Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Prolactinomas: evolution after menopause

ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Miocardiopatía periparto: caso clínico / Per partum cardiomyopathy: case report

Se presenta el caso clínico de una mujer de 20 años que presenta insuficiencia cardíaca de rápida instalación, asociada a síntomas de infección respiratoria viral, 9 semanas post parto. Previamente había presentado hipertensión en el puerperio precoz. Se demostró una severa disfunción sistólica (FE 12 por ciento). Se recuperó con medidas convencionales del tratamiento de Insuficiencia cardíaca y finalmente recibió bromocriptina basado en reportes favorables de la literatura respecto del uso de este fármaco. En el control al año de su alta, se mantenía asintomática pero persistía severa disminución de la FE (18 por ciento) y dilatación de cavidades izquierdas. Se revisa la información acerca de esta patología.

A 20 year old woman developed rapidly progressive heart failure 9 weeks after delivery. For a few weeks she was hypertensive. A severe systolic dysfunction with an EF of 12 percent was shown on echocardiography. She recovered on conventional treatment of congestive heart failure. Eventually she received bromocriptine con the basis of favorable literature reports. A follow up control at one year showed an asymptomatic patient, however severe systolic dysfunction with EF 18 percent was still present.

Resultados visuales en pacientes con macroprolactinoma tratados con agonistas de dopamina / Visual outcome in patients with macroprolactinoma treated with dopamine agonists

Background: Dopamine agonists (DA) effectively reduce tumor size of macroprolactinomas, with the consequent improvement of eventual visual impairment. Aim: To study the visual outcomes in patients with macroprolactinoma treated with DA. Material and Methods: Retrospective cohort study which included patients with macroprolactinoma controlled at a Neuro-endocrinology and Neuro-ophthalmology Department between 1997'and2011, and treated exclusively with DA (bromocriptine or cabergoline). Patients who were operated or had previous radiotherapy and those with an incomplete follow up, were excluded. We analyzed and compared the visual status before and after the beginning of DA treatment. Results: Thirty one patients aged 8 to 59years, were included. Eighteen patients (58%) had visual impairment at the moment of diagnosis (group 1) and 13 had no alterations (group 2). Mean follow up was 36.5 months. Fifteen patients from group 1 (83%) had visual improvement, two remained stable (11 %) and one had a visual deterioration (6%). In group 2, only one non-compliant patient had a visual deterioration. Conclusions: DAs are effective in the management of neuro-ophthalmic complications associated to macroprolactinomas and should be considered asfirst choice therapy in these tumors.

Bromocriptine for Control of Hyperthermia in a Patient with Mixed Autonomic Hyperactivity after Neurosurgery: A Case Report

Mixed autonomic hyperactivity disorder (MAHD) among patients with acquired brain injury can be rare. A delayed diagnosis of MAHD might exacerbate the clinical outcome and increase healthcare expenses with unnecessary testing. However, MAHD is still an underrecognized and evolving disease entity. A 25-yr-old woman was admitted the clinic due to craniopharyngioma. After an extensive tumor resection, she complained of sustained fever, papillary contraction, hiccup, lacrimation, and sighing. An extensive evaluation of the sustained fever was conducted. Finally, the cause for MAHD was suspected, and the patient was successfully treated with bromocriptine for a month.

Mastalgia cíclica: abordagem clínica / Cyclic mastalgia: clinical approach

A mastalgia é uma queixa comum nos consultórios de mastologia. Devido à intensidade da dorou pelo medo do câncer de mama, mulheres com mastalgia buscam orientação com o mastologista.Nesse sentido, o mastologista deve estar familiarizado com o tema. Considerando que aqueixa de dor mamária está entre as mais frequentes em mastologia, conduziu-se uma revisão daliteratura, enfatizando-se a abordagem terapêutica da mastalgia.

Mastalgia is a common complaint in mastology offices. Women who are experiencing mastalgia seekclarification with the breast cancer specialist due to the intensity of the pain or because they fear breastcancer. Therefore, the specialist shall understand such issue. Considering that the complaint concerningbreast pain is one of the most frequent complaints in mastology, a literature review was carried outemphasizing the therapeutic approach of mastalgia.

A comparison of bromocriptine & cabergoline on fertility outcome of hyperprolactinemic infertile women undergoing intrauterine insemination.

Background & objectives: The aim of this study was to compare the effects of bromocriptine versus cabergoline on pregnancy in hyperprolactinaemic infertile women. Methods: A total of 183 infertile women with hyperprolactinemia undergoing intrauterine insemination (IUI) were randomly divided into two groups. Group A: 94 with bromocriptine and group B:89 with cabergoline. The efficacy and safety was evaluated on the basis of normalization of prolactin levels, normalization of menstrual cycle, disappearance of galactorrhea, occurrence of pregnancy and adverse effects with each of these medications. Results: The presence of galactorrhea and irregular menstruation were significantly lower in patients of group B than group A (P<0.001 and P=0.011, respectively) with a significant lower prevalence of side effects in cabergoline group. Pregnancy was significantly more achieved among the women with the treatment of cabergoline (82%) as compared to bromocriptine (56.4%) (P<0.001). Interpretation & conclusions: Our results suggest that cabergoline treatment in infertile women with prolactinemia is more effective. It lowers prolactin with better tolerability and much more effective in the achievement of pregnancy.

Dor mamária: propedêutica e terapêutica / Breast pain: propaedeutic and therapeutic

Mastalgia é um dos sintomas mais comuns em mulheres, tendo uma prevalência de 41 a 69% e pode se apresentar como um leve desconforto até dor severa, que interfere na qualidade de vida. A principal preocupação das pacientes que consultam por este sintoma é o medo do câncer. Essa é classificada em mastalgia cíclica, acíclica ou extramamária. Cíclica quando se apresenta no período pré-menstrual; na acíclica não há relação com o ciclo e, geralmente, acomete pacientes na pós-menopausa. A extramamária é a dor referida na mama, porém usualmente é de origem musculoesquelética. Na presença de achados clínicos e radiológicos normais, aproximadamente 85% das pacientes melhoram apenas com orientação e tranquilização, não necessitando de medicação. Foi realizada uma revisão sistemática para avaliar as possibilidades terapêuticas e seus níveis de evidência. Os anti-inflamatórios não esteróides tópico, para mastalgia cíclica ou acíclica, e o fitoterâpico Agnus castus, para mastalgia cíclica, demonstraram boa eficácia e tolerabilidade e podem ser usados como medida inicial. O tamoxifeno e o danazol são medicamentos eficazes, porém apresentam mais efeitos colaterais. Para casos especiais, ainda há a alternativa de usar bromocriptina e goserelina. O manejo da dor mamária pode ser sintetizado em três itens: excluir câncer, orientar e tranquilizar ao máximo e medicar ao mínimo.(AU)

Breast pain or mastalgia is one of the most common symptoms in women, with a prevalence ranging from 41 to 69%. It presents as a mild discomfort to severe pain, that interferes with the quality of life. The main concern of patients consulting for this symptom is the fear of cancer. It is classified as cyclical, acyclical or extra-mammary. When presented during the premenstrual period, it is cyclical; acyclical, when not cycle-related and usually affects patients in post-menopausal. Extra-mammary is the breast referred pain, but it is usually of muscle-skeptical origin. In the presence of normal clinical and radiological findings, approximately 85% of patients improve only with reassurance, not requiring medication. A systematic review was performed to assess the therapeutic possibilities and their evidence levels. Topical non-steroidal anti-inflammatory drugs, for cyclic or acyclic mastalgia, and the phytotherapic Agnus castus, for cyclic mastalgia, showed good efficacy and tolerability and can be used as an initial measure. Tamoxifen and danazol are effective drugs, but they present more side effects. For special cases, there is the alternative of using bromocriptin and goserelin. Breast pain management can be summarized in three items: exclude cancer, maximum reassurance and minimum medication.(AU)

Utilidad de la cabergolina en pacientes portadores de prolactinoma resistentes o intolerantes a bromocriptina / Usefulness of cabergoline in patients with prolactinemia and resistant or intolerant to bromocriptine

Introducción: La terapia de elección de los prolactinomas son los agonistas dopaminérgicos, cuyo principal exponente es la bromocriptina, sin embargo, hay pacientes que no responden o presentan severos efectos secundarios (resistentes o intolerantes a bromocriptina, respectivamente). El objetivo en este estudio fue valorar la respuesta al uso de cabergolina en pacientes con prolactinomas, intolerantes o resistentes a bromocriptina Material y métodos: Se estudiaron 27 pacientes (25 mujeres y dos varones) en quienes se realizó determinación basal de prolactina y cada mes hasta completar tres meses, registrando los datos asociados a hiperprolactinemia y los efectos secundarios. La dosis inicial fue de 0.25 mg los lunes y jueves durante la primera semana, y 0.5 mg a partir de la segunda. El análisis estadístico incluyó la prueba de Shapiro-Wilk, Kruskal-Wallis y Anova. Resultados: 22 pacientes presentaron microadenomas y cinco macroadenomas. En los intolerantes (n = 11) el valor inicial de prolactina de 61.45 ± 19.82 disminuyó al tercer mes a 4.94 ± 1.79 (p < 0.024). En los resistentes (n = 16), el valor basal fue 119.53 ± 11.52; 15 pacientes redujeron significativamente a 12.95 ± 3.66 (p < 0.005) al tercer mes de tratamiento. En ambos, los signos atribuibles a la hiperprolactinemia mejoraron significativamente, con poca incidencia de efectos secundarios. Conclusiones: La cabergolina es útil en la mayoría de los pacientes considerados intolerantes o resistentes a la bromocriptina.

BACKGROUND: Dopaminergic agonists are the treatment of choice for prolactinomas with bromocriptine (BCE) being the primary agent used. There is a group of patients who are not responders to such therapy or have severe side effects (resistant or intolerant to BCE, respectively). We undertook this study to evaluate the response to the administration of cabergoline (CBG) in patients intolerant or resistant to BCE. METHODS: Twenty seven patients (25 females and 2 males) were recruited with prolactin-pituitary tumors, obtaining basal serum prolactin (PRL) samples and again each month up to 3 months. We recorded signs associated with hyperprolactinemia and secondary effects of CBG. The initial dose was 0.25 mg twice weekly during the first week, with an increase to 0.5 mg twice weekly from the second week until the conclusion of the study. Statistical analysis included Shapiro-Wilk, Kruskal-Wallis and ANOVA tests. RESULTS: Twenty two patients had microadenomas and five had macroadenomas. In the intolerant group (n= 11), the initial PRL value (61.45 +/- 19.82) decreased by the third month to 4.94 +/- 1.79 (p<0.024). In the resistant group (n= 16), basal PRL values were 119.53 +/- 11.52. In 15 of these patients, the PRL value significantly decreased to 12.95 +/- 3.66 ng/ml (p<0.005) by the third month of treatment. In both groups the signs related to hyperprolactinemia significantly improved, with a low incidence of secondary effects due to CBG. CONCLUSIONS: CBG is useful in most patients considered as intolerant or resistant to BCE.

Electroconvulsive therapy in drug resistant neuroleptic malignant syndrome.

We report a case of a 20 years female referred to us with a history of a brief psychotic episode for which she was given inj. Haloperidol. The patient presented in an unconscious state with high grade fever. The diagnosis was kept as neuroleptic malignant syndrome after ruling out other possibilities. The patient did not respond to Bromocriptine and Dantrolene. With the recent evidence of electroconvulsive therapy being useful in these patients, we went ahead with the same. We present this case to share our experience of the excellent response of neuroleptic malignant syndrome to electroconvulsive therapy.

Discordância entre IGF-1 e GH pós-sobrecarga de glicose no rastreamento de acromegalia em paciente com macroprolactinoma: relato de caso e revisão sobre o tema / Discrepancy between IGF-1 and GH during 75 g oral glucose tolerance test measures to acromegaly screening in a patient with macroprolactinoma: case report and literature review

Neste artigo, descrevemos o caso de um paciente com diagnóstico de macroprolactinoma, que apresentava valores discordantes entre IGF-1 (elevado) e GH (hormônio de crescimento) pós-teste de tolerância oral à glicose (normal) realizados para pesquisa de co-secreção de GH pelo tumor. Houve normalização dos níveis de prolactina após uso de bromocriptina, porém, durante o acompanhamento, o paciente persistiu com níveis elevados de IGF-1 sem clínica aparente, sugerindo tratar-se de possível forma subclínica de acromegalia. Após o desenvolvimento de novos métodos laboratoriais, mais sensíveis, para a dosagem de GH, casos de discordância entre esses testes vêm sendo observados, levando alguns autores a sugerir que o nadir de GH pós-teste de tolerância à glicose oral (TTGO) para diagnóstico e tratamento da acromegalia pode ser bem menor do que o limite considerado atualmente (1,2). Assim, se isto for confirmado, casos subclínicos ou oligossintomáticos de acromegalia serão diagnosticados mais precocemente.

We describe a patient with macroprolactinoma and discrepant insulin-like growth factor (IGF-1) concentration (elevated) and growth hormone (GH) values during a 75 g oral glucose tolerance test (normal), that were measured to evaluate the co-secretion of GH by tumor. With the bromocriptin use, the patient achieved normalization of prolactin, but persisted with high levels of IGF1, suggesting to be subclinical acromegaly. After the development of new more sensitive GH assays, cases of discrepant GH and IGF-1 results have been observed and taken to some authors to suggest that GH nadir concentration during 75 g OGTT used to acromegaly diagnosis and treatment could be lower than values considered currently normal. Thus, if this is confirmed, subclinical and oligosymptomatic acromegaly cases could have earlier diagnoses.

Galactorrhea in a 14-year-old girl.

The authors report a 14-year-old girl who had galactorrhea with regular menstruation. Furthermore, this galactorrhea case was associated with hyperprolactinemia and prolactinoma. The patient tolerated and responded well to therapy with bromocriptine. The serum prolactin levels decreased from 103.27 ng/mL to 24.25 ng/mL after 8 weeks of treatment and 12.48 ng/mL after 6 months of treatment. No pituitary tumor was demonstrated after 12 months of therapy and the galactorrhea had not recurred 1 year after ending the bromocriptine treatment.

Breastfeeding a baby with mother on Bromocripine.

Prolactinomas, the most common pituitary adenomas, are important causes of infertility. Bromocriptine remains the treatment of choice for managing hyperprolactinemia in most of these cases. Breastfeeding in mothers receiving bromocriptine is often doubtful and matter of concern for most people. Here we report a case, where by timely intervention and skilled counseling, exclusive breastfeeding could be established in a mother receiving bromocriptine for the treatment of hyperprolactinemia.

Abulia: no will, no way.

Abulia refers to impaired ability to perform voluntary actions, show initiative, make decisions along with decrease in movements, speech, thought and emotional reactions. We describe here two patients who developed this condition following bilateral insult to different sites in the centromedial core of the brain, the first following the cerebral venous thrombosis and the second after the right ACA and MCA infarct. Both these patients improved following treatment with Bromocriptine. These cases are described for proper identification and management by the clinicians.

Aspectos clínicos e terapêuticos de prolactinomas em homens / Clinical and therapeutic aspects of prolactinoma in men

Em homens, macroprolactinomas predominam em relação aos microprolactinomas e têm maior invasividade que nas mulheres. O tratamento clínico é a primeira opção tanto em macro como em microadenomas, independente do sexo. Comparamos apresentação clínica, níveis de prolactina, invasividade neurorradiológica e resposta da prolactinemia em 42 homens com prolactinomas, 23 com terapia clínica (grupo 1) e 19 que também utilizaram tratamento cirúrgico e/ou radioterápico (grupo 2). Os dados obtidos foram submetidos a análise estatística utilizando-se os testes de qui-quadrado ou exato de Fisher para comparações de proporções. Para comparar médias foi aplicado o teste t de Student ou, na ausência de distribuição normal ou com número pequeno de eventos, o não paramétrico de Mann-Whitney. O nível de significância adotado foi de 5 por cento (p<0,05). Os grupos foram similares para idade (p=0,23), período entre primeiro sintoma e diagnóstico (p=0,82), níveis de prolactina pré tratamento (p=0,41) e proporção de macroadenomas invasivos (p=0,096). Ocorreu percentual significativamente maior de cefaléia (p=0,009), deficit visual (p=0,025), tempo de terapia (p=0,007) e período de acompanhamento (p=0,0005) no grupo 2. Variações dos níveis de prolactina antes e após terapia não apresentaram diferença significativa nos grupos (p=0,49), nem o percentual de normalização da prolactina após tratamento (p=0,20). Concluímos, enfatizando a importância do diagnóstico precoce do prolactinoma em homens, tendo em vista a morbidade demonstrada, e reforçamos a necessidade do uso do agonista dopaminérgico como opção terapêutica inicial independente do tamanho do adenoma

Del Castello syndrome--an unusual presentation.

Del Castello syndrome in a 28-year-old female, characterised by bilateral galactorrhoea, amenorrhoea and hyperinvoluted uterus, has been described. She had hyperprolactinaemia without any demonstrable pituitary tumour. She was successfully treated with two short courses of bromocriptine and was spontaneously cured after her second conception. The case is discussed with a brief review of the literature.

Hiperprolactinemia e distúrbios psiquiátricos / Hyperprolactinemia and psychiatric disturbance

Sintomas psicológicos, especialmente ansiedade e depressao, têm sido associados à hiperprolactinemia. Para avaliar a presença desses sintomas, foram submetidos à entrevista através do Composed International Diagnostic Interview, seguido pela escala de Hamilton para depressao, 32 pacientes (5 homens e 27 mulheres) com hiperprolactinemia de várias etiologias e 16 normoprolactinêmicos. A prolactina sérica na época da avaliaçao variou de 28 a 180 ng/mL, sendo que 11 dos pacientes usavam bromocriptina. Detectou-se presença atual de distúrbios de ansiedade em 18 pacientes (56,2 por cento) e 5 controles (31,2 por cento), depressao em 10 pacientes (31,2 por cento) e 2 controles (12,5 por cento), distmia em duas pacientes e outros diagnósticos psiquiátricos em 6 pacientes (18,7 por cento). Os escores da depressao variaram entre 16 e 31 nos pacientes e foram 12 e 16 nos controles. A frequência de sintomas psiquiátricos como um todo, foi significativamente maior nos hiperprolactinêmicos (teste do qui-quadrado), mas a diferença nao foi significativa na análise isolada de ansiedade ou depressao. A hiperprolactinemia representa um fator de risco de 3,57 para depressao, 3,32 para ansiedade e 3,84 para outros sintomas psiquiátricos. Nao houve diferença significativa na frequência de sintomas psiquiátricos entre portadores ou nao de adenomas hipofisários e usuários ou nao de bromocriptina. Nao houve correlaçao (r= 0,07) entre a prolactina e a frequência de sintomas psiquiátricos. Conclui-se pela necessidade de atentar para a concomitância de hiperprolactinemia e distúrbios psiquiátricos, cujo reconhecimento permitirá abordagem terapêutica específica

Efectos de la hiperprolactinemia sobre el metabolismo hidrocarbonado / Effects of hyperprolactinemia on the carbohidrate metabolism

Con el objetivo de evaluar el efecto de la hiperprolactinemia sobre el metabolismo hidrocarbonado, se estudiaron, antes de iniciar el tratamiento con bromocriptina, 21 pacientes con hiperprolactinemia de causa idiopática, normopesos y sin antecedentes de otras enfermedades y una muestra de 48 mujeres sanas, con normopeso y edades similares a las del grupo de estudio. Se realizó una prueba de tolerancia a la glucosa oral (PTG-o) para medir glucemia e insulinemia después de una sobrecarga oral de 75 g de glucosa. Se calculó el índice insulinogénico inicial (IIo-30) y el de resistencia a la insulina (RI) para cada mujer. El grupo con hiperprolactinemia se dividió en 2 subgrupos según los valores de la prolactina plasmática (Prl), uno con Prl< 2 500 mU/L (subgrupo 1a) y otro con Prl > 2 500 mU/L (subgrupo 1b). Los valores de la glucemia plasmática en respuesta a la sobrecarga de la glucosa oral, en todos los momentos de la PTG, fueron superiores significativamente en el grupo de las mujeres híperprolactinémicas en relación con el grupo control, con la mayor diferencia (p < 0,01) a los 30 min (mediana = 5,8 mmol/L y 4,1 mmol/L, respectivamente). El subgrupo 1a, no presentó diferencias significativas con el grupo control en ningún momento de la PTG-o, mientras que el subgrupo 1b, mantuvo cifras superiores al control, y de manera significativa a los 30, 90 y 120 min (p < 0,05). No hubo diferencias en ningún momento de la PTG-o ni en el área bajo la curva de insulina entre el grupo hiperprolactinémico y el control. Los índices (II0-30 y de RI) fueron similares en ambos grupos. En conclusión, hubo menor tolerancia a la glucosa oral en las mujeres con hiperprolactinemia, en especial aquéllas con los valores más altos de PRL; esta diferencia no se asoció a un estado de hiperinsulinismo ni de resistencia a la insulina(AU)

21 patients with hyperprolactinemia of idiopathic cause, with normal weight and no history of other diseases, and a sample of 48 sound women with normal weight and ages similar to those of the study group were studied aimed at evaluating the effect of hyperprolactinemia on the carbohidrate metabolism before beginning the treatment with bromocriptine. Glucose tolerance test was made to determine glucaemia and insulinaemia after an overload of 75 g of glucose. The initial insulinogenic index (II0-30) and that of insulin resistance (IR) were calculated for each woman. The group with hyperprolactinemia was divided into subgroups according to the values of plasmatic prolactin (Prl), one with Prl<2 500 mU/L (subgroup 1a) and the other with Prl ?_2 500 mU/L (subgroup 1b). The values of plasmatic glucaemia in response to the overload of oral glucose during the GTT were always significantly higher in the group of hyperprolactinemic women compared with the control group. The highest difference (p<0.01) was observed at the 30 minutes (mean = 5.8 mmol/L and 4.1 mmol/L, respectively). In the subgroup 1a there were not marked differences in comparison with the control group at any moment of the GTT; however, in subgroup 1b there were figures over those of the control group that were significant at the 30, 90 and 120 minutes (p < 0.05). There were no differences either during the GTT or in the area under the insulin curve between the hyperprolactinemic group and the control group. The indexes (II0-30 and IR) were similar in both groups. To conclude, oral glucose tolerance was lower in women with hyperprolactinemia, specially in those with the highest values of Prl. This difference was not associated either with a state of hyperinsulinism or with insulin resistance(AU)