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.

Sex-specific differences in the clinical profile among psychiatric patients with pulmonary Embolism: a hospital-based retrospective study.

BACKGROUND: Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE. METHODS: This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences. RESULTS: Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05). CONCLUSION: PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

Clinical and radiographic characteristics of patients with non-functioning pituitary adenomas categorized according to their serum prolactin concentration: novel predictors of postoperative transient diabetes insipidus following surgery.

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.

Diagnostic workup of endocrine dysfunction in recurrent pregnancy loss: a cross-sectional study in Northeast China.

Objective: To evaluate the prevalence of abnormal endocrine dysfunction for recurrent pregnancy loss (RPL) amongst patients with two versus three or more pregnancy losses. Methods: This cross-sectional study retrospectively collected pre-pregnancy data of 537 women diagnosed with RPL in Shengjing Hospital of China Medical University from 2017 to 2022, including the baseline data of patients and the test results of endocrine factors. Several endocrine dysfunction included in this study were: thyroid dysfunction, obesity, hyperprolactinemia, polycystic ovary syndrome and blood glucose abnormality. Furthermore, vitamin D level were collected to study its relationship with endocrine dysfunction. Finally, we subdivided the patients according to the number of previous pregnancy loss and compared the prevalence of endocrine dysfunction between subgroups. Results: Among 537 RPL patients, 278 (51.8%) patients had abnormal endocrine test results. The highest incidence of endocrine dysfunction was thyroid dysfunction (24.39%, 131/537), followed by hyperprolactinemia (17.34%, 85/490), obesity (10.8%, 58/537), polycystic ovary syndrome (10.50%, 56/533), and abnormal blood glucose (5.29%, 27/510). Only 2.47%(13/527) of patients have vitamin D level that reach the standard. After subdividing the population according to the number of pregnancy loss, we did not find that the incidence of endocrine dysfunction (P=0.813), thyroid dysfunction (P=0.905), hyperprolactinemia (P=0.265), polycystic ovary syndrome (P=0.638), blood glucose abnormality (P=0.616) and vitamin D deficiency (P=0.908) were different among patients with two versus three or more pregnancy losses. However, obesity (P=0.003) was found more frequently observed in patients with more times of pregnancy loss. Conclusion: The prevalence of endocrine dysfunction in RPL population is high. There is no difference in the prevalence of endocrine dysfunction, except for obesity, among patients with two or more pregnancy losses, which may suggest investigations of endocrine dysfunction when patients have two pregnancy losses.

The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS.

Introduction: Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes. Methods: This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia. Results: The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes. Conclusion: Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.

Epidemiological and clinical profiles of Saudi patients with hyperprolactinemia in a single tertiary care center.

BACKGROUND: Prolactin is a hormone of the pituitary gland whose main function is the production of milk. Hyperprolactinemia is defined as an increase in prolactin levels above 25 µg/L in women and 20 µg/L in men. Causes of hyperprolactinemia include pituitary tumors, especially prolactinomas. Hyperprolactinemia can manifest clinically with a variety of symptoms, including galactorrhea and menstrual irregularities in women and erectile dysfunction in men. There are limited data on the epidemiology of hyperprolactinemia in the Middle East region. OBJECTIVES: Description of the epidemiology and clinical features of hyperprolactinemia in a cohort from Saudi Arabia. DESIGN: Medical record review SETTING: Tertiary medical center in Riyadh PATIENTS AND METHODS: The study included adult patients with hyperprolactinemia in King Abdulaziz Medical City in Riyadh. The patients were treated in endocrinology clinics from 2015 to 2019. Patients of both sexes older than 14 years were enrolled in the study. Patients with insufficient follow-up were excluded. Data were collected on demographic characteristics, symptoms, prolactin level, cause of high prolactin level, and treatment. MAIN OUTCOME MEASURES: The frequency of different etiologies and symptoms in patients with hyperprolactinemia. SAMPLE SIZE: 295 patients RESULTS: The majority of patients with hyperprolactinemia were female 256 (86.8%). Hyperprolactinemia was diagnosed more frequently in patients in the age groups 21-30 years (42.6%) and 31-40 years (24.1%). The majority of the study population was obese or overweight: 136 (46.3%) and 74 (25.2%), respectively. Most of the cases were symptomatic (192, 65.1%). In women, the most common symptom was oligomenorrhea (35%). In men, infertility and erectile dysfunction were the most common clinical symptoms (50% and 44.7%, respectively). Idiopathic causes were the most common etiology (108, 36.6%), followed by pituitary adenomas (81, 27.5%). The majority of patients were treated (184,62.4%), with cabergoline being the most commonly used medication (173, 94.0%). CONCLUSION: The demographic and clinical presentations and causes of hyperprolactinemia in male and female Saudi patients were similar to that in studies in other populations. LIMITATIONS: Single-center retrospective chart review study. CONFLICT OF INTEREST: None.

[Ovulatory disorders under "common therapeutic principle for different diseases": essence of "Tiangui" and relationship with ovulation disorders].

The essence of the "common therapeutic principle for different diseases"(Yibing Tongzhi in Chinese for short) is the disease-syndrome combination, which is the classic mode of understanding and treating diseases in traditional Chinese medicine(TCM). This study holds the view that Yibing Tongzhi is the optimal treatment mode of ovulation disorders since ovulation disorders have the common pathogenesis, i.e., "kidney-Tiangui(reproduction-stimulating essence)-Chongren(thoroughfare and conception vessels)-uterus axis" disorder. Kidney is an important basis of the reproductive axis, where kidney essence, kidney yang, and kidney Qi are the key substances and driving forces promoting the operation of the reproductive axis. Chongren is an important transmission path. "Tiangui", the upstream substance related to the heart, brain and kidney with a connecting effect, plays a key role in the ovulation mechanism and is a representative of the reproductive axis function. There are four common Tiangui abnormalities in ovulatory disorders, including hypomenorrhea, yin and yang deficiency, abnormal exuberance of extreme yin, and abnormal phase. The dynamic changes of "Tiangui" can induce different diseases, such as polycystic ovary syndrome and hyperprolactinemia, which ultimately lead to anovulatory infertility. Therefore, with "Tiangui" as the entry point, it is the treatment trend for ovulatory disorders under Yibing Tongzhi.

The prevalence of hyperprolactinaemia in subfertile ovulatory women and its impact on fertility treatment outcome.

Subtle hyperprolactinaemia is not an uncommon finding in ovulatory subfertile women. The objective of this study is to evaluate the prevalence of hyperprolactinaemia in subfertile ovulatory and oligo-anovulatory women, and to determine if hyperprolactinaemia influences fertility treatment outcome. All women (n = 1010) who attended the fertility clinic of a UK tertiary hospital during 2015-2019 were included. Out of 804 eligible women analysed, 575 women (71.5%) were ovulatory and 229 (28.5%) were oligo-anovulatory. Prevalence of hyperprolactinaemia was higher in the ovulatory group than in the oligo-anovulatory group (26.8% vs. 14.4%; OR: 2.2; 95% confidence interval (CI): 1.4-3.2). On sub-group analysis, the prevalence of mild, moderate and severe hyperprolactinaemia was 23.0%, 3.7% and 0.2% in ovulatory women and 11.8%, 1.7% and 0.9% in oligo-anovulatory women. Mild hyperprolactinaemia was found to be more prevalent in the ovulatory group (OR: 2.2; 95%CI: 1.4-3.5). Ongoing pregnancy/livebirth rates were similar between hyperprolactinaemic and normoprolactinaemic women (42.8% vs. 46.7%). Hyperprolactinaemia did not have an impact on ongoing pregnancy/livebirth rates in both ovulatory and oligo-anovulatory women (OR:0.8; 95%CI: 0.5-1.1; OR: 1.2; 95%CI: 0.6-2.5, respectively). Hyperprolactinaemia is prevalent among ovulatory women, although most had mildly raised clinically insignificant levels. Elevated prolactin levels in ovulatory women do not seem to impact on pregnancy outcome. Impact StatementWhat is already known on this subject? Prolactin has been linked to ovulation and fertility. Prolactin testing is not generally recommended for subfertile women with regular menstrual cycles, which is a surrogate marker of ovulation. However, some clinicians, particularly in the general practice, still perform prolactin test as part of baseline endocrine profile.What do the results of this study add? Prevalence of hyperprolactinaemia in subfertile ovulatory women was 26.8% (154/575), of which 86% (132/154) were mild. Further, the livebirth/ongoing pregnancy rates were similar between hyperprolactinaemic and normoprolactinaemic women. Prolactin being a sensitive hormone, responsive to even minimal stress and its high levels not influencing clinical pregnancy outcome, prolactin measurement is not needed in women having regular menstrual cycles.What are the implications of these findings for clinical practice and/or further research? Hyperprolactinaemia was not uncommon in ovulatory women, although most had mildly elevated levels. Hyperprolactinaemia did not have any impact on fertility treatment outcome. Serum prolactin should not be tested in ovulating women, as mild elevations are commonly present and have no clinical significance.

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.

Sex and age differences among patients with acromegaly.

INTRODUCTION: Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations between sex and age at the time of diagnosis and the course of acromegaly have been a focus of debate. OBJECTIVES: The aim of our study was to evaluate the association between sex and age at the time of diagnosis of acromegaly and the clinical features, biochemical status, severity of the disease, and comorbidities. PATIENTS AND METHODS: This was a single­center study conducted in a group of consecutive patients with acromegaly and no family history of PitNETs. The participants were divded into 2 subgroups according to sex (male, female) and 3 subgroups according to age at the time of diagnosis: i) younger (≤40 years), ii) middle­aged (41-59 years), and iii) elderly patients (≥60 years). RESULTS: Our study included 101 patients (41 men, 60 women) who met the eligibility criteria. The mean (SD) age at the time of diagnosis was 47.3 (14.1) years and the median diagnostic delay was 5 years (interquartile range, 3-10). Age at the time of diagnosis and diagnostic delay were not statistically different in men and women. Levels of insulin­like growth factor 1 (IGF­1) above the upper limit of age­adjusted normal range (%ULN IGF­1) were greater in men than in women (mean [SD], 174.8% [98.9%] vs 109.4% [66.6%]; P = 0.002), while there was no significant difference in terms of %ULN IGF­1 between the age groups. Median basal and nadir GH levels did not differ between the sexes. Men presented with hypogonadism more frequently than women (54% vs 26%; P = 0.005). Hyperprolactinemia, hypogonadism, and macroadenoma were more frequently observed in the younger patients than in the middle­aged and elderly individuals (all P <0.05). CONCLUSIONS: According to our results, hypogonadism and greater IGF­1 values were more frequently observed in men with acromegaly. Hyperprolactinemia, hypogonadism, and macroadenoma were more frequent in patients with acromegaly aged 40 years or younger.

Sexual dysfunction in people treated with long-acting injectable antipsychotics in monotherapy or polypharmacy: a naturalistic study.

Sexual dysfunction, psychosis, and antipsychotics are known to be related, but the precise association between them is still unknown. Most evidence about the prevalence of sexual dysfunction in people treated with antipsychotic drugs comes from studies with restrictive samples. That is why our main objective was to determine the prevalence of sexual dysfunction in a real-life sample of outpatients treated with antipsychotics, considering gender. A cross-sectional naturalistic study was developed, including people treated with long-acting injectable antipsychotics, with or without other psychotropic drugs. Participants were interviewed to assess sexual satisfaction through a Likert scale (0 to 10) and the presence of sexual dysfunction (the Psychotropic-Related Sexual Dysfunction Questionnaire, PRSexDQ-SALSEX). The participants also had a blood test to determine prolactin (men and women) and testosterone levels (men only). A total of 131 people participated in the study (90 men and 41 women). Some extent of sexual dysfunction was found in 62.2% of men and 51.2% of women. The most frequent sexual dysfunction symptom for both genders was the loss of libido (45%). Hyperprolactinemia was present in 56% of men and 61% of women. The presence of sexual dysfunction was associated with higher doses of antipsychotics, hyperprolactinemia, and smoking in men and with smoking and hyperprolactinemia in postmenopausal women. This study provides real-life evidence of sexual dysfunction and hyperprolactinemia in persons treated with long-acting injectable antipsychotics segregated by gender. The high rates of sexual dysfunction and hyperprolactinemia detected corroborate the need to consider these aspects in clinical practice.

Occurrence of macroprolactinemia in schizophrenia patients treated with risperidone or amisulpride.

OBJECTIVE: To investigate macroprolactinemia caused by antipsychotics and its clinical significance. METHODS: A total of 133 patients with schizophrenia were selected, all of whom were treated with either risperidone or amisulpride alone. The levels of total prolactin (T-PRL) and macroprolactin (MPRL) were measured before treatment as well as the second, fourth, and sixth weeks of treatment. RESULTS: After 2 weeks of treatment, 75.09% (100/133) of the patients met the diagnostic criteria for hyperprolactinemia, the incidence of macroprolactinemia was 43% (43/100), and MPRL levels were positively correlated T-PRL levels. CONCLUSION: Risperidone and amisulpride caused hyperprolactinemia and macroprolactinemia; thus, detection of MPRL in the clinical setting should be performed as this phenomenon appears early in treatment (the second week) and continues, that can avoid unnecessary examination and treatment for asymptomatic patients with macroprolactinemia.

Establishment of reference intervals of monomeric prolactin to identify macroprolactinemia in Chinese patients with increased total prolactin.

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.

Endocrine contribution to the sexual dysfunction in patients with advanced chronic kidney disease and the role of hyperprolactinemia.

In this study, we investigated the prevalence of sexual dysfunction among males with advanced chronic kidney disease and the effect of treating hyperprolactinemia among these patients. In this prospective study, patients were assessed with history, physical examination, hormonal assessment, and two questionnaires, IIEF and AIPE. Patients with hyperprolactinemia received treatment with cabergoline 0.5 mg once per week for 6 months and were re-evaluated. A total of 102 patients were included in this study, 75 (73.53%) were on hemodialysis, 13 (12.75%) on peritoneal dialysis and 14 (13.73%) on medical treatment alone. Ninety (88.24%) patients had premature ejaculation, 85 (83.33%) had anything from mild-to-moderate-to-severe erectile dysfunction. The incidence of hypogonadism and hyperprolactinemia was 34.4%. Patients treated with cabergoline (n = 26) showed a significant increase in LH levels (p = .003) and a significant decrease in prolactin levels (p = .003). Testosterone levels and the incidence of erectile dysfunction or premature ejaculation did not improve significantly. There is a high incidence of sexual dysfunction among patients. Treatment of hyperprolactinemia is effective in correcting prolactin levels, but does not improve erectile dysfunction or premature ejaculation. Therefore, treating hyperprolactinemia is not an overall effective treatment for erectile dysfunction in these patients.

Vitamin D status determines the impact of metformin on circulating prolactin levels in premenopausal women.

WHAT IS KNOWN AND OBJECTIVE: Metformin was found to normalize secretory function of overactive pituitary cells. Its effect on circulating thyrotropin levels was more pronounced in women receiving exogenous vitamin D. The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia. METHODS: The study population consisted of three groups of women with prediabetes and elevated prolactin levels: vitamin D-naïve women with vitamin D insufficiency (group 1; n = 19), women receiving vitamin D preparations because of vitamin D deficiency (group 2 n = 20), as well as vitamin D-naïve women with normal vitamin D status (group 3 n = 23). All participants were then treated with metformin (2.55-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin were determined at baseline and six months later. RESULTS AND DISCUSSION: At baseline, prolactin levels were higher in group 1 than in the remaining groups of patients. Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3. Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels. The impact on prolactin levels correlated with 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin D. WHAT IS NEW AND THE CONCLUSION: The results of the current study suggest that the impact of metformin on secretory function of overactive lactotropes depends on the vitamin D status of patients.

Efficacy and safety in the treatment of hyperprolactinemia: A systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. METHODS: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA). RESULTS AND DISCUSSION: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA. WHAT IS NEW AND CONCLUSION: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.

A Focused Review of the Metabolic Side-Effects of Clozapine.

The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates of extrapyramidal symptoms and hyperprolactinemia compared to other antipsychotic drugs. However, clozapine tends to be underutilized in clinical practice due to a number of disabling and serious side-effects. These are characterized by a constellation of metabolic side-effects which include dysregulation of glucose, insulin, plasma lipids and body fat. Many patients treated with clozapine go on to develop metabolic syndrome at a higher rate than the general population, which predisposes them for Type 2 diabetes mellitus and cardiovascular disease. Treatments for the metabolic side-effects of clozapine vary in their efficacy. There is also a lack of knowledge about the underlying physiology of how clozapine exerts its metabolic effects in humans. In the current review, we focus on key studies which describe how clozapine affects each of the main symptoms of the metabolic syndrome, and cover some of the treatment options. The clinical data are then discussed in the context of preclinical studies that have been conducted to identify the key biological substrates involved, in order to provide a better integrated overview. Suggestions are provided about key areas for future research to better understand how clozapine causes metabolic dysregulation.

Altered immunoglobulin G glycosylation in patients with isolated hyperprolactinaemia.

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.

Is idiopathic mild hyperprolactinemia a cardiovascular risk factor?

BACKGROUND: There is a strong relationship between arterial stiffness and endothelial dysfunction and hypertension. How arterial stiffness is affected in elevated PRL conditions is uncertain. Biological action of prolactin contributing to the atherosclerotic process is a new research area. AIMS: We aimed at investigating cardiovascular risk predictability by conducting arterial stiffness measurement in patients with idiopathic hyperprolactinemia. SUBJECTS AND METHODS: The biochemical parameters and arterial stiffness analyses of 54 patients with idiopathic hyperprolactinemia, who had applied to our polyclinic in 2017 and 2018, and 55 healthy volunteers having similar characteristics with regard to age, sex and body mass index. RESULTS: The median prolactin level of the idiopathic hyperprolactinemia patients with a median age of 31 was found to be 45 ng/mL. The peripheral and central blood pressures and pulse wave velocities (PWV) of both the patient group and the control group were found to be similar. Any relations between prolactin levels and blood pressure and arterial stiffness could not be found. DISCUSSION: Our study showed that arterial stiffness did not increase in young patients with idiopathic mild hyperprolactinemia. However, the long-term effects of mildly elevated prolactin levels are unknown. Prospective randomized studies are required, that could reveal more clearly the prolactin-cardiovascular risk relation, and the clinical effects of extra-pituitary hyperprolactinemia.