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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.)

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.)

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.)

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.)

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.)

Implantation in humans is a complex, closely regulated, highly selective and relatively poorly understood process. Humans have the highest rate of miscarriage in mammals and various pharmacological manipulations have been used to minimize pregnancy losses in both spontaneous pregnancies and pregnancies resulting from assisted reproduction technology. The widespread application of protocols using numerous drugs in assisted reproduction treatment has led to an increasing number of pregnancies exposed to these drugs. The vast majority of these protocols have been based on data from a few observational and often retrospective clinical studies. This paper reviews the recent literature on drug interventions in early pregnancy after assisted reproduction treatment. It is concluded that there are still numerous issues about the safety of most drugs for both the women and their fetus. In many cases, the benefits are theoretical and the possible long-term side-effects are untested. There is an urgent need for more epidemiological studies and randomized controlled trials to explore the use, efficacy and side-effects of both old and new drugs in early pregnancy after assisted reproduction treatment.

Prolactin is a polypeptide hormone that is synthesized and secreted from specialised cells of the anterior pituitary gland, known as lactotrophs. The hormone was given it's name because extracts from the bovine pituitary gland caused growth of the crop sac and stimulated the elaboration of crop milk in pigeons, and promoted lactation in rabbits. Although prolactin is best known for the multiple effects it exerts on the mammary gland, it has over 300 separate biological activities not represented by its name. It sub serves multiple roles in reproduction other than lactation and is an important modulator of homeostasis in the mammalian organism. Hence Bern and Nicoll suggested renaming it "omnipotin or versatilin". Schizophrenia is a severe psychiatric disorder that affects approximately one percent of the population worldwide. It is well established that traditional typical anti-psychotics elevate prolactin levels. It is also agreed that the serum prolactin concentration is not elevated in patients with schizophrenia who are not receiving anti-psychotic medication. Hyperprolactinaemia has direct effects on the brain and on other organs. Direct consequences include galactorrhoea. Indirect consequences of hyperprolactinaemia include oligomenorrhoea and amenorrhoea, erratic or absent ovulation, sexual dysfunction, reduced bone mineral density and cardiovascular disease. With the advent of prolactin sparing anti-psychotics, ample consideration needs to be given to the physiological consequences of hyperprolactinaemia in schizophrenic patients. In this paper we will examine molecular biology, secretion and physiology of prolactin. The consequences of hyperprolactinaemia in humans including effects on fertility, sexual dysfunction, bone mineral density, cardiovascular disease, changes in psychopathology and movement disorders will be reviewed. The literature on the association between schizophrenia, anti-psychotic medication and hyperprolactinaemia and more specifically on the consequences of this hyperprolactinaemia in schizophrenic patients will also be reviewed.

Prolactin (PRL), a polypeptide hormone secreted mainly by the pituitary and, to a lesser extent, by peripheral tissues, affects more physiological processes than all other pituitary hormones combined since it is involved in > 300 separate functions in vertebrates. Its main actions are related to lactation and reproduction. The initial step of PRL action is the binding to a specific membrane receptor, the PRLR, which belongs to the class 1 cytokine receptor superfamily. PRL-binding sites have been identified in a number of tissues and cell types in adult animals. Signal transduction by this receptor is mediated, at least in part, by two families of signaling molecules: Janus tyrosine kinases and signal transducers and activators of transcription (STATs). Disruption of the PRLR gene has provided a new mouse model with which to identify actions directly associated with PRL or any other PRLR ligands, such as placental lactogens. To date, several different phenotypes have been analyzed and are briefly described in this review. Coupled with the SAGE technique, this PRLR knockout model is being used to qualitatively and quantitatively evaluate the expression pattern of hepatic genes in two physiological situations: transcriptomes corresponding to livers from both wild type and PRLR KO mice are being compared, and following statistical analyses, candidate genes presenting a differential profile will be further characterized. Such a new approach will undoubtedly open future avenues of research for PRL targets. To date, no pathology linked to any mutation in the genes encoding PRL or its receptor have been identified. The development of genetic models provides new opportunities to understand how PRL can participate to the development of pathologies throughout life, as for example the initiation and progression of breast cancer.

A young female with organic delusional syndrome induced by hyperprolactinemia was admitted to the Psychiatry Clinic of Ankara Social Security Hospital. The most striking characteristic of her history was either worsening of the endocrinologic clinical outcome under conventional neuroleptic treatment or worsening of clinical psychiatric outcome under bromocriptine therapy. A new atypical neuroleptic, melperone, suggested to minimally affect plasma prolactin levels, was started. Her psychotic complaints significantly subsided and she was devoid of any symptomatological change regarding her endocrinological status. These results were discussed.

In the review of the physiological, pathological and therapeutical aspects of the role of hormones in the erectile process four main topics are discussed: gonadotrop axis dysfunction, hyperprolactinemia, impotence and the potential climacteric male deficit. The conclusion for therapy is that only organic lowering of testosterone should be treated with a dosage adapted to the level of the decrease.

The possibility of interactions between the effects of cyclosporine (CyA) and prolactin to regulate various physiological functions has been suggested. To further analyze these interactions, the effect of chronic CyA administration on the secretion of adenohypophyseal hormones in hyperprolactinemic male rats, was studied. Male rats were grafted one pituitary gland under the kidney capsule or were sham-operated at 30 days of age. Both pituitary-grafted and sham-operated rats were given s.c. injections of vehicle or CyA (5 mg/kg/day) for 30 days beginning on the day of surgery. Pituitary-grafting increased the plasma levels of prolactin and decreased the plasma levels of luteinizing hormone (LH), whereas growth hormone (GH), thyroid stimulating hormone (TSH) and follicle stimulating hormone (FSH) did not change. CyA treatment to sham-operated rats did not modify plasma prolactin levels and decreased plasma levels of GH and LH. Administration of the immunosuppressor to pituitary-grafted rats decreased plasma prolactin levels and augmented plasma levels of LH and FSH. Plasma TSH levels did not change after CyA treatment either in sham-operated or in pituitary-grafted rats. These data suggest that CyA may modify the effects induced by prolactin on pituitary hormone secretion, although direct effects of the drug on the hypothalamic-pituitary axis cannot be excluded, according to the data obtained in sham-operated rats.

We studied the chronic effects of hyperprolactinemia, induced by ectopic pituitary grafting, on blood glucose and lipid levels in adult male mice. For one year after pituitary grafting, we measured the blood levels of prolactin, growth hormone (GH), insulin, glucose and free fatty acid (FFA) at various intervals. The graft caused consistent hyperprolactinemia without changes in the serum GH levels. Hypoglycemia developed at 1 and 3 months after grafting but was not accompanied by any changes of the serum insulin levels. Thereafter, the blood glucose and serum insulin levels began to increase in the pituitary-grafted (PG) mice, and at 12 months after the operation, both levels became significantly higher in PG mice than controls. The serum FFA levels and the weight of epididymal fat bodies were significantly lower in PG mice than controls from 3-12 months after the grafting. Thus, hyperprolactinemia leads to persistent hypolipidemia and biphasic changes in the blood glucose level.

We examined a possible GH-releasing activity of vasoactive intestinal peptide (VIP) and its homologous peptide, peptide histidine methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 micrograms) and PHM (100 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Our objective was to clarify the relationship between the nocturnal melatonin surge and the nocturnal prolactin release in women with normoprolactinemia and mild hyperprolactinemia., Study Design: Nocturnal serum melatonin and prolactin levels were determined for a various awake/sleep and light/dark conditions in a total of 23 healthy normoprolactinemia and 9 mild hyperprolactinemia. Patterns of prolactin and melatonin levels were subject to analysis of variance., Results: During sleep deprivation under continuous illumination in normoprolactinemia, neither melatonin nor prolactin increased in concentration. In contrast, during sleep deprivation in a dark environment, both hormones were increased. The maximal prolactin levels in mild hyperprolactinemia under physiologic sleep/dark were significantly higher (p < 0.01) and were reached 2 hours earlier than in normoprolactinemia. However, each woman with mild hyperprolactinemia had similar melatonin surges. Oral administration (1 mg) of melatonin to normoprolactinemia and mild hyperprolactinemia in the daytime resulted in release of prolactin in a fashion similar to that observed during the night., Conclusion: Melatonin can regulate nocturnal prolactin secretion independent of sleep-related factors. Furthermore, the nature of the response to exogenous melatonin administration suggests that mild hyperprolactinemia may be unusually sensitive to melatonin.

In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.

Many physicians routinely measure the gonadotropins PRL, LH, and FSH and the androgens dehydroepiandrosterone (DHEA), androstenedione (ADIONE), and testosterone, as well as testosterone's biologically active fractions in the evaluation of hirsute women. Is this cost effective? To answer this question, 38 consecutive premenopausal hirsute women were evaluated. Two women each had minor elevations in PRL and FSH, and 11 had minor elevations in LH. Three women had minor elevations in the LH/FSH ratio, and only one was above a ratio of 3, believed to be indicative of polycystic ovarian syndrome. Because these gonadotropin elevations did not correlate with the androgens measured and were of no value in the diagnosis or management of these women, they were not believed to be cost effective. Their routine measurements should be abandoned.

To determine if the inhibitory effects of hyperprolactinemia on sexual arousal and serum LH levels could be dissociated from those on erectile function, copulatory behavior was examined in pituitary-grafted, adrenalectomized male rats that had been castrated and given 20mm subcutaneous testosterone implants. Whereas transplantation of three pituitaries under the kidney capsules inhibited mounting rates in intact animals, pituitary grafting did not significantly reduce mounting rates in the adrenalectomized group beyond the effect of adrenalectomy alone. In contrast, the effects of pituitary grafting on erectile function were enhanced in the adrenalectomized animals. Hyperprolactinemia also caused a significant reduction in serum LH, but only in the intact animals. These results suggest that: 1. the effects of hyperprolactinemia on erectile function occur independently from those on sexual arousal, and 2. the inhibitory effects of hyperprolactinemia on sexual arousal are linked to the effects of hyperprolactinemia on LH release.

Prolactin, administered exogenously, has been shown to be trophic to the liver, causing increases in the liver weight-to-body weight ratio. In ornithine decarboxylase activity, and in thymidine kinase activity. To investigate the effect of endogenous hyperprolactinemia on hepatic regeneration, pituitary isografts were placed beneath the renal capsule in rats 2 weeks before the rats underwent a two-thirds partial hepatectomy. Prolactin levels 2 weeks after the transplant were greater in the animals with the pituitary isografts compared with levels in controls. The increase in the liver weight-to-body weight ratio after hepatectomy was similar in the rats with pituitary transplant and the controls. However, chronic hyperprolactinemia was associated with increased basal levels of ornithine decarboxylase activity and thymidine kinase activity. Both ornithine decarboxylase activity and thymidine kinase activity increased after partial hepatectomy, and the magnitude of the changes was similar for both groups of animals. The levels of estrogen receptor activity before the partial hepatectomy and the reduction in receptor activity that follows partial hepatectomy were similar in the two groups of animals. Moreover, the levels of androgen receptor activity within the liver before partial hepatectomy and the increase in receptor activity after hepatectomy were similar in the two groups of animals. Thus, chronic sustained hyperprolactinemia has no beneficial effect on the hepatic regenerative response, despite induction of both basal ornithine decarboxylase and thymidine kinase activities.

Although many causes of hyperprolactinemia exist, medications and prolactin-secreting pituitary tumors (prolactinomas) are the most common etiologies. The mainstay of medical management for pituitary tumors as well as for most causes of hyperprolactinemia is bromocriptine. The drug can be used alone or in conjunction with other therapeutic modalities, including surgical resection and pituitary irradiation, depending on the clinical scenario. Bromocriptine can lower serum prolactin, reduce tumor size, and restore fertility in those patients during pregnancy. As bromocriptine is not always well tolerated and requires frequent dosing, newer agents that may diminish side effects and improve compliance are under investigation.

The human prolactin molecule has been isolated and its structure characterized. This anterior pituitary hormone plays an important function in the induction and maintenance of lactation in the post-partum nursing mother. Prolactin-producing tumors cause inappropriate lactation in the nonpregnant woman. Bromocriptine, an ergot derivative, mimics the action of dopamine in the anterior pituitary gland and does not cure the underlying pathology. Prior to the development of bromocriptine, there was no effective treatment for the symptoms of amenorrhea and galactorrhea. Although the methods of therapy are more sophisticated today, there remain a number of unanswered questions. The unknown long-term risks of bromocriptine therapy must be balanced against the potential risk of osteopenia.

The present investigation was aimed at comparing the influence of the partial dopamine (DA) receptor agonist (-)-3-PPP (preclamol) on prolactin release in acutely hyperprolactinemic but otherwise intact female rats and female rats subjected to chronic DA depletion. One group of animals received daily vehicle injections (controls) and another group daily reserpine (1 mg/kg) injections for a period of seven days. On the eighth day all animals were administered 10 mg/kg of reserpine in order to eliminate endogenous DA and elevate serum prolactin levels. In the control group (-)-3-PPP lowered serum prolactin levels only moderately. In contrast, in the chronically reserpinized female rats, a pronounced reduction of prolactin secretion was observed. It is suggested that this increase in intrinsic activity of (-)-3-PPP following chronic DA depletion reflects an enhanced responsiveness of hypophyseal DA receptors, possibly due to conformational changes in the receptor molecules. Our observations lend further support to the hypothesis that an inverse relationship exists between the intrinsic activity of a mixed agonist/antagonist and the degree of previous receptor occupancy.