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Objective: Transsphenoidal surgery for lactotroph pituitary neuroendocrine tumor (PitNET) lowers serum prolactin concentrations, occasionally below the normal range. However, the clinical significance of postoperative hypoprolactinemia is still unclear. In this study, we retrospectively reviewed the female patients with lactotroph PitNET who were treated with transsphenoidal surgery to elucidate the influence of postoperative hypoprolactinemia on regular menstruation restoration and endocrinological remission., Results: The serum prolactin levels in all thirty three participating females had decreased following surgery. Serum prolactin levels in seven patients had decreased below the lower limit of normal ranges (hypoproactinemia group) and in the remaining twenty six patients, it was within the normal range (non-hypoproractinemia group). In hypoprolactinemia group, regular menstruation was restored in all patients with only lactotroph axis deficiency. Nine patients from the non-hypoprolactinemia group experienced re-elevation of serum prolactin concentration (27%). No patient in hypoprolactinemia group experienced the relapse of hyperprolactinemia. These data suggest that early postoperative hypoprolactinemia after transsphenoidal surgery for lactotroph PitNET is not only a good predictive factor for endocrinological remission but also no unfavorable effects on regular menstruation restoration., (© 2024. The Author(s).)

Prolactin is a proteic hormone best known for its role in enabling the production of milk by female mammals. Secreted by the pituitary gland in response to the stimuli of eating, estrogen treatment, mating, ovulation and nursing, prolactin is involved in over 300 separate processes in a range of vertebrates, including humans. The hormone is released in a pulsatile manner and plays an essential role in metabolism, as well as in the regulation of the immune system and pancreatic development. Nevertheless, prolactin exerts other relevant roles, as it acts at the central nervous system level to modulate behavior, arousal and sexuality. In this experts' opinion, we aim to give insights into the main activities of prolactin to advance the ability of medical doctors and specialists in obstetrics and gynecology to provide more emphasis in their clinical practices to the link between prolactin and sexuality.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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

In recent years, it has been found that kisspeptin plays some key roles in the physiological processes of the brain, such as gender differentiation, positive and negative feedback of sex hormones, onset of puberty, and transduction of energy signals in the body, which suggests that kisspeptin may be a key molecule for the maturation and regulation of female reproductive function. In addition to the systemic roles of the kisspeptin, its local roles in reproductive organs are constantly being discovered. With the discovery that kisspeptin is involved in the pathological process of reproductive endocrine diseases such as isolated hypogonadotropic hypogonadism (IHH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF) and pathological hyperprolactinemia, exogenous application of kisspeptin to solve reproductive problems has become a new hot topic. The review focuses on the research progress of kisspeptin in the female reproductive system, especially on its application in assisted reproduction.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Hyperprolactinemia is responsible for 20 to 25% of consultations of secondary amenorrhea and 17% for female infertility. Dopamine agonists are the gold standard treatment of hyperprolactinemia. Although they are associated with various adverse effects, cabergoline is generally preferred due to better compliance, limited side effects and good therapeutic response. However, bromocriptine is widely and satisfactorily used in a context of limited availability of cabergoline. We sought to describe clinical manifestations of hyperprolactinemia and response to cabergoline in a sub Saharan Africa (SSA) setting. We describe the profile of all patients with a diagnosis of hyperprolactinaemia from 1 st July 2012 to 15 th May 2014 at the Endocrinology Department of Yaoundé Central Hospital. Patients with physiological hyperprolactinemia were not considered. All patients were routinely started on cabergoline at 0.5mg/week or at 1mg/week in case of macroprolactinoma or desire to become pregnant. The duration of follow up was 8-16 months. After three months of treatment, 8 of 10 patients with amenorrhea had menses and serum prolactin levels decreased significantly at month 2-3 (p = 0.025). In conclusion, our study suggests that cabergoline yields an excellent therapeutic response in a short period of time and may thus be cost saving in sub Saharan context despite its unit price., Competing Interests: The authors declare no competing interests., (© Martine Claude Etoa Etoga et al.)

Aim: To investigate whether treated hyperprolactinemia has an impact on pregnancy outcomes in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)., Methods: A retrospective cohort study was conducted on 535 women who underwent IVF/ICSI-ET between January 2012 and December 2016, of which 123 had treated hyperprolactinemia (case group), 369 were matched controls. Besides, 43 remained hyperprolactinemic after treatment consisted of abnormal group. Cumulative live birth rate (CLBR) after one oocyte retrieval cycle was taken as the primary outcome. A time-to-event analysis using Fine and Gray's test was used to compare CLBR between case and control groups., Results: The median prolactin level was 80.00 ng/mL before dopamine agonist treatment in case group, and it reduced to 14.80 ng/mL after the treatment, similar to the level of control group (15.17 ng/mL, P = 0.316). No significant differences in baseline characteristics were found between case and control groups. The CLBR after one oocyte retrieval cycle were 69.1% (85/123) and 66.4% (245/369) in the case group and control group, respectively (P = 0.580). No significant differences were found between case and control groups in perinatal outcomes. Pregnancy and perinatal outcomes of abnormal group were similar to those of case and control groups., Conclusion: Impact of treated hyperprolactinemia on CLBR and perinatal outcomes in IVF-ET was not evident., (© 2019 Japan Society of Obstetrics and Gynecology.)

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented., (Published by Oxford University Press on behalf of Society for the Study of Reproduction 2019.)

The female hormone 17β-estradiol is postulated to be protective against schizophrenia onset and severity. Hypoestrogenism is a common phenomenon in women with schizophrenia that has serious effects that adds to the burden of an already very onerous disease. The cause of hypoestrogenism is largely attributed to antipsychotic-induced hyperprolactinemia. Evidence suggest however that a significant portion of female schizophrenia patients develop hypoestrogenism either before antipsychotic treatment or without regard to the level of prolactin, suggesting that for a sizeable segment of female patients, gonadal abnormality may be an innate and early aspect of the disease. This review aims to summarise the available literature that examines gonadal dysfunction in schizophrenia through this prism as well as to outline some recent developments in treatment strategies that may provide feasible ways to successfully tackle hypoestrogenism in schizophrenia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Jaundice is a common neonatal problem. This study was conducted to determine the effect of metoclopramide on neonatal bilirubin and maternal prolactin (primary outcomes) and milk volume (secondary outcome)., Methods: This triple-blind, randomized, controlled, clinical trial was conducted on 112 mothers. The participants were assigned to the intervention (metoclopramide) and control groups (placebo) using block randomization. Ten-mg metoclopramide and placebo tablets were taken by the participants three times a day. The intervention began in the first 2-10 hours after childbirth and continued until the fifth day. The mothers' prolactin level was measured on the first morning after the intervention and on the sixth day (1 day after the intervention was over). Neonatal total bilirubin was also measured before the intervention and on the sixth day., Results: After the intervention, the two groups did not differ significantly in terms of the mean neonatal indirect bilirubin (P = 0.565) and milk volume (P = 0.261), but the mean serum prolactin was significantly higher in the metoclopramide group compared to the placebo group (adjusted mean difference 37; 95% confidence interval 58.1-16.5; P = 0.001)., Conclusions: Metoclopramide increased maternal serum prolactin but had no effects on neonatal jaundice. The insufficient numbers of studies on this subject mandate further research.

Purpose: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations., Material and Methods: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities., Results: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin., Conclusion: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Objective: Hyperprolactinemia in patients with nonfunctioning pituitary adenomas (NFPAs) has been explained by the stalk compression of large pituitary adenomas. However, not all large NFPAs are associated with high serum prolactin levels. We aimed to elucidate and compare clinical, hormonal, and radiographic characteristics of NFPAs with and without hyperprolactinemia., Methods: We included 201 patients with clinically NFPAs who underwent transsphenoidal surgery performed by a single surgeon during 2010-2017 at a single center in Korea. We measured the three-dimensional diameters (anteroposterior [AP], width, height) and volumes of NFPA on magnetic resonance imaging. We conducted morning basal hormone measurements and dynamic tests preoperatively and 3 months postoperatively., Results: All NFPAs were macroadenomas, and mean tumor volume was 10.4 ± 7.7 cm 3 . Of 201 patients, 59 (29.4%) had preoperative hyperprolactinemia. Hormone recovery rate was higher in patients with hyperprolactinemia compared with patients without hyperprolactinemia after age, sex, body mass index, tumor volume, and gross total resection adjustments (odds ratio [95% confidence interval]: 2.55 [1.10-5.92]). Tumor width/AP diameter ratio positively correlated with serum prolactin levels (r = 0.186, P = 0.008). Tumor volume was not significantly different between the 2 groups., Conclusions: Preoperative prolactin level is a useful marker to predict hormone recovery after surgery. Patients with NFPA and hyperprolactinemia tended to have a higher width/AP diameter ratio. Hyperprolactinemia of NFPA is more likely affected by tumor growth pattern, such as width/AP diameter ratio, than tumor volume., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Antipsychotics are a known cause of hyperprolactinaemia and can be associated with significant health issues in short term and long term. The effects vary with gender and age of the individual and can contribute towards non-concordance and hence relapse in mental health of our patients. Clinicians need to educate the patients about this significant side effect of not only antipsychotic medications but other medications causing hyperprolactinaemia commonly prescribed in primary care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Gynecomastia-the enlargement of male breast tissue in men-is a common finding, frequently observed in newborns, adolescents, and old men. Physiological gynecomastia, occurring in almost 25 % of cases, is benign and self-limited; on the other hand, several conditions and drugs may induce proliferation of male breast tissue. True gynecomastia is a common feature often related to estrogen excess and/or androgen deficiency as a consequence of different endocrine disorders. Biochemical evaluation should be performed once physiological or iatrogenic gynecomastia has been ruled out. Non-endocrine illnesses, including liver failure and chronic kidney disease, are another cause of gynecomastia which should be considered. Treating the underlying disease or discontinuing medications might resolve gynecomastia, although the psychosocial burden of this condition might require different and careful consideration.

Introduction: Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination., Methodology: An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV)., Results: Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old, amenorrhea>6 months, or early menopause to avoid fracture risk., (Copyright © 2016 SEP y SEPB. Published by Elsevier España. All rights reserved.)

Hyperprolactinemia is a frequent neuroendocrinological condition that should be approached in an orderly and integral fashion, starting with a complete clinical history. Once physiological causes such as pregnancy, systemic disorders such as primary hypothyroidism and the use of drugs with dopamine antagonistic actions such as metochlopramide have been ruled out, the most common cause of hyperprolactinemia is a PRL-secreting pituitary adenoma or prolactinoma. Prolactinomas are usually classified as microprolactinomas (less than 1 cm) or macroprolactinomas (larger than 1 cm), which can either be confined or invasive. The hormonal consequence of hypeprolactinemia is hypogonadism; in women, this is manifested as amenorrhea/oligomenorreha, anovulation and galactorrhea, whereas in men the main complaints are a diminished libido and erectile dysfunction. Macroprolactinomas can also present with symptoms and signs resulting form mass effect of the tumor, such as headaches and visual field defects. Other structural causes of hyperprolactinemia include non-functioning pituitary adenomas and infiltrative disorders, which can interrupt the inhibitory, descending dopaminergic tone. The primary treatment of prolactinomas is pharmacological with dopamine agonists such as cabergoline.

A large number of scientific papers have reported the relationship between the development of hyperprolactinemia and the use of psychotropic drugs, especially the role of antipsychotics which are antidopaminergic drugs. However, less information is known about the role of antidepressants in the development of hyperprolactinemia, specially the selective reuptake inhibitors (SSRIs). The prevalence of hyperprolactinemia as a pharmacological side effect of SSRIs is still unknown, despite the widespread use over the last decade. The aim of this review is to explore the relationship between hyperprolactinemia and SSRIs.

Aim: This study investigated the prevalence of disease-causing chronic anovulation and proposes a logical investigation flowchart to facilitate diagnosis in women presenting with chronic anovulation., Material and Methods: The cross-sectional retrospective study was performed using 293 reproductive-aged women who were diagnosed with chronic anovulation at the Gynecologic Endocrinology Unit, Faculty of Medicine, Chiang Mai University between January 2008 and December 2012. The demographic data, laboratory investigations and diagnoses were collected., Results: Among 293 patients recruited into the study, the common causes of anovulation were polycystic ovary syndrome (PCOS) (73.4%), prolactin disorder (13.3%) and unexplained chronic anovulation (7.5%). The less common causes were thyroid disorders, congenital adrenal hyperplasia, adrenal tumors and Cushing's disease. There was a strong positive association between the levels of 17-hydroxyprogesterone and/or dehydroepiandrosterone sulfate with the levels of testosterone and androstenedione. The sensitivity and specificity of serum luteinizing hormone to accurately diagnose PCOS were 29.38% and 55.56% (P = 0.03). The luteinizing hormone/follicle-stimulating hormone ratio ≥ 3 had a sensitivity and specificity at 18.56% and 92.86% (P = 0.03) for PCOS diagnosis., Conclusion: Serum androstenedione, testosterone, thyroid-stimulating hormone, prolactin levels and pelvic ultrasonography should be included in the initial investigations for anovulation. The 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels can be used for secondary anovulation evaluations., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

Context: Secondary amenorrhea--the absence of menses for three consecutive cycles--affects approximately 3-4% of reproductive age women, and infertility--the failure to conceive after 12 months of regular intercourse--affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases., Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis., Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception.

Purpose: To evaluate the effects of ovariectomy and the hyperprolactinemia procedure in the tibial epiphyseal growth plate of female mice., Methods: In this study, the epiphyseal growth plate of ovariectomized (OVX) and/or rendered hyperprolactinemic female mice by 50 days of treatment with 200 μg metoclopramide (M) was evaluated morphologically, morphometrically and immuno-histochemically. Forty female and adult mice were divided into four groups according to treatment: V group--animals treated with saline solution; H group--hyperprolactinemic animals; Ovx/V group--ovariectomized animals and treated with saline solution; Ovx/H group--hyperprolactinemic and ovariectomized animals. After the treatment period, the animals were sacrificed, tibia was removed and fixed in 10% buffered formalin and decalcified in 10% formic acid. The material was immersed in paraffin and subjected to histological processing in paraffin. The sections were stained with Masson's trichrome and immunohistochemistry was carried out for the pro-apoptotic protein BCL-2. The images for the morphological and morphometric study were analyzed with the imaging program AxioVision 4.8 (Carl-Zeiss(r), Germany)., Results: The combination of hyperprolactinemia and the ovariectomy procedure decreased the number of resting chondrocytes 1.5-fold, the number of proliferative chondrocytes 1.8-fold; the percentage of resting cartilage 2.4-fold and the percentage of trabecular bone 2.1-fold, compared with respective control animals., Conclusion: The procedure of ovariectomy combined with the metoclopramide-induced hyperprolactinemia in female mice has showed marked bone degeneration due to significant decrease of cell proliferation in the epiphyseal growth plate and bone formation.

Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood-brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state.

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects). Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Background: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment., Objective: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia., Method: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia., Results: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here., Conclusions: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

Background: Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it., Literature Findings: Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don't mention them spontaneously and clinicians underestimate their prevalence. In the long-term, hypogonadism involves a premature bone loss in men and women. Klibanski and colleagues showed that this loss is significant only in women with hyperprolactinemia associated with amenorrhea. That suggests that prolactin is not directly responsible for this clinical feature. Nevertheless, prolactin seems to be involved in the development of breast cancer, but its role is unclear for prostate cancer., Discussion: Our review promotes a check-up before beginning a treatment with antipsychotic agents. First, a baseline prolactin level should be measured. It should also include the research on previous treatment with antipsychotic-drugs and the assessment of adverse effects suggestive of hyperprolactinemia. Questioning should finally look for any contra-indication to antipsychotics. Monitoring during antipsychotic treatment has been studied by a group of international experts in psychiatry, medicine, toxicology and pharmacy who made a critical review of clinical guidance on hyperprolactinemia. Experts notify that it is important to check whether patients have any sexual dysfunction, such as loss of libido or menstrual irregularity, and galactorrhoea. Prolactin level should also be controlled after three months of stable dose treatment, or if any clinical feature of hyperprolactinemia appears. If a patient prescribed antipsychotic-drugs has a confirmed prolactin level above the normal range, it is necessary to exclude other causes of hyperprolactinemia. If antipsychotics are really involved, the management should be adapted with the prolactin level and the patient him/herself. To summarize, clinicians can decrease the dose of the antipsychotic or switch to a prolactin-sparing drug. Oral contraceptives can be added whether to prevent pregnancy or to prevent bone loss and osteoporosis. Finally, experts recommend reserving dopamine agonists to treat antipsychotic-induced hyperprolactinemia in very exceptional circumstances as it can worsen the mental illness., (Copyright © 2013. Published by Elsevier Masson SAS.)

Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.

Background: Psychotropic medications, particularly select antipsychotics, are a common cause of drug-induced hyperprolactinemia. As high prolactin may be associated with hypogonadism, reproductive dysfunction, and bone loss, it is important to recognize this condition and understand its management., Objective: The aim of this review is to evaluate the causes, signs, and symptoms associated with hyperprolactinemia, to describe mechanisms through which psychotropic medications elevate prolactin, and to suggest an evidence-based management approach for patients with psychotropic drug-induced hyperprolactinemia., Methods: A PubMed/MEDLINE search was conducted on the topic of psychotropic agents as a cause of hyperprolactinemia. The material with most relevance to current psychiatric practice and of highest level of evidence was included in this review., Conclusion: Hyperprolactinemia should be evaluated in adult patients receiving psychotropic agents if signs and symptoms associated with hyperprolactinemia are present. It is also important to exclude pituitary and hypothalamic disease by magnetic resonance imaging if hyperprolactinemia is not definitely caused by psychotropic medications. As bone loss may occur because of hyperprolactinemia-mediated hypogonadism, bone mineral density (BMD) should be evaluated in patients with persistent high prolactin and reproductive dysfunction. Aripiprazole or other prolactin-sparing atypical antipsychotics may be alternatives or aripiprazole can be considered as adjunctive therapy in select cases of psychotropic-induced hyperprolactinemia., (Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this investigation was to evaluate the effects of hyperprolactinaemia on thyroid function, volume and nodularity in patients with prolactinoma., Context: Hyperprolactinaemia has been associated with various autoimmune diseases; however, the data on the correlation between the level of prolactin (PRL) and thyroid disorders have not been adequately clarified., Design: Case-control study., Patients: Forty-eight subjects with new diagnosis of hyperprolactinaemia (group 1) and 39 subjects undergoing treatment for prolactinoma (group 2) were recruited from our outpatient clinic. Fifty-two healthy subjects were included as a control group (group 3)., Measurements: The serum PRL, thyroid-stimulating hormone (TSH), thyroxine (free T4), thyroidal microsome (anti-TPO) and antithyroglobulin antibodies (TgAb) levels were evaluated, and ultrasonographic thyroid volume was calculated., Results: The frequencies of positive anti-TPO and TgAb were significantly higher in group 1 than in groups 2 and 3 (P = 0·008). Also, the percentage of patients with thyroid heterogeneity were significantly higher in groups 1 and 2 than in group 3 (P < 0·05). The percentage of patients with thyroid nodules were higher in group 1 than in groups 2 and 3 (p1-2 = 0·03, p1-3 = 0·05 and p2-3 = 0·637). The mean thyroid volume was significantly higher in group 1 (P = 0·001), and a positive correlation was found between thyroid volume and the level of PRL (r = 0·616; P = 0·0001). Prolactin had a significant effect on the total volume according to stepwise multiple linear regression analysis (adjusted R(2) is 0·268; P < 0·0001)., Conclusions: Patients with hyperprolactinaemia have significantly increased thyroid volume, thyroid autoimmunity and nodule prevalence., (© 2013 John Wiley & Sons Ltd.)

The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

Objective: To evaluate the effects of hyperprolactinemia on the sulfated glycosaminoglycans (GAGs) of the murine uterus., Design: Experimental research., Setting: University biochemistry laboratory., Animal(s): Eighty female mice were divided into two groups of 40 animals each and treated with 0.2 mL of saline solution (controls, Ctr) and 200 μg of metoclopramide (experimental, HPrl). Treatments lasted for 50 consecutive days. The animals were divided into four subgroups of 10 animals each per treatment (Ctr and HPrl) and sacrificed according to the phase of the estrous cycle. The uterine horns were removed for biochemical analyses, and blood samples were collected for hormone measurements., Intervention(s): Induced hyperprolactinemia., Main Outcome Measure(s): To quantify the sulfated GAGs, and PRL and sex steroid levels., Result(s): The endometrium during the estrus phase was significantly thicker in the HPrl animals than in the Ctr mice. The levels of chondroitin and dermatan sulfate were significantly increased in the HPrl group than in the Ctr group during all phases except metestrus. The amounts of heparan sulfate were lower during estrus and diestrus and higher in the metestrus phase in HPrl than in Ctr animals. Serum PRL levels were increased whereas the levels of E2 and P were decreased in all phases in the HPrl group than in the Ctr group., Conclusion(s): The hyperprolactinemia changed the amounts of uterine sulfated GAGs. Our data suggest that these changes may not be correlated with ovarian steroid levels., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the effect of PRL on liver growth and angiogenesis before and after partial hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal endothelial cell (SEC) proliferation, and hepatic expression of VEGF were measured before and after PH in hyperprolactinemic rats, generated by placing two anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic expression. Also, liver regeneration was increased in AP-grafted rats and was accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression compared with nongrafted controls. Lowering circulating PRL levels with CB-154, an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and soon after PH, they displayed an approximately twofold increased mortality and elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However, liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates normal liver growth, promotes survival, and regulates liver regeneration by mechanisms that may include hepatic downregulation of IL-6 and upregulation of SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to physiological liver growth and has potential clinical utility for ensuring survival and regulating liver mass in diseases, injuries, or surgery of the liver.

Literature on hyperprolactinemia in the setting of a nipple piercing is limited to individuals with concomitant breast/chest wall infection. It is unclear if chronic nipple stimulation from a piercing alone can cause sustained elevations of serum prolactin. Nipple piercing is emerging as a more mainstream societal form of body art, and the answer to this clinical question would potentially alter patient management. Our aim was to assess serum prolactin levels in subjects with nipple piercing. Inclusion criteria were as follows: men and women ≥ 18 years old with nipple piercing(s) present > 6 months. Exclusion criteria included: women who are pregnant, lactating or < 6 months postpartum; subjects on medications known to increase prolactin levels; chest wall/breast infection at the time of phlebotomy or conditions known to be associated with hyperprolactinemia. Three men and eight women were enrolled. Median (range) ages for men and women were 33 (24-42) and 27 years (23-42), respectively. All except one subject had bilateral piercings. The median interval from nipple piercing to blood draw was 4.0 (2.0-12.0) years. None of the subjects had hyperprolactinemia. Median (range) prolactin levels for men and women were 5.6 ng/mL (3.8-7.4) and 8.0 ng/mL (2.8-10.9), respectively. Our results suggest that in the absence of any concomitant infection, chronic nipple piercing is not associated with hyperprolactinemia.

Antipsychotic medications are associated to different degrees with sexual dysfunction mainly through their potential to induce hyperprolactinemia. Prolactin (PRL) secretion is mainly regulated by the hypothalamic dopaminergic systems. We conducted this 6-month, parallel-group study to prospectively investigate the effects of the dopamine agonist cabergoline on sexual dysfunction in clinically stable patients with schizophrenia (DSM-IV, AP 194) and hyperprolactinemia (PRL > 20 ng/ml for men and PRL > 25 ng/ml for women). In total 80 patients were enrolled; 33 were receiving risperidone, 17 haloperidol, 11 amisulpride, and 8 risperidone microspheres long acting. Based on PRL levels (< 50, 50-99, or > 100 ng/ml), patients were assigned in 3 cabergoline doses (0.25, 0.5, and 1 mg/day in 38, 23, and 19 patients, respectively). The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS), and sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale (ASEX). PRL levels were reduced in all patients, from 73.3 (± 46.8) to 42.0 (± 27.8) at Month 3 and 27.1 (± 20.4) at Month 6 (p < .001). ASEX scores declined from 19.1 (± 5.1) to 17.6 (± 5.5) at Month 3 and 15.0 (± 6.5) at Month 6 (p < .001). PANSS scores were reduced in the third and in the sixth month (p = .001 at 6 month vs. baseline). The decrease in PRL was not statistically different between groups. Our data suggest that cabergoline administration to clinically stable patients with schizophrenia may improve sexual functioning without adversely affecting their psychopathologic status, provided that the dose has been suited to the severity of the hyperprolactinemia., (PsycINFO Database Record (c) 2013 APA, all rights reserved)

In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics., (Copyright © 2013. Published by Elsevier B.V.)

Because andrology is relatively undeveloped in France, the dermatologist is often the doctor first consulted for diseases of the nipple in men. All dermatological diseases can in fact occur at this site. There are some specific nipple diseases such as gynaecomastia, congenital abnormalities, hyperplasia, benign tumours and breast cancer. All clinical examinations and laboratory examinations should focus on diagnosis of this type of cancer and its elimination., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Data on the prevalence of macroprolactinemia in patients with prolactinomas is quite limited as the presence of high-molecular prolactin forms is suspected mainly in subjects with mild hyperprolactinemia and negative pituitary imaging., Objective: The main objective of this observational case-control study was to assess the prevalence and clinical significance of macroprolactinemia among patients with prolactinomas., Methods: The study population consisted of 239 subjects: 131 prolactinoma patients and 108 sex-, age- and ethnicity- matched healthy controls. Macroprolactinemia was defined by a PRL recovery after PEG precipitation of<40%., Results: The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients did not differ statistically from the prevalence in the control group (3.5 vs. 3.7%; p=1.000) but was lower although non-significantly than the subgroup of patients treated with dopamine agonists (DA) (3.5 vs.10.8%; p=0.072). Significant association between disruptions of ovarian function and serum levels of the monomeric as well as high-molecular prolactin isoform was found., Conclusions: In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To investigate the contractile characteristics of the seminal vesicles in rats, in which hyperprolactinemia and hypoprolactinemia was induced by prolactin and bromocriptine administration., Materials and Methods: A total of 24 Wistar albino rats were randomly divided into 3 groups: control group, hyperprolactinemia group, and hypoprolactinemia group. The rats in the control group were administered 0.1 mL saline subcutaneously for 21 days. The rats in group 2 received prolactin 51 μg/kg subcutaneously for 21 days. The rats in the third group received intraperitoneal bromocriptine mesylate at a dose of 66 μg/kg. All the rats were decapitated at 21 days. The seminal vesicles were removed using a microsurgical technique, and the tissue sections were prepared (0.5 × 0.2 cm). These sections were suspended in the organ bath. Subsequently, contractions were induced using 10 μmol acetylcholine or 100 mmol potassium chloride., Results: The amplitude values induced by potassium chloride in the prolactin group were significantly greater than those in the bromocriptine group or control group. Similarly, the amplitude values induced by acetylcholine were also significantly greater in the prolactin group than in the other 2 groups., Conclusion: Experimental hyperprolactinemia results in an increase in the smooth muscle contraction and tonus of the seminal vesicles. The alterations in the smooth muscle tonus in the seminal vesicles and genitourinary tract might be involved in the etiology of infertility occurring in hyperprolactinemia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The growth rate of piglets is limited by sow milk yield, which reflects the extent of epithelial growth and differentiation in the mammary glands (MG) during pregnancy. Prolactin (PRL) promotes both the growth and differentiation of the mammary epithelium, where the lactational success of pigs is absolutely dependent on PRL exposure during late gestation. We hypothesized that inducing hyperprolactinemia in primiparous gilts during late gestation by administering the dopamine antagonist domperidone (DOM) would increase MG epithelial cell proliferation and differentiation, subsequent milk yield, and piglet growth. A total of 19 Yorkshire-Hampshire gilts were assigned to receive either no treatment (CON, n = 9) or DOM (n = 10) twice daily from gestation d 90 to 110. Serial blood sampling during the treatment period and subsequent lactation confirmed that plasma PRL concentrations were increased in DOM gilts on gestation d 91 and 96 (P < 0.001). Piglets reared by DOM-treated gilts gained 21% more BW during lactation than controls (P = 0.03) because of increased milk production by these same gilts on d 14 (24%, P = 0.02) and 21 (32%, P < 0.001) of lactation. Milk composition did not differ between the 2 groups on d 1 or 20 of lactation. Alveolar volume within the MG of DOM-treated gilts was increased during the treatment period (P < 0.001), whereas epithelial proliferation was unaffected by treatment. Exposure to DOM during late gestation augmented the postpartum increase in mRNA expression within the MG for β-casein (P < 0.03), acetyl CoA carboxylase-α (P < 0.01), lipoprotein lipase (P < 0.06), α-lactalbumin (P < 0.08), and glucose transporter 1 (P < 0.06). These findings demonstrate that late gestational hyperprolactinemia enhances lactogenesis within the porcine MG and increases milk production in the subsequent lactation.

Immunohistochemistry with semiquantitative image analysis showed that cholestasis induced an increase in the manifestation of mrp3 in cholangiocytes of female rats, but did not affect this parameter in the studied structures of kidney. Under conditions of normal liver function, mrp3 expression in cholangiocytes was also elevated during hyperprolactinemia. Expression of mrp3 in cholangiocytes directly correlated with prolactin receptor expression. In cholestasis, prolactin increased mrp3 manifestation of only in the distal renal tubules. Thus, mrp3 manifestation increases in liver cells, but remains unchanged in kidney cells. The hyperprolactinemia-induced changes in the mrp3 levels and their correlations with prolactin receptor expression were shown to differ in the kidney and liver cells. It was hypothesized that prolactin produced a direct effect on mrp3 expression in cholangiocytes.

Objectives: To determine the frequency of macroprolactinemia in a cohort of hyperprolactinemic women, describing 1) the association of macroprolactinemia with clinical variables and morphological changes in the pituitary gland and 2) clinical status and prolactin levels after 10 years of follow-up., Design: Blood samples were obtained from 32 patients for hormonal assessment. Treatment with cabergoline or bromocriptine was interrupted 3 months before the determination of serum prolactin and macroprolactin. Macroprolactin was measured using the polyethylene glycol (PEG) precipitation method. Computed tomography was performed in all patients., Results: The frequency of macroprolactinemia was 28.1%. In 19 patients prolactin remained elevated (persistent hyperprolactinemia). In 13, prolactin returned to normal (former hyperprolactinemia). Nine patients with PEG recovery between 40 and 50%, and the only two macroprolactinemic patients with previous hyperprolactinemia were excluded from the analysis of clinical outcomes. Only one of seven macroprolactinemic patients had an abnormal pituitary image (empty sella). None had galactorrhea., Main Findings: Classic symptoms of hyperprolactinemia and abnormal imaging findings are not common in patients in whom macroprolactin is the predominant form of PRL., Conclusions: Women with hyperprolactinemia, especially if asymptomatic, should be routinely screened for macroprolactinemia. Macroprolactinemia remains stable in the long term.

Objective: To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate (Seroquel) in the treatment of Chinese Han patients with schizophrenia., Methods: In this 6-week, multicenter, randomized, rater single-blind study, a total of 119 patients with schizophrenia were randomly assigned to quetiapine (n = 60, 750 mg/day) or risperidone (n = 59, 4 mg/day). The efficacy was assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Change (CGI-C) and the Calgary Depression Scale for Schizophrenia (CDSS). Safety and tolerability assessments included treatment-emergent adverse events, laboratory tests and electrocardiograms., Results: The primary analysis demonstrated no significant difference between treatment in the two groups (quetiapine vs. risperidone: 31.9 ± 17.5 vs. 33.3 ± 17.3; P = 0.668). Improvements with both treatments were comparable for total PANSS, positive and negative subscores, general psychopathology subscales, and excitement and attack symptoms. Improvements in CGI-S were similar between treatment groups (P = 0.046). A more favorable trend was detected for quetiapine than risperidone in the reduction of CDSS scores from baseline, especially at week 1 (1.1 ± 2.2 vs. 0.3 ± 2.1, P < 0.050). The rate of extrapyramidal symptom (EPS) and hyperprolactinemia-related adverse events was significantly lower in the quetiapine group than the risperidone group (13.3% vs. 43.3%, P < 0.001). Dizziness and somnolence were more common in the quetiapine group than the risperidone group., Conclusion: Quetiapine fumarate (750 mg/day) has broad clinical efficacy comparable to 4 mg/day risperidone. Dizziness was common in the quetiapine group (P = 0.029), but the rate of somnolence was similar between the two groups (P = 0.114). EPS and hyperprolactinemia rates were significantly higher with risperidone (P < 0.001). Key limitations of this study include small sample size, short treatment periods, and no increase to 6 mg/day for risperidone because of its safety profile.

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25-34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists.

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p = 0.03) specifically, pleuritis (33% vs. 17%, p = 0.02), pericarditis (30% vs. 12%, p = 0.002), and peritonitis (15% vs. 0.8%, p = 0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p = 0.02) and marginally more proteinuria (65.5% vs. 46%, p = 0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia.

Hyperprolactinemia is the most common abnormality of the hypothalamic-pituitary axis. The aim of this study was to investigate the clinical and radiological features of patients with macroprolactinemia. The study population consisted of patients with elevated serum prolactin (PRL) concentrations who presented to our Endocrinology outpatient clinic. Detection of macroprolactin (macroPRL) was performed using the polyethylene glycol precipitation method. Patients in which macroPRL made up more than 60% of total PRL levels were stratified into the macroPRL group, while the remaining patients were placed in the monomeric prolactin (monoPRL) group. A total of 337 patients were enrolled with a mean age of 33.8 ± 10.8 (16-66) years and a male/female ratio of 29/308. Eighty-eight of the patients (26.1%) had an elevated macroPRL level. The mean age in the monoPRL group was higher than in the macroPRL group (35.0 ± 10.1 vs. 30.7 ± 9.8, P = 0.016). The mean PRL levels (ng/ml) in the macroPRL and monoPRL groups were similar (168.0 ± 347.0 vs. 238.8 ± 584.9, P = 0.239). Frequency of amenorrhea, infertility, irregular menses, gynecomastia, and erectile dysfunction were also similar in both groups. More patients in the macroPRL group were asymptomatic compared to the monoPRL group (30.2 vs. 12.0%, P = 0.006). Compared to the macroPRL group, the monoPRL group had a higher frequency of galactorrhea (39.2 vs. 57.1%, P = 0.04) and abnormal magnetic resonance imaging findings (65.3 vs. 81.1%, P = 0.02). Elevated macroPRL levels should be considered a pathological biochemical variant of hyperprolactinemia that may present with any of the conventional symptoms and radiological findings generally associated with elevated PRL levels.

Prolactin-secreting pituitary tumors are a common cause of amenorrhea and infertility in premenopausal women. The goals of therapy are to normalize prolactin, restore gonadal function and fertility, and reduce tumor size, and dopamine agonists are the preferred therapy. Clinically significant tumor enlargement during pregnancy is uncommon and dependent on tumor size and prepregnancy treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Studies on the impact of subclinical hypothyroidism in infertility are scarce and this seeks to determine the proportion of infertile Nigerian women with hyperprolactinaemia that had subclinical hypothyroidism. Serum prolactin and thyroid stimulating hormone were determined using ELECSYS 1010 auto analyzer. Two hundred infertile women were evaluated and 67(33.7%) had hyperprolactinaemia. Subclinical hypothyroidism was observed in 14.9% of women with hyperprolactinaemia, 4.5% and 10.5% of women with primary and secondary infertility, while hyperprolactinaemia was observed in 29.9% and 70.1% in primary and secondary infertility respectively. Mean levels of thyroid stimulating hormone and prolactin were higher in secondary infertility than primary infertility. Subclinical hypothyroidism and hyperprolactinaemia were higher in secondary infertility than primary infertility. The ratio of proportions between hypothyroidism and hyperprolactinaemia was 1:7.

Diabetic retinopathy is a disease of the retinal microvasculature that develops as a complication of diabetes mellitus and constitutes a major cause of blindness in adults of all ages. Diabetic retinopathy is characterized by the loss of capillary cells leading to increased vasopermeability, ischemia, and hypoxia that trigger the excessive formation of new blood vessels in the retina. The influence of the pituitary gland in the pathophysiology of diabetic retinopathy was recognized nearly six decades ago, but the contribution of pituitary hormones to this disease remains unclear. Recent studies have shown that the pituitary hormone prolactin is proteolytically cleaved to vasoinhibins, a family of peptides with potent antivasopermeability, vasoconstrictive, and antiangiogenic actions that can protect the eye against the deleterious effects of the diabetic state. In this review, we summarize what is known about the changes in the circulating levels of prolactin and vasoinhibins during diabetes and diabetic retinopathy as well as the implications of these changes for the development and progression of the disease with particular attention to hyperprolactinemia in pregnancy and postpartum. We discuss the effects of prolactin and vasoinhibins that may impact diabetic retinopathy and suggest these hormones as important targets for therapeutic interventions., (Copyright © 2011 Wiley Periodicals, Inc.)