RESUMO
BACKGROUND: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. METHODS: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. RESULTS: The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. CONCLUSION: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.
Assuntos
Cabergolina , Clomifeno , Hipogonadismo , Neoplasias Hipofisárias , Prolactinoma , Humanos , Masculino , Adulto , Prolactinoma/tratamento farmacológico , Pessoa de Meia-Idade , Hipogonadismo/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hipofisárias/tratamento farmacológico , Cabergolina/uso terapêutico , Cabergolina/administração & dosagem , Clomifeno/uso terapêutico , Clomifeno/administração & dosagem , Resultado do Tratamento , Testosterona/sangue , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Ergolinas/uso terapêutico , Ergolinas/administração & dosagem , Prolactina/sangueRESUMO
OBJECTIVE: Discontinuation of dopamine agonist (DA) treatment in women with prolactinoma after menopause is a potential approach; studies systematically assessing long-term outcomes are lacking. Our aim was to investigate the natural history of prolactinoma in this group. DESIGN/PATIENTS: Retrospective cohort study of women with prolactinoma diagnosed before menopause and who after menopause were not on DA. RESULTS: Thirty women were included. Twenty-eight received DA (median duration 18 years, median age at DA withdrawal 52 years). At last assessment (median follow-up 3 years) and compared with values 6-12 months after stopping DA, Prolactin (PRL) increased in 15%, decreased but not normalized in 33% and was normal in 52%; PRL levels or visible adenoma on imaging before DA withdrawal, treatment duration and presence of macro-/microadenoma at diagnosis were not predictors of normoprolactinaemia at last review, whereas PRL values 6-12 months after stopping DA were. Adenoma regrowth was detected in 2/27 patients (7%), who showed gradual increase in PRL. Comparison with 28 women who had DA withdrawal before their menopause revealed lower risk of hyperprolactinaemia recurrence in the postmenopausal group (HR:0.316, 95% CI: 0.101-0.985, P < .05). Two women with microprolactinoma diagnosed in perimenopausal period had not been offered DA; PRL decreased (but not normalized) during observation of 1 and 8 years. CONCLUSIONS: Prolactin normalized over time in nearly half of the women and serum PRL 6-12 months after DA withdrawal is useful predictor. Nonetheless, 7% of the patients demonstrated adenoma regrowth which, given the life expectancy postmenopause, necessitate regular monitoring of the cases with persistent hyperprolactinaemia.
Assuntos
Agonistas de Dopamina/uso terapêutico , Menopausa/fisiologia , Prolactinoma/tratamento farmacológico , Adolescente , Adulto , Bromocriptina/administração & dosagem , Bromocriptina/uso terapêutico , Cabergolina/administração & dosagem , Cabergolina/uso terapêutico , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Ergolinas/uso terapêutico , Feminino , Humanos , Pós-Menopausa , Prolactina/sangue , Prolactinoma/sangue , Estudos Retrospectivos , Suspensão de Tratamento , Adulto JovemRESUMO
OBJECTIVE: The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle. STUDY DESIGN: It is a prospective controlled study, where 250 CCR-PCOD women (n = 250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n = 120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg) was added when a leading follicle reaches 14-16 mm combined with oral Cb in a dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25 IU/L, ± 14 d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3 months for the possible development of any signs and symptoms of OHSS. RESULTS: None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n = 3, 15%) in group B compared with group A (p < .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed. CONCLUSION: LOD could be considered a good prophylactic measure against OHSS, in addition to improving the total outcome of IVF cycles in women with CCR-PCOS.
Assuntos
Ergolinas/administração & dosagem , Procedimentos Cirúrgicos em Ginecologia/métodos , Antagonistas de Hormônios/administração & dosagem , Laparoscopia/métodos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Ovário/cirurgia , Prevenção Secundária/métodos , Adulto , Cabergolina , Quimioprevenção/métodos , Clomifeno/uso terapêutico , Resistência a Medicamentos , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Infertilidade Feminina/terapia , Síndrome de Hiperestimulação Ovariana/etiologia , Indução da Ovulação/efeitos adversos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/terapia , Gravidez , Falha de TratamentoRESUMO
Human and animal data indicate that the dopaminergic system plays a crucial role in sexual drive and function. Using a double-blind, placebo-controlled crossover design, this prototype study investigated the effect of the D2 dopamine agonist cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital parameters were monitored continuously. Sexual drive and function were measured using self-report sexual experience scales. In contrast to previous theories and assumptions, we found that cabergoline did not alter objective and subjective sexual parameters in healthy women. This finding suggests that there may be sex differences in the influence of the dopaminergic system on human sexual functioning.
Assuntos
Nível de Alerta/efeitos dos fármacos , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Adulto , Cabergolina , Método Duplo-Cego , Feminino , HumanosRESUMO
INTRODUCTION: Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood. This condition is preferentially treated with dopamine agonists. Resistance to these drugs is rare. CASE REPORT: We describe the case of a boy diagnosed with macroadenoma at the age of 9 and followed up for 21 years. He did not fully respond to treatment with dopamine agonists. His initial prolactin level was 2,400 ng/mL (in males, normal values are <16.0 ng/mL) and never normalized. At the last assessment, his prolactin level was 21.5 ng/mL, recorded after 21 years of treatment with the dopamine agonist cabergoline at a dose as high as 4.5 mg per week. Although the prolactin level remained elevated throughout the follow-up period, the patient never presented a low testosterone level and had normal pubertal development. An MRI of the sella turcica showed that the tumor became progressively cystic and disappeared, but a normal pituitary gland was observed. The pituitary gland retained its normal functions despite a partially empty sella. DISCUSSION: Long-term treatment with high doses of cabergoline may cause cystic degeneration of a prolactinoma considered to be resistant to this treatment, but we cannot rule out the possibility that this outcome represents the natural development of the tumor.
Assuntos
Agonistas de Dopamina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Ergolinas/administração & dosagem , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Cabergolina , Criança , Seguimentos , Humanos , Masculino , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Prolactinoma/sangueRESUMO
OBJECTIVE: To assess the efficacy of coasting alone, cabergoline alone, or combining both interventions for preventing ovarian hyperstimulation syndrome (OHSS) among high-risk patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles. METHODS: The present randomized controlled trial was conducted at the IVF unit of a university hospital in Cairo between October 28, 2013, and July 31, 2015. Patients undergoing IVF/ICSI considered at risk of OHSS were randomly allocated to coasting, cabergoline, or combined coasting and cabergoline. The primary outcome was the rate and degree of symptomatically assessed OHSS. Data were analyzed on a per-protocol basis. RESULTS: There were 100 patients recruited to each group. The occurrence of early OHSS was lowest in the combination group compared with the other groups (P=0.002). CONCLUSION: Combining coasting and cabergoline was associated with a lower OHSS rate compared with either therapy alone. CLINICALTRIALS.GOV: NCT01984320.
Assuntos
Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Cabergolina , Estradiol/sangue , Feminino , Humanos , Síndrome de Hiperestimulação Ovariana/epidemiologia , Gravidez , Taxa de GravidezRESUMO
Uterine fibroids (UFs) are the most common tumors of the female genital tract. The effect of UFs on the quality of life and the overall cost of treatment are significant issues worldwide. Tumor size and location are the two specific factors which influence the occurrence of symptoms, the need for, and method of, treatment (some tumors require surgery while some can be treated with selected drugs). Primary prevention and treatment of early UF disease are worthy goals that might have a great impact on health care systems. Several treatments and prophylactic methods can be used in this endeavor. This publication presents current data about lesser-known substances which may have a beneficial effect on the treatment or prophylaxis of UFs and can be administered orally, serving as an alternative to (or complement of) surgery or selective progesterone receptor modulators (SPRMs). Early prevention and treatment of UFs in women from high-risk groups should be our priority. Innovative forms of UF management are under intensive investigation and may be promising options in the near future. Many of them evaluated vitamin D, paricalcitol, epigallocatechin gallate (EGCG), elagolix, aromatase inhibitors (AIs), and cabergoline and deemed them to be safe and effective. The next step in such projects should be properly constructed randomized control trials (RCTs), carried out by successive phases.
Assuntos
Antineoplásicos/administração & dosagem , Leiomioma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Administração Oral , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/uso terapêutico , Cabergolina , Catequina/administração & dosagem , Catequina/análogos & derivados , Catequina/uso terapêutico , Ergocalciferóis/administração & dosagem , Ergocalciferóis/uso terapêutico , Ergolinas/administração & dosagem , Ergolinas/uso terapêutico , Feminino , Humanos , Hidrocarbonetos Fluorados/administração & dosagem , Hidrocarbonetos Fluorados/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Qualidade de Vida , Vitamina D/administração & dosagem , Vitamina D/uso terapêuticoRESUMO
Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment.
Assuntos
Antineoplásicos/uso terapêutico , Ergolinas/uso terapêutico , Hipogonadismo/diagnóstico , Hipotireoidismo/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Adulto , Antineoplásicos/administração & dosagem , Cabergolina , Terapia Combinada , Diagnóstico Diferencial , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Ergolinas/administração & dosagem , Fibrose/induzido quimicamente , Humanos , Hipogonadismo/complicações , Hipotireoidismo/complicações , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Prolactinoma/cirurgia , Tiroxina/administração & dosagem , Tiroxina/uso terapêutico , Insuficiência da Valva Tricúspide/induzido quimicamenteRESUMO
Context: The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death. Objective: To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers. Results: In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II. Conclusion: The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloroquina/administração & dosagem , Ergolinas/administração & dosagem , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Animais , Cabergolina , Morte Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Nus , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Ratos , Ratos Endogâmicos F344 , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The purpose of this study was to examine the efficacy of daily cabergoline administration on oestrus induction in bitches. METHODS AND RESULTS: Of 20 multiparous Beagle bitches, 15 were not mated with sires in their last oestrus and 5 bitches that had been mated whelped. All bitches were in early or mid-anoestrus and received 5 µg/kg/day cabergoline PO. Oestrus was induced in the mid-anoestrus bitches at a higher rate than in the early anoestrus bitches. Comparing the different histories of previous pregnancy among the mid-anoestrus bitches, the rate of oestrus induction in the non-pregnant bitches was higher than in the bitches that whelped. CONCLUSION: Cabergoline is effective for oestrus induction in mid-anoestrus bitches.
Assuntos
Cães/fisiologia , Ergolinas/administração & dosagem , Estro/efeitos dos fármacos , Indução da Ovulação/veterinária , Anestro/efeitos dos fármacos , Animais , Cruzamento , Cabergolina , Estro/fisiologia , Feminino , Gravidez , Taxa de Gravidez , ProgesteronaRESUMO
Galactocele is a rare cystic formation, a benign breast lesion, occurring when breast duct is blocked and engorged. It generally affects postpartum women, either breastfeeding or not. Only a few cases have been reported in the literature and they were not related to lactation, as in the case of postmenopausal women or of men; moreover, their relationship to the overproduction of prolactin, a growth factor stimulating mammary epithelial cells, is not very well defined at this time. We here report the unusual case of a 30-year old patient with no personal history of childbirth or abortion. She was treated in the Division of Endocrinology for pituitary microadenoma with Cabergoline, that she stopped for 1 year. Even taking into account this rare association, it is important to emphasize the role of hormones in the progression of breast anatomy.
Assuntos
Cisto Mamário/etiologia , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Adulto , Antineoplásicos/administração & dosagem , Cisto Mamário/patologia , Cabergolina , Ergolinas/administração & dosagem , Feminino , Humanos , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactinoma/tratamento farmacológico , Prolactinoma/patologiaRESUMO
Cushing's disease (CD) is rare during pregnancy and is associated with significant maternal and fetal complications. It is important to control hypercortisolism during pregnancy, either surgically or medically, for a successful maternal and fetal outcome. We report a patient with recurrent CD who was treated with low-dose cabergoline (CAB) for persistent hypercortisolism throughout pregnancy. A 36-year-old woman was diagnosed with CD at the age of 23. She underwent trans-sphenoidal surgery with initial complete remission. However, 4 years after surgery, CD recurred and she underwent Gamma Knife radiosurgery (GKRS). Following GKRS, her cortisol levels remained elevated despite no evidence of visible tumour on pituitary MRI. Medical treatment was commenced with ketoconazole and cyproheptadine. This was changed to CAB as she was keen for pregnancy. She conceived spontaneously and was on CAB throughout pregnancy. She delivered a healthy male neonate, weighing 3195 g at 40 weeks of gestation.
Assuntos
Antineoplásicos/uso terapêutico , Ergolinas/uso terapêutico , Hipersecreção Hipofisária de ACTH/diagnóstico , Complicações na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Adulto , Antineoplásicos/efeitos adversos , Cabergolina , Diagnóstico Diferencial , Ergolinas/administração & dosagem , Feminino , Humanos , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/tratamento farmacológico , Recidiva , Indução de RemissãoRESUMO
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.
Assuntos
Bromocriptina/farmacologia , Agonistas de Dopamina/farmacologia , Ergolinas/farmacologia , Hiperprolactinemia/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Hipofisárias/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Prolactinoma/tratamento farmacológico , Adulto , Bromocriptina/administração & dosagem , Bromocriptina/efeitos adversos , Cabergolina , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Ergolinas/administração & dosagem , Ergolinas/efeitos adversos , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To assess the outcome of using low-dose aspirin, dopamine agonist and triggering ovulation by low dose of HCG in combination with GnRH agonist in fixed GnRH antagonist protocol in patients at risk of OHSS. STUDY DESIGN: This prospective cohort study was conducted on 50 infertile women who were at high risk of OHSS. They received low dose aspirin from first day of stimulation, cabergoline 0.5mg daily from the day of HCG for 8days and low dose of HCG (2500 IU) in combination with GnRH agonist for final oocyte maturation in fixed GnRH antagonist protocol. RESULTS: The study was conducted on 50 cases and all of them completed the study protocol. The clinical pregnancy rate was 40% (20 cases of 50) and no cases developed severe or critical OHSS. Only 8% (4 cases) developed moderate OHSS. CONCLUSION: Combining aspirin, cabergoline, and triggering with low dose of HCG in combination with GnRH agonist produced excellent clinical pregnancy rate, and decreased hospital admissions with severe or critical OHSS.
Assuntos
Aspirina/administração & dosagem , Gonadotropina Coriônica/administração & dosagem , Ergolinas/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Substâncias para o Controle da Reprodução/administração & dosagem , Adulto , Cabergolina , Quimioterapia Combinada , Feminino , Humanos , Infertilidade Feminina/terapia , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Índice de Gravidade de DoençaRESUMO
Background: Metformin as well as dopaminergic agents exert a beneficial effect on glucose and lipid metabolism, often impaired in patients with hyperprolactinemia. Objective: The aim of this study was to compare metabolic- and prolactin-lowering effects of low-dose bromocriptine/metformin combination therapy and cabergoline in patients with elevated prolactin levels. Methods: The study included 27 women with hyperprolactinemia and impaired glucose tolerance who were treated with moderate doses of bromocriptine but experienced adverse effects of this treatment. In 12 of these patients bromocriptine was replaced with cabergoline (group A), while the remaining ones continued treatment with bromocriptine, the dose of which was halved, and administered together with metformin (group B). Plasma lipids, glucose homeostasis markers, as well as serum levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed before and after 4 months of metformin treatment. Results: Both groups did not differ in baseline levels of plasma glucose and lipids, in insulin sensitivity, as well as in circulating levels of all measured hormones. All patients from group A and 12 patients from group B completed the study. Cabergoline reduced prolactin levels, while no effect on plasma prolactin was found in group B. Neither cabergoline nor bromocriptine plus metformin affected circulating levels of thyrotropin and IGF-1. Both treatment options, particularly low-dose bromocriptine plus metformin, improved glucose and lipid homeostasis. Conclusions: Low-dose bromocriptine combined with metformin may be an interesting alternative to cabergoline in patients with mild hyperprolactinemia and early glucose metabolism abnormalities, in whom moderate doses of bromocriptine are poorly tolerated.
Assuntos
Bromocriptina , Hiperprolactinemia/sangue , Hiperprolactinemia/tratamento farmacológico , Metformina/administração & dosagem , Adulto , Bromocriptina/administração & dosagem , Bromocriptina/efeitos adversos , Cabergolina , Ergolinas/administração & dosagem , Ergolinas/efeitos adversos , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Lipídeos/sangue , Pessoa de Meia-Idade , Prolactina/sangue , Tireotropina/sangueRESUMO
OBJECTIVE: To evaluate the effect of letrozole in combination with cabergoline and letrozole alone on regression of symptomatic uterine myomas in women of reproductive age. DESIGN: Randomized controlled clinical trial. SETTING: University hospital. PATIENTS: Ninety-one women of reproductive age were enrolled in the study and 88 women were eligible. Eight participants were excluded from the study. INTERVENTIONS: Eighty women of reproductive age with symptomatic myomas >4cm were evaluated in two groups. Participants in Group 1 received 2.5mg letrozole once daily and cabergoline 0.5mg/week from the first day of the menstrual cycle for 12 weeks, and participants in Group 2 received letrozole alone. MAIN OUTCOME MEASURES: Changes in uterine size and volume; myoma size, volume and number; and side effects of treatment. RESULTS: Overall, 76 patients completed the study. Compared with baseline values, mean uterine volume was reduced significantly in both groups (p=0.01), and there was no significant difference between groups (p=0.99). The mean number of dominant myomas was reduced significantly in both groups (p=0.03), with no significant difference between groups (p=0.6). The mean volume of myomas was reduced significantly in both groups (p=0.01), with no significant difference between groups (p=0.45). Although a significant decrease in number and volume of myomas was documented in each group (p<0.05), the intergroup analyses did not reveal significant differences between the two groups in terms of the change in number (p=0.28) and volume (p=0.96) of myomas. Headache was significantly more common in the letrozole+cabergoline group (nine vs two cases, p=0.02), but the two groups were comparable for the remaining minor side effects. CONCLUSION: This study showed that 12 weeks of treatment with letrozole with and without cabergoline improved the size and volume of the uterus and myomas, led to symptom improvement, and could be used for short-term treatment prior to surgery or fertility programmes. CONDENSATION: Condensation letrozole in combination with cabergoline in the management of uterine fibroids.
Assuntos
Antineoplásicos/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Ergolinas/administração & dosagem , Leiomioma/tratamento farmacológico , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Neoplasias Uterinas/tratamento farmacológico , Adulto , Cabergolina , Quimioterapia Combinada , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Útero/efeitos dos fármacosRESUMO
PURPOSE: Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone. METHODS: To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. RESULTS: Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. CONCLUSION: Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.
Assuntos
Acromegalia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Suspensão de Tratamento , Adulto , Idoso , Cabergolina , Ergolinas/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Prognóstico , Estudos Prospectivos , Indução de RemissãoRESUMO
CONTEXT: Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. OBJECTIVE: Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. DESIGN: Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. SETTING: Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included. RESULTS: There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.
Assuntos
Agonistas de Dopamina/efeitos adversos , Ergolinas/efeitos adversos , Doenças das Valvas Cardíacas/induzido quimicamente , Doenças das Valvas Cardíacas/diagnóstico por imagem , Hiperprolactinemia/tratamento farmacológico , Adulto , Idoso , Cabergolina , Agonistas de Dopamina/administração & dosagem , Ecocardiografia , Ergolinas/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reino UnidoRESUMO
PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.
Assuntos
Acromegalia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Ergolinas/farmacologia , Hormônio do Crescimento Humano/análogos & derivados , Fator de Crescimento Insulin-Like I/metabolismo , Peptídeos Cíclicos/farmacologia , Somatostatina/análogos & derivados , Cabergolina , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Ergolinas/química , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/química , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/química , Somatostatina/farmacologiaRESUMO
Problema de investigación: Describir los costos y la efectividad del pramipexol comparado con levodopa y cabergolina para el tratamiento de pacientes con síndrome de piernas inquietas.Tipo de evaluación económica\r\nAnálisis de costo-utilidad. Población objetivo: Población adulta con diagnóstico de síndrome de piernas inquietas. Intervención y comparadores: Intervención: Pramipexol, Comparadores: Levodopa y cabergolina. Horizonte temporal: 16 semanas. Perspectiva Sistema: General de Seguridad Social en Salud (SGSSS). Tasa de descuento: No aplica. Estructura del modelo: Modelo de Markov. Fuentes de datos de efectividad y \r\nseguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: Años de vida ajustados por calidad (AVAC). Costos incluidos: Costos de medicamentos, Costos de procedimientos. Fuentes de datos de costos:SISMED, Manual tarifario ISS 2001. Resultados del caso base: En el escenario del caso base, pramipexol es una estrategia costo-efectiva con respecto a levodopa. El costo por AVAC ganado con pramipexol es de $7.480 comparado con levodopa. Análisis de sensibilidad: El análisis de sensibilidad determinístico y el diagrama de tornado mostraron que la variable con mayor impacto sobre las estimaciones de costo-efectividad es el precio de levodopa. No se realizó análisis de sensibilidad probabilístico. Conclusiones y discusión: Pramipexol ofrece una mejor relación entre costos y efectividad respecto a levodopa y cabergolina. De acuerdo con el criterio de los expertos clínicos la cabergolina no hace parte de la práctica clínica habitual para este trastorno y la \r\nlevodopa tiene un uso que requiere de supervisión por el efecto que agudiza las manifestaciones clínicas. La principal limitación de este estudio está relacionada con la poca información proveniente de estudios de investigación clínica y evaluaciones económicas.(AU)