Ropinirole for the Treatment of Hyperprolactinemia: A Dose-Escalation Study of Efficacy and Tolerability.

CONTEXT: Treatment of hyperprolactinemia with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. OBJECTIVE: This study examines the efficacy and tolerability of the nonergot DA ropinirole for the long-term treatment of hyperprolactinemia. METHODS: Twelve hyperprolactinemic women were treated with ropinirole in a 6-month, open-label, dose-escalation trial; 7 of the 12 continued treatment in an extension study for up to 17 months. Ropinirole doses were uptitrated to achieve normal prolactin (PRL) levels, restore menses, and eliminate galactorrhea. RESULTS: Two of the 12 participants were DA naive; 6 of 12 were ergot DA intolerant; and 1 of 12 had known ergot DA resistance. Baseline PRL levels were 126.2 ± 41.4 ng/mL (SEM). Ropinirole was uptitrated from 0.125 to 0.25 mg/h to a median total daily dose (TDD) of 2 mg/d (1-4 mg/d [interquartile range]). PRL normalization was achieved in 50% of the participants (5 with microadenomas and 1 with idiopathic hyperprolactinemia) at a median effective TDD of 1 mg/d. Of the patients achieving PRL normalization, 83% were ergot DA intolerant. A persistent partial biochemical response (PRL reduction >50% from baseline) was achieved in 17% of the participants. During treatment, menses resumed in 67% of amenorrheic patients; galactorrhea resolved in 67%. Mild adverse effects were reported in 92% of participants; however, ropinirole was not discontinued because of intolerance even among the 50% of individuals with a prior history of ergot DA intolerance and resultant medication discontinuation. CONCLUSION: These data demonstrate the efficacy and tolerability of ropinirole for the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia and suggest ropinirole may represent a novel therapeutic alternative for treating hyperprolactinemic disorders in patients with ergot DA intolerance.

Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study.

OBJECTIVE: Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce. METHOD: Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician's-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly. RESULTS: Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61), galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001). CONCLUSION: Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

Methods and Success Factors of Induced Lactation: A Scoping Review.

BACKGROUND: Induced lactation enables a woman who has not given birth to breastfeed a child. Lactation may be induced through both pharmacological and non-pharmacological methods, although the desired outcome cannot always be achieved. RESEARCH AIMS: The aims of this scoping review was to assess the different methods used to induce lactation, as well as the factors related to sucking the breast effectively and the production of human milk. METHODS: We searched five databases from June 2019-February 2020 for studies referring to methods and factors related to breast suckling and/or the volume of milk produced after inducing lactation, using the following search terms and Boolean operators: breastfeeding AND induced lactation AND adoptive mothers OR surrogate mothers OR female homosexuality OR non-gestating. The final review included a total of 24 articles. RESULTS: Pharmacological methods were not always used to produce milk, although breast stimulation was essential. The age of the child, interference due to bottle feeding, breast stimulation, and the support received were important factors in the induction of lactation. There were several factors that may account for the differences between developing and higher income countries in methods of induced lactation and the amount of milk that study participants produced. There was no consensus over whether previous pregnancy and/or breastfeeding experience influenced induced lactation. CONCLUSION: Health professionals need to have adequate knowledge about induction methods, the preferences of each woman, and the reasons for inducing lactation, to provide proper assistance. However, the lack of standardization about induction of lactation makes it difficult.

Clinical, Hormonal, and Neuroradiological Characteristics and Therapeutic Outcomes of Prolactinomas in Children and Adolescents at a Single Center.

Background/Purpose: A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum, treatment, and outcomes of prolactinomas in childhood and adolescence. In this single-center cohort study, we assessed the clinical, hormonal, and neuroradiological characteristics and therapeutic outcomes of children and adolescents with prolactinomas. Methods: This retrospective cohort study included 25 patients with prolactinomas diagnosed before 19 years of age, who presented at Samsung Medical Center during a 15-year period (March 2005 to August 2019). Results: The median age at diagnosis was 16.9 (range 10.1-18.5) years, and 80% of the patients were female. The common clinical manifestations at diagnosis were galactorrhea (10/20, 50%) and amenorrhea (9/20, 45%) among females and visual field defects (3/5, 60%) and headaches (2/5, 40%) among males. In our cohort, macroadenomas accounted for 56% of cases, and the rate of overall responsiveness to dopamine agonists (DAs) was 56% (10/18). Male gender, the prolactin (PRL) level at diagnosis, and the presence of panhypopituitarism were positively correlated with maximum tumor diameter (r = 0.443, P = 0.026; r = 0.710, P < 0.001; and r = 0.623, P = 0.001, respectively). After the trans-sphenoidal approach (TSA), 53% (8/15) of patients showed normalization of the PRL level. Three patients, who underwent gamma knife surgery (GKS) owing to either resistance or intolerance to DAs or recurrence after the TSA, achieved a normal PRL level accompanied with marked tumor reduction and symptom remission. Conclusions: A macroprolactinoma is more prevalent than a microprolactinoma in children and adolescents than in adults. Male gender, increased PRL levels, and the presence of panhypopituitarism at diagnosis are closely related to macroprolactinomas in children and adolescents.

Galactorrhea Following Minimally Invasive Reoperative Mitral Valve Replacement: An Unexpected Complication.

Galactorrhea, or nonpuerperal lactation, is a rare complication that can occur after trauma to the chest wall. Although galactorrhea has been reported after thoracic surgery, it has not been previously noted as a potential outcome following cardiac surgery. We present a unique case of hyperprolactinemic galactorrhea experienced by a 39-year-old nongravid female patient after having undergone reoperative mitral valve replacement via a right minithoracotomy. To the best of our knowledge, this is the first reported case of spontaneous lactation occurring after cardiac surgery.

Bromocriptine as a Potential Glucose-lowering Agent for the Treatment of Prolactinoma with Type 2 Diabetes.

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the treatment of prolactinoma, bromocriptine 2.5 mg/day was started. After seven days, her post-prandial blood glucose levels, homeostasis model assessment of insulin resistance and plasma C-peptide levels were significantly improved. These results indicate that traditional bromocriptine can be an effective therapeutic alternative in patients with prolactinoma complicated with type 2 diabetes.

Más allá del botón mamario y la ginecomastia puberal / Beyond de breas buds and pubertal gynecomastia. Knowing the breast pathology

Introducción. Los pediatras estamos poco familiarizados con la patología de la mama de niños y adolescentes, debido en parte a su baja incidencia en la edad pediátrica y al escaso conocimiento que tenemos de. las diferentes patologías que pueden asentar en ella. Es importante ampliar nuestros conocimientos en esta patología, sobre todo en relación con la patología del adolescente, para así mejorar el manejo de estas patologías. Material y métodos. Revisamos las historias de 7 pacientes atendidos en el Servicio de Urgencias y en las consultas de Pediatría en relación a patología de la mama, y revisamos la bibliografía al respecto. Conclusiones. Queremos hacer hincapié en las diferentes patologías de la mama en la edad pediátrica para facilitar el diagnóstico y manejo de esta patología (AU)

Introduction. Pediatricians are not very familiar with breast diseases of children and adolescents due to the low incidence in pediatric age and our spare knowledges. It's important to improve our understanding, above all concerning the adolescent group. Material and methods. We reviewed the medical records of 7 patients attended in the emergency department or in the consulting rooms of the hospital diagnosed of different breast diseases. We also reviewed the related references. Conclusion. We want to remember the different breast diseases to case diagnosis and management of these pathologies (AU)

[Treatment of antipsychotic drug-induced phlegm dampness type amenorrhea by Wuji Powder and a small dose aripiprazole: a clinical study].

OBJECTIVE: To assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea. METHODS: Seventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated. RESULTS: The treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05). CONCLUSIONS: Both WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.

Hyperprolactinemia as a rare cause of hypertension in chronic renal failure.

Chronic renal failure (CRF) is associated with a high risk for hypertension. An individualized treatment should be initiated after the diagnosis of hypertension and underlying etiology. Many metabolic and endocrinal abnormalities are encountered in CRF. We present an 11-year-old boy with CRF developing galactorrhea and hyperprolactinemia associated with α-methyldopa, defective dopaminergic control, and resistance to multi-antihypertensive therapy. Cabergoline, a dopamine receptor agonist, was effectively used in the treatment of hypertension. It is important to remember that sometimes treatment of an illness becomes the cause of this illness.

[Inappropriate lactation syndrome in goats--case collection and experiences with mastectomy]. / Lactatio falsa bei der Ziege - Fallsammlung und Erfahrungen mit der Amputation des Gesäuges.

OBJECTIVE: Hobby keeping of goats and sheep confronts veterinarians with new challenges that rarely have to be faced in livestock husbandry. During the last five years five goats were presented to the Clinic for Animal Reproduction, Faculty of Veterinary Medicine, Freie Universität Berlin, Germany, with inappropriate lactation syndrome. Four of these animals had been previously treated with cabergoline without enduring success. According to the request of the owners (informed consent) and the clinical severity of the cases, a mastectomy was performed in all five animals. MATERIAL AND METHODS: Surgery was performed under general anaesthesia using ketamine and xylazine, and with the patients in a recumbent position. RESULTS: Mastectomy in small ruminants requires knowledge of the anatomy of the udder and the possible positions of the supplying blood vessels. Our patients displayed a variety of dispositions of the Vena epigastrica caudalis superficialis. Special attention should be paid to a careful and blunt dissection of the mammary gland, and immediate control of haemorrhage, to maintain a clear view on the anatomic structures. Furthermore, dissection of the glandular tissue should be strictly avoided to prevent milk contamination of the surgical area. A sufficient skin flap has to be left to cover the surgical area after removal of the udder. CONCLUSION AND CLINICAL RELEVANCE: Even though udder amputation appears to be a radical and high-risk procedure, all five goats survived the surgery. The wound healing occurred in a reasonable time without any severe complications. In goats that are kept as "hobby animals" and in which an inappropriate lactation syndrome cannot be treated conservatively, mastectomy is a reasonable and promising therapy.

Pregnancy rate following bromocriptine treatment in infertile women with galactorrhea.

OBJECTIVE: Infertility is one of the most common causes of women refer to gynecology clinics. Galactorrhea is defined as one of the causes of infertility caused by luteal phase defect and anovulatory cycles. The study aim was to investigate the effect of bromocriptine on pregnancy rate in infertile women with galactorrhea with or without high prolactin level. MATERIALS AND METHODS: In a prospective study, consecutive women with infertility and galactorrhea who referred to Afzalipour Hospital and a private clinic during 5 years from May 2001 to May 2006 were included. The study was conducted on 205 infertile women (18-39 years) with galactorrhea. They were treated with 2.5 mg bromocriptine BID for up to 6 months. RESULTS: The mean duration of sterility was 43.1 +/- 37.1 months (range, 12-16). 76.1% of patients showed positive signs for pregnancy. The pregnancy rate was 81.7% in the patients with high prolactin level (>20 ng/dl) and 74.3% in the patients with normal prolactin level (P = 0.26). There was a significant difference between mean duration of treatment with bromocriptine in women with and without pregnancy, 103.71 and 193.03 days, respectively (P < 0.001). CONCLUSION: Considering the efficacy of bromocriptine in the treatment of infertile women with galactorrhea, we suggest treatment with bromocriptine in these patients regardless of serum prolactin level.

[Effect of Tongdatang Serial Recipe on antipsychotic drug-induced galactorrhea-amenorrhea syndrome].

OBJECTIVE: To observe the clinical effect of self-formulated Tongdatang serial recipe (TDT) in treating antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS). METHODS: One hundred female schizophrenic patients with antipsychotic drug-induced GAS were selected and equally assigned to the treatment group and the control group at random. Both received antipsychotic drug-therapy, but combined with TDT and placebo respectively. The efficacy was evaluated by determining prolactin level before, 4 and 8 weeks after treatment. RESULTS: The treatment course was completed in 96% of patients. Therapeutic efficacy on the 49 patients of the treatment group was cured in 31 (63.3%), markedly effective in 11 (22.4%), effective in 4 (8.2%) and ineffective in 3 (6.1%), with total effective rate of 93.9%, while in 47 patients of the control group, the corresponding cases (%) was 0, 3 (6.4%) , 7 (14.9%) and 37 (78.7%), respectively, with the total effective rate of 21.3%. Prolactin levels in the two groups were insignificantly different before treatment, it reduced in the treatment group after treatment (P < 0.01), and the decrement in the treatment group was more significant than that in the control group (P < 0.05). CONCLUSION: Satisfactory effect could achieved by using TDT for treatment of antipsychotic drug-induced GAS.

Galactorrhea and amenorrhea in burn patients.

INTRODUCTION: Galactorrhea and/or amenorrhea, although uncommonly reported in post-burn patients, is a complex problem to treat. Patient is reluctant to volunteer history of these symptoms, unless asked specifically. AIM: To study profile of adult female patients with galactorrhea and/or amenorrhea in post burn period. MATERIALS AND METHOD: A prospective study of all adult female patients presenting with or detected to have galactorrhea and/or amenorrhea in post burn period was conducted over 6 month's period. Detailed clinical examination, estimation of LH, FSH, Prolactin levels and X-ray of skull was done in all patients. The data collected was analyzed. Patients with hyperprolactinemia and galactorrhea were treated with Bromocriptine for 3 weeks to 3 months. In all patients with amenorrhea, pregnancy was ruled out by gynecological examination and urine pregnancy test. RESULTS: During this period, 30 patients (15.15%) were detected to have galactorrhea and/or amenorrhoea. The extent of burn in these patients was 20-65%of body surface area. Out of 30 patients, 5 had galactorrhea and amenorrhea, 1 galactorrhea alone and 24 had amenorrhea alone. Analysis of voluntary disclosures and detection on interrogation was done. Till the end of study, 4 patients with galactorrhea had complete relief, 2 patients reported reduction in discharge. DISCUSSION: Galactorrhea was distressing for all and was always associated with high prolactine levels .The reverse was not true. All the patients had chest burns besides other body areas. Association was noted between menstrual aberration and ovulatory phase at the time of burn. CONCLUSION: Galactorrhea and menstrual disturbances do exist in female patients in reproductive age group in post burn period and patients should be especially interrogated for these symptoms by the burn care providers.

Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine.

This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not significantly different between groups. Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and standing blood pressure than non-switched patients. Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia.

[Verapamil-induced hyperprolactinemia--a case report]. / Hiperprolaktynemia spowodowana przez werapamil. Opis przypadku.

In many cases hyperprolactinemia can be caused by taking medications. Occasionally, verapamil-treated patients experience a slight asymptomatic increase in serum prolactin level. In this article we report the case of 42-year woman with manifest verapamil-induced hyperprolactinemia whose clinical symptoms suggested the occurrence of prolactinoma. A marked increase in prolactin levels and the preserved reactivity of this hormone in dynamic tests suggested that the patient exhibited "hypersensitivity" to verapamil. In the described state of the examined female detection of the disease, verapamil withdrawal and temporary bromocriptine administration have led to a full normalization of patient's clinical status.