The utility of rested prolactin sampling in the evaluation of hyperprolactinaemia.

BACKGROUND AND AIMS: Serum prolactin levels may be elevated by venepuncture stress. We investigated the utility of a rested prolactin sample, obtained through an indwelling venous cannula, in preventing the overdiagnosis of hyperprolactinaemia. METHODS: Patients at our institution undergo serial prolactin sampling, usually over 40 min, when investigating hyperprolactinaemia. We retrospectively reviewed all serial prolactin sampling performed during a 3-year period. Patients with possible medication-induced hyperprolactinaemia and macroprolactin interference were excluded. We assessed the effect of venepuncture-associated stress on hyperprolactinaemia with the main outcome being normalisation of serum prolactin at the end of serial sampling. RESULTS: Ninety-three patients with documented hyperprolactinaemia (range 360-1690 mU/L) were included in the analysis. Prolactin decreased during serial sampling in 73 patients (78%), suggesting a prevalent effect of venepuncture stress. The final prolactin sample was normal in 50 patients (54%), consistent with stress hyperprolactinaemia rather than pathological hyperprolactinaemia. Patients with a referral prolactin result greater than two times the upper reference limit (URL) were less likely (15%) to have a normal prolactin result on serial sampling. Measurement of a single rested prolactin sample from an indwelling cannula showed the same diagnostic utility as serial sampling. CONCLUSION: Serum prolactin results are frequently elevated by the stress of venepuncture. Confirmation of pathological hyperprolactinaemia in a rested sample obtained from an indwelling venous cannula is recommended in patients with mild hyperprolactinaemia, particularly when the referral prolactin is less than two times the URL.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinaemia: A cross-sectional study in outpatient gastroenterology clinics.

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.

Significance of Duodenal Prolactin Receptor Modulation by Calcium and Vitamin D in Sulpiride-Induced Hyperprolactinemia.

Background and Objectives: Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor (Prlr) gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Materials and Methods: Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess Prlr gene expression in the duodenum, vertebrae, and kidneys. Results: In Group S, Prlr gene expression was notably decreased in the duodenum (p < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum (p < 0.01) alongside elevated expression in the vertebrae and kidneys. Conclusions: In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.

Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts.

BACKGROUND: Gilts experiencing sustained hyperprolactinemia from d 90 to 109 of gestation showed an early onset of lactogenesis coupled with premature mammary involution. To better understand the molecular mechanisms underlying the premature mammary involution observed in these gilts, a transcriptomic analysis was undertaken. Therefore, this study aimed to explore the effect of hyperprolactinemia on the global transcriptome in the mammary tissue of late gestating gilts and identify the molecular pathways involved in triggering premature mammary involution. METHODS: On d 90 of gestation, gilts received daily injections of (1) canola oil until d 109 ± 1 of gestation (CTL, n = 18); (2) domperidone (to induce hyperprolactinemia) until d 96 ± 1 of gestation (T7, n = 17) or; (3) domperidone (until d 109 ± 1 of gestation (T20, n = 17). Mammary tissue was collected on d 110 of gestation and total RNA was isolated from six CTL and six T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array was used for hybridization. Functional enrichment analyses were performed to explore the biological significance of differentially expressed genes, using the DAVID bioinformatics resource. RESULTS: The expression of 335 genes was up-regulated and that of 505 genes down-regulated in the mammary tissue of T20 vs CTL gilts. Biological process GO terms and KEGG pathways enriched in T20 vs CTL gilts reflected the concurrent premature lactogenesis and mammary involution. When looking at individual genes, it appears that mammary cells from T20 gilts can simultaneously upregulate the transcription of milk proteins such as WAP, CSN1S2 and LALBA, and genes triggering mammary involution such as STAT3, OSMR and IL6R. The down-regulation of PRLR expression and up-regulation of genes known to inactivate the JAK-STAT5 pathway (CISH, PTPN6) suggest the presence of a negative feedback loop trying to counteract the effects of hyperprolactinemia. CONCLUSIONS: Genes and pathways identified in this study suggest that sustained hyperprolactinemia during late-pregnancy, in the absence of suckling piglets, sends conflicting pro-survival and cell death signals to mammary epithelial cells. Reception of these signals results in a mammary gland that can simultaneously synthesize milk proteins and initiate mammary involution.

Hyperprolactinemia modifies extracellular matrix components associated with collagen fibrillogenesis in harderian glands of non- and pregnant female mice.

The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia.

Antipsychotic polypharmacy and adverse drug reactions among adults in a London mental health service, 2008-2018.

BACKGROUND: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25]. METHODS: We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively. RESULTS: We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87-3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33-2.31) in the period following the APP prescribing. CONCLUSIONS: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

Evidence-Based Recommendations for the Pharmacological Treatment of Women with Schizophrenia Spectrum Disorders.

PURPOSE OF REVIEW: Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia. RECENT FINDINGS: We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.

Hyperprolactinemia-induced acute ischemic stroke.

Strokes are the fifth leading cause of death in the United States with almost 800,000 patients seeking emergency care each year-most of whom are seen for ischemic strokes. Acute ischemic strokes (AIS) can be caused by emboli in diseases such as atrial fibrillation as well as thrombus formation in the form of platelet deposition in patients with atherosclerotic disease. Platelet activation by immunomodulators including thromboxane A2 (TXA2), serotonin, and thrombin have been extensively delineated; however, the activation by hormones such as prolactin has only recently been revealed. We present a case of a 25-year-old male with a history of pituitary microadenoma and hyperprolactinemia who presented with an acute ischemic stroke in the setting of medication non-compliance. To our knowledge, this is the first known case of AIS in a patient with known hyperprolactinemia who presented with a stroke due to be medication non-compliance.

Therapeutic outcomes wide association scan of different antipsychotics in patients with schizophrenia: Randomized clinical trials and multi-ancestry validation.

AIM: This study identified discrepant therapeutic outcomes of antipsychotics. METHODS: A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables. RESULTS: In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (ß = -2.17); ziprasidone related to higher risk of increased QT interval (ß range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort. CONCLUSION: Future precision medicine should focus on personalized side-effects.

[Association of the Level of Serum Prolactin with Polymorphic Variants of the GRIN2A, GPM3, and GPM7 Genes in Patients with Schizophrenia Taking Conventional and Atypical Antipsychotics].

The dopamine, serotonin and glutamate systems are jointly involved in the pathogenesis and pharmacotherapy of schizophrenia. We formulated a hypothesis that polymorphic variants of the GRIN2A, GRM3, and GRM7 genes may be associated with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics as basic treatment. 432 Caucasian patients diagnosed with schizophrenia were examined. DNA was isolated from peripheral blood leukocytes using the standard phenol-chloroform method. For pilot genotyping, 12 SNPs in the GRIN2A gene, 4 SNPs in the GRM3 gene, and 6 SNPs in the GRM7 gene were selected. Allelic variants of the studied polymorphisms were determined by real-time PCR. The level of prolactin was determined by enzyme immunoassay. Among persons taking conventional antipsychotics, there were statistically significant differences in the distribution of genotype and allele frequencies in groups of patients with normal and elevated prolactin levels for the GRIN2A rs9989388 and GRIN2A rs7192557 polymorphic variants, as well as differences in serum prolactin levels depending on the genotype of the GRM7 rs3749380 polymorphic variant. Among persons taking atypical antipsychotics, statistically significant differences were found in the frequencies of genotypes and alleles of the GRM3 rs6465084 polymorphic variant. An association of polymorphic variants of the GRIN2A, GRM3, and GRM7 genes with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics has been established for the first time. The identified associations of polymorphic variants of the GRIN2A, GRM3 and GRM7 genes with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics have been established for the first time. These associations not only confirm the close connection of the dopaminergic, serotonergic, and glutamatergic systems in the development of schizophrenia, but also demonstrate the potential of taking into account the genetic component during therapy.

The effect of antipsychotic medication and the associated hyperprolactinemia as a risk factor for periodontal diseases in schizophrenic patients: a cohort retrospective study.

BACKGROUND: Periodontal disease is a major health problem that results in tooth loss and thus affects oral health, which affects quality of life. In particular, schizophrenic patients are at higher risk for periodontal disease due to several factors, including the effect of antipsychotic medications received by those patients. Accordingly, the aim of the present cohort retrospective study is to explore the effect of antipsychotics on periodontal health and the possible effect of antipsychotic-induced hyperprolactinemia as a risk factor for periodontal disease progression in schizophrenic patients. METHODS AND OUTCOMES: The study population consisted of three groups: Group A (n = 21): schizophrenic patients that have been taking "prolactin-inducing" antipsychotics for at least 1 year; Group B (n = 21): schizophrenic patients who have been taking "prolactin-sparing" antipsychotics for at least 1 year; and Group C (n = 22): newly diagnosed schizophrenic patients and/or patients who did not receive any psychiatric treatment for at least 1 year. The study groups underwent assessment of periodontal conditions in terms of pocket depth (PD), clinical attachment loss (CAL), gingival recession, tooth mobility, and bleeding on probing (BOP). Also, bone mineral density was evaluated using DEXA scans, and the serum prolactin level was measured by automated immunoassay. RESULTS: Results revealed a statistically significant difference in PD, CAL, and serum prolactin levels (P ≤ 0.001, P = 0.001, and P ≤ 0.001, respectively) among the 3 study groups. For both PD and CAL measurements, group A has shown significantly higher values than both groups B and C, whereas there was no statistically significant difference between the values of groups C and B. Concerning serum prolactin levels, group A had significantly higher values than groups B and C (P ≤ 0.001 and P ≤ 0.001 respectively). There was a statistically significant difference (P ≤ 0.001) between the 3 study groups in terms of bone mineral density. Moreover, there was a statistically significant direct relation between serum prolactin level and other parameters including clinical attachment loss, pocket depth measurements and bone mineral density. CONCLUSION: According to our results, it could be concluded that all antipsychotics contribute to the progression of periodontal disease, with a higher risk for prolactin-inducing antipsychotics. However, further long term, large sampled, interventional and controlled studies are required to reach definitive guidelines to allow clinicians properly manage this group of patients.

Withdrawal of dopamine agonist treatment in patients with hyperprolactinaemia: A systematic review and meta-analysis.

OBJECTIVE: To estimate the proportion of patients with persistent normoprolactinaemia following dopamine agonist (DA) withdrawal and to identify predictors of successful withdrawal in patients with hyperprolactinaemia. DESIGN, PATIENTS, AND MEASUREMENTS: A systematic review of observational eligible studies were identified by searching PubMed and Embase. The primary outcome was the proportion of patients with normoprolactinaemia after cessation of DA treatment. Secondary outcome included the proportion of patients with normoprolactinaemia after DA withdrawal using individual patient data. Risk of bias was assessed by using Newcastle-Ottawa Scale. Pooled proportions were estimated using a random effects model in case I2 ≤ 75% or by reporting range of effects if I2 > 75%. RESULTS: Thirty-two observational studies enroling 1563 patients were included. The proportion of patients with persistent normoprolactinaemia ranged from 0% to 75% (I2 = 84%). Heterogeneity was partly explained by age with more successful withdrawal in patients of higher age. Individual patient data analyses suggested that the proportion of patients with persistent normoprolactinaemia 6 months after DA withdrawal with a low maintenance dose and full regression of the prolactinoma was 87.7% (95% confidence interval [CI] = 60.7-97.1; I2 = 0%) and 58.4% (95% CI = 23.8-86.3; I2 = 75%) for microadenomas and macroadenomas, respectively. CONCLUSIONS: The proportion of patients with persistent normoprolactinaemia following DA withdrawal treatment varied greatly, partly explained by the mean age of participants of the individual studies. Individual patient data analysis suggested that successful withdrawal was likely in patients with full regression of prolactinomas using a low maintenance dose before cessation.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

Amisulpride withdrawal akathisia responding to aripiprazole with propranolol in first-onset psychosis: a case report.

BACKGROUND: Akathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon. CASE PRESENTATION: A 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient's psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100-200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient's prolactin levels had normalized after 6 months of aripiprazole monotherapy. CONCLUSIONS: The present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Prospective analysis of serum prolactin levels, clinical symptomatology and sexual functions in patients with schizophrenia switched to paliperidone palmitate 3-monthly from paliperidone palmitate 1-monthly: Preliminary findings of the first 3 months.

OBJECTIVE: Long-acting injectable (LAI) antipsychotics were developed to improve adherence to schizophrenia treatment. Paliperidone palmitate (PP) has two LAI forms: Monthly (PP1M) and three-monthly (PP3M). PP3M shows less difference in Peak-to-Trough drug concentration levels. This could be related to a lower incidence of hyperprolactinemia, which may negatively affect adherence. We aimed to compare prolactin levels and investigate relationships between prolactin levels, symptomatology and sexual function in patients with schizophrenia after switching from PP1M to PP3M. METHODS: Twenty-five patients were enrolled. The sociodemographic data form, the Positive and Negative Syndromes Scale (PANSS) and the Arizona Sexual Experience Scale (ASEX) were used. Morning blood samples were drawn to determine prolactin levels. RESULTS: Prolactin level (p < 0.001), the total score and arousal sub-score of ASEX (respectively; p = 0.015, p = 0.020) and the total score and positive scale of PANSS (respectively; p = 0.017, p = 0.021) were decreased on the 90th day (±15 days). CONCLUSIONS: After switching to PP3M, the decreases in prolactin levels and potentially related sexual side effects was statistically significant. There may be a difference between two formulations of the same drug in terms of side effects, and there is a need for prospective follow-up studies with larger samples.

Proton pump inhibitors therapy and risk of hyperprolactinemia with associated sexual disorders.

Proton pump inhibitors (PPIs) are the most widely prescribed medications in the world. According to numerous studies, PPIs have been linked to hyperprolactinemia, which can lead to a variety of sexual and reproductive issues. This review summarizes the effects of numerous PPIs on the blood prolactin levels and associated sexual dysfunctions, which have an effect on the patient's life quality and fertility. The study is taken into account all the available resources till January 31, 2021. Out of total 364, only 27 relevant resources were involved in this review. In certain studies, short-term PPIs use has been shown to have little or no effect on the blood prolactin and other reproductive hormones levels. PPIs have been linked to the development of hyperprolactinemia in several case studies with varying degrees of the blood prolactin levels increase seen in individuals taking PPI alone or in combination with medications, like prokinetics. The relative risk of the sexual consequences development, such as gynecomastia, has been documented using lansoprazole and omeprazole in various cohort studies. On the other hand, other bits of data are insufficient to establish a definite relationship that can turn a possibility into certainty. The majority of the literature data is comprising of double-blind, randomized, crossover studies, case reports, and adverse drug reaction incidents reported to various pharmacovigilance centers. To investigate this link, high-quality studies in patients taking PPIs for a longer time period are needed. We conclude this article with a comprehensive discussion of the hyperprolactinemia clinical implications and the PPIs' function.

Sociodemographic and clinical characteristics related with hyperprolactinaemia in psychiatric clinical population.

BACKGROUND: Hyperprolactinaemia (HyperPRL) induced by psychotropic drugs is a high-prevalence consequence which has repercussions in psychical and mental health in the psychiatric population, so this research had the objective to expand which sociodemographic and clinical features are associated with prolactin (PRL) elevation in patients treated with antidepressant and/or antipsychotic drugs. METHODS: An observational, cross-sectional, comparative and retrolective study was conducted on 300 patients who received clinical attention in a third level of psychiatric care unit in Mexico during 2017. These patients have been reported to show PRL levels greater than 25 ng/mL among women and greater than 20 ng/mL among men. In the same way, sociodemographic and clinical variables were collected, as well as psychiatric diagnosis and type of psychopharmacological treatment used by the patients. RESULTS: HyperPRL was more frequent in women (80.7%) than men (19.3%). The mean levels of PRL were 68.94 ± 62.28 ng/mL with higher levels in women (71.9 ± 67.3, p=.02). Regarding the treatment, 78.3%, 71.3% and 49.7% consumed antipsychotics, antidepressants, and both drugs, respectively. The relationship between hyperPRL (>100 n/mL) and typical antipsychotics was dose-dependent (33.23 ± 13.24 mg, p=.01). In the multivariate regression models according to the type of treatment, as well as the demographic and clinical features, hyperPRL was associated independently with the use of antipsychotic treatment, pituitary adenoma and hypertension (R2=0.05). CONCLUSIONS: HyperPRL is a complex clinical syndrome frequent in the psychiatric population with detrimental long-term consequences, as well as its relationship with the use of psychotropic drugs as in the case of antipsychotics. Effective actions should be implemented in the prevention, approach and treatment of this condition paying special attention to the accompanying medical comorbidities.

Prolactin ordering patterns in psychiatric inpatients and the impact this has on patient management.

OBJECTIVE: Guidelines stipulate that baseline prolactin be ordered prior to commencing antipsychotic treatment to facilitate investigation of any subsequent hyperprolactinaemic symptoms. The aim was to observe when and why prolactin levels are ordered for psychiatry inpatients commencing or continuing antipsychotics and how this alters clinical management. METHODS: Psychiatry inpatients admitted to the Alfred Hospital, Melbourne, Australia, in 2018 with the diagnoses of psychosis, schizophrenia, schizo-affective disorder or bipolar affective disorder were retrospectively analysed. Results and clinical history data were collected in patients in whom prolactin was ordered during or within 12 months of the relevant admission. RESULTS: Of 592 patients admitted during this period, 90 had prolactin ordered. Eight (8.9%) of the 90 tests were for hyperprolactinaemic symptoms, while the remainder were routine blood work. The results altered clinical management in 10 of the 90 (11.1%) patients. Of these 10, 8 were symptomatic. In the six patients with first episode psychosis, only one had prolactin ordered prior to antipsychotic commencement. CONCLUSIONS: Adherence to guideline recommendations of baseline prolactin testing was poor. When established on antipsychotics, measuring prolactin rarely changed management in asymptomatic patients; however, it did in those with hyperprolactinaemic symptoms. Measuring prolactin in asymptomatic patients on antipsychotics appears unhelpful.

Hyperprolactinemia and Antipsychotic Therapy in Schizophrenic Patients with Hashimoto's Thyroiditis.

INTRODUCTION: Hyperprolactinemia (HPRL) is known as a side effect of some antidepressants and antipsychotics. These medicines are common in treatment of schizophrenia. Thus, HPRL is often observed in schizophrenic patients. It is also known that HPRL can occur in Hashimoto's thyroiditis due to prolactoliberin effect of thyroliberin. The clinical pathophysiology of the patients with the comorbidity of schizophrenia and Hashimoto's thyroiditis, receiving antipsychotics, is of special interest. It's fair to assume that these patients have higher risks of HPRL. To analyze risks of HPRL with antipsychotic treatment, to identify an association between the antipsychotic therapy (AT) and HPRL in Hashimoto's patients receiving AT, to explore the association of HPRL and other laboratory parameters in patients with Hashimoto's thyroiditis and schizophrenia during AT. SUBJECTS AND METHODS: We studied 17 patients with HT in comorbidity with schizophrenia receiving AT (mean age 46.5±12.8 years), all euthyroid or with light hypothyroidism. Different laboratory parameters such as anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies, blood levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and prolactin (PRL) were analysed. RESULTS: The study revealed the high levels of PRL, anti-TPO and anti-TG autoantibodies. Thus, patients were classified into 3 groups by the degree of expected HPRL risk from the antipsychotics used: without expected risk, with low and high expected risks. The correlation analysis detected an inverse significant correlation (R=-0.51; p=0.037) between expected level of drug-associated HPRL risk and actual PRL levels in studied group. At the same time, we detected a positive significant correlation between the levels of PRL and FT4 in the groups (R=0.53; p=0.03). The correlations between the levels of PRL and other parameters such as TSH, FT3, anti-TPO, anti-TG, anti-TSH receptor antibodies were not statistically significant. CONCLUSIONS: HPRL in the group was not associated with taking of antipsychotic drugs with high expected HPRL risk. Yet, a significant positive correlation existed between the levels of PRL and FT4. Hence, in Hashimoto's thyroiditis accompanied with treated mental illness there are some non-iatrogenic stimulants of prolactogenesis. It cannot be ruled out that antipsychotics may interfere with prolactin metabolism, which creates a false effect of a positive correlation between prolactin and free thyroxine levels, in contrast to common HPRL of hypothyroidism.

[Hyperprolactinemia and antipsychotics: it's not always what it seems to be]. / Jongeren met hyperprolactinemie bij antipsychoticagebruik: denk aan macroprolactine.

Hyperprolactinemia is a relatively frequent laboratory abnormality (30-80%) as a result of antipsychotics and a reason to reduce or stop them. We describe two youngsters with autism spectrum disorder whose hyperprolactinemia was based on a false-positive laboratory finding due to macroprolactin. The consequences were: unnecessary endocrinological evaluation including a brain MRI, and undesirable antipsychotic dose reduction. Thus, hyperprolactinemia can be due to a falsely elevated prolactin concentration. There should be an addition to the current guidelines in which a work-up for macroprolactin screening is included.