hypoprolactinaemia affects male sexual function and depressive symptoms. MethodsThe study population consisted of three groups of young and middle-aged men. Two groups were treated with dopamine agonists because of previous hyperprolactinaemia but differed in current prolactin levels, which were <3ng/ml (n=12; group 1) or within the reference range (3–20ng/ml) (n=20; group 2). The control group (group 3) included 24 dopamine agonist-naïve normoprolactinaemic men. During the study, doses of dopaminergic agents in group 1 were reduced by 25–50% compared to doses before the start of the study. Circulating levels of prolactin, testosterone, free calculated testosterone, dehydroepiandrosterone-sulphate, oestradiol and gonadotropins were measured upon enrolment in the study and six months later. Moreover, at the beginning and the end of the study, all men enrolled completed questionnaires assessing sexual functioning (IIEF-15) and depressive symptoms (BDI-II). ResultsGroup 1 differed from groups 2 and 3 in domain scores for sexual desire and erectile function, and in the overall BDI-II score. It was also characterised by lower levels of total testosterone and calculated free testosterone. Reduction of drug doses normalised sexual desire and erectile function, reduced BDI-II scores and increased prolactin as well as total and free calculated testosterone. Groups 2 and 3 did not differ from each other in sexual functioning, depressive symptoms or hormone levels. ConclusionsThe results obtained indicate that men with dopamine agonist-induced hypoprolactinaemia are characterised by impaired sexual functioning and reduced wellbeing. These disturbances are a consequence of subnormal prolactin levels and do not seem to reflect adverse effects of dopamine agonists.

Dopamine agonist for the rapid improvement of visual field defects in giant and macro-prolactinomas

To evaluate effect of first-line dopamine agonist (DA) therapy as an alternative to surgery for visual field defect (VFD) recovery in giant and macro-prolactinoma. In this retrospective study, 125 patients with giant and macro-prolactinoma, except those with a history of previous surgery or radiotherapy, were evaluated. Those who underwent visual field examinations using the Humphrey Visual Field analyser upon initial assessment and after treatment were included for analysis. Twelve patients with VFD were included. The effects of DA therapy on both VFD and tumor size were evaluated within the first three months. There were twelve patients analysed: three females and nine males, five giant and seven macroprolactinomas; eight patients received cabergoline (CAB) and four patients received bromocriptine (BRC). The mean adenoma diameter was 35±13mm (range 15-60), and the mean PRL level was 3,523ng/dL (range 312-11,703). Eight patients (67%) complained of blurred vision, while four patients (33%) reported no visual symptoms. After a median duration of three weeks, the VFD completely resolved in ten patients (83%) but only partially improved in two (17%). The mean initial doses of CAB and BRC that provided VFD improvement were 0.5±0.2mg/week and 6.3±1.4mg/day, respectively. After a mean duration of 2.2±0.9months, the mean decrease in adenoma size was 43.6±24.5% (range 10-95%). The use of DA as a first-line treatment for at least one month before deciding on surgery is recommended in giant and macro-prolactinomas with VFD. Surgery should be considered only in cases with DA resistance or persistent visual impairment despite medical therapy.

Change in Insulin Sensitivity and Lipid Profile After Dopamine Agonist Therapy in Patients With Prolactinoma.

BackgroundProlactinomas are prolactin(PRL)-secreting neoplastic lesions that can lead to metabolic disturbances and insulin resistance. We aimed to find the change in insulin sensitivity and lipid profile in prolactinoma patients after dopamine therapy. MethodologyA prospective observational study was conducted at the Hayatabad Medical Complex, Peshawar between June 2019 to July 2020. All patients with newly diagnosed prolactinoma were eligible to partake in the study. Individuals with multiple hormone-producing pituitary tumors, hyperprolactinemia secondary to other causes than tumors, and those taking medication for hypercholesterolemia were excluded. Diagnosis of prolactinoma was established on the basis of elevated PRL levels on at least two occasions three days apart in addition to an MRI detecting prolactinoma on the hypothalamic-pituitary area. The mean dose for dopamine agonist was 5.8 ± 4.1 mg per day with a range between 1.25 to 15 mg. To assess the change in insulin resistance, the homeostatic model assessment insulin resistance (HOMA-IR) was computed. All data were recorded in a predefined proforma. Results The difference between pre- and post-treatment values for mean PRL levels was statistically significant (p<0.0001). There was a significant association between dopamine agonist treatment and the BMI (pre- vs. post-treatment; 28.9 ± 4.28 vs. 24.53 ± 2.2, p<0.0001). Both low-density lipoprotein (LDL)-cholesterol and HOMA-IR scores were significantly lower in the post-treatment group as compared to the pre-treatment group (p<0.0001). ConclusionThe present study indicated that dopamine agonist therapy was effective not only in lowering the serum PRL levels but also improved insulin sensitivity and decreased lipid metabolism, resulting in improved BMI. Further studies should explore the long-term side effects of dopamine agonists on patients with prolactinoma.