Recurrent Granulosa Cell Tumor in a Postmenopausal Woman: A Case Report and Literature Review.

Ovarian cancer is among the most common types of cancer suffered by the female population. As of United States Cancer Statistics (USCS) 2019, the National Cancer Institute reports the prevalence of ovarian cancer as 11.4 cases per every 100,000 each year. The highest prevalence is in the seventh decade of life. Of all the types, sex cord-stromal tumors (SCSTs) account for 5-8% of cases. They are a heterogeneous group of rare neoplasms originating from the ovarian matrix, and nearly 90% of the hormone-producing tumors are SCSTs. Hence, patients with SCSTs are known to present with excess estrogen and androgen signs and symptoms. Many SCSTs are known for their indolent course and tendency to affect the unilateral ovary. The prognosis of the malignancy depends on the subtype of SCST, the stage of the patient's disease, and age. Among all the types, 20-50% of the ovaries' granulosa cell tumors tend to recur decades after the initial presentation, and 70% of the recurrences end up with a very poor prognosis. This case will discuss a 68-year-old woman who presented with a recurrence of an adult granulosa cell tumor after 13 years in remission. The patient had been previously diagnosed with an adult granulosa cell tumor of the right ovary at age 55 and had undergone surgical resection along with chemotherapy.

Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis.

PROBLEM: Endometriosis (EMS) is an estrogen-dependent disease which is characterized with estrogen-dependent growth of ectopic endometrium and increased local estrogen production. EMS performs tumor-like biological functions such as invasiveness and angiogenesis. Rab27b is a member of the Rab family of GTPases, which is strongly associated with the growth, invasion and metastasis of a variety of tumors. However, little is known about the function of Rab27b in EMS. In this study, we intended to investigate the impact of Rab27b and its downstream molecule in the development of EMS. METHOD OF STUDY: Normal endometrium and endometriotic lesions were collected to investigate the expression levels of Rab27b. Then, ESCs were transfected with Rab27b siRNA. We analyzed the influence of Rab27b on the proliferation and invasive activity of ESCs. Conditioned media harvested from Rab27b siRNA-treated ESCs were used to treat HUVECs. HUVEC Tube formation and ELISA were performed to explored the interactions between ESCs and HUVEC. In addition, ESCs were treated with different concentrations of estrogen. Based on biological database predictions, we explored possible mechanisms through which estrogen regulates the expression of Rab27b. RESULTS: The expressions of Rab27b were significantly higher in endometriotic lesions than that in normal endometrium. Rab27b can promote the cell proliferation, migration and invasion of ESCs. The elevated expression of Rab27b, on the one hand, promotes the secretion of MMP9 and increases the invasiveness of ESCs. On the other hand, Rab27b may play a key role in the communication between ESC and endothelial cells, by simulating VEGF secretion and neovascularization. Besides, estrogen upregulated phosphorylated FOXO1 levels in ectopic ESCs, resulting in the promotion of Rab27b expression levels. CONCLUSION: Rab27b plays a key role in the development of EMS, which may provide new insights into the pathogenesis of EMS. Our findings may also contribute to the development of therapeutic interventions for EMS.

Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis.

RESEARCH QUESTION: Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment? DESIGN: Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes. Pregnancy and ongoing pregnancy rates were the primary outcomes. Blood oestradiol concentration after treatment with an aromatase inhibitor was a secondary outcome. RESULTS: Patients with severe adenomyosis presented with hyperestrogenism due to local production from the lesions even after long-term treatment with GnRHa. Treatment with an aromatase inhibitor reduced hyperestrogenism and improved clinical outcomes in adenomyosis patients who have experienced previous embryo transfer failures. CONCLUSION: Women with severe adenomyosis would benefit from letrozole or a combination of GnRHa plus letrozole before receipt of treatment with assisted reproductive technology. For women with severe adenomyosis, GnRHa treatment alone may be insufficient to suppress oestrogen production by adenomyotic lesions. Thus, it should be mandatory to test for oestradiol concentrations in patients with severe adenomyosis who have received long-term GnRHa treatment. Also, GnRHa may not always be the sole strategy for medical management of adenomyotic lesions. Letrozole is safe and can improve IVF outcomes for patients with adenomyosis.

Hyperandrogenism and Hyperestrogenism Secondary to Mixed Germ-Cell Testicular Tumor.

Testicular cancer with androgen and estrogen secretion is classically associated with Leydig cell tumors. Rare case reports have described this finding in germ-cell tumors along with signs of androgen and estrogen excess including gynecomastia and infertility. We report the case of a 19-year-old male with a non-seminomatous testicular germ-cell tumor found to have hyperandrogenism, hyperestrogenism, and suppression of central sex hormones. Similar findings may be underreported in the literature, and males with suspected testicular malignancy should be appropriately screened for signs of androgen and/or estrogen excess so they can be offered appropriate monitoring and counseling.

Tree nut consumption is associated with a lower risk of hyperestrogenism in men.

Hyperestrogenism may affect 2% to 8% of men globally. Previous studies indicate that tree nut consumption is associated with sex hormones in women. Whether this is the case in men remains unknown. This study hypothesized that consumption of tree nuts was inversely associated with circulating estradiol and prevalence of hyperestrogenism in men. This cross-sectional study included 3340 men aged ≥20 years from the US National Health and Nutrition Examination Survey from 2013 to 2016. Associations of tree nut consumption with circulating estradiol and prevalence of hyperestrogenism were assessed using weighted linear regression and binary logistic regression, respectively. Among the 3340 men, 207 consumed tree nuts. The mean usual intake of tree nuts among tree nut consumers was 34.2 g/d. Amounts of usual intake of tree nuts were inversely associated with bioavailable estradiol (ß = -0.032, P = .037) after adjustment for all confounders. Usual intake of tree nuts of ≥ 30 g/d (vs <30 g/d) or ≥42.52 g/d (vs <42.52 g/d) was associated with a 24% or 7% lower multivariate-adjusted risk of hyperestrogenism, respectively. Further analyses showed that usual intake of tree nuts was positively associated with circulating folate, and the latter was inversely associated with circulating estradiol. In conclusion, higher tree nut consumption was independently associated with lower circulating levels of bioavailable estradiol and a lower risk of hyperestrogenism in men. Further research is needed to verify the effectiveness of using tree nuts to treat hyperestrogenism in men.

Unilateral Nevoid Telangiectasia in a Healthy Man.

We report the case of a healthy 26-year-old man presenting telangiectatic macules on the left thorax and arm since childhood. The main diagnostic hypothesis were unilateral nevoid telangiectasia (UNT), hereditary benign telangiectasia, atrial myxoma, segmental serpiginous angioma, circumscribed neviform angiokeratoma, and nevus vascularis mixtus. The diagnosis retained was UNT characterized by congenital or acquired telangiectasia distributed asymmetrically along the upper extremities, or the third or fourth cervical dermatomes. The congenital form is extremely rare, predominant in men, and persists in adulthood. The acquired form is most frequent, affects preferentially women, usually appears at puberty or during pregnancy and tends to disappear. Estrogen excess triggers the formation of telangiectasia. UNT is rarely associated with liver or thyroid disorder. Pulsed-dye lasers and normalization of estrogen are proposed as therapeutic options. We report a rare diagnosis of UNT in a young man with no other underlying condition. We would like to highlight that in the presence of unilateral telangiectasia, a complete clinical examination must be performed to rule out signs of hyperestrogenism in man, ocular or neurological abnormalities, a blood test to exclude pregnancy, hepatic and thyroid dysfunctions, and ultrasonography in case of suspicion of atrial myxoma.

Long-term estradiol-17ß exposure decreases the cholinergic innervation pattern of the pig ovary.

Elevated levels of endogenous estrogens in the course of pathological states of ovaries, as well as xenoestrogens, may lead to hyperestrogenism. It has previously been demonstrated that long-term estradiol-17ß (E2) administration in adult gilts affected the population of sympathetic intraovarian nerve fibers. The aim of this study has been to determine the effect of long-term E2 exposure on the cholinergic innervation pattern of porcine ovaries. Intraovarian distribution and the density of nerve fibers immunoreactive (IR) to vesicular acetylocholine transporter (VAChT) and/or neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) were determined. From day 4 of the first estrous cycle to day 20 of the second studied cycle, experimental gilts were intramuscularly injected with E2, while control gilts received corn oil. The ovaries were then collected and processed for double-labelling immunofluorescence. After E2 administration, the total number of fibers IR to VAChT, nNOS and VIP decreased significantly. The numbers of VAChT-, nNOS- and VIP-IR fibers within the ground plexus were significantly lower, while they were significantly higher around small or medium tertiary follicles. In the E2-affected ovaries, the numbers of nNOS- and VIP-IR fibers were significantly higher near secondary follicles and VAChT-IR in the vicinity of medullar blood vessels. In turn, around the latter structures there were significantly lowered populations of nNOS- and VIP-IR nerve fibers. These results suggest that the elevated E2 levels that occur during pathological states may affect the cholinergic innervation pattern of ovaries and their function(s).

Meningioma en gestante afecta de endometriosis profunda. A propósito de un caso / Meningioma in pregnant women affected by deep endometriosis. About a case

RESUMEN El siguiente caso clínico trata de una paciente, gestante tras fecundación in vitro, afecta de endometriosis profunda. Dicha paciente debutó durante el embarazo con un síndrome del seno cavernoso con cefalea e hipoestesia facial, siendo diagnosticada tras una exploración neurológica detallada y las pruebas complementarias pertinentes de un meningioma. Por este motivo, tuvo que ser sometida a una cesárea previa al abordaje terapéutico del tumor, dado el empeoramiento clínico progresivo que se estaba produciendo. Dado que en la literatura científica la asociación entre la endometriosis y la aparición de meningiomas ya ha sido descrita, con este caso clínico intentaremos acercarnos a las posibles causas de dicha asociación, como podría ser el ambiente predominantemente estrogénico de las pacientes con endometriosis. De igual modo, abordaremos el manejo del meningioma tanto dentro como fuera del embarazo, sirviéndonos para ello de la bibliografía disponible.

ABSTRACT A pregnancy woman affected by deep endometriosis is presented in this clinical case. A cavernous sinus syndrome was diagnosed during her pregnancy. She started suffering from headache and facial hypoesthesia. After a detailed neurological examination and the relevant complementary tests the patient was diagnosed of a meningioma. Given the progressive clinical worsening that was taking place, she had to undergo a cesarean section prior to the therapeutic approach of the tumor. Through this clinical case we will try to approach the possible causes of the association between endometriosis and meningioma, such as the predominantly estrogenic environment of patients with endometriosis. Similarly, we will address the management of meningioma both inside and outside of pregnancy, using the related available literature.

Reproductive Medicine in Ferrets.

In the United States, desexing is performed routinely in ferrets at the age of 6 weeks, therefore reproductive tract diseases are not so common. However, in Europe most ferrets are desexed when they are several months old, or they are kept as intact animals. For this reason, diseases of the reproductive organs and a prolonged estrus are far more frequent in Europe than in the United States. This article summarizes and reviews the anatomy, reproductive physiology, management of reproduction (including surgical and hormonal contraception) and reproductive tract diseases in male and female ferrets.

Bone marrow bi-hypoplasia in a dog with a sertoli cell tumor / Hipoplasia dupla de medula óssea em um cão com tumor de células de sertoli

A 20-year-old unneutered male poodle presented prostration, apathy, staggering gait, lack of appetite and tick infestation. The dog was diagnosed with a Sertoli cell tumor in an undescended testicle by cytological, histopathological and immunohistochemical tests. Pancytopenia with moderate nonregenerative anemia, leukopenia and severe thrombocytopenia were detected in the complete blood count. Cytological and histopathological evaluation of the bone marrow revealed a cellularity of 30%, with erythroid (59%), lymphoid (40%) and mast cells (1%), and an absence of granulocytic, monocytic and megakaryocytic lineage cells. In post-mortem examinations, changes related to hemostatic disorders were found. The absence of microorganisms in molecular tests and an estrogen serum concentration over reference values confirmed hyperestrogenism as a possible cause of pancytopenia. The literature describes a Sertoli cell tumor hyperestrogenism that induced pancytopenia, along with bone marrow hypoplasia of all hematopoietic lineages. In contrast, in the present case, the erythroid precursor cells were preserved in the bone marrow, although there were no reticulocytes circulating in the blood. This case, therefore, should be considered in future investigations of pancytopenia induced by Sertoli cell tumor hyperestrogenism.(AU)

Um cão Poodle, macho, de 20 anos, não castrado, apresentou prostração, apatia, andar cambaleante, falta de apetite e infestação por carrapatos. Nesse animal, foi diagnosticado tumor de células de Sertoli em um testículo não descendente, utilizando-se citologia, histopatologia e imuno-histoquímica. Pancitopenia com anemia moderada não regenerativa, leucopenia e trombocitopenia intensas foram detectadas no hemograma. Na avaliação citológica e histopatológica da medula óssea, havia celularidade de 30%, constituída pelas linhagens eritroide (59%) e linfoide (40%) e por mastócitos (1%), com ausência de células das linhagens granulocítica, monocítica e megacariocítica. Em exames post mortem, mudanças relacionadas à hemostasia foram encontradas. A ausência de micro-organismos nos testes moleculares e a concentração sérica de estrogênio acima dos valores de referência confirmaram hiperestrogenismo como a possível causa da pancitopenia. A literatura descreve hiperestrogenismo em tumores de células de Sertoli induzindo pancitopenia associada com hipoplasia da medula óssea de todas as linhagens hematopoiéticas. Em contraste, no presente caso, as células precursoras eritróides estavam preservadas na medula óssea, embora não houvesse reticulócitos no sangue. Assim, o relato apresentado deve ser considerado em futuras investigações de pancitopenia induzida por hiperestrogenismo em tumor de células de Sertoli.(AU)

Adenomyosis and its impact on women fertility.

Adenomyosis is a widespread disease affecting the reproductive period of women's life. In the last ten years, different pathogenetic hypotheses have been proposed to explain the initiation and development of the disease. This article aims to present and discuss the most important pathophysiologic mechanisms underlying adenomyosis development in order to clarify the relationship between adenomyosis and infertility. A PubMed search was undertaken for English language literature using the MeSH terms 'adenomyosis', 'infertility', 'treatment', and 'pathogenesis'. Although the exact etiology of adenomyosis is unknown, many theories have been proposed. We analysed the most important pathogenic theories expressed and evaluated the potential consequences on women fertility. A better comprehension of the adenomyosis pathogenesis has allowed realizing that adenomyosis may affect young women and may have a great impact on their fertility through different mechanisms. The understanding of these mechanisms helps to clarify the potential usefulness of current therapies.

Is the endometrial evaluation routinely required in patients with adult granulosa cell tumors of the ovary?

OBJECTIVE: Granulosa cell tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCT patients treated in MITO centers. METHODS: A retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities. RESULTS: A total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40years. All patients with endometrial cancer were older than 40years and postmenopausal. CONCLUSIONS: Endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients >40years; based on these data, endometrial sampling should be performed in symptomatic women at least 40years of age. In asymptomatic women <40years, endometrial sampling is of low yield.

Estrogen mediates metabolic syndrome-induced erectile dysfunction: a study in the rabbit.

INTRODUCTION: Estrogen receptor (ER) α is critical in mediating the harmful effects of hyperestrogenism in fetal or neonatal life on the developing penis. In contrast, little is known on the impact of an excess of estrogens on penile function in adulthood. AIM: To investigate the effect of estrogens on metabolic syndrome (MetS)-associated erectile dysfunction (ED). METHODS: We employed a recently established animal model of high fat diet (HFD)-induced MetS. Subgroups of MetS rabbits were dosed with either testosterone (T) or tamoxifen. We evaluated penile responsiveness to acetylcholine (Ach) as well as the expression of genes related to penile smooth muscle relaxation and contractility. MAIN OUTCOME MEASURE: Associations between MetS-induced penile alterations and sex steroids were investigated in an animal model of HFD-induced MetS. To understand the role of either androgen deficiency or estrogen excess on ED, we treated subgroups of MetS rabbits with either T or tamoxifen, a classical ER antagonist. RESULTS: Feeding an HFD-induced MetS was associated to elevated estradiol (E2) and low T levels. E2, but not T, was independently and negatively associated with genes able to affect penile erection. Smooth muscle-related markers decreased as a function of E2 and were positively associated with all the variables investigated. Increasing concentrations of circulating E2 were negatively associated with Ach-induced relaxation. In HFD rabbits, in vivo T dosing significantly improved MetS and completely normalized circulating E2. Conversely, in vivo tamoxifen dosing reduced visceral adiposity and partially restored T level. Ach-induced relaxation was severely impaired by HFD and significantly restored, up to the control level, by both tamoxifen and T dosing. In rabbit smooth muscle cells cultures 17ß-E2 (1 nM) significantly reduced the expression of α-smooth muscle actin, transgelin, and phosphodiesterase type 5. The effects of 17ß-E2 were completely reverted by tamoxifen (100 nM). CONCLUSIONS: This study demonstrates, for the first time, that HFD-induced ED is more associated with a high E2, rather than to a low T, milieu. HFD-induced ED is partially restored by in vivo treatment not only with T but also with the nonsteroidal ER antagonist, tamoxifen.

Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies.

Recognition of the two main pathologic mechanisms equally leading to breast cancer development may provide explanations for the apparently controversial results obtained by sexual hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperandrogenism and estrogen deficiency, but during these ongoing pathologic processes, ER defect also develops. Conversely, when estrogen resistance is the onset of hormonal and metabolic disturbances, initial counteraction is hyperestrogenism. Compensatory mechanisms improve the damaged reactivity of ERs; however, their failure leads to secondary insulin resistance. The final stage of both pathologic pathways is the breakdown of estrogen surveillance, leading to breast cancer development. Among premenopausal breast cancer cases, insulin resistance is the preponderant initiator of alterations with hyperandrogenism, which is reflected by the majority of studies suggesting a causal role of hyperandrogenism in breast cancer development. In the majority of postmenopausal cases, tumor development may also be initiated by insulin resistance, while hyperandrogenism is typically coupled with elevated estrogen levels within the low postmenopausal hormone range. This mild hyperestrogenism is the remnant of reactive estrogen synthesis against refractory ERs that were successfully counteracted at a younger age. When refractoriness of ERs is the initiator of pathologic processes, reactively increased estrogen levels may be found in both young and older breast cancer cases, while they may exhibit clinical symptoms of estrogen deficiency. Studies justifying a causal correlation between hyperestrogenism and tumor development compile such breast cancer cases. In conclusion, the quantitative evaluation of ER refractoriness in breast cancer cases has great importance, since the stronger the estrogen resistance, the higher the promising dose of estrogen therapy.

Serotonergic 5-HT2A/2C receptors are involved in prolactin secretion in hyperestrogenic rats.

Serotonin (5-HT) has been shown to participate in prolactin secretion through a complex process resulting in both positive and negative effects. Estrogen has also been recognized as being involved in this serotonergic effect on prolactin release. Therefore, the aim of the present study was to assess whether estradiol modulates serotonergic involvement in prolactin secretion though 5-HT1A and/or 5-HT2A/2C receptors. Ovariectomized female Wistar rats, treated for 2 weeks with estrogen to induce a hyperprolactinemic status (hyperestrogenic rats) or with sunflower oil vehicle (hypoestrogenic rats), were injected daily with normal saline solution or 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), an 5-HT2A/2C receptor agonist, for 4 days. Other groups of ovariectomized animals received 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or pindolol, an agonist and antagonist of the 5-HT1A receptor respectively, on the last day of treatment with estrogen or vehicle. Prolactin levels were compared among groups in each experiment under the distinct drug treatments. MK-212 was found to increase prolactin concentrations both in hyper- and hypoestrogenic females compared to controls (p<0.05). In contrast, prolactin levels remained similar to those of controls both in hyperestrogenic animals treated with 8-OH-DPAT and pindolol and in hypoestrogenic rats administered the same treatments. In conclusion, our findings indicate the involvement of 5-HT2A/2C receptors on prolactin release through serotonergic pathways in female animals, especially in hyperestrogenic states.

Alimentação de leitoas pré-púberes com dietas contendo zearalenona / Feeding of pre-pubertal gilts with diets containing zearalenone

O desempenho, o peso de alguns órgãos e a morfologia vulvar de leitoas pré-púberes, alimentadas por 28 dias com dietas contendo zearalenona, foram avaliados. O delineamento experimental utilizado foi inteiramente ao acaso, com dois tratamentos, dieta controle (DC) e dieta controle + 2mg kg-1 de zearalenona (DZ), e seis repetições cada. Não houve diferença (P>0,05) entre os tratamentos para consumo médio diário de ração (1,24 x 1,19kg), ganho médio diário de peso (0,68 x 0,71kg), conversão alimentar (1,86 x 1,71) e peso vivo (PV); (30,9 x 30,4kg). A zearalenona não alterou (P>0,05) os pesos absoluto e relativo do coração (137 x 141g e 0,45 x 0,45 por cento PV), fígado (699 x 699g e 2,31 x 2,26 por centoPV), rins (47 x 49g e 0,15 x 0,16 por centoPV) e baço (166 x 171g e 0,55 x 0,55 por centoPV). Houve aumento (P<0,05) no comprimento (17 x 27cm) e no peso (23 x 157g e 0,07 x 0,51 por centoPV) do trato reprodutivo das leitoas do grupo DZ. O volume vulvar ao final do período foi 820 por cento maior (P<0,05) nos animais alimentados com zearalenona (941 x 8658mm³/kgPV0,6). Os resultados indicam que em suínos a zearalenona e seus metabólitos possuem atividade estrogênica, mas não interferem no desempenho dos animais.

The performance, the weights of some organs, and the vulvae morphology in pre-pubertal gilts fed diets containing zearalenone were evaluated during 28 days. The experimental design was completely randomized with two treatments (control diet, ZD - control diet + 2mg kg-1 of zearalenone) and six replications of each were done. No differences (P>0.05) between treatments for daily feed intake (1.24 x 1.19kg), average daily gain (0.68 x 0.71kg), feed conversion ratio (1.86 x 1.71), and live weight (30.9 x 30.4kg) were observed. Zearalenone did not change (P>0.05) the absolute and relative weights of heart (137 x 141g and 0.45 x 0.45 percentBW), liver (699 x 699g and 2.31 x 2.26 percentBW), kidneys (47 x 49g and 0.15 x 0.16 percentBW), and spleen (166 x 171g and 0.55 x 0.55 percent BW). However, zearalenone increased (P<0.05) the length (17 x 27cm) and weight (23 x 157g and 0.07 x 0.51 percentBW) of the reproductive tract. The final vulvae volume was 820 percent larger (P<0.05) in gilts fed diets containing zearalenone than those fed control diet (941 x 8658mm³/kgBW0.6). Results suggested that zearalenone and its metabolites have an estrogenic activity in pigs without changing the animal performance.

Histopathologic Findings & Expression of bcl-2 of the Endometrium Analysis of 1,000 consecutive biopsies of uterine bleeding

We evaluated 1,000 consecutive endometrial curettage samples obtained over a 30 month period. The clinico-pathologic correlation was analysed according to Hendrickson's five criteria based on the practical view. The causes of uterine bleeding in decreasing order of occurrence were as follows: 1) hormonal imbalance lesions (49.2%) encompassing glandular and stromal breakdown suggesting anovulatory bleeding, proliferative phase endometrium, and disordered proliferative endometrium, 2) pregnancy associated lesions (24.2%), 3) organic lesions (13.5%), 4) endometrial hyperplasia (6.9%), and 5) inadequate specimen (6.2%). According to age, pregnancy related lesions were most frequent in the third decade. In the fourth, fifth, and sixth decades, hormonal imbalance lesions were the most common cause. In approximately 30% of the samples, there were two or three morphologic patterns such as anovulatory bleeding with an endometrial polyp, postabortal bleeding with inflammation, and glandular-stromal dissociation with a polyp, which suggested there was a variable histologic morphology in the same disease spectrum. Using immunohistochemical techniques we studied the hormonal dependency of bcl-2 oncoprotein in anovulatory bleeding, endometrial hyperplasia, and proliferative endometrium. 70% of anovulatory bleeding specimens showed weak positivity in the epithelial cytoplasm, and all cases of endometrial hyperplasia and carcinoma showed a strong positivity. These results suggest that there is a estrogenic hormonal dependency of apoptosis in the endometrium.