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Pituitary Feb 2016Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for... (Review)
Review
INTRODUCTION
Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for complementary classification. Treatment protocols for prolactinomas are also devoid of molecular targets, leaving those refractory to standard treatments without many options.
METHODS
A systematic literature review was performed utilizing the PRISMA guidelines. We aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion. A PubMed search of select MeSH terms was performed to identify all studies reporting gene and protein expression findings in prolactinomas from 1990 to 2014.
RESULTS
1392 abstracts were screened and 51 manuscripts were included in the analysis, yielding 54 upregulated and 95 downregulated genes measured by various direct and indirect analytical methods. Of the many genes identified, three upregulated (HMGA2, HST, SNAP25), and three downregulated (UGT2B7, Let7, miR-493) genes were selected for further analysis based on our subjective identification of strong potential targets.
CONCLUSIONS
Many significant genes have been identified and validated in prolactinomas and most have not been fully analyzed for therapeutic and diagnostic potential. These genes could become candidate molecular targets for biomarker development and precision drug targeting as well as catalyze deeper research efforts utilizing next generation profiling/sequencing techniques, particularly genome scale expression and epigenomic analyses.
Topics: Gene Expression Regulation, Neoplastic; Humans; Pituitary Neoplasms; Prolactinoma
PubMed: 26238304
DOI: 10.1007/s11102-015-0674-1 -
Journal of Clinical Pharmacy and... Dec 2021Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia.
METHODS
Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA).
RESULTS AND DISCUSSION
Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA.
WHAT IS NEW AND CONCLUSION
This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.
Topics: Dopamine Agonists; Female; Galactorrhea; Humans; Hyperprolactinemia; Menstruation Disturbances; Network Meta-Analysis; Prolactin; Randomized Controlled Trials as Topic
PubMed: 34137053
DOI: 10.1111/jcpt.13460 -
The Breast Journal 2023Idiopathic granulomatous mastitis is a rare and benign disease that primarily affects young women of reproductive age. Various factors have been suggested as possible... (Meta-Analysis)
Meta-Analysis Review
Idiopathic granulomatous mastitis is a rare and benign disease that primarily affects young women of reproductive age. Various factors have been suggested as possible causes, including pregnancy, breastfeeding, history of taking birth control pills, hyperprolactinemia, smoking, and history of trauma. Due to unknown etiology, opinions on its treatment have varied, resulting in differing recurrence rates and side effects. Therefore, conducting a comprehensive systematic review and meta-analysis can aid in understanding the causes and recurrence of the disease, thereby assisting in the selection of effective treatment and improving the quality of life. A systematic literature review was conducted using predefined search terms to identify eligible studies related to risk factors and recurrence up to June 2022 from electronic databases. Data were extracted and subjected to meta-analysis when applicable. A total of 71 studies with 4735 patients were included. The mean age of the patients was 34.98 years, and the average mass size was 4.64 cm. About 3749 of these patients (79.17%) were Caucasian. Patients who mentioned a history of pregnancy were 92.65% with 76.57%, 22.7%, and 19.7% having a history of breastfeeding, taking contraceptive pills, and high prolactin levels, respectively. Around 5.6% of patients had previous trauma. The overall recurrence rate was 17.18%, with recurrence rates for treatments as follows: surgery (22.5%), immunosuppressive treatment (14.7%), combined treatment (14.9%), antibiotic treatment (6.74%), and observation (9.4%). Only antibiotic and expectant treatments had significant differences in recurrence rates compared to other treatments ( value = 0.023). In conclusion, factors such as Caucasian race, pregnancy and breastfeeding history, and use of contraceptive hormone are commonly associated with the disease recurrence. Treatment should be tailored based on symptom severity and patient preference, with surgery or immunosuppressive options for recurrence.
Topics: Pregnancy; Female; Humans; Adult; Granulomatous Mastitis; Quality of Life; Breast Neoplasms; Neoplasm Recurrence, Local; Immunosuppressive Agents; Anti-Bacterial Agents; Contraceptive Agents; Recurrence
PubMed: 37794976
DOI: 10.1155/2023/9947797 -
Schizophrenia Research Aug 2020Different therapeutic strategies are used for lowering prolactin concentrations in patients with psychotic disorders with antipsychotic-induced hyperprolactinaemia. We... (Meta-Analysis)
Meta-Analysis Review
Different therapeutic strategies are used for lowering prolactin concentrations in patients with psychotic disorders with antipsychotic-induced hyperprolactinaemia. We aimed to examine the evidence from open-label studies and randomized clinical trials (RCTs) that studied four prolactin-lowering therapeutic strategies in people with psychotic disorders and hyperprolactinaemia: 1) switching to prolactin-sparing antipsychotics; 2) adding aripiprazole; 3) adding dopamine agonists; and 4) adding metformin. RCTs were included in a meta-analysis. Effect sizes (Hedges' g) of prolactin reductions with each strategy were calculated. Withdrawal rates were also considered. We identified 26 studies. Nine studies explored switching antipsychotic treatment to aripiprazole (n = 4), olanzapine (n = 1), quetiapine (n = 2), paliperidone palmitate (n = 1) or blonanserin (n = 1). Twelve studies tested the addition of aripiprazole. Six studies explored the addition of cabergoline (n = 3), bromocriptine (n = 2) or terguride (n = 1). We also found one meta-analysis testing the addition of metformin to antipsychotic treatment but no other individual studies. A meta-analysis could only be performed for the addition of aripiprazole, the strategy with the best level of evidence. Five RCTs testing the addition of aripiprazole yielded a significant reduction in prolactin concentration compared to placebo (N = 3) or maintaining antipsychotic treatment (N = 2): Hedges' g was -1.35 (CI 95%: -1.93 to -0.76, p < 0.001). The three placebo-controlled RCTs for aripiprazole addition showed similar withdrawal rates for aripiprazole (10.1%) and placebo (11.5%), without significant differences in the meta-analysis. Our study suggests that, in terms of levels of evidence, adding aripiprazole is the first option to be considered for lowering prolactin concentrations in patients with schizophrenia and hyperprolactinaemia.
Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Hyperprolactinemia; Prolactin; Psychotic Disorders
PubMed: 32507371
DOI: 10.1016/j.schres.2020.04.031 -
The Cochrane Database of Systematic... Apr 2016Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation.
OBJECTIVES
To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies.
SELECTION CRITERIA
Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence).
AUTHORS' CONCLUSIONS
Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.
Topics: Administration, Oral; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delayed-Action Preparations; Humans; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 27078222
DOI: 10.1002/14651858.CD004161.pub2 -
Journal of the Endocrine Society Oct 2021Surgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain...
CONTEXT
Surgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain unclear.
OBJECT
While transsphenoidal surgical resection (TSSR) is important second-line therapy in prolactinoma patients, predictors of surgical cure and biochemical remission following TSSR remain sparse.
METHODS
A retrospective review of prolactinoma patients undergoing TSSR at the USC Pituitary Center from 1995 to 2020 was conducted. Participants were categorized as surgical cure (normalization of serum prolactin without medical treatment), surgical noncure, biochemical control (prolactin normalization with or without adjuvant therapy), and nonbiochemical control. A systematic review of the outcomes of surgically managed prolactinomas was performed.
RESULTS
The 40 female and 16 male participants had an average age of 35.6 years. Prior treatment included transsphenoidal resection (6, 11%) and dopamine agonist treatment (47, 84%). The 40 macroadenomas and 15 microadenomas exhibited suprasellar extension (24, 43%) and parasellar invasion (20, 36%). Fifteen (27%) were purely intrasellar. Gross total resection was achieved in 25 patients (45%) and subtotal in 26 (46%). Surgical cure was achieved in 25 patients (46%) and biochemical control in 35 (64%). Surgical cure was more likely in smaller, noninvasive tumors, those that were fully resected, and patients with lower preoperative (< 1000 ng/mL) and immediately postoperative (< 7.6 ng/mL) prolactin levels. Ten of 26 patients (38%) undergoing adjuvant therapy achieved biochemical control, which was less likely in men and those with higher preoperative prolactin or invasive tumors.
CONCLUSION
Surgical resection of prolactinomas is a safe procedure that, when offered judiciously, can achieve symptom and/or biochemical control in a majority of patients. A variety of predictors may be useful in advising patients on likelihood of postoperative remission.
PubMed: 34466765
DOI: 10.1210/jendso/bvab074 -
Frontiers in Endocrinology 2023Three dopamine agonists [bromocriptine, cabergoline, and quinagolide (CV)] have been used for hyperprolactinemia treatment for decades. Several studies have reviewed the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Three dopamine agonists [bromocriptine, cabergoline, and quinagolide (CV)] have been used for hyperprolactinemia treatment for decades. Several studies have reviewed the efficacy and safety of bromocriptine and cabergoline. However, no systematic review or meta-analysis has discussed the efficacy and safety of CV in hyperprolactinemia and prolactinoma treatment.
METHODS
Five medical databases (PubMed, Web of Science, Embase, Scopus, and Cochrane Library) were searched up to 9 May 2022 to identify studies related to CV and hyperprolactinemia. A meta-analysis was implemented by using a forest plot, funnel plot, sensitivity analysis, meta-regression, and Egger's test software R 4.0 and STATA 12.
RESULTS
A total of 1,211 studies were retrieved from the five medical databases, and 33 studies consisting of 827 patients were finally included in the analysis. The pooled proportions of patients with prolactin concentration normalization and tumor reduction (>50%) under CV treatment were 69% and 20%, respectively, with 95% confidence intervals of 61%-76% and 15%-28%, respectively. The pooled proportion of adverse effects was 13%, with a 95% confidence interval of 11%-16%.
CONCLUSION
Our study showed that CV is not less effective than cabergoline and bromocriptine in treating hyperprolactinemia, and the side effects were not significant. Hence, this drug could be considered an alternative first-line or rescue treatment in treating hyperprolactinemia in the future.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022347750.
Topics: Humans; Bromocriptine; Cabergoline; Drug-Related Side Effects and Adverse Reactions; Hyperprolactinemia; Pituitary Neoplasms; Aminoquinolines
PubMed: 36761195
DOI: 10.3389/fendo.2023.1027905 -
Clinical Psychopharmacology and... Aug 2019The relationship between serum prolactin and bone mineral density (BMD) in schizophrenia is unclear. We conducted a literature review of databases from inception until...
The relationship between serum prolactin and bone mineral density (BMD) in schizophrenia is unclear. We conducted a literature review of databases from inception until December 2018 for cross-sectional, case-control, prospective and retrospective studies analyzing correlations between serum prolactin and BMD measured using dual energy X-ray absorptiometry or quantitative ultrasound at any skeletal site in people with schizophrenia. Data was summarized with a best evidence synthesis. This review identified 15 studies (1 longitudinal study, 10 cross-sectional and 4 case-control studies; 1,360 individuals with a psychotic disorder; mean age 45.1 ± 9.4 [standard deviation] years, female 742 [54.6%], mean illness duration 17.7 ± 11.3 years) assessing the relationship between serum prolactin and BMD in schizophrenia. There was a statistically significant inverse correlation between serum prolactin and BMD identified in eight of the studies (53% of all studies), suggesting mixed evidence for an association between serum prolactin and BMD. Of those studies which identified a significant inverse correlation between serum prolactin and BMD (n = 5), 152 (52.1%) of patients were treated with prolactin raising antipsychotics, compared to 197 (48.1%) of patients in those studies which did not identify a significant correlation between prolactin and BMD. Available studies cannot resolve the link between excess prolactin and reduced BMD in schizophrenia. Future studies should be longitudinal in design and combine measures of serum prolactin along with other risk factors for reduced BMD such as smoking and vitamin D and sex hormone levels in assessing the relationship between prolactin and BMD in schizophrenia.
PubMed: 31352700
DOI: 10.9758/cpn.2019.17.3.333 -
The World Journal of Men's Health Apr 2023Whether COVID-19 reduces male fertility remains requires further investigation. This meta-analysis and systematic review evaluated the impact of COVID-19 on male...
PURPOSE
Whether COVID-19 reduces male fertility remains requires further investigation. This meta-analysis and systematic review evaluated the impact of COVID-19 on male fertility.
MATERIALS AND METHODS
The literature in PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library up to January 01, 2022 was systematically searched, and a meta-analysis was conducted to investigate the effect of COVID-19 on male fertility. Totally 17 studies with a total of 1,627 patients and 1,535 control subjects were included in our meta-analysis.
RESULTS
Regarding sperm quality, COVID-19 decreased the total sperm count (p=0.012), sperm concentration (p=0.001), total motility (p=0.001), progressive sperm motility (p=0.048), and viability (p=0.031). Subgroup analyses showed that different control group populations did not change the results. It was found that during the illness stage of COVID-19, semen volume decreased, and during the recovery stage of COVID-19, sperm concentration and total motility decreased <90 days. We found that sperm concentration and total motility decreased during recovery for ≥90 days. Fever because of COVID-19 significantly reduced sperm concentration and progressive sperm motility, and COVID-19 without fever ≥90 days, the sperm total motility and progressive sperm motility decreased. Regarding disease severity, the moderate type of COVID-19 significantly reduced sperm total motility, but not the mild type. Regarding sex hormones, COVID-19 increased prolactin and estradiol. Subgroup analyses showed that during the illness stage, COVID-19 decreased testosterone (T) levels and increased luteinizing hormone levels. A potential publication bias may have existed in our meta-analysis.
CONCLUSIONS
COVID-19 in men significantly reduced sperm quality and caused sex hormone disruption. COVID-19 had long-term effects on sperm quality, especially on sperm concentration and total motility. It is critical to conduct larger multicenter studies to determine the consequences of COVID-19 on male fertility.
PubMed: 36326165
DOI: 10.5534/wjmh.220091 -
Gynecological Endocrinology : the... May 2022Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast cancer. Breast cancer represents the most prevalent malignancy in women, and the second cause of death in several countries. This tumor can be arise due to several molecular alterations, among them PRL has been the object of increasing interest from researchers worldwide.
OBJECTIVE
To assess the association between elevated levels of plasma prolactin and breast cancer development.
METHODS
A total of 158 studies were found in search databases (48 from PubMed, 69 from Scopus, 88 from Cochrane, 25 from Embase and 10 retrieved from the gray literature) after removing duplicates. Of these, 104 studies were excluded after title and abstract reading, and 54 studies were then read in full, of which only 14 were selected for this review because they had evaluated the association between PRL and breast cancer. Meta-analysis was carried out using the relative risk (RR), mean and standard deviation, confidence interval (95% CI), and the total number of patients for each study. Fixed- and random-effect models were used as applicable and, for the analysis.
RESULTS
The meta-analysis showed a positive association between elevated levels of PRL and breast cancer occurrence (RR 1.26; 95%CI 1.15-1.37). Additionally, the patient sub-group analyses showed a positive association between PRL and invasive breast cancer (1.42; 1.24-1.60), ER+/PR+ (1.49; 1.23-1.75), and post-menopausal status (1.29; 1.16-1.43).
CONCLUSION
The results showed a positive association between plasma prolactin levels and breast cancer, especially in women with ER+/PR + tumors, of post-menopausal age and those with invasive cancer.
Topics: Breast Neoplasms; Female; Humans; Prolactin
PubMed: 35266411
DOI: 10.1080/09513590.2022.2047173