Cardiovascular disease, mainly coronary atherothrombosis, is an essential contributor to all-cause mortality, accounting for approximately 30% of all global deaths. Imbalances in hormone profiles may play a role in the evolution of atherothrombosis. In the last decade, our clinical research focused on the hormone prolactin (PRL) and its contribution to premature cardiovascular disease. In this narrative review, we aimed to give current insights into how PRL could modulate the inflammatory cascade within the microenvironment of the atherosclerotic plaque, which could lead to increased cardiovascular morbidity and mortality.

Background: Untreated hyperprolactinemia and autoimmune thyroiditis (Hashimoto's disease) seem to increase cardiometabolic risk. The cardiometabolic effects of cabergoline were less significant in young women with concurrent euthyroid Hashimoto's illness. This study sought to investigate if the detrimental effects of this condition on cabergoline efficacy are also evident in postmenopausal women. Methods: The study comprised 50 postmenopausal women exhibiting increased prolactin levels, with half qualifying for euthyroid Hashimoto's illness. The subjects with thyroid autoimmunity were matched with those without thyroid disease according to age, body mass index, and prolactin levels. In addition to prolactin, we assessed thyroid-stimulating hormone (TSH), thyroid antibodies, and glucose homeostasis markers: fasting glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and glycated hemoglobin (HbA1c). Furthermore, we assessed plasma lipids, plasma uric acid levels, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and the urine albumin-to-creatinine ratio (UACR). The decadal cardiovascular risk was assessed with the Framingham Risk Score (FRS). Results: Before therapy, disparities existed among groups in HOMA1-IR, HDL cholesterol, antibody titers, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS. After six months of treatment, cabergoline successfully corrected prolactin levels (both total and monomeric) in women without thyroid disorders. This normalization correlated with decreases in HOMA1-IR, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS, as well as an elevation in HDL cholesterol. In women diagnosed with Hashimoto's disease, cabergoline's effects were limited to a reduction in prolactin levels, HOMA1-IR, and UACR, as well as an elevation in HDL cholesterol, with these alterations being less pronounced compared to women without thyroid illness. Conclusions: The cardiometabolic benefits of cabergoline were associated with the degree of prolactin concentration reduction. In women diagnosed with Hashimoto's disease, connections were noted between baseline levels and treatment-induced alterations in hsCRP. These data indicate that concurrent euthyroid autoimmune thyroiditis mitigates the cardiometabolic consequences of cabergoline.

Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls.

Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36).

Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05).

Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation.

This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829).

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders.

Prolactin (PRL) is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data have outlined the potential prognostic value of PRL in various clinical settings.

This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum PRL levels and risk of mortality in adults without prolactinoma.

A systematic literature search was conducted up to June 10, 2023, to identify studies reporting the association of serum PRL levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death (CVD) during follow-up.

Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum PRL levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23 596 individuals. Each unit of PRL increase was independently associated with increased risk of all-cause (pooled aHR = 1.17 [1.08-1.27]; I2 = 48%) and CV mortality (pooled aHR = 1.54 [1.14-2.09]; I2 = 89%). Individuals belonging to the highest PRL category had significantly higher risk for all-cause (pooled aHR = 1.81 [1.43-2.30]; I2 = 65%) and CV (pooled aHR = 1.59 [1.04-2.42]; I2 = 82%) mortality compared to their lowest-PRL category counterparts. The association between PRL levels and in-hospital death did not reach statistical significance.

PRL levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk-stratification tool can be delineated in clinical practice.

The association between prolactin and mortality has been less studied, and findings were inconsistent among different populations. We aimed to investigate the association between serum prolactin (PRL) and mortality among patients with type 2 diabetes.

We performed a retrospective cohort study of 10 907 patients with at least 2 prolactin measurements within 2 years since their first inpatient diagnosis of type 2 diabetes. Baseline and mean values of serum PRL were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association between PRL and mortality. During a mean follow-up of 5.34 years, 863 patients died, of whom 274 were due to cardiovascular events. Multivariable-adjusted hazard ratios (aHRs) based on different levels of baseline PRL (<100, 100-199, 200-299, and ≥300 mIU/L) were 1.00, 1.10 [95% confidence interval (CI), 0.90-1.36], 1.35 (95% CI 1.11-1.67), and 1.49 (95% CI 1.18-1.84) for all-cause mortality and 1.00, 1.24 (95% CI 0.86-1.81), 1.71 (95% CI 1.14-2.62), and 2.42 (95% CI 1.55-3.78) for cardiovascular mortality, respectively. Positive associations were also found when we used the mean values of PRL as the exposure. These associations were consistent among patients of different baseline characteristics. Further sensitivity analyses excluding patients with subclinical or clinical hypothyroidism at baseline and who died within the first 6 months since baseline demonstrated similar results.

A positive association between baseline PRL and mortality was observed among patients with type 2 diabetes. Prolactin may be considered a potential biomarker of mortality among patients with type 2 diabetes.

Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists.

Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks.

The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1.

Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA.

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline's cardiometabolic effects.

Although dopaminergic agents are the drugs of choice in treatment of prolactin excess, women who cannot be treated with these agents are recommended to receive estrogen preparations. The aim of this study was to compare cardiometabolic effects of both treatment options. The study population included three groups of young women. Subjects with mild-to-moderate hyperprolactinemia received either low-dose cabergoline or oral combined contraceptives (ethinyl estradiol plus desogestrel), while normoprolactinemic women were drug-naive. Plasma prolactin, glucose homeostasis markers, lipids, circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, and the urinary albumin-to-creatinine ratio (UACR) were assessed at entry and six months later. Hyperprolactinemic women differed from normoprolactinemic ones in glucose homeostasis markers, high-density lipoprotein (HDL)-cholesterol, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine and UACR. Cabergoline decreased total and monomeric prolactin levels, which was accompanied by normalization of glucose, insulin sensitivity, glycated hemoglobin, HDL-cholesterol, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine and UACR. Despite a neutral effect on prolactin levels, combined contraceptives worsened insulin sensitivity and increased triglycerides, hsCRP, fibrinogen and UACR. At follow-up, cabergoline-treated women were characterized by a better cardiometabolic profile than women receiving ethinyl estradiol plus desogestrel. Our findings suggest that only cabergoline reduces cardiometabolic risk in young women with hyperprolactinemia.

Despite the myocardial prolactin (PRL) binding activity and the known effect of enhancing contractility in the isolated rat heart, little information is available concerning the cardiovascular consequences of hyperprolactinemia in humans. To elucidate the effects of chronic hyperprolactinemia on cardiac structure and function, twenty-four patients with isolated PRL-secreting adenoma and twenty-four controls underwent a complete mono- and two-dimensional Doppler-echocardiography. Blood pressure and heart rate were similar in the two groups, and no significant differences were observed as to left ventricular (LV) geometry between patients and controls. Resting LV systolic function was normal in patients with hyperprolactinemia, as shown by similar values of fractional shortening and cardiac output. Conversely, hyperprolactinemic patients exhibited a slight impairment of LV diastolic filling, as demonstrated by the prolongation of the isovolumetric relaxation time and the increase of the atrial filling wave of mitral Doppler velocimetry (58 ± 13 vs. 47 ± 8 cm/s, p < 0.05) with a subgroup of females (16%) having a clear diastolic dysfunction, and a worse exercise capacity (6 min walking test 452 ± 70 vs. 524 ± 56; p < 0.05). In conclusion, hyperprolactinemia in humans may be associated with a slight impairment of diastolic function, with an overt diastolic dysfunction in a subgroup of females which correlated with poorer exercise performance, in the absence of significant abnormalities of LV structure and systolic function.

Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated.

To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed.

PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23-kDa PRL (named full-length PRL) and vasoinhibins (including 5.6-18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.

Epicardial adipose tissue thickness (EATT) is considered to be a surrogate for visceral fat and a novel cardiovascular risk indicator. Hyperprolactinemia has been shown to be associated with increased cardiovascular risk. The aim was to evaluate the association between EATT, carotid intima media thickness (CIMT), and cardiac functions in patients with prolactinoma.

Patients with the diagnosis of prolactinoma were included. The control group consisted of healthy age matched individuals with normal prolactin levels. Prolactin, fasting blood glucose (FBG), insulin, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), total cholesterol, triglycerides, and high (HDL) and low density lipoprotein (LDL) cholesterol were measured. EATT, CIMT, cardiac systolic, and diastolic functions were determined using echocardiography.

We evaluated 67 patients with prolactinoma (aged 40.7 ± 11.9 years, F/M: 51/16) and 57 controls (aged 42.5 ± 7.4 years, F/M: 36/21). Of the 67 patients, 24 had normal prolactin levels. FBG level was higher in prolactinoma patients than in controls. Patients and controls had similar HbA1c, HOMA-IR, ALT, total, HDL, LDL cholesterol, and triglycerides levels, and similar cardiac systolic and diastolic functions. Prolactinoma patients had greater EATT (3.0 ± 0.5 mm vs. 2.6 ± 0.4 mm, p < 0.001) and CIMT (0.57 ± 0.08 mm vs. 0.52 ± 0.04 mm, p = 0.03) than controls. EATT was correlated with body mass index, FBG, HbA1c, and triglyceride levels.

EATT and CIMT were greater in patients with prolactinoma, although they had normal cardiac systolic and diastolic functions.

The secreting function of pituitary adenomas (PAs) plays a critical role in making the treatment strategies. However, Magnetic Resonance Imaging (MRI) analysis for pituitary adenomas is labor intensive and highly variable among radiologists. In this work, by applying convolutional neural network (CNN), we built a segmentation and classification model to help distinguish functioning pituitary adenomas from non-functioning subtypes with 3D MRI images from 185 patients with PAs (two centers). Specifically, the classification model adopts the concept of transfer learning and uses the pre-trained segmentation model to extract deep features from conventional MRI images. As a result, both segmentation and classification models obtained high performance in two internal validation datasets and an external testing dataset (for segmentation model: Dice score = 0.8188, 0.8091 and 0.8093 respectively; for classification model: AUROC = 0.8063, 0.7881 and 0.8478, respectively). In addition, the classification model considers the attention mechanism for better model interpretation. Taken together, this work provides the first deep learning-based tumor region segmentation and classification models of PAs, which enables early diagnosis and subtyping PAs from MRI images.

Mediterranean diet was evaluated on erectile performance and cardiovascular hemodynamics, in chronic heart failure patients.

150 male stable heart failure patients were enrolled in the study (62 ± 10 years, New York Heart Association (NYHA) classes I-II, ejection fraction ≤40%). A detailed echocardiographic evaluation including estimation of the global longitudinal strain of the left ventricle and the systolic tissue doppler velocity of the tricuspid annulus was performed. Erectile dysfunction severity was assessed by the Sexual Health Inventory for Men-5 (SHIM-5) score. Adherence to the Mediterranean diet was evaluated by the MedDietScore.

The SHIM-5 score was positively correlated with the MedDietScore (p = 0.006) and augmentation index (p = 0.031) and inversely correlated with age (p = 0.002). MedDietScore was negatively associated with intima-media-thickness (p < 0.001) and serum prolactin levels (p = 0.05). Multi-adjusted analysis revealed that the inverse relation of SHIM-5 and prolactin levels remained significant only among patients with low adherence to the Mediterranean diet (p = 0.012).

Consumption of Mediterranean diet benefits cardiovascular hemodynamics, while suppressing serum prolactin levels. Such physiology may enhance erectile ability independently of the of the left ventricle ejection fraction.

CKD has a high prevalence worldwide, mainly due to its main etiologies-diabetes and hypertension. It has high cardiovascular morbidity and mortality, with traditional risk factors such as atherosclerosis, hypertension, diabetes, smoking, and left ventricular hypertrophy being common. Nontraditional cardiovascular risk factors, such as anemia, hyperparathyroidism, chronic inflammation, and microalbuminuria, are also well studied. Prolactin is a hormone not only related to lactation but also being considered a uremic toxin by some authors. It accumulates with loss of renal function, and it is associated with cardiovascular outcomes in both normal renal function population and CKD population. The purpose of this narrative review is to raise the main common aspects of CKD, prolactinemia, and cardiovascular risk.

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.

The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia.

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.

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.

The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia.

Prolactinomas are the most common secretory pituitary adenoma. They typically occur in women in the 3rd-6th decade of life and rarely in the pediatric population or after menopause. Most women present with irregular menses and/or infertility. Dopamine (DA) agonists, used in their treatment, are safe during pregnancy, but in most cases are discontinued at conception with close monitoring for signs or symptoms of tumor growth. Breastfeeding is safe postpartum, provided there was no significant growth during pregnancy. Some women will experience normalization of prolactin levels postpartum. Menopause may also decrease prolactin levels and even those with macroprolactinomas may consider discontinuing their DA agonist with close follow-up. Prolactinomas may be associated with decreased quality of life scores in women, and play a role in bone health and cardiovascular risk factors. This review discusses the current literature and clinical understanding of prolactinomas throughout the entirety of the female life cycle.

To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma.

Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database.

A total of 2233 patients with prolactinoma and 10 355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings.

During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 "nonexposed" individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61, P = .968)] in female patients and 1.94 (95% CI: 1.29-2.91, P = .001) in male patients. These findings remained robust in sensitivity analyses restricting to patients with documented record of dopamine agonist treatment and those with newly diagnosed prolactinoma.

In contrast to females, men with prolactinoma have increased risk for incident CVD; the aetiology of this gender-specific finding remains to be elucidated.

Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.

Hyperprolactinemia has been associated with endothelial dysfunction and a wide range of cardiovascular risk factors, thus it can potentially lead to cardiac dysfunction. The present study was designed to interrogate our hypothesis that hyperprolactinemia can contribute to preclinical impaired left ventricular function.

Thirty-one prolactinoma patients and 60 healthy volunteers were prospectively recruited. Left ventricular function was evaluated using conventional two dimensions and M-mode echocardiography, as well as Doppler tissue imaging (DTI).

The Tei index (0.45 ± 0.06 vs. 0.41 ± 0.03, P = .005) and ratio of transmitral and myocardial early diastolic velocities (E/Em; 6.30 ± 1.45 vs. 5.64 ± 0.69, P = .045) were significantly higher, and septal systolic velocity (Sm; 9.88 ± 1.45 vs. 11.58 ± 1.28 cm/s, P<.001) was significantly lower in prolactinoma patients. Furthermore, significant motional abnormalities were detected in regional segments of prolactinoma patients. Pearson's correlation analysis revealed that prolactin level was inversely associated with Sm (r = -0.373, P = .009) and late diastolic phase (Am; r = -0.293, P = .043). Moreover, inverse correlations between prolactin and partial left ventricular segment wall motion were found, including the basal (r = -0.363, P = .014), middle (r = -0.418, P = .004), and apical segment (r = -0.574, P<.001) of the posterior ventricular septum. Multivariate linear regression analysis revealed that prolactin (β = -0.28, 95% confidence interval -0.011 to 0, P = .035), as a single factor, can significantly predict decreased Sm, independent of traditional vascular risk factors.

Our results suggest that subclinical cardiac dysfunction occurs in untreated prolactinoma patients and is characterized by impaired systolic and diastolic function of the left ventricle, as well as regional segment motional abnormality.

A = transmitral late diastolic velocity Am = late diastolic phase Apo = apolipoprotein DTI = Doppler tissue imaging E = transmitral early diastolic velocity Em = myocardial early diastolic velocity FMD = flow-mediated dilation HOMA-IR = homeostasis model assessment of insulin resistance hsCRP = high-sensitivity C-reactive protein IMT = intima media thickness LDL-C = low-density lipoprotein cholesterol LV = left ventricular PPCM = postpartum cardiomyopathy Sm = septal systolic velocity.

In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia.

The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55-3g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6months of treatment.

Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups.

The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone.

Elevated prolactin levels are associated with metabolic and hormonal complications. No previous study has investigated the effect of any fibrate on plasma levels of lipids and other cardiometabolic risk factors in patients receiving dopamine agonist therapy.

The study included 36 premenopausal women with mixed dyslipidemia and slightly increased prolactin levels, 17 of whom had already been treated with bromocriptine (5.0-7.5mg daily). The included patients received micronized fenofibrate (200mg daily) for 6 months. Plasma lipids, glucose homeostasis markers, as well as plasma levels of prolactin, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 weeks of fenofibrate therapy.

Insulin sensitivity was more expressed while baseline plasma levels of hsCRP and fibrinogen were lower in patients treated with bromocriptine than in women not receiving dopamine agonist therapy. Although fenofibrate improved plasma lipids and insulin sensitivity, as well as reduced plasma levels of the investigated cardiometabolic risk factors in both groups of patients, its action on HDL cholesterol, triglycerides, insulin sensitivity, hsCRP and fibrinogen was stronger in subjects receiving bromocriptine. Moreover, only in bromocriptine-naïve patients, fenofibrate increased plasma homocysteine.

Our study shows that the effect of fenofibrate on plasma lipids and circulating levels of cardiometabolic risk factors may be potentiated by bromocriptine treatment. They also suggest that hyperprolactinemic women with mixed dyslipidemia and early glucose metabolism abnormalities may receive the greatest benefits from concomitant treatment with a fibrate and bromocriptine.

The aim of the study was to determine whether atherosclerotic risk markers exist at the moment and after withdrawal of cabergoline (CAB) therapy in patients who had taken a suitable dose of CAB therapy for a suitable period of time before cessation of CAB.

This study was designed as prospective cross-sectional. Out of a total of 115 patients with prolactinoma, 42 non-obese women with microprolactinoma, who met the Pituitary Society criteria (2006) for the withdrawal of long-term CAB therapy, and 30 healthy patients participated in our study. The number of patients excluded from the study were as follows: 34 patients with tumor shrinkage of less than 50%; 10 who received DA treatments for less than 2 years; 9 who were treated with bromocriptine; and 20 who had diabetes mellitus, hypertension, hyperlipidemia, obesity, renal disease, coronary arterial disease, or were tobacco smokers. The patients were evaluated for anthropometric, metabolic, and inflammatory parameters at the time of cessation of CAB therapy and at the 3rd and 12th months after the withdrawal of CAB therapy. Endothelial dysfunction was determined by flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), which were assessed by high resolution ultrasonography (USG) by the same practitioner.

At the moment of cessation of CAB therapy, the FMD percentage in patients with prolactinoma was worse than that in healthy controls (p=0.0029). After the withdrawal of CAB treatment, fibrinogen (p=0.036), mean platelet volume (MPV) (p<0.001), carotid IMT (p=0.041), and high-density lipoprotein cholesterol (HDL C) (p=0.048) were worse in the relapse patients than those in the remission patients. Furthermore, only MPV values were found to be significantly related to a relapse of hyperprolactinemia among all atherosclerotic risk markers [area under the curve: 0.830 (95% CI 0.685-0.974) (p<0.001)].

Unfavorable cardiovascular risk profiles are a problem for patients with prolactinoma during cessation and after CAB withdrawal.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

Hyperprolactinemia is often associated with hyperinsulinemia, insulin resistance, atherogenic dyslipidemia, and subclinical atherosclerosis. Dopamine agonists were found to reduce the prevalence of metabolic syndrome and cardiometabolic risk. The aim of this study was to compare the effect of statin therapy on cardiovascular risk factors between patients treated with a dopamine agonist and patients treated with metformin.

The study included two age-, weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5.0-7.5 mg daily, n = 14) and subjects receiving metformin (1.7-2.55 g daily, n = 17). Plasma prolactin, lipids, glucose homeostasis markers, and plasma levels of cardiometabolic risk factors were assessed before and after 12 weeks of atorvastatin treatment.

Baseline levels of the investigated variables were similar in women treated with bromocriptine and metformin. Apart from lowering total and LDL cholesterol, atorvastatin decreased plasma levels of uric acid, hsCRP, homocysteine, and fibrinogen, with no difference between treatment groups.

The obtained results suggest that the effect of atorvastatin on plasma lipids and circulating levels of cardiometabolic risk factors does not differ between patients receiving bromocriptine and metformin. Bromocriptine-statin combination therapy may be an alternative to metformin-statin combination therapy in hypercholesterolemic patients with glucose metabolism abnormalities in whom metformin administration is either contraindicated or results in adverse effects.

Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55-3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy.

Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function.

The pituitary-derived hormone prolactin has been suggested to stimulate the development of atherosclerosis and cardiovascular disease through its effects on metabolism and inflammation. In this study, we aimed to challenge the hypothesis that inhibition of prolactin function may beneficially affect atherosclerosis burden. Hereto, atherosclerosis-susceptible LDL receptor (Ldlr) knockout mice were transplanted with bone marrow from transgenic mice expressing the pure prolactin receptor antagonist Del1-9-G129R-hPRL or their non-transgenic littermates as control. Recipient mice expressing Del1-9-G129R-hPRL exhibited a decrease in plasma cholesterol levels (-29%; P<0.05) upon feeding a Western-type diet (WTD), which could be attributed to a marked decrease (-47%; P<0.01) in the amount of cholesterol esters associated with pro-atherogenic lipoproteins VLDL/LDL. By contrast, Del1-9-G129R-hPRL-expressing mice did not display any change in the susceptibility for atherosclerosis after 12 weeks of WTD feeding. Both the absolute atherosclerotic lesion size (223 ± 33 × 10(3) μm(2) for Del1-9-G129R-hPRL vs 259 ± 32 × 10(3) μm(2) for controls) and the lesional macrophage and collagen contents were not different between the two groups of bone marrow recipients. Importantly, Del1-9-G129R-hPRL exposure increased levels of circulating neutrophils (+91%; P<0.05), lymphocytes (+55%; P<0.05), and monocytes (+43%; P<0.05), resulting in a 49% higher (P<0.01) total blood leukocyte count. In conclusion, we have shown that prolactin receptor signaling inhibition uncouples the plasma atherogenic index from atherosclerosis susceptibility in Ldlr knockout mice. Despite an associated decrease in VLDL/LDL cholesterol levels, application of the prolactin receptor antagonist Del1-9-G129R-hPRL does not alter the susceptibility for initial development of atherosclerotic lesions probably due to the parallel increase in circulating leukocyte concentrations.