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.

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.

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.

[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.

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.

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.

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.

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.

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

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

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

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

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.

Evidence for hyperprolactinemia in migraineurs: a systematic review and meta-analysis.

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 I2% 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.

Evaluation of autoantibodies and immunoglobulin G subclasses in women with suspected macroprolactinemia.

BACKGROUND: Macroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia. METHODS: From January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA). RESULTS: The higher the post-PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL-IgG complexes according to the immunoprecipitation experiments. CONCLUSION: The patients with post-PEG PRL recovery rates of <40% and 40%-60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia.

Erectile dysfunction in patients with first-episode psychosis.

Sexual dysfunction is more prevalent in psychotic patients than in the nonpsychotic population. The objective of this study was to identify correlations between serum prolactin levels, testosterone levels and erectile dysfunction in patients with first-episode psychosis (n = 40) compared to age-matched healthy controls (n = 40). All subjects underwent clinical evaluation, international index of erectile function (IIEF5) score assessment and measurement of serum prolactin and total testosterone levels. In first-episode psychotic patients, the IIEF-5 score and total testosterone levels were significantly lower, while serum prolactin levels were higher. We concluded that men with first-episode psychosis are at an increased risk for development of erectile dysfunction, and increased duration of untreated psychosis leads to a higher incidence of erectile dysfunction and hyperprolactinemia.

Hyperprolactinemia in psychotic patients treated in monotherapy with long-acting injectable antipsychotics.

Objectives: Hyperprolactinemia (HPRL), defined as plasma prolactin (PRL) >25 ng/ml, is a frequent adverse effect of the treatment with some antipsychotics. The objectives of this study were to determine the prevalence of HPRL among schizophrenic patients treated with long-acting injectable (LAI) antipsychotic drugs at our hospital, and to estimate gender effects in PRL levels in these patients. Methods: This cross-sectional, retrospective, study analyzed 165 psychotic patients treatment with LAI antipsychotics in monotherapy from February to May of 2017 at the Psychiatry Specialized Care Units of the Elche General Hospital (Spain). Results: The prevalence of antipsychotic-derived HPRL in our hospital was 52.41%. Patients treated with LAI formulations of paliperidone and risperidone presented the highest levels of HPRL. A linear regression model showed that female patients presented 24.95 ng/ml (CI95 = 16.85, 33.05) higher levels of PRL than male patients (p < .0001). For women, age >45 years was associated to reduced levels of PRL with respect to younger patients (mean= -18.86 ng/ml, CI95 = -35.59, -2.13, p < .05). Conclusions: Our study confirmed the effects of LAI paliperidone and risperidone on PRL levels. Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotics, with younger women presenting higher rates of HPRL than men. Key points HPRL is a common adverse effect of the treatment with antipsychotics, detectable in over half of the patients treated in our hospital. Our study showed that treatment with LAI formulations of paliperidone and risperidone resulted in the highest levels of HPRL. Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotic drugs, with younger women presenting higher rates of HPRL than men.

Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions.

BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1. RESULTS: We found that the two hyperprolactinemia-inducing antipsychotics, risperidone and pimozide, prompted precancerous lesions to progress to cancer while aripiprazole, which did not cause hyperprolactinemia, did not. We observed that risperidone and pimozide (but not aripiprazole) caused precancerous cells to activate STAT5 and suppress apoptosis while exerting no impact on proliferation. Importantly, we demonstrated that these effects of antipsychotics on early lesions required the STAT5 gene function. Furthermore, we showed that only two-week treatment of mice with ruxolitinib, a JAK1/2 inhibitor, blocked STAT5 activation, restored apoptosis, and prevented early lesion progression. CONCLUSIONS: Hyperprolactinemia-inducing antipsychotics instigate precancerous cells to progress to cancer via JAK/STAT5 to suppress the apoptosis anticancer barrier, and these cancer-promoting effects can be prevented by prophylactic anti-JAK/STAT5 treatment. This preclinical work exposes a potential breast cancer risk from hyperprolactinemia-inducing antipsychotics in certain patients and suggests a chemoprevention regime that is relatively easy to implement compared to the standard 5-year anti-estrogenic treatment in women who have or likely have already developed precancerous lesions while also requiring hyperprolactinemia-inducing antipsychotics.

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin.

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

Prevalence and risk factors of hyperprolactinemia among patients with various psychiatric diagnoses and medications.

OBJECTIVES: Hyperprolactinemia is a common adverse event associated with psychotropic medications (mainly antipsychotics) used in the management of schizophrenia and bipolar disorders. The aim of this study was to estimate the prevalence of hyperprolactinemia in psychiatric patients and to evaluate its association with various psychiatric diagnoses and the use of various psychotropic medications. METHODS: A cross-sectional observational study was conducted between July 2012 and June 2014. Patients were recruited from a number of hospitals located in the five regions of Saudi Arabia. Hyperprolactinemia was defined as blood prolactin levels >25 ng/mL in females and >20 ng/mL in males, regardless of the presence of symptoms. RESULTS: A total of 997 patients (553 males and 444 females) were included in the current analysis. The average blood prolactin level was 32.6 ± 44.1 ng/mL, with higher levels among females than males (42.9 ± 61.3 versus 24.4 ± 18.6, p < .001). The prevalence of hyperprolactinemia was 44.3%, with no significant gender difference (41.9% in females versus 46.3% in males, p = .164) but with huge variability according to individual antipsychotic and other psychotropic medications. In the multivariate analysis adjusted for demographic and clinical characteristics, hyperprolactinemia was independently and positively associated with using antipsychotic medications (OR = 2.08, 1.26-3.42, p = .004). Additionally, previous hospitalisation, diabetes and hypothyroidism were positively associated, whereas having primary depressive disorders was negatively associated. CONCLUSIONS: We report a high prevalence of hyperprolactinemia among a large sample of psychiatric patients in Saudi Arabia, which was linked to the use of antipsychotic medications. Routine measurement of blood prolactin levels for all patients maintained on antipsychotic agents is recommended, regardless of symptoms.

The epidemiology of hyperprolactinaemia over 20 years in the Tayside region of Scotland: the Prolactin Epidemiology, Audit and Research Study (PROLEARS).

OBJECTIVE: To estimate the prevalence and incidence of hyperprolactinaemia. Hyperprolactinaemia is a common problem in endocrine practice, but its epidemiology has not been accurately established. STUDY DESIGN: A population-based retrospective follow-up study in Tayside, Scotland (population 400,000), from 1993 to 2013. PATIENTS: Record linkage technology (biochemistry, prescribing, hospital admissions, radiology, mortality and maternity data) was used to identify all patients with a serum prolactin measurement. From these, cases were defined as those with a prolactin greater than 1000 mU/L (47·2 ng/ml) or at least three prescriptions for a dopamine agonist. MEASUREMENTS: Number of prevalent and incident cases of hyperprolactinaemia per calendar year by age, sex and cause of hyperprolactinaemia. RESULTS: A total of 32289 patients had a serum prolactin assay undertaken, of which 1301 had hyperprolactinaemia not related to pregnancy: 25·6% patients had pituitary disorder, 45·9% were drug-induced, 7·5% had macroprolactin and 6·1% had hypothyroidism, leaving 15·0% idiopathic. Over the 20 years, there was a fourfold increase in the number of prolactin assays performed, and prevalence of hyperprolactinaemia was initially 0·02%, but rose to 0·23% by 2013. Overall incidence was 13·8 cases per 100000 person-years (20·6 in 2008-13) and was 3·5 times higher in women than in men. The highest rates were found in women aged 25-44 years. Drug-induced causes tripled during the 20 years. CONCLUSIONS: Rising prevalence of hyperprolactinaemia is probably due to an increased ascertainment and increased incidence of psychoactive drug-related causes. Rates are higher in women than in men but only before the age of 65 years.