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Laboratory diagnostic methods are the main tools in the practice of a doctor of any specialty, including an endocrinologist. Factors were identified that could change the concentration of the biologically active fraction of the test substance, subsequently complicating the interpretation of laboratory results and making the right clinical decision. The literature describes a variety of circulating autoantibodies involved in binding to pituitary hormones (prolactin (PRL), thyroid-stimulating hormone (TSH), growth hormone, luteinizing, follicle-stimulating, and adrenocorticotropic hormones), hypothalamus (vasopressin and oxytocin), pancreas (insulin and glucagon) , parathyroid glands (parathyroid hormone), as well as with thyroid hormones. As a rule, the resulting macromolecules lead to an increase in laboratory parameters, in which the prevailing fraction of the hormone does not have biological activity, which determines the main problem of this phenomenon. The most common variants include immune complexes with PRL and TSH, causing the phenomena of macroprolactinemia and macrothyrotropinemia (macro-TSH-emia/macro-TSH), respectively. Most laboratory test systems used in clinical practice are capable of determining only the total amount of PRL and TSH. The presented clinical observation describes a combination of the phenomena of macro-TSH and macroprolactinemia in a patient with autoimmune thyroiditis (AIT) and vitiligo.

Objective: Determining the etiology of hyperprolactinemia is fundamental for selecting the most appropriate treatment strategy. The aim of this study was to evaluate the usefulness and accuracy of prolactin levels in predicting the etiology of nonphysiological hyperprolactinemia., Subjects and Methods: In this retrospective study, we reviewed medical records of patients with nonphysiological hyperprolactinemia seen at two neuroendocrine reference centers located in Recife, Brazil, from January 2000 to December 2019., Results: The study included 770 patients aged 12-73 years (65% female). The three most frequent etiologies of hyperprolactinemia were prolactinomas (n = 263; 34.2%), drug-induced hyperprolactinemia (n = 160; 20.8%), and macroprolactinemia (n = 120; 15.6%). The highest mean prolactin levels were observed in cases of prolactinomas and idiopathic hyperprolactinemia. Most patients with hyperprolactinemia due to other etiologies had prolactin levels < 100 ng/mL, but these levels were also found in 16.5% of patients with microproplactinomas and in 20% of those with idiopathic hyperprolactinemia. Likewise, prolactin levels largely overlapped among patients with microprolactinomas, macroprolactinemia, and drug-induced hyperprolactinemia. Notably, prolactin levels > 250 ng/mL enabled a clear distinction between the etiologies of macroprolactinoma and nonfunctioning pituitary adenoma. Moreover, prolactin levels > 500 ng/mL were highly suggestive of macroprolactinomas, although they were also found in very few patients (<2%) with microprolactinomas or drug-induced hyperprolactinemia., Conclusion: Despite considerable overlap in prolactin levels among the different etiologies of hyperprolactinemia, values > 250 ng/mL allowed a clear distinction between macroprolactinomas and nonfunctioning pituitary adenomas. Furthermore, prolactin levels > 500 ng/mL were almost exclusively found in patients with prolactinomas., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Background: Prolactin (PRL) is a peptide hormone secreted by the anterior pituitary that provides lactation during the postpartum period. The causes of hyperprolactinemia are pituitary tumors, medications, primary hypothyroidism, polycystic ovary syndrome (PCOS), renal failure, idiopathic, and other physiological causes such as pregnancy and lactation. In this study, we aimed to investigate the prevalence of hyperprolactinemia etiologies and the mean/median prolactin levels in different etiologies., Methods: The patients admitted to our outpatient clinic between January 2009-December 2019 were retrospectively screened from our hospital database with ICD-10 codes. Four hundred patients were included in the study; 69.5% of the patients were women. Their mean age was 43.67±13.42 years, the duration of illness was 7.8±5.6 years. The most frequent causes of hyperprolactinemia were found as follows: 52.5% (N.=210) prolactinoma, 7% (N.=28) gonadotropinoma, 6.5% (N.=26) drug-related, 6.5% (N.=25) PCOS, 5.8% (N.=23) idiopathic, 5% (N.=20) acromegaly, 4.8% (N.=19) nonfunctioning adenoma 2.3% (N.=9) craniopharyngioma. Patients with gonodotropinoma were significantly older, and the patients with PCOS were significantly younger than the patients with hyperprolactinemia due to the other etiologies. Patients with prolactinoma had significantly higher prolactin levels and longer duration of the illness when compared to other etiologies of hyperprolactinemia (168.00* ng/mL [14-23,500] [168]); 8* years (0-39) (5.00) years respectively, *median values, (min-max levels) and (interquartile range), respectively., Results: There was no significant difference between prolactin levels of other etiologic groups except prolactinoma. Surprisingly, we found PCOS patients with prolactin levels greater than 100 ng/mL and acromegaly or drug-induced hyperprolactinemia with prolactin levels greater than 200 ng/mL. In our study, unlike the literature, macroprolactinemia can be seen alone or together with other pathologies. Except for macroprolactinoma, it is not possible to diagnose according to prolactin level. Similar to the literature, prolactinoma was the most common cause of hyperprolactinemia. The causes of hyperprolactinemia, in order of decreasing frequency, were determined to be gonodotropinoma, drug-related, PCOS, idiopathic, and acromegaly. The range of prolactin detected in PCOS is given as new information. It was found that the pediatric group and the adult group had a similar etiology and PRL level., Conclusions: A large spectrum of physiologic/pathologic conditions increases the prolactin levels, and prolactin levels may vary from person to person. So, the serum prolactin level alone does not guide a clinical diagnosis or make a differential diagnosis.

Background: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis., Methods: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration., Results: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category., Conclusions: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study., (© 2024. The Author(s).)

Purpose: Non-functioning pituitary adenomas (NFPAs) are often associated with hyperprolactinemia, which is known as the "stalk effect". However, the relationships between hyperprolactinemia and the radiographic characteristics of the tumor that affects the pituitary stalk have not been well characterized. We aimed to identify the differences in the clinical and radiographic characteristics of patients with NFPA, with and without hyperprolactinemia., Methods: We enrolled 107 patients with NFPA and allocated them to hyperprolactinemia and non-hyperprolactinemia groups using two different cut-off values: (1) the upper limit of the normal reference range, adjusted for sex and menopausal status, and (2) the upper quartile across the cohort, and compared their clinical and radiographic characteristics. These analyses were conducted to clarify the relationship between the "stalk effect" and the postoperative change in antidiuretic hormone secretion., Results: The specific radiographic characteristics of the patients included the presence of a cystic or hemorrhagic tumor and the presence of pituitary stalk deviation, which were more frequent in the patients with hyperprolactinemia. Interestingly, the incidence of postoperative transient diabetes insipidus was statistically significantly higher in the hyperprolactinemia group (≥40 ng/mL) and in the group with radiologic evidence of stalk deviation, which were shown to be independent risk factors on multivariate analysis., Conclusion: The presence of a "stalk effect" was associated with a higher risk of postoperative transient diabetes insipidus, reflecting perioperative pituitary stalk dysfunction following NFPA surgery, especially in patients with serum prolactin concentrations ≥40 ng/mL and radiologic evidence of stalk deviation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

The present paper aims to analyze and discuss the available evidence supporting the relationship between male sexual function and elevated prolactin (PRL) levels (HPRL). Two different sources of data were analyzed. Clinical data were derived from a series of patients seeking medical care for sexual dysfunction at our Unit. Out of 418 studies, 25 papers were used with a meta-analytic approach to evaluate the overall prevalence of HPRL in patients with erectile dysfunction (ED) and to study the influence of HPRL and its treatment on male sexual function. Among 4215 patients (mean age 51.6 ± 13.1 years) consulting for sexual dysfunction at our Unit, 176 (4.2%) showed PRL levels above the normal range. Meta-analytic data showed that HPRL is a rare condition among patients with ED (2 [1;3]%). Either clinical and meta-analytic data confirm a stepwise negative influence of PRL on male sexual desire (S = 0.00004 [0.00003; 0.00006]; I = -0.58915 [-0.78438; -0.39392]; both p < 0.0001 from meta-regression analysis). Normalization of PRL levels is able to improve libido. The role of HPRL in ED remains inconclusive. Data from a meta-analytic approach showed that either HPRL or reduced T levels were independently associated with ED rates. The normalization of PRL levels only partially restored ED. HPRL did not significantly contribute to ED severity, in our clinical setting. In conclusion, treating HPRL can restore normal sexual desire, whereas its effect on erection is limited., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To describe a series of cases with pharmacological hyperprolactinemia in primary care setting and the prolactin levels, clinical implications of different causes of pharmacological hyperprolactinemia., Methods: A retrospective study of all patients with detected hyperprolactinemia in hormonal studies was performed between 2019 and 2020 in 20 Spanish primary care centers. Hyperprolactinemia is defined as a serum prolactin >19.4ng/ml in men and >26.5ng/ml in women. Four pharmacological causes of hyperprolactinemia were established: (i) oral contraceptives (OCPs) and other hormonal treatments; (ii) antipsychotics and antidepressants; (iii) other drugs (calcium antagonists, antiemetics, H2 antihistamines, opioids, and anabolic agents); and (iv) hyperprolactinemia due to several drugs., Results: From a sample of 501 patients with elevated serum prolactin, 39.4% (n=162) had pharmacological hyperprolactinemia. The most common cause of pharmacological hyperprolactinemia in women was OCPs (n=61) while in men antipsychotics/antidepressants (n=21). In the cases of hyperprolactinemia due to antipsychotics/antidepressants, the prolactin levels were significantly higher in patients taking classical antipsychotics than in those taking second-generation antipsychotics (80.0±43.17 vs. 50.7±28.66 ng/dL, P=0.035). The antidepressant/antipsychotic group showed hyperprolactinemia-related symptoms more frequently than the group of other treatments (58.9% vs. 32%, P=0.001). The concomitant use of several drugs caused hyperprolactinemia-related symptoms more frequently than one drug alone (73% vs. 44%, P=0.031)., Conclusion: In this series of cases, drugs represented the 39.4% of the causes of hyperprolactinemia. The most common drugs were OCPs in women and antipsychotics/antidepressants in men. Antidepressants/antipsychotics were drugs that caused the greatest elevation of the prolactin levels and showed hyperprolactinemia-related symptoms more frequently., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities., Methods: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out., Results: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women., Conclusion: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice., (© 2024. The Author(s).)

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism., (© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Purpose: Studies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients., Methods: This is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery., Results: Hyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); p =0.012], hypogonadism [HR=1.32 (1.01-1.73); p =0.047], and hypothyroidism [HR=3.49 (1.90-6.44); p <0.001] had higher recurrence rates than those without. Age, sex, body mass index, tumor size, invasiveness, prolactin staining, ki-67 index, and GH/IGF-1 levels were significantly correlated with preoperative hypopituitarism and hyperprolactinemia. At median 34-month follow-up after surgery, hyperprolactinemia in 95% and axis-specific hypopituitarism in 54%-71% of patients recovered, whereas new-onset hypopituitarism (hypogonadism, 6.2%; hypothyroidism, 4.0%; adrenal insufficiency, 3.2%) was also diagnosed. A shorter tumor diameter was associated with the normalization of preoperative hyperprolactinemia after surgery. Cavernous sinus non-invasion, a shorter tumor diameter, cure at follow-up, and a lower GH nadir level were associated with the improvement of preoperative hypopituitarism after surgery. A larger tumor diameter was associated with the newly developed hypopituitarism after surgery., Conclusion: Hyperprolactinemia and hypopituitarism are common among acromegaly patients and predict worse surgical outcomes. After surgery, improvement and worsening of HPEO axes function co-exist. Correlated factors are identified for clinical management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Zhang, Zhang, Wang, Gao, Yao, Deng, Bao, Feng, Xu, Yang, Lian, Wang, Ma and Xing.)

Introduction: Cabergoline is the treatment of choice for prolactinomas. However, 10-20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas., Subjects and Methods: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26-61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38-386 ng/mL) under cabergoline treatment (2-7 mg/week) for at least 6 months (6-108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0-2.5 g v.o./day) was given according to patients' tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30-60 days) and long-term (120-180 days) metformin treatment., Results: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30-60 days, and at 120-180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0-2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin., Conclusion: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels., (© 2021 S. Karger AG, Basel.)

Objective: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation., Methods: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment., Results: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%)., Conclusion: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021 John Wiley & Sons Ltd.)

Background: Prolactin (PRL) is a protein hormone secreted by the anterior pituitary gland that regulates pituitary hormones. Hyperprolactinemia (HPRL), a pathological phenomenon of excessive PRL, can cause infertility in severe cases and is currently treated mainly with Western drugs, such as bromocriptine, a dopamine agonist (DA). Unfortunately, DAs produce psychological side effects which limit their long-term use. Traditional Chinese medicine (TCM) has minimal side effects and good results spanning many years of research. The combined treatment of TCM and Western medicine may enhance treatment efficacy and improve the long-term prognosis in HPRL. To analyze the effects of Bu-shen-zhu-yun decoction (BSZY-D) combined with bromocriptine on serum hormones, anxiety, and pregnancy in hyperprolactinemic infertile patients., Methods: One hundred patients diagnosed with HPRL infertility from June 2020 to June 2021 in the gynecology clinic of Jiangsu Provincial Hospital of Traditional Chinese Medicine were selected and grouped by envelope method. After excluding patients who withdrew or missed visits, 37 cases assigned to the control group were treated with bromocriptine, and 40 cases assigned to the observation group were treated with bromocriptine combined with BSZY-D. The patients' PRL and kisspeptin (KP) serum indexes, improvements in infertility, Anxiety Self-Assessment Scale (SAS) scores, and improvements in the Insomnia Severity Index Scale (ISI) scores were compared between the two groups., Results: At 3 and 6 months of treatment, serum PRL, SAS, and ISI scores were significantly lower, and serum KP was significantly higher in the observation group than in the control group (P<0.05). During the study period, the pregnancy rates were 62.50% (25/40) and 37.84% (14/37) in the observation and control groups, respectively. The observation group also had significantly fewer early miscarriages [10.00% (4/40) vs. 32.43% (12/37)] and less adverse reactions [7.50% (3/40) vs. 24.32% (9/37)] than the control group (all P<0.05)., Conclusions: The combination of bromocriptine with BSZY-D was superior to bromocriptine alone in treating HPRL and HPRL-related infertility, which also demonstrated a positive effect on patients' sleep and low mood.

Background: Macroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG)., Methods: Post-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared., Results: Reference intervals for monomeric prolactin in females and males were 3.4-18.5 and 2.7-13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9 %) patients while the other 879 (77.1 %) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05)., Conclusions: The prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy., (© 2021. The Author(s).)

Most prolactinomas are diagnosed in women of reproductive age and are generally microadenomas. Prolactinomas diagnosed in postmenopausal women are less common and are not usually associated with the typical syndrome induced by prolactin excess, including infertility and oligo-amenorrhea. This implies that the diagnosis of prolactinomas after menopause may be delayed and require greater clinical effort. Limited data are available on the management and prognosis of prolactinomas in postmenopausal women. However, the physiologic decline of prolactin levels during menopause and the lack of fertility concerns, which represent specific indications for medical treatment with dopamine agonists, might require a careful reassessment of therapeutic management in such patients. Postmenopausal women with microprolactinoma may be successfully withdrawn from medical therapy with dopamine agonists, whereas in those with macroprolactinomas greater caution is advisable before dopamine agonists are discontinued, considering the potential, although rare, tumor enlargement. This review focuses on the diagnostic challenges and therapeutic management of prolactinomas in postmenopausal women., (Copyright © 2021. Published by Elsevier B.V.)

Background: Prolactin (Prl) is a pleiotropic hormone initially described for its regulation of lactation in mammals but later associated with metabolic and immune homeostasis, stress, inflammatory response and human behavior. Its regulation through dopamine receptors highlights its importance in psychiatry mostly because hyperprolactinemia is a common secondary side effect of dopamine antagonists. Despite its undeciphered patho-physiological mechanisms, hyperprolactinemia in naïve psychosis patients has been widely described. Its consequences might underlie the increased morbidity and early mortality found in naïve subjects as described in the general population where prolactin values have been correlated with inflammatory, immune and metabolic parameters., Methods: We aimed to evaluate the correlation between prolactin values and other biochemical parameters (C-reactive Protein-CrP, blood cell count, lipid and hepatic profile, fasting glucose) in a cohort of first episode psychosis naïve subjects (N = 491) stratified by sex. Regression analyses with confounders were performed to evaluate the association., Findings: Prl displayed significant correlations with C-Reactive Protein (CrP), Low-Density Lipoprotein (LDL), Aspartate Transaminase (AST) for females and High-Density Lipoprotein (HDL) and eosinophil count for males. However, and despite previous specific sex correlations, significant associations were described for CrP, HDL, LDL, AST and ALT without sex interaction and despite confounders such as age, Body Mass Index or smoking status., Conclusions: Our results show a specific relation of Prl with immune and metabolic parameters describing a heterogeneous pattern. Our results suggest that prolactin might underlie the excess of morbidity and early mortality in naïve patients through a specific pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To optimize a screening method for macroprolactinemia and improve the accuracy of free prolactin (freePRL) detection., Method: Overall efficiency, calculated as the product of the immunoglobulin G (IgG) precipitation rate and the freePRL recovery rate were employed to determine the concentration of the precipitant polyethylene glycol (PEG). Then, an optimized screening method for macroprolactinemia was established. The concentrations of freePRL, obtained by gel filtration chromatography (GFC), from 66 cases were used as the gold standard, and the sensitivity, specificity, accuracy and precision of the optimized and traditional methods for detecting macroprolactinemia were compared., Results: (1) The IgG precipitation rate increased with increasing PEG6000 concentration, and the freePRL recovery rate decreased with increasing PEG6000 concentration; the overall efficiency first increased and then decreased. When the IgG concentrations in the mixture were 10 g/L, 25 g/L and 40 g/L, the concentrations of PEG6000 with the highest overall efficiency were 24%, 20% and 18%, respectively. (2) The effect of high and low IgG on the overall efficiency was 4.7% when using 20% PEG6000, which was lower than the effects when using 18% or 24% PEG6000 (9.2% and 13.2%). (3) In the optimized method established using 20% PEG6000, the macroprolactin (macroPRL) chromatographic peak disappeared, but the freePRL chromatographic peak was retained. The sensitivity of this macroprolactinemia screening method was 96.7%, and the specificity was 100%. (4) The freePRL concentrations obtained by the optimized method for samples from 30 macroprolactinemia cases and 36 true hyperprolactinemia cases were 15.8 (10.2-21.4) ng/mL and 60.2 (51.8-79.9) ng/mL; the concentrations were similar to those obtained using the GFC method (16.3 (11.9-27.2) ng/mL and 68.1 (49.5-92.9) ng/mL, respectively (p > 0.05)) and higher than those obtained using the traditional method (9.1 (6.1-17.6) ng/mL and 51.4 (43.7-71.9) ng/mL), respectively, p < 0.05)). (5) The relative deviation between the optimized and GFC methods was -7.0%, which was significantly lower than the relative deviation between the traditional and GFC methods (-21.4%, p < 0.01). (6) The in-batch coefficients of variation (CVs) for the dual-level quality control materials measured by the optimized method were 1.88% and 1.87%, and the within-laboratory CVs were 2.55% and 2.29%, which were slightly lower than the in-batch CVs (1.93% and 2.81%) and within-laboratory CVs (2.75% and 2.81%) measured by the traditional method., Conclusion: The established optimized method for screening macroprolactinemia using 20% PEG6000 as a precipitant can completely precipitate macroPRL components and effectively retain freePRL components. Compared with traditional methods, the optimized method is simpler, more accurate and more stable for the quantitative detection of freePRL., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Psychotropic medication treatment can cause elevated serum prolactin levels and hyperprolactinaemia (HPRL). Reports have suggested that aripiprazole may decrease elevated prolactin. The aim of this review was to assess evidence for the efficacy of adjunct aripiprazole in the treatment of psychotropic-induced HPRL. PubMed and Google Scholar were searched to identify randomised placebo-controlled trials (RCTs) of adjunct aripiprazole in patients with HPRL attributed to primary psychotropic medications. Data for individual patients from case studies, chart reviews and open-label studies were also identified and assessed. Six RCTs, with a total of 609 patients, met inclusion criteria. Primary psychotropics included risperidone, haloperidol, paliperidone, fluphenazine and loxapine. Reductions in prolactin from baseline, before the introduction of aripiprazole, were significantly greater for adjunct aripiprazole than for adjunct placebo in all the studies (p = 0.04 to p < 0.0001). Normalisation of serum prolactin levels was significantly more likely with adjunct aripiprazole than adjunct placebo (p = 0.028 to p < 0.001, data from three studies). Improvement or resolution of HPRL-related symptoms (galactorrhoea, oligomenorrhoea, amenorrhoea and sexual dysfunction) were reported in three studies. Prolactin levels decreased in all case reports and in both of two open-label studies; they normalised in 30/41 patients (73.2%) in case studies and 12/29 (41.4%) in the open-label studies. Adjunct aripiprazole was statistically significantly effective in treating elevated serum prolactin levels in six RCTs. Evidence from case reports and open-label studies suggests a degree of effectiveness in most patients.

Dendritic cells (DCs) play key roles in regulating the immune response using the specialized function of processing and presenting antigens. Prolactin (PRL), a hormone produced by the pituitary gland, participates in DC maturation and function. The present study was aimed to determine the frequencies of peripheral blood DC subpopulations of myeloid DC (MDC) and plasmacytoid DC (PDC) in hyperprolactinemic (HPRL) women compared to normal healthy volunteers. This study was conducted on 70 women, including 35 HPRL patients and 35 matched healthy controls, whose PRL serum levels were in the normal range (lower than 25 ng/mL). Serum thyroid-stimulating hormone (TSH) levels were measured in both groups as an indicator of normal thyroid function. The electrochemiluminescence immunoassay method was applied to measure the serum levels of TSH and PRL. The frequencies of MDC and PDC in the peripheral blood samples of both groups were determined by flow cytometry. The mean serum PRL levels in the HPRL patients and healthy individuals were 46.41±21.96 and 13.75±11.19, respectively (p<0.0001); however TSH levels in both groups were similar and within the normal range (0.4-4.5 mIU/mL) (p=0.2). The frequencies of both MDC and PDC subpopulations in the peripheral blood of HPRL patients were significantly lower than they were in the healthy controls. However, the ratio of MDCs/PDCs in HPRL patients was not significantly different between the two groups (p=0.8). Our study revealed that an increased level of serum PRL may lead to a reduction in the number of MDC and PDC subpopulations. These results could help clarify the complex relationship between the immune system and the neuroendocrine axis and may be of potential use in understanding the pathogenesis of endocrine and immune disorders.

Prolactin is a peptide hormone produced in the anterior pituitary, which increase in several physiological and pathological situations. It is unclear if hyperprolactinaemia may affect glycosylation of immunoglobulin G (IgG). Twenty-five patients with hyperprolactinemia and 22 healthy control subjects were included in the study. The groups had similar age and gender distribution. A panel of hormonal and haematological analyses, creatinine, glucose, liver enzymes and immunoglobulins were measured by routine clinical methods. IgG was purified from serum by Protein G Sepharose. Sialic acid was released from IgG by use of neuraminidase followed by quantification on high performance anion-exchange chromatography with pulsed amperometric detection. Tryptic glycopeptides of IgG was analysed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Hormone and immunoglobulin levels were similar in the two groups, except for IgA and prolactin. Significantly higher IgG1 and IgG2/3 galactosylation was found in the patient group with hyperprolactinaemia compared to controls. (A significant correlation between prolactin and IgG2/3 galactosylation (Rs 0.61, p<0.001) was found for samples with prolactin values below 2000 mIU/L. The relative amount of sialylated and bisecting glycans on IgG did not differ between patients and controls. The four macroprolactinaemic patients showed decreased relative amount of bisecting IgG2/3 glycans. Hyperprolactinaemia was found to be associated with increased galactosylation of IgG1and IgG2/3. This may have impact on IgG interactions with Fc-receptors, complement and lectins, and consequently lead to an altered immune response., Competing Interests: The authors have declared that no competing interest exist.

Introduction: High prolactin (PRL) concentrations are found in laboratory test results of patients on majority of antipsychotic drugs. Prevalence rates and degrees of severity of hyperprolactinemia (HPRL) based on PRL concentration may depend on the presence of macroprolactin in the serum. The aim of the study was to investigate the difference between PRL concentrations before and after precipitation of macroprolactin and to examine if there were any changes in the categorization of HPRL between samples prior and after precipitation., Materials and Methods: Total of 98 female patients (median age 33; range 19-47 years) diagnosed with a psychotic disorder, proscribed antipsychotic drugs, and with HPRL were included. Total PRL concentration and PRL concentration after macroprolactin precipitation with polyethylene glycol (postPEG-PRL) were determined by the chemiluminometric method on the Beckman Coulter Access2 analyser., Results: Total PRL concentrations (median 1471; IQC: 1064-2016 mlU/L) and postPEG-PRL concentrations (median 1453; IQC: 979-1955 mlU/L) were significantly correlated using intraclass correlation coefficient for single measurements (mean estimation 0.96; 95%CI 0.93-0.97) and average measurement (mean estimation 0.98; 95%CI 0.96-0.99), and all investigated female patient had HPRL according to PRL and postPEG-PRL concentration. The median PRL recovery following PEG precipitation was 95; IQC: 90-100%. There was substantial agreement (kappa test = 0.859, 95% CI: 0.764-0.953) between the categories of HPRL severity based on total PRL concentrations and postPEG-PRL concentrations., Conclusion: The study demonstrated that HPRL was present in all subjects using the reference interval for total PRL concentration and postPEG-PRL concentration with no significant impact of macroprolactin presence in the serum on the categorization of patients according to severity of HPRL., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Metformin reduced prolactin levels only in women with hyperprolactinemia., Objective: The purpose of this case-control study was to compare metformin action on lactoctrope function between women receiving oral contraceptive pills and women not using hormonal contraception., Methods: The study included two groups of matched women with elevated prolactin levels and new-onset prediabetes or diabetes. The first group consisted of 20 women using oral contraceptive pills for at least 12 months before entering the study, while the second group included 20 patients not using any hormonal contraception. Over the whole study period, all women were treated with metformin (1.7-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, adrenocorticotropic hormone, gonadotropins and insulin-like growth factor-1 were measured at the beginning and at the end of the study (16 weeks later)., Results: Thirty-eight patients completed the study. Metformin reduced plasma glucose levels and improved insulin sensitivity but the latter effect was stronger in women receiving oral contraceptive pills than in women not using any contraception. Although metformin treatment decreased plasma prolactin levels in both study groups, this effect was stronger in women taking oral contraceptive pills. Only in this group of women, metformin increased plasma luteinizing hormone levels. The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity. Metformin did not affect plasma levels of thyrotropin, free thyroxine, free triiodothyronine, follicle-stimulating hormone, adrenocorticotropic hormone and insulin-like growth factor-1., Conclusions: The obtained results suggest that the effect of metformin on overactive lactotropes depends on estrogen levels., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

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.

Not required for Clinical Vignette.

Background: Macroprolactinemia is a condition associated with the presence of large amounts of high molecular weight complexes of prolactin. Despite high prevalence, clinical significance of macroprolactin remains poorly understood., Objective: The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia., Methods: The study population included 11 men with isolated macroprolactinemia, 14 subjects with monomeric hyperprolactinemia and 14 men with prolactin levels within the reference range. Glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined in all included patients., Results: Compared to healthy counterparts, men with isolated macroprolactinemia had higher levels of 2-h postchallenge glucose, hsCRP and fibrinogen, lower levels of 25-hydroxyvitamin D and reduced insulin sensitivity. Patients with monomeric hyperprolactinemia were characterized by increased plasma levels of 2-h postchallenge glucose, triglycerides, uric acid, hsCRP, fibrinogen and homocysteine, reduced insulin sensitivity and decreased plasma concentrations of HDL cholesterol and 25-hydroxyvitamin D. Subjects with isolated macroprolactinemia differed from patients with monomeric hyperprolactinemia in postchallenge plasma glucose, insulin sensitivity, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D. In men with monomeric hyperprolactinemia, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D, while in men with elevated levels of macroprolactin, uric acid, hsCRP, fibrinogen and 25-hydroxyvitamin D correlated with a content of monomeric prolactin or macroprolactin, respectively, as well as with a degree of insulin sensitivity., Conclusions: The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

What Is Known and Objective: Vitamin D administered together with selenomethionine has been reported to markedly reduce thyroid antibody titres in patients with autoimmune thyroiditis. Hyperprolactinaemia exerts a complex pro-inflammatory effect. This study was aimed at investigating whether prolactin excess determines the effect of vitamin D/selenomethionine combination therapy on thyroid autoimmunity., Methods: The study included two age-, body mass index-, hormone- and thyroid antibody-matched groups of young euthyroid women with Hashimoto's thyroiditis: 19 women with mild-to-moderate hyperprolactinaemia and 19 individuals with prolactin levels within the reference range. All participants were then treated with vitamin D (4000 IU daily) and selenomethionine (200 µg daily). Serum titres of thyroid peroxidase and thyroglobulin (TgAb) antibodies, serum levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin and 25-hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis, were determined at baseline and 6 months later., Results and Discussion: All women completed the study. With the exception of prolactin and 25-hydroxyvitamin D levels, there were no differences between the study groups in the investigated parameters. In both study groups, vitamin D/selenomethionine combination therapy reduced thyroid peroxidase and TgAb antibody titres, decreased the free thyroxine:free triiodothyronine ratio and increased 25-hydroxyvitamin D levels and SPINA-GD. The decrease in antibody titres, as well as the improvement in vitamin D status, was more pronounced in subjects with prolactin levels within the reference range than in subjects with hyperprolactinaemia and was inversely correlated with prolactin levels. Moreover, only in normoprolactinaemic women, the treatment reduced thyrotropin levels and increased SPINA-GT., What Is New and Conclusion: The obtained results suggest that hyperprolactinaemia attenuates the impact of vitamin D/selenomethionine combination on thyroid autoimmunity., (© 2020 John Wiley & Sons Ltd.)

Because of contradictory results, clinical significance of elevated levels of macroprolactin (macroprolactinemia) remains unclear. The aim of this study was to investigate whether macroprolactinemia determines levothyroxine action on hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers in women with autoimmune hypothyroidism. The study population included 2 age-, body mass index-, hormone-, and thyroid antibody-matched groups of premenopausal women with untreated autoimmune subclinical hypothyroidism: 15 subjects with coexisting macroprolactinemia and 29 individuals with prolactin levels within the reference range. All included patients were then treated with levothyroxine for 6 months. Serum levels of thyrotropin, free thyroid hormones, prolactin and 25-hydroxyvitamin D, titers of thyroid peroxidase and thyroglobulin antibodies, as well as macroprolactin content were assessed at the beginning and at the end of the study. Except for 25-hydroxyvitamin D levels and macroprolactin content, there were no significant differences between both study arms in the investigated markers. All participants completed the study. In both treatment arms, levothyroxine treatment decreased thyrotropin levels, increased free thyroxine and free triiodothyronine levels, as well as reduced thyroid peroxidase titers, but this effect was less pronounced in women with macroprolactinemia. In women with normal prolactin levels, levothyroxine reduced also thyroglobulin antibody titers and increased 25-hydroxyvitamin D levels. In this group of patients, treatment-induced changes in hormone levels and thyroid antibody titers correlated with treatment-induced changes in 25-hydroxyvitamin D levels. The obtained results suggest that macroprolactin excess attenuates the impact of levothyroxine on hypothalamic-pituitary-thyroid axis activity and thyroid autoimmunity., (© 2020, The American College of Clinical Pharmacology.)

Introduction: Hyperprolactinemia may be due to physiological or pathological causes, and may be asymptomatic or induce hypogonadism, infertility, and/or galactorrhea. It is important to take prolactin samples while avoiding stress, as this may increase prolactin levels. Therefore, our aim was to assess the value of prolactin serial sampling after brachial vein cannulation., Patients and Methods: Sixty-six patients (34.9±11.8 years of age, 92.4% female) with an initial elevated random prolactin level were included. A prolactin sample was drawn at baseline and after a 30min rest., Results: The median referral prolactin level was 37.4ng/ml (interquartile range [IQR* 23.3), the baseline prolactin level at serial sampling was 19.5ng/ml (IQR 8), and the value after a 30min rest was 17.1ng/ml (IQR 7.9). Hyperprolactinemia was not confirmed by serial sampling in 45 patients (68.2%). There were no statistically significant differences in referral prolactin levels between patients with and without confirmed hyperprolactinemia (41.2ng/ml and 36.7ng/ml respectively, p=0.3). Galactorrhea was found in 13.6% of patients, amenorrhea or oligomenorrhea in 28.8%, infertility in 7.6%, erectile dysfunction in 4.6%, and gynecomastia in 3%, while 45.5% were asymptomatic. There were no statistical differences regarding the presence or absence of any of these symptoms and subsequent confirmed hyperprolactinemia. Fifty-seven patients (86.4%) were discharged after the results of the prolactin serial sampling were obtained., Conclusions: Prolactin serial sampling may be a useful test to detect artefactual hyperprolactinemias, thus avoiding unnecessary additional tests and treatments., (Copyright © 2020 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment. Antipsychotic blood levels are influenced by cytochrome P450 enzymes, primarily CYP2D6. Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia. We undertook a systematic review and meta-analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia. The systematic review identified 16 relevant papers, seven of which were suitable for the meta-analysis (n = 303 participants including 134 extreme metabolisers). Participants were classified into four phenotype groups as poor, intermediate, extensive, and ultra-rapid metabolisers. A random effects meta-analysis was used and Cohen's d calculated as the effect size for each primary study. We found no significant differences in prolactin levels between CYP2D6 metabolic groups. Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia. However, statistical power is limited. Future studies with larger samples and including a range of prolactin-elevating drugs are needed.

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The prevalence of hyperprolactinemia among psychiatric patients receiving antipsychotic medications was estimated to be between 30% and 70%. A review of the literature on prolactin and schizophrenia symptoms suggests that the correlation between them is complex and not limited to the adverse effects of antipsychotics. Relations with specific symptom dimensions have not been found consistently across studies. The association between increased prolactin and recurrent episodes of schizophrenia needs to be replicated in larger samples and in a population of female patients. The aim of this study was to find out whether elevated prolactin is related to specific symptoms or dimensions of schizophrenia, which is a heterogenic entity., Subjects and Methods: The sample consisted of 119 consecutively acute admitted women, aged 18 to 45 years with recurrent schizophrenia diagnosed on bases of DSM-5 criteria. Assessment for all the enrolled subjects comprised a psychiatric evaluation and blood draw to determine the prolactin level. Symptoms of schizophrenia were determined using the Positive and Negative Syndrome Scale (PANSS). Data were analyzed by regression analysis and the Independent Samples t Test. Values are given as means ±SD., Results: Hyperprolactinemia was detected in 74.79% patients (n=89), whereas the group without hyperprolactinemia comprised 25.21% of the sample. When plasma prolactin levels and clinical features between groups were compared, there was a statistically significant difference in the negative subscale scores of the PANSS (p=0.0011), positive subscale scores of the PANNS (p=0.0043), general subscale scores of the PANSS (p=0.0226) and total scores of the PANNS (p=0.0003)., Conclusion: There were statistically significant differences in the clinical symptoms between two compared groups in total score and in the positive, negative and general subscores.

Ethnopharmacological Relevance: Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells., Aim: To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action., Materials and Methods: Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-β1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined., Results: Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-β1 and its downstream genes, type II TGF-β receptor, type I TGF-β receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-β1 concentration and hepatic TGF-β1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-β1 signals in MMQ cells were attenuated., Conclusions: This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-β1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper reviews the prevalence, implications, prevention and management of antipsychotic-induced hyperprolactinemia in aging populations. Antipsychotics are indicated mainly for the treatment of psychotic illness but are also used in other conditions. Complications induced by antipsychotics increase with age, due to age-related changes in drug metabolism and excretion. Almost all antipsychotics lead to hyperprolactinemia by blocking dopamine D2 receptors in the anterior pituitary gland, which counteracts dopamine's inhibitory action on prolactin secretion. The main findings of this narrative review are that, though many of the known side effects of high prolactin levels lose their salience with age, the risk of exacerbating osteoporosis remains critical. Methods of preventing antipsychotic-induced hyperprolactinemia in older individuals include using antipsychotic medication (AP) as sparingly as possible and monitoring AP serum levels, regularly measuring prolactin levels, closely monitoring bone density, treating substance abuse, and teaching patients stress management techniques. When hyperprolactinemia symptoms cannot be otherwise managed, adjunctive drugs are available. Potential helpful adjuncts are: dopamine agonists, antipsychotics with partial agonist properties (e.g. aripiprazole), selective estrogen receptor modulators, and metformin. Because a gold standard for prevention/treatment has not been established, clinical decisions need to be made based on safety and individual circumstance., Competing Interests: Declaration of competing interest The authors report no conflicts of interest regarding the content of the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Prolactin (PRL) has direct and indirect effects on bone metabolism. Experimental studies showed that in the presence of high PRL levels bone resorption was increased as well as bone formation was suppressed. Increased PRL levels in humans caused a reduction in sex hormone levels which turn may have detrimental effects on bone. Patients with hyperprolactinemia did have often decreased bone mineral density as well as an increased risk of fractures. Since PRL control may be relevant to bone health it is a clinical open issue the inclusion of skeletal health in future guidelines as indication to proactive screening, prevention and treatment particularly in high risk patients such as hyperprolactinemic women after menopause and patients with drug induced hyperprolactinemia.

Macroprolactinemia frequently causes misdiagnosis, unnecessary investigation and inappropriate treatment in hyperprolactinemic patients. Aim of this study is to investigate the prevalence and clinical characteristics of Thai patients with macroprolactinemia. We performed a cross-sectional study in 56 hyperprolactinemic patients (51 women and 5 men) whose sera were subsequently tested for the presence of macroprolactin. Recovery of less than 40% of serum prolactin after polyethylene glycol (PEG) precipitation was indicative of macroprolactinemia. Our study revealed 19.64% (11/56) of patients with hyperprolactinemia were found to have a preponderance of macroprolactin. All patients with macroprolactinemia were women, of which eight of them were initially diagnosed as idiopathic hyperprolactinemia and mistreated with dopamine agonist medications. Interestingly, neuroradiological abnormalities were reported in three patients with macroprolactinemia, 2 cases with prolactinoma and one case with stalk effect hyperprolactinemia. In conclusion, nearly one-fifth of our patients with hyperprolactinemia have macroprolactinemia. This finding suggests that the diagnostic algorithm of all patients with hyperprolactinemia should include the PEG precipitation test as the initial step. Domain: Endocrinology., Competing Interests: The authors declare no competing interests., (© Phronpan Chutpiboonwat et al.)

Background: Macroprolactin is an immunoglobulin-prolactin complex that is not bioactive in vivo but the prolactin component remains immunoreactive. The complex is a universal source of interference in prolactin immunoassays and commonly results in misdiagnosis of hyperprolactinemia with consequent clinical mismanagement of patients. Removal of macroprolactin by precipitation with polyethylene glycol (PEG) is an effective technique for identifying such patients but unfortunately not universally employed due to the manual nature of the procedure., Methods: We developed a modified PEG precipitation technique using magnetic nanoparticles that we termed Magnetically Assisted PEG Precipitation (MAPP). This procedure was verified against an established PEG precipitation procedure., Results: The MAPP procedure we developed was robust, reproducible, and affords the potential for automation of macroprolactin screening in clinical laboratories. Comparisons of prolactin levels obtained following MAPP in sera from patients with either true hyperprolactinemia or macroprolactinemia generated results comparable to that of conventional PEG precipitation., Conclusions: The MAPP technique yields results comparable to those of traditional PEG precipitation. Elimination of the need for centrifugation affords the possibility of automation and hence more widespread adoption of routine PEG screening by clinical laboratories., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p<0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (>3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

The pituitary hormone prolactin (PRL) regulates a variety of functions beyond reproduction. The association between physiological (pregnancy) and pathological (prolactinoma) hyperprolactinemia and metabolic alterations led to the concept of this hormone being diabetogenic. However, large cohort clinical studies have recently shown that low circulating PRL levels are associated with metabolic disease and represent a risk factor for type 2 diabetes (T2D), whereas high PRL levels are beneficial. Moreover, PRL acts on the pancreas, liver, adipose tissue, and hypothalamus to maintain and promote metabolic homeostasis. By integrating basic and clinical evidence, we hypothesize that upregulation of PRL levels is a mechanism to maintain metabolic homeostasis and, thus, propose that the range of PRL levels considered physiological should be expanded to higher values., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Perturbations in serum prolactin secretion, both over- and underproduction, are observed in zoo African elephants ( Loxodonta africana ) that exhibit abnormal ovarian cycles. Similar prolactin problems are associated with infertility in other species. Pituitary prolactin is held under constant inhibition by a hypothalamic-derived neurotransmitter, dopamine; thus, regulation by exogenous treatment with agonists or antagonists may be capable of reinitiating normal ovarian cycles. This study tested the efficacy of oral administration of cabergoline (agonist) and domperidone (antagonist) as possible treatments for hyperprolactinemia or chronic low prolactin, respectively. Hyperprolactinemic (overall mean prolactin, >30 ng/ml), acyclic elephants were administered oral cabergoline (2 mg, n = 4) or placebo (dextrose capsule, n = 4) twice weekly. Overall mean prolactin concentration decreased in treated females compared with controls (32.22 ± 14.75 vs 77.53 ± 0.96 ng/ml; P = 0.01). Interestingly, overall mean progestagen concentrations also increased slightly ( P < 0.05) in treated females (0.15 ± 0.01 ng/ml) compared with controls (0.07 ± 0.01 ng/ml), but no reinitation of normal cyclic patterns was observed. Chronic low prolactin (overall mean prolactin, <10 ng/ml), acyclic females were orally administered domperidone (2 g/day, n = 4) or placebo (dextrose capsule, n = 4) for 4 wk, followed by 8 wk of no treatment (four cycles) to simulate the prolactin pattern observed in normal cycling elephants. Overall mean prolactin concentrations increased ( P = 0.005) during domperidone treatment (21.77 ± 3.69 ng/ml) compared with controls (5.77 ± 0.46 ng/ml), but progestagen concentrations were unaltered. Prolactin regulation by dopamine was confirmed by expected responses to dopamine agonist and antagonist treatment. Although prolactin concentrations were successfully reduced by cabergoline, and domperidone initiated the expected cyclic prolactin pattern, neither treatment induced normal ovarian activity.

An association between prolactinemia with disability, clinical forms, and sex of patients with multiple sclerosis (MS) remains unclear. The aim of this study was to evaluate the association of prolactin with clinical forms and accumulating disability over time in patients with MS. A longitudinal study was carried out with 101 patients with relapsing-remitting MS (RRMS) and 19 with progressive forms of MS (ProgMS). The disability over time, as well as prolactin and ferritin serum levels were evaluated at baseline (T0), 8-month follow-up (T8), and 16-month follow-up. The disability at T0, T8, and T16 was higher among patients with ProgMS than those with RRMS. Prolactin and ferritin levels did not differ over time between both groups. Initially, prolactin was associated with MS disability. After introducing age and sex, the effects of prolactin on disability were no longer significant. Prolactin was associated with age and sex, whereby age was positively associated with disability. In the same way, after introducing age and sex, the effects of diagnosis on prolactin levels, as well as the association between prolactin and ferritin, were no longer significant (P = 0.563 and P = 0.599, respectively). Moreover, 21.6% of the variance in the disability was predicted by age (P < 0.001), and sex (P = 0.049), while prolactin was not significant. In conclusion, the effects of prolactin on the disability and clinical forms of MS patients may be spurious results because those correlations reflect the positive associations of age with the disability and the negative association of age with prolactin.

Background: Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis., Methods and Findings: The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (β = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (β = -0.23, p<0.003), and the duration of psychosis over 10 years (β = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for., Conclusions and Relevance: Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels., Competing Interests: The authors have declared that no competing interests exist.

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case-control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55-3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone-binding globulin adrenocorticotropic hormone, insulin-like growth factor-1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment-induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objective: To demonstrate how effectively aripiprazole can be utilized to manage antipsychotic-induced hyperprolactinemia., Methods: The files of 3 female patients with a history of psychotic illness and hyperprolactinemia who were treated at a state hospital between February 2018 and May 2019 were retrospectively analyzed. All were found to have elevated prolactin levels and underwent treatment with aripiprazole in addition to their concomitant medications., Results: In general, the addition of aripiprazole to the treatment regimen of each of the patients corresponded to a decline in their serum prolactin levels., Conclusions: Hyperprolactinemia is frequently observed in patients treated with antipsychotic medications. Low-dose treatment with aripiprazole may offer a relatively rapid relief from sustained hyperprolactinemia and associated adverse effects even after a long-acting injectable is discontinued., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Methods: Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment., Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache., Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma., Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms., Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients., Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Background: One of the hypothalamus-pituitary axis hormones which may play a crucial role in pathophysiology of migraine is prolactin which is secreted from anterior pituitary gland and synthesized by various immune system cells as well. Whether prolactin blood levels can affect the migraine pathogenesis is an open question. Therefore, investigating prolactin circulatory levels in migraineurs may pave the way to underpin the mechanisms of migraine pathophysiology at biochemical levels. In the current investigation, the prolactin blood levels in the migraine subjects were investigated using systematic review and meta-analysis., Methods: Using online and specialized biomedical databases including Google Scholar, Medline, Pubmed, Pubmed Central, Embase, and Scopus, without the beginning date restriction until Feb 2019, the systematic review retrieved 11 publications in this systematic review after fulfilling for the inclusion and exclusion criteria. For heterogeneity, extent calculation statistical testing was applied. In the present study, the levels of circulatory prolactin in migraineurs assessed using standardized mean difference (SMD) as the effect size., Results: Q quantity and I 2 % statistic index showed a high heterogeneity in the 13 selected publications (188.370 and 92.568, respectively) and random-effects model was chosen for further analyses. The meta-analysis on a total number of 460 migraineurs and 429 healthy controls found that the weighted pooled SMD for the effects of prolactin blood concentrations on migraine pathogenesis was as follows: SMD = 1.435 (95% confidence interval, 0.854-2.015)., Conclusion: The current investigation presents evidence that prolactin blood levels are higher in migraineurs than healthy subjects.

Premenopausal women with macroprolactinemia are characterized by increased cardiometabolic risk. No previous study has investigated the impact of any lipid-lowering agent on circulating levels of cardiometabolic risk factors in patients with elevated macroprolactin content. We studied 2 groups of women matched for age, body mass index, plasma lipids, and blood pressure: 12 women with macroprolactinemia and 14 women with prolactin levels within the reference range. Because of coexistent isolated hypercholesterolemia, all subjects were then treated with atorvastatin (20 mg daily). Glucose homeostasis markers, plasma lipids, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before entering the study and 6 months later. The treatment arms differed in baseline values of hsCRP and 25-hydroxyvitamin D, as well as in insulin sensitivity. Atorvastatin decreased total and low-density lipoprotein cholesterol levels stronger in women without than in women with macroprolactinemia. In normoprolactinemic women, atorvastatin decreased circulating levels of uric acid, hsCRP, fibrinogen, homocysteine, and increased concentrations of 25-hydroxyvitamin D, whereas in women with macroprolactinemia the drug decreased levels of hsCRP and homocysteine, as well as impaired insulin sensitivity. Both study groups differed in post-treatment insulin sensitivity and post-treatment values of prolactin before polyethylene glycol precipitation, macroprolactin, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. In conclusion, the obtained results suggest that macroprolactinemia may attenuate cardiometabolic effects of atorvastatin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To characterize a cohort of elderly men with prolactinomas and their response to treatment., Methods: We have identified 28 elderly men diagnosed after the age of 65 with prolactinomas at seven different endocrine clinics in Israel. A retrospective electronic chart review identified a control group of 76 younger men with macroprolactinomas treated in one of the centers., Results: Mean age at diagnosis was 71.3 ± 5.6 (range 65-86) years, and current age 76.6 ± 7.5 years. Initial complaints leading to diagnosis included sexual dysfunction in 17 males (61%), headaches in two patients (7%), and visual abnormalities in two (7%). Three men presented with osteoporosis. Ten patients (36%) were diagnosed incidentally following brain imaging for unrelated reasons. Seventeen patients (61%) had macroadenoma, while eleven (39%) presented with a microadenoma or no visible adenoma. Mean prolactin (PRL) at presentation was 1594 (median 382; range 50-18,329) ng/ml. Testosterone was low in 21 men. Patients were treated with cabergoline (max dose, 1.1 ± 0.5 mg/week), except for one given bromocriptine; none required pituitary surgery or radiotherapy. Treatment normalized PRL in 24 patients, and in three men PRL suppressed to <2 ULN. Fifteen men normalized testosterone, three improved without normalization, and in three the normal baseline level increased. After a mean follow-up of 5.3 years, 14/15 patients harboring a macroadenoma showed significant adenoma shrinkage. Most patients reported improvement of low libido/erectile dysfunction. In the control group 60 men (79%) achieved PRL normalization., Conclusions: Elderly men with prolactinomas are diagnosed incidentally in 36% of cases. Long-term medical therapy is successful, achieving biochemical remission, adenoma shrinkage, and clinical improvement in almost all patients.