Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study

ABSTRACT BACKGROUND: Endometrial polyps are common in postmenopausal women, and the effect of tamoxifen use (a risk factor for endometrial polyps) on their pathogenesis is unclear. OBJECTIVES: To evaluate the expression of hormone receptors and markers for proliferation/apoptosis (Ki-67 and Bcl-2) in endometrial polyps in postmenopausal users and nonusers of tamoxifen. DESIGN AND SETTING: Cross-sectional analytical study in a tertiary-level academic hospital. METHODS: 46 women (14 tamoxifen users and 32 nonusers) with postmenopausal bleeding underwent hysteroscopic resection of endometrial polyps. Polyp samples were immunohistochemically assessed for detection of Ki-67, Bcl-2 and estrogen and progesterone receptors. RESULTS: Analysis on the glandular component of the polyps revealed progesterone receptor expression in the polyps of 96.9% of the nonusers of tamoxifen, and 92.3% of the tamoxifen users (P = 0.499). All polyps in nonusers and 92.3% of those in users were also positive for estrogen receptors (P = 0.295). Ki-67 was expressed in 75% of the polyps in the tamoxifen users and 82.8% of those in the nonusers. All endometrial polyps expressed Bcl-2. CONCLUSIONS: The immunohistochemical analysis on endometrial polyps demonstrated that, although tamoxifen is considered to be a risk factor for endometrial polyps, there were no significant differences in the expression of hormone receptors between users and nonusers of tamoxifen. There were no between-group differences in Ki-67 and Bcl-2 expression, and all patients displayed inhibition of apoptosis by Bcl-2, thus supporting the theory that polyps develop due to inhibition of apoptosis, and not through cell proliferation.

Estrogen Antagonist and Development of Macular Hole

To describe the clinical and optical coherence tomography (OCT) features of a macular hole (MH) or its precursor lesion in patients treated with systemic antiestrogen agents. We reviewed the medical history of the patient, ophthalmic examination, and both fundus and OCT findings. Three female patients receiving antiestrogen therapy sought treatment for visual disturbance. All of the patients showed foveal cystic changes with outer retinal defect upon OCT. Visual improvement was achieved through surgery for the treatment of MH in two patients. Antiestrogen therapy may result in MH or its precursor lesion, in addition to perifoveal refractile deposits. OCT examination would be helpful for early detection in such cases.

Terapia médica de la ginecomastia con tamoxifeno. Influencia del volumen y duración de la ginecomastia en el resultado terapéutico / Influence of size and duration of gynecomastia on its response to treatment with tamoxifen

Background. Gynecomastia is treated when it is painful, there are psychosocial repercussions or it does not revert in less tan two years. It is treated with the antiestrogenic drug tamoxifen, but there are doubts about its effectiveness in high volume gynecomastias or in those lasting more than two years. Aim. To assess the effectiveness and safety of tamoxifen for gynecomastia and the influence of its volume and duration on the response to treatment. Patients and methods. Forty three patients with gynecomastia, aged 12 to 62 years, were studied. Twenty seven patients had a pubertal physiological gynecomastia, in eight it was caused by medications, in four it was secondary to hypogonadism, in three it was idiopathic and in one it was due to toxic exposure. Twenty patients had mastodynia and in 33, gynecomastia had a diameter over 4 cm. It lasted less than two years in 30 patients, more than two years in nine and four did not recall its duration. All were treated with tamoxifen 20 mg/dayfor 6 months. A follow up evaluation was performed at three and six months of treatment. Results. Mastodynia disappeared in all patients at three months. At six months gynecomastia disappeared in 26 patients (62 percent), but relapsed in 27 percent. All gynecomastias caused by drugs with antiandrogen activity disappeared. Fifty two percent of gynecomastias over 4 cm and 90 percent of those of less than 4 cm in diameter disappeared (p<0.05). Fifty six percent of gynecomastias lasting more than two years and 70 percent of those of a shorter duration disappeared (p=NS). Two patients had diarrhea or flushes associated to the therapy. Conclusions: Tamoxifen is safe and effective for the treatment of gynecomastia. Larger lesions have a lower response to treatment.

Toxicidade ocular por tamoxifeno / Ocular toxicity by tamoxifen use

O tamoxifeno é um modulador seletivo dos receptores de estrogênio, sendo considerado uma das principais drogas utilizadas no tratamento do câncer de mama. A despeito do comprovado benefício de sua utilização, diversos efeitos adversos têm sido relacionados a ele, como o câncer de endométrio, fenômenos tromboembólicos, sarcomas uterinos e toxicidade ocular. Neste artigo de revisão, descrevemos as principais alterações oculares relacionadas ao uso do tamoxifeno, suas características e o diagnóstico diferencial. Em decorrência da freqüência com que ocorre a toxicidade ocular, chamamos atenção para a avaliação quanto ao acompanhamento periódico das pacientes sob uso desta medicação, sendo por vezes necessária à interrupção da medicação e sua substituição por drogas de outros grupos terapêuticos visando à preservação visual dessas pacientes.

Compuestos disruptores endocrinos y su participación en la programación del eje reproductivo / Endocrine disruptor compounds and their role on the developmental programming of the reproductive axis

Different perturbations during fetal and post natal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming"'. Endocrine disruptor compounds (EDC) are widely spread on the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lypophilyc and stored for long periods on the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women at the BO and 60 to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated to the fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.

Diversas perturbaciones durante el desarrollo fetal y posnatal desencadenan adaptaciones endocrinas que modifican permanentemente el metabolismo, incrementando la susceptibilidad para el desarrollo de enfermedades, proceso conocido como "programación durante el desarrollo". Los compuestos disruptores endocrinos (CDE) se encuentran en el medio ambiente y presentan actividad estrogénica, antiestrogénica o antiandrogénica; son altamente lipofílicos y se almacenan por periodos prolongados en el tejido adiposo. La exposición materna a CDE durante el embarazo y la lactancia permite su paso al producto a través de la placenta y la leche materna. Estudios epidemiológicos y experimentales han demostrado alteraciones en el eje reproductivo como consecuencia de la exposición intrauterina y/o neonatal a CDE. El compuesto mejor documentado es el dietilestilbestrol (DES), este estrógeno sintético fue administrado a mujeres embarazadas durante los 50s y 60s y retirado del mercado por su implicación en anormalidades urogenitales de los bebés expuestos in útero. Las denominadas "hijas del DES" son mujeres con alta incidencia de hipoplasia vaginal, malformaciones uterinas, irregularidades menstruales, baja fertilidad y alta prevalencia de aborto espontáneo y parto prematuro. Por su parte, "los hijos del DES" presentan una entidad clínica conocida como síndrome de disgenesia testicular caracterizado por hipospadias, criptorquidia y baja calidad del semen. Este síndrome también se asocia a la exposición fetal a compuestos antiandrogénicos como la ñutamida. Los efectos en el eje reproductivo dependen del estadio de desarrollo y del tiempo de exposición, así como de la dosis y el compuesto del que se trate. La extensa presencia de CDE en el ambiente afecta la salud humana e impacta al ecosistema en general por lo cual es de suma importancia el estudio de los mecanismos involucrados en su acción.

Toxicidade ocular causada pelo tamoxifeno: relato de caso / Ocular toxicity caused by tamoxifen: case report

O objetivo desse trabalho é relatar um caso de toxicidade ocular pelo tamoxifeno. Para isso, aferiu-se a melhor acuidade visual corrigida de ambos os olhos em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, oftalmoscopia, angiofluoresceinografia e retinografia numa paciente de 63 anos, sexo feminino, cor branca, em uso de tamoxifeno 20 mg/dia há 4 anos, com acuidade visual corrigida de 20/70 e 20/40. A biomicroscopia do segmento anterior apresentava ceratopatia verticilata e catarata nuclear e cortical posterior de 1+/4 em ambos os olhos. A oftalmoscopia, foi verificado alteração do brilho macular de ambos os olhos. E a angiofluoresceinografia mostrou hiperfluorescência na área macular em fase precoce (defeito em janela). Relata-se um caso de ceratopatia e maculopatia causadas pelo tamoxifeno.

Aspectos morfológicos da junção escamo-colunar de ratas em estro permanente e tratadas com associação de estrogênio e glicocorticóide / Morphological aspects of the squamocolumnar junction of rats in permanent estrus treated with an association of estrogen and glucocorticoid

OBJETIVO: avaliar o efeito da associação de dexametasona com estrogênio sobre a junção escamo-colunar (JEC) de ratas em estro permanente e ovariectomizadas (Ovx). MÉTODOS: trinta ratas foram divididas em seis grupos com cinco animais cada: GEF em estro fisiológico, tendo recebido propilenoglicol (veículo); GOVX em estro fisiológico com ovariectomia e tratadas com o veículo; GEP em estro permanente (EP); GEPOVX em EP, Ovx e tratadas com veículo; GESTR - em EP, Ovx e tratadas com 10 mg/dia de benzoato de estradiol e GDEXAR em EP, Ovx e tratadas com 10 mg/dia de benzoato de estradiol e 0,8 mg/dia de dexametasona. O EP foi induzido com 1,25 mg/animal de propionato de testosterona logo após o nascimento. Após 90 dias, as ratas foram ovariectomizadas nos grupos GOVX, GEPOVX, GESTR e GDEXAR. Após 21 dias de castração, os animais foram tratados por cinco dias consecutivos. No final do experimento, todos os animais foram sacrificados e o útero removido para rotina histológica. RESULTADOS: a JEC do GEP tinha limites irregulares e pouco nítidos, com vários brotamentos em direção da lâmina própria, bem como redução do número de leucócitos comparado a GEF. A JEC do GOVX e do GEPOVX se mostrou pouco nítida, com epitélio cúbico na parte endometrial e diminuição das camadas do epitélio escamoso, com atrofia estromal. No GESTR, a JEC apresentou-se bem mais desenvolvida que nos grupos GOVX e GEPOVX, mas assemelhando-se mais ao GEP devido aos limites pouco nítidos e aumento dos brotamentos. Já no GDEXAR, a JEC foi bem delimitada, se aproximando do aspecto do GEF. CONCLUSAO: nossos dados sugerem que a dexametasona associada ao estrogênio seria importante na restauração da morfologia normal da JEC em ratas que foram previamente induzidas a estro permanente e subseqüentemente submetidas a castração.

Eletrorretinograma multifocal em pacientes tratadas com tamoxifeno em baixa dosagem / Multifocal ERG in patients treated with low-dose tamoxifen

OBJETIVO: O tamoxifeno é um antiestrógeno utilizado como agente terapêutico eficaz no câncer de mama. A droga pode causar efeitos tóxicos oculares em dosagens altas. O objetivo deste estudo foi determinar possíveis efeitos retino-tóxicos centrais usando o eletrorretinograma multifocal (mfERG) em grupo de pacientes tratadas com baixa dosagem de tamoxifeno (20 mg/dia) após cirurgia do câncer de mama. MÉTODOS: O eletrorretinograma multifocal (mfERG) de 30 graus centrais da retina foi obtido em 3 diferentes grupos: Grupo experimental - 15 mulheres (41-59 anos, média 48,6 ± 4,5) com fundo de olho normal, tratadas com tamoxifeno em baixa dosagem por 1 a 55 meses. Grupo controle - 6 mulheres (30 -76 anos, média 49,9±18,8) com diagnóstico prévio de câncer de mama que não receberam tratamento com tamoxifeno até o teste do eletrorretinograma multifocal. Grupo controle normal - 15 voluntárias normais (30-71 anos, média 47,7 ± 12,9). A amplitude e a latência de eletrorretinograma multifocal para N1-P1 foram analisados estatisticamente (análise de variância de uma via). RESULTADOS: As amplitudes médias N1-P1 (nV/grau²) foram comparáveis para respostas de diferentes excentricidades (0 a 25 graus) nos três grupos. Não houve diferença estatisticamente significativa para a latência de N1 e P1 (ms) do eletrorretinograma multifocal entre os 3 grupos. CONCLUSÕES: O tratamento com baixa dosagem de tamoxifeno não mostrou efeitos retino-tóxicos em pequeno grupo de mulheres após cirurgia do câncer de mama. Investigação seriada proporcionará melhor compreensão desses efeitos.

Hereditary and acquired angioedema: experience with patients in Puerto Rico

Hereditary (HAE) and acquired (AAE) angioedema are vascular reactions involving the sub mucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries. HAE and AAE are clinical disorders characterized by angioedema that require prompt differentiation from other causes of angioedema in order to receive the most pertinent and effective therapeutic interventions. The aim of this report is to describe the clinical characteristics of patients with both HAE and AAE identified and followed at the Immunology Clinic of the University Hospital at the Puerto Rico Medical Center, their response and side effects to danazol therapy and their comparison with other series of similar patients reported in the literature. Overall, the patients in this sample presented a similar clinical profile compared to other reported series in the literature.

Antiestrógenos: mecanismo de acción y aplicaciones clínicas / Antiestrogens: Mechanism of action and clinical applications

Los antiestrógenos son compuestos que antagonizan la acción de los estrógenos compitiendo por su receptor. Los estrógenos están implicados en la proliferación y diferenciación de las células blanco y se consideran entre los principales factores de riesgo para el desarrollo de cáncer de mama y útero. Algunos antiestrógenos, entre ellos el Tamoxifén, son utilizados como terapia coadyuvante en el tratamiento del cáncer de mama y se ha propuesto su inclusión en los programas de prevención, en mujeres con alto riesgo. Los antiestrógenos se clasifican en tipo I o parciales (agonista/antagonista), y tipo II o puros (antagonista puro), los cuales tienen mecanismos de acción diferentes. Debido al continuo avance en el desarrollo de nuevos compuestos con actividad antiestrogénica, y su importancia aplicativa en clínica. En este documento se presenta una revisión del estado actual del conocimiento de estos compuestos, su mecanismo de acción y su aplicación clínica. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

Spectrum of benign breast disorders in a university hospital.

In a period of 2 years, 234 cases of benign breast disorder were studied. Breast pain and modularity was the commonest group (70.1%) followed by fibroadenoma (17.5%). Cyclical mastalgia (61.5%) is more common than non-cyclical mastalgia (38.5%). The age of the patients with cyclical mastalgia was significantly lesser than patients with non-cyclical mastalgia. Cyclical mastalgia was seen only in premenopausal females while non-cyclical mastalgia was also seen in postmenopausal females. Treatment with vitamin E showed 41% response rate with minimal side-effects while treatment with danazol showed 72.1% response rate but was associated with side-effects in one third of the patients.

Antiestrogen U23,469 induced alterations of catecholamine levels on plasma and central nervous system

The effect of antiestrogen U23,469 administration in vivo on the centration of dopamine, norepinephrine and epinephrine in the plasma, cerebral cortex and hypothalamus in ovariectomized rats was investigated. Rats were treated with estradiol benzoate, progesterone and U23,469 in different doses, s.c., daily for 6 days. Control group was injected with sesame oil. Catecholamines were estimated by radioenzymatic assay. Six days of U23,469, estradiol benzoate, progesterone or its combination altered the catecholamine levels compared to the control. Dopamine decreased in plasma with progesterone and U23.469. In the cerebral cortex, progesterone and U23,469 increased significantly and in the hypothalamus all the treatments produced a decrease of catecholamines. The levels of NE were reduced with estradiol benzoate, progesterone and U23,469; there was no significant difference in the norepinephrine levels after different treatments in the cerebral cortex, but the NE levels were significantly decreased inthe hypothalamus. Epinephrine Showed differences related to the treatment, as in plasma, as in cerebral cortex and hypothalamus. These resultas suggest that antiestrogen treatment compared with the estradiol benzoate or progesterone may affect the catecholamine levels of the central nervous system and plasma and support the idea that AE could have an indirect effect on the catecholaminergic system