Impaired Cardiometabolic Effects of Bromocriptine in Men With Early-Onset Androgenic Alopecia.

Both hyperprolactinemia and early-onset androgenic alopecia are associated with increased cardiometabolic risk. The aim of this study was to assess whether early-onset male-pattern baldness modifies cardiometabolic effects of bromocriptine in men with prolactin excess. The study included 2 groups of men with prolactin excess: individuals with early-onset androgenic alopecia (group 1) and individuals with normal hair growth (group 2). Both groups were matched for age, smoking habits, body mass index, blood pressure, and prolactin levels. Over the entire study period (4 months), all participants were treated with bromocriptine (7.5 mg daily). Plasma levels of hormones (prolactin, total testosterone, and bioavailable testosterone), glucose homeostasis markers, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and the urinary albumin-to-creatinine ratio (UACR) were measured at the beginning and at the end of the study period. The two groups differed in total testosterone, bioavailable testosterone, insulin sensitivity, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine, and UACR. In both groups, bromocriptine reduced prolactin, increased total and bioavailable testosterone, improved insulin sensitivity, and decreased uric acid, hsCRP, and homocysteine. The impact on prolactin, insulin sensitivity, uric acid, hsCRP, and homocysteine was stronger in group 2 than in group 1. Only in group 2 did the drug increase HDL cholesterol and decrease triglycerides, fibrinogen, and UACR. The impact on cardiometabolic risk factors correlated with a reduction in prolactin levels and an improvement in insulin sensitivity, and, in group 1, inversely correlated with testosterone levels. The obtained results suggest that men with early-onset androgenic alopecia are partially resistant to the cardiometabolic effects of bromocriptine.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

Bromocriptine therapy: Review of mechanism of action, safety and tolerability.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.

Pregnancy and Tumor Outcomes in Women with Prolactinoma.

Context Management of prolactinomas during pregnancy has always been a challenge. There is a concern about the risk of tumor growth, as well as the effects of the treatment on the developing fetus. Another issue that has been less studied is the outcome of women with prolactinoma after pregnancy and lactation. Objectives To evaluate remission of hyperprolactinaemia after pregnancy and lactation in women with prolactinoma. To describe the safety of dopamine agonists for the fetus and pregnancy outcomes. Methods A retrospective study of 32 pregnancies in women with prolactinoma was conducted in a single-centre. Other causes of hyperprolactinemia were excluded. Prolactin level was recorded at the time of diagnosis, during treatment, and during follow-up. Results The pregnancies resulted in one spontaneous abortion (3.1%) and 31 live births (96.9%). No stillbirths, multiple or ectopic pregnancies or trophoblastic disease were recorded. There was only one malformation (club foot) recorded (3.1%) and normalisation of prolactin after pregnancy without medical treatment occurred in 12% of patients. Conclusions Fetal exposure to bromocriptine or cabergoline during pregnancy is not associated with an increased risk of adverse neonatal or pregnancy disclosures. There is considerable diversity among endocrinologists in the management of prolactinomas during pregnancy and after birth, which indicates that there is a need for better consensus and for carefully drawn-up guidelines to follow.

Progressão de Valvopatia Esquerda durante o Uso de Dopaminérgicos / Progression of Left Valve Disease during Use of Dopaminergic Drugs

A cabergolina e a bromocriptina são drogas dopaminérgicas derivadas do ergot e utilizadas para tratamento de distúrbios hiperprolactinêmicos idiopáticos ou adenomas hipofisários, cujo mecanismo de ação é decorrente da redução da secreção de prolactina. Alguns relatos na literatura demonstram que a cabergolina pode causar valvopatia após sua administração a longo prazo. Relatamos o caso de um paciente com diagnóstico de macroprolactinoma que fez uso intercalado de cabergolina e bromocriptina e desenvolveu alterações valvares antes inexistentes

Analysis of bromocriptine treatment in pregnant pituitary prolactinoma patients.

OBJECTIVE: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma. MATERIALS AND METHODS: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine. RESULTS: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05). CONCLUSION: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

Dopa-testotoxicosis: disruptive hypersexuality in hypogonadal men with prolactinomas treated with dopamine agonists.

Dopamine agonists are the first line of therapy for prolactinomas, with high rates of biochemical control and tumour shrinkage. Toxicity is considered to be low and manageable by switching of agents and dose reduction. Dopamine agonist-induced impulse control disorders are well described in the neurology setting, but further data are required regarding this toxicity in prolactinoma patients. We performed a multicenter retrospective cohort study of eight men with prolactinomas and associated central hypogonadism. The eight men had no prior history of psychiatric disease, but each developed disruptive hypersexuality whilst on dopamine agonist therapy at various doses. Cabergoline, bromocriptine and quinagolide were all implicated. Hypersexuality had manifold consequences, including relationship discord, financial loss, reduced work performance, and illicit activity. We hypothesise that this phenomenon is due to synergy between reward pathway stimulation by dopamine agonists, together with rapid restoration of the eugonadal state after prolonged hypogonadism. We refer here to this distinct drug toxicity as 'dopa-testotoxicosis'. Given the profound impact in these patients and their families, cessation of dopamine agonists should be considered in men who develop hypersexuality, and pituitary surgery may be required to facilitate this. Awareness of this distinct impulse control disorder should enable further research into the prevalence, natural history and management of dopa-testotoxicosis. The condition is likely under-reported due to the highly personal nature of the symptoms and we suggest a simple written questionnaire to screen for hypersexuality and other behavioural symptoms within the first six months of dopamine agonist treatment.

A review of dopamine agonist therapy in type 2 diabetes and effects on cardio-metabolic parameters.

Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long-acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma.

Transient psychosis in women on clomiphene, bromocriptine, domperidone and related endocrine drugs.

BACKGROUND: There have been reports of transient psychosis in women medicated for gynecologic conditions. OBJECTIVE: The aim of this paper was to explore this literature. METHOD: The PubMed and Google Scholar databases were searched for relevant case reports Results: The following reports were found: psychosis induced by gonadotropin-releasing hormone in the treatment of endometriosis, by clomiphene treatment for infertility, by bromocriptine treatment for milk suppression and by the withdrawal of domperidone prescribed as a galactologue as well as by the withdrawal of estrogen replacement therapy. CONCLUSION: In susceptible women, psychotic symptoms can result from treatments that reduce estrogen levels, such as leuprolide acetate or clomiphene, or treatments that increase dopamine levels (bromocriptine). Psychosis can also be caused indirectly when estrogen treatment is discontinued or dopamine antagonism (e.g. domperidone) withdrawn. Estrogen-reducing and dopamine-increasing treatments used in gynecology need to be carefully monitored.

Severe adverse effects of bromocriptine in lactation inhibition: a pharmacovigilance survey.

OBJECTIVE: To assess the nature and conditions of the occurrence of adverse drug reactions (ADRs) of bromocriptine, which is used to inhibit lactation. DESIGN: Observational study. SETTING: Cases from the French pharmacovigilance database and the marketing authorisation holders. SAMPLE: Serious ADRs reported between 1994 and 2010 in association with bromocriptine used for lactation inhibition in France. METHODS: Each case was checked to confirm the bromocriptine indication, the seriousness of the ADR, the modalities of bromocriptine use, and to identify possible associated predisposing factors. MAIN OUTCOME MEASURES: Number and description of serious ADRs, with a particular focus on misuse and associated predisposing factors. RESULTS: Among 105 serious ADRs, including two fatal cases, the most frequent were cardiovascular (70.5%), neurological (14.3%), and psychiatric (8.6%) disorders. Cardiovascular disorders primarily consisted of ischaemic manifestations (n = 47): acute ischaemic stroke (n = 18, one death), myocardial infarction (n = 11, one death), and reversible postpartum cerebral angiopathy (n = 10). Misuse was identified in 52 cases (70.3%) of cardiovascular disorders, and mostly consisted of bromocriptine continuation despite the occurrence of first symptoms suggesting an ADR or the absence of a progressive titration of bromocriptine. About half of these women had cardiovascular predisposing factors, mainly tobacco smoking, overweight or obesity, or a history of hypertension or pre-eclampsia. CONCLUSIONS: This survey, together with published data, provides further evidence that serious ADRs still occur after bromocriptine use in lactation inhibition, and that most of these ADRs could have been avoided. The use of bromocriptine should therefore be limited to cases where no other options are available to inhibit lactation.

Divergent long-term consequences of chronic treatment with haloperidol, risperidone, and bromocriptine on traumatic brain injury-induced cognitive deficits.

Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH (p=0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy.

Endoscopic transsphenoidal treatment of a prolactinoma patient with brain and optic chiasmal herniations.

Bromocriptine has been the most widely used and effective agent to treat macroprolactinoma, and chiasmal herniation in a macroprolactinoma patient following the treatment with bromocriptine is a well-recognized complication. However, herniation of the inferior mesial frontal lobe into the sella has been rarely reported. The present clinical report is the second radiographic demonstration of herniation of the inferior mesial frontal lobe into the sella. After the treatment with transsphenoidal endoscopic chiasmopexy, the patient's visual disturbance improved dramatically. We suggest that transsphenoidal endoscopic chiasmopexy is an effective treatment option for the prolactinoma patient with brain and chiasmal herniations following the treatment with bromocriptine.

Young female with acromegaloid features and pituitary macroadenoma: what is your diagnosis?

Pseudoacromegaly is a extremely rare condition previously described and characterized by acromegaloid changes, tissue overgrowth, without elevations in insulin-like growth factor or growth hormone as seen in Acromegaly. We present the case of a young female seen initially with acromegaloid features and a pituitary microadenoma. After work-up the patient was diagnosed as insulin-mediated pseudoacromegaly. Only a few cases of pseudoacromegaly has been reported and should always be considered when evaluating patients for acromegaloid features with negative biochemical and hormonal levels.

["Mid-stimulation psychosis" in the course of in vitro fertilization procedure with the use of clomiphene citrate and bromocriptine - case study]. / Przypadek "psychozy okolostymulacyjnej" w przebiegu procedury zaplodnienia pozaustrojowego z zastosowaniem cytrynianu klomifenu oraz bromokryptyny.

AIM: A few cases of psychosis induced by clomiphene citrate have been described so far. However, data on the prevalence of psychotic symptoms among women treated for infertility are inconclusive. Still a little is known about possible psychiatric complications of medications used in assisted reproduction techniques (ART). We present a case of a patient who developed transient psychotic symptoms in the course of the in vitro fertilization procedures. To our kiiowledge, this is the first case of 'mid-stimulation psychosis', which has been observed during ART using clomiphene.citrate and bromocriptine. The aim of this study is to describe the determinants ofpharmacotherapy undertaken in ART,.which can result in the development of psychotic symptoms. METHODS: The Case presentation. CONCLUSIONS: The use of clomiphene citrate for ovulation induction in combination with bromocriptine used for chronic hyperprolactinemia is a likely mechanism that might have triggered psychotic symptoms in the case presented. However, combination therapy with clomiphen citrate and.bromocriptine may be the pharmacological model of hyper-dopaminergia followed by chaotic changes in serum estrogen levels and might lead to an increased sensitivity of dopamine receptors. The above therapeutic schema may increase susceptibility to the development of psychotic symptoms in treated women. This impact should be considered in the case of any psychotic complications in patients undergoing assisted reproduction techniques

Impulse control disorder in a patient on long-term treatment with bromocriptine for a macroprolactinoma.

Impulse control disorders (ICDs) constitute socially disruptive behaviors such as pathological gambling, impulsive eating, compulsive shopping, and hypersexuality. These conditions are well recognized in patients on dopamine agonist (DA) therapy for Parkinson disease. Dopamine agonists are widely used as first-line agents in the treatment of prolactinomas, but ICDs in this group of patients are relatively rare, perhaps because of lower therapeutic doses used. A review of the literature yielded only a few cases of ICDs in patients on DA treatment for prolactinomas. These symptoms are perhaps underreported because of lack of awareness among patients and health care professionals. Impulse control disorders are recognized psychiatric disorders that have significant psychological and social implications, and patients need to be counselled about this rare possibility when embarking on prolonged DA therapy. We describe a young patient with severe, socially disruptive impulsivity manifesting with pathological gambling who had been on long-term bromocriptine therapy for a macroprolactinoma.

The effects of bromocriptine on VEGF, kidney function and ovarian hyperstimulation syndrome in in vitro fertilization patients: a pilot study.

The aim of this study was to evaluate the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty-eight women were randomly divided into two groups and were administered daily oral capsules for 14 days, starting on the day of human chorionic gonadotropin (hCG) administration. Group A received 2.0 mg of folic acid, whereas Group B was given 2.5 mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and again 7 days later. No differences in ovarian hyperstimulation syndrome, urine volume, creatinine clearance, urine sodium concentration or serum VEGF levels were found between the two groups. Thus, these results indicate that bromocriptine does not affect blood levels of VEGF, kidney function or the incidence of ovarian hyperstimulation syndrome in high-risk patients subjected to in vitro fertilization.