Combined oral contraceptive in female mice causes hyperinsulinemia due to ß-cell hypersecretion and reduction in insulin clearance.

Oral contraception is the most commonly used interventional method in the world. However, several women employ the continuous use of these hormones to avoid pre- and menstruation discomforts. Some studies indicate that oral contraceptives are associated with disturbances in glycemia and the effects of the use of a continuous regime are poorly elucidated. Herein, we evaluated the effects of the continuous administration of a combined oral contraceptive (COC) composed by ethinyl estradiol (EE) and drospirenone (DRSP) on glucose homeostasis in female mice. Adult Swiss mice received 0.6 µg EE and 60 µg DRSP (COC group) or vehicle [control (CTL)] daily by gavage for 35 days. COC treatment had no effect on body weight or adiposity, but increased uterus weight and induced hepatomegaly. Importantly, COC females displayed normal glycemia and glucose tolerance, but hyperinsulinemia and lower plasma C-peptide/insulin ratio, indicating reduced insulin clearance. Furthermore, COC mice displayed reduced protein content of the ß subunit of the insulin receptor (IRß) in the liver. Additionally, pancreatic islets isolated from COC mice secreted more insulin in response to increasing glucose concentrations. This effect was associated with the activity of steroid hormones, since INS-1E cells incubated with EE plus DRSP also secreted more insulin. Therefore, we provide the first evidence that the continuous administration of EE and DRSP lead to hyperinsulinemia, due to enhancement of insulin secretion and the reduction of insulin degradation, which possibly lead to the down-regulation of hepatic IRß. These findings suggest that the continuous administration of COC could cause insulin resistance with the prolongation of treatment.

Morphology and histomorphometry of the bladder and urethra in ovariectomized rats after long-term use of tibolone.

BACKGROUND: This study aimed to evaluate the effect of long-term high-dose tibolone on the bladders and urethras of ovariectomized rats. METHODS: Bilateral ovariectomy was performed in 14 young adult rats randomly divided into 2 groups. Experimental rats (n = 9) received 1 mg/day of tibolone orally; control rats (n = 6) received a placebo. After 150 days, the bladders and urethras were removed. Bladder cell proliferation was analyzed by Ki-67 immunohistochemistry. A histomorphometric analysis was performed for epithelial thickness and the percent areas of collagen fibers and blood vessels. Data were compared using a Mann-Whitney test (significance level at p < 0.05). RESULTS: Urothelial thickness and the percent area of collagen fibers and blood vessels were not significantly different between the tibolone and control groups in the bladder and urethra. In addition, urothelium cell proliferation in the bladder showed a low immunopositivity in both groups. Furthermore, the glycogen and glycoprotein contents in urethral epithelium were slightly modified by tibolone and no change was observed in the bladder. CONCLUSION: Long-term administration of tibolone has no effect on urothelial trophism, collagen fibers, the number of vessels, or cell proliferation in the urethra and bladder of the ovariectomized rat.

Efeito do uso contínuo de hormônios esteroides sexuais na mama de ratas wistar / Effect of continuous use of sex steroid hormones in the breast of Wistar rats

Não há consenso sobre o efeito do uso cumulativo de esteroides sexuais no desenvolvimento de neoplasias mamárias. O objetivo deste estudo é verificar, na mama de ratas castradas, o efeito da terapia hormonal (TH) com tibolona (T), estradiol (E2) ou estradiol/progesterona combinado (E2Pg), após uso de anticoncepcional hormonal (AH) durante a vida reprodutiva...O uso de qualquer TH aumentou significativamente a expressão de genes associados à proliferação e de RE alfa vs pl+SHAM+pl. O perfil de modificações da expressão gênica pelo uso de TH com tibolona com ou sem AH prévio, apresentou-se diferente das outras TH. O uso de anticoncepcional hormonal durante a vida reprodutiva pode aumentar o risco de desenvolvimento de câncer de mama, já que acarreta hiperplasia de brotos alveolares, independente da utilização de terapia hormonal na pós-menopausa.

Efeito da tibolona na morfologia do músculo esquelético, nas enzimas hepáticas e no nível sérico de glicose em ratas castradas / Effect of tibolone on the morphology of skeletal muscle, liver enzymes and blood glucose level in castrated female rats

INTRODUÇÃO: O fígado é uma estrutura de elevada complexidade e é fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funções. OBJETIVO: Analisar a influência da tibolona no metabolismo hepático por meio da avaliação de enzimas e metabólitos comumente utilizados em provas de função hepática. MÉTODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4) e tibolona (n = 6), em status de menopausa cirúrgica. A tibolona (1 mg) foi administrada diariamente por gavagem durante 20 semanas, com avaliação periódica do peso corporal. Após sedação, efetuou-se coleta de sangue para avaliação bioquímica de albumina (Alb) sérica, fosfatase alcalina (FA), transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT]), gama-glutamiltranspeptidase (GGT) e glicose, mediante espectrofotometria. O músculo esquelético da coxa foi avaliado por histomorfometria em cortes histológicos corados com hematoxilina e eosina (HE). RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alterações musculares esqueléticas e discretas alterações bioquímicas. Além disso, AST e FA estavam diminuídas e GGT estava mais elevada, porém sem significância estatística. A histomorfometria do músculo revelou uma tendência de menor volume celular nesse grupo. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, não interfere de forma significativa nas funções metabólicas e de síntese hepáticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressão genômica da GGT. A tibolona apresenta influência sistêmica associada a menor peso e diminuição da massa muscular e aumento significativo no peso relativo do fígado, além de alteração da glicogenólise hepática e muscular, da gliconeogênese hepática e dos níveis de glicose circulante.

INTRODUCTION: The liver is a highly complex structure and it is essential to understand how certain substances may affect its structure and functions. OBJECTIVE: Analyze the influence of tibolone on hepatic metabolism by assessing metabolites and enzymes commonly used in liver function tests. METHODS: Ten Wistar rats in surgical menopausal status were divided into two groups: control (n = 4) and tibolone (n = 6). Tibolone (1 mg) was administered by gavage daily for 20 weeks and body weight was periodically assessed. After sedation, blood sampling was performed for biochemical evaluation of serum albumin (Alb), alkaline phosphatase (ALP), transaminases (aspartat aminotranferase and alanine aminotranferase [AST/ALT]), gamma glutamyltranspeptidase (GGT) and glucose by spectrophotometry. Hematoxylin and eosin-stained histological sections of the skeletal thigh muscle were assessed by histomorphometry. RESULTS: The animals in the tibolone group showed lower body weight, skeletal muscle alterations and slight biochemical changes. In the tibolone group, AST and ALP were decreased GGT was higher, but without a statistically significant difference. The muscle histomorphometry showed that the tibolone group tended to present a lower cell volume. CONCLUSION: Tibolone administered in high doses and for a prolonged period does not interfere significantly neither with liver metabolic functions nor liver synthesis, nor with cell membrane permeability. However, it seems to modulate the genomic expression of GGT. Tibolone has systemic influence on lower body weight, reduced muscle mass, and significant increase in relative liver weight. Additionally, liver and muscular glycogenolysis, liver gluconeogenesis and circulating glucose levels are altered.

Influence of estrogen deficiency and tibolone therapy on trabecular and cortical bone evaluated by computed radiography system in rats.

PURPOSE: To verify the effects of tibolone administration on trabecular and cortical bone of ovariectomized female rats by computed radiography system (CRS). METHODS: The experiment was performed on two groups of rats previously ovariectomized, one received tibolone (OVX+T) while the other did not (OVX), those groups were compared to a control group (C) not ovariectomized. Tibolone administration (1mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs and tibias collected. Computed radiographies of the bones were obtained and the digital images were used to determine the bone optical density and cortical thickness on every group. All results were statistically evaluated with significance set at P<0.05%. RESULTS: Tibolone administration was shown to be beneficial only in the densitometric analysis of the femoral head, performing higher optical density compared to OVX. No difference was found in cortical bone thickness. CONCLUSION: Ovariectomy caused bone loss in the analyzed regions and tibolone administered in high doses over a long period showed not to be fully beneficial, but preserved bone mass in the femoral head.

Influence of estrogen deficiency and tibolone therapy on trabecular and cortical bone evaluated by computed radiography system in rats / Influência da deficiência estrogênica e do tratamento com tibolona no osso trabecular e cortical avaliada pelo sistema de radiografia computadorizada em ratas

PURPOSE: To verify the effects of tibolone administration on trabecular and cortical bone of ovariectomized female rats by computed radiography system (CRS). METHODS: The experiment was performed on two groups of rats previously ovariectomized, one received tibolone (OVX+T) while the other did not (OVX), those groups were compared to a control group (C) not ovariectomized. Tibolone administration (1mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs and tibias collected. Computed radiographies of the bones were obtained and the digital images were used to determine the bone optical density and cortical thickness on every group. All results were statistically evaluated with significance set at P<0.05 percent. RESULTS: Tibolone administration was shown to be beneficial only in the densitometric analysis of the femoral head, performing higher optical density compared to OVX. No difference was found in cortical bone thickness. CONCLUSION: Ovariectomy caused bone loss in the analyzed regions and tibolone administered in high doses over a long period showed not to be fully beneficial, but preserved bone mass in the femoral head.

OBJETIVO: Verificar o efeito da administração de tibolona no tecido ósseo cortical e trabecular de ratas castradas através de radiografia computadorizada. MÉTODOS: O experimento foi realizado em dois grupos de ratas previamente ooforectomizadas, onde um grupo recebeu tibolona (OVX+T) e o outro não (OVX). Esses grupos foram comparados a um grupo controle (C) não ooforectomizado. A administração de tibolona (1mg/dia) começou trinta dias após a ooforectomia e o tratamento teve duração de cinco meses. No final, os animais foram mortos e fêmures e tibias coletados. As radiografias computadorizadas dos ossos foram obtidas e as imagens digitais usadas para determinar a densidade óssea e a espessura cortical em todos os grupos. Todos os resultados foram avaliados estatisticamente com significância estabelecida a 5 por cento. RESULTADOS: A administração de tibolona mostrou ser benéfica apenas para análise densitométrica da cabeça do fêmur, apresentando maiores valores de densidade comparada ao grupo OVX. Nenhuma diferença significativa foi encontrada para espessura óssea cortical. CONCLUSÃO: A ooforectomia ocasionou perda óssea nas regiões analisadas e a tibolona administrada, em dose elevada e durante um longo período, mostrou não ser totalmente benéfica, porém preservou a massa óssea na cabeça femoral.

Effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats.

The aim of this study was evaluate the effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats. Bilateral ovariectomy was performed on 14 rats weighing 250 g. Thirty days later, vaginal smears were collected verifying the menopause status by anoestrus cytology. Rats were divided randomly into groups: experimental rats (n = 9) received 1 mg tibolone/day orally and control rats (n = 6) received placebo (carboxymethylcellulose). After 150 days, all rats were sedated and euthanized by cervical displacement. The vagina was removed, fixed in 10% buffered formalin, sampled and processed for paraffin embedding. Histological sections were stained with haematoxylin and eosin, picrosirius red, periodic acid Schiff (PAS) and PAS-diastase, and Weigert's resorcin-fuchsin. Cell proliferation was analysed by immunohistochemistry to detect Ki67. Histomorphometric analyses were performed for epithelial thickness, per cent area of collagen fibres and blood vessels, mast cells and Ki67-positive nuclei per mm of basal membrane. Means and standard error of means were calculated, and data were compared using the Mann-Whitney test, with significance level at P < 0.05. In the vagina, epithelial thickness, number of Ki67-positive nuclei per mm of basal membrane, number of vessels and number of mast cells were significantly higher in the tibolone group when compared with the control group. Furthermore, the content of glycogen and glycoproteins in the vaginal epithelium was modified by tibolone. Tibolone administered in high dose and for a long period has a trophic effect, reversing vaginal atrophy, and has no dysplastic or neoplastic effect in the vagina of ovariectomized rats.

Histomorfometria do tecido ósseo em ratas castradas tratadas com tibolona / Bone tissue histomorphometry in castrated rats treated with tibolone

INTRODUÇÃO E OBJETIVO: O efeito da tibolona utilizada em alta dose e por tempo prolongado foi analisado mediante estudo histomorfométrico de tíbias e fêmures de ratas castradas. MÉTODOS: O experimento utilizou 20 ratas Wistar, com peso médio de 250 g. Os animais foram distribuídos aleatoriamente em três grupos: ooforectomizado recebendo tibolona (OVX + T) (n = 9), ooforectomizado (OVX) (n = 6) e grupo controle não ooforectomizado (C) (n = 5). Deu-se início ao protocolo experimental 30 dias após a ooforectomia, perdurando por 20 semanas, com administração de tibolona (1 mg/dia) a OVX + T e carboximetilcelulose a OVX. O grupo C não foi submetido a qualquer tratamento. Tíbias e fêmures direitos foram fixados em formol a 10 por cento tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados mediante hematoxilina-eosina para análise histomorfométrica. Mediram-se a espessura cortical e a cavidade medular em cortes transversais de tíbia e fêmur e percentual de porosidade e densidade trabecular em cortes longitudinais de fêmur. RESULTADO E DISCUSSÃO: Não houve diferença estatística entre OVX e OVX + T nas diversas análises. Os resultados demonstram que a tibolona não melhorou de forma significativa a qualidade óssea, porém preservou a massa óssea cortical, nas diáfises femoral e tibial, e o osso trabecular, nos côndilos femorais. O uso prolongado de tibolona em concomitância com alta dose pode ter influenciado tais efeitos, já que estudos recentes têm preconizado a utilização de doses mais baixas na prevenção da osteoporose. CONCLUSÃO: A ooforectomia ocasionou perda óssea nas regiões analisadas; a tibolona, apesar de não ter aumentado a massa óssea, manteve-a em níveis satisfatórios.

INTRODUCTION AND OBJECTIVE: The effect of tibolone administered in high dose over a prolonged period was analyzed through histomorphometry of tibia and femur samples from castrated rats. METHODS: The experiment was performed in 20 Wistar rats with average weight of 250 g. The animals were randomly divided into three groups: oophorectomized receiving tibolone (OVX + T) (n = 9), oophorectomized (OVX) (n = 6) and non-oophorectomized as control group (C) (n = 5). The experimental protocol was initiated 30 days after oophorectomy and lasted 20 weeks. Tibolone (1 mg/day) was administered to OVX + T rats and carboxymethyl cellulose to OVX. C rats did not go through any treatment. Right side tibias and femurs were fixed in 10 percent buffered formalin, decalcified and embedded in paraffin. Histological sections were stained by hematoxylin-eosin for histomorphometric analysis. The cortical thickness and medullary cavity were measured in transverse tibia and femur sections. The percentage of porosity and the trabecular density were determined in longitudinal femur sections. RESULTS AND DISCUSSION: There was no significant statistical difference between OVX and OVX + T in several analyses. The results showed that tibolone did not improve bone quality significantly, although it preserved cortical bone mass in femoral and tibial diaphyses and the trabecular bone in femoral condyles. The administration of tibolone in high dose for a prolonged period may have influenced these effects inasmuch as recent studies have recommended the use of lower doses in osteoporosis prevention. CONCLUSION: Oophorectomy caused bone loss in the analyzed regions. Despite the fact tibolone did not augment bone mass, this was kept at satisfactory levels.

[Effect of high doses of tibolone in body weight and lipid profile of ovariectomized rats]. / Efeito de doses elevadas de tibolona sobre o peso corporal e perfil lipídico de ratas ooforectomizadas.

PURPOSE: to evaluate the effect of the prolonged use of a high dose of tibolone on the body weight variation and lipid profile of oophorectomized female rats. METHODS: 15 Wistar rats weighing 250 g were randomly divided into two groups. The Experimental Group (n=9) received 1 mg/day of oral tibolone. The Control Group (n=6) received daily 0.5 mL of 0.5% carboxymethylcellulose by gavage. Bilateral oophorectomy was performed 30 days before the beginning of the experiment. On day 0 of the experiment, the animals began to receive the respective treatment for 20 weeks. Body weight was controlled every seven days and food consumption was measured every three to four days along the experiment, in order to establish the daily mean consumption per animal. The results were compared by the Student's t-test, with the significance level set at p<0.05. RESULTS: the daily food consumption of the Tibolone Group was significantly lower (12.7+/-1.2 g, p<0.001) compared to the Control Group (14.5+/-1.4 g). This difference was also significant when the body weight was compared between the Tibolone and Control Groups (p<0.001), with the Tibolone Group having lower weight along the experiment. At the end of the experiment, the mean body weight was 215.6+/-9.3 g in the Tibolone Group and 243.6+/-6.4 g in the Control Group. Regarding the lipid profile, the Tibolone Group had significantly (p<0.001) lower total cholesterol compared to the Control Group (30.3 versus 78.6 mg/dL). The level of HDL-c was also significantly different (p<0.001), with the Tibolone Group showing lower levels than the Control Group (9.0 versus 52.0 mg/dL). No significant difference between the groups was registered in the other biochemical parameters examined (LDL-c, VLDL-c and triglycerides). CONCLUSIONS: tibolone causes a significant reduction of HDL-c and total cholesterol and has a deleterious effect on the body weight of oophorectomized rats, which may be related to the lower food ingestion by these animals.

Efeito de doses elevadas de tibolona sobre o peso corporal e perfil lipídico de ratas ooforectomizadas / Effect of high doses of tibolone in body weight and lipid profile of ovariectomized rats

OBJETIVO: avaliar o efeito do uso prolongado de alta dose de tibolona na variação do peso corporal e no perfil lipídico de ratas ooforectomizadas. MÉTODOS: foram utilizadas 15 ratas Wistar, pesando 250 g, que foram divididas aleatoriamente em dois grupos. O Grupo Experimental (n=9) recebeu diariamente 1 mg/dia de tibolona via oral. O Grupo Controle (n=6) recebeu diariamente solução de carboximetilcelulose a 0,5 por cento, por gavagem, em volume de 0,5 mL/rata. Foi realizada ooforectomia bilateral 30 dias antes do início do experimento. No dia 0 do experimento, os animais começaram a receber os respectivos tratamentos por 20 semanas. O peso corporal foi controlado semanalmente e o consumo de ração foi medido a cada três a quatro dias ao longo do experimento, estabelecendo o consumo médio/dia por animal. Os resultados foram comparados pelo teste t de Student, com nível de significância de p<0,05. RESULTADOS: o Grupo Tibolona teve consumo de ração diário significativamente (p<0,001) menor (12,7±1,2 g), quando comparado ao Grupo Controle (14,5±1,4 g). Essa diferença também foi significativa em relação ao peso dos animais, uma vez que o Grupo Tibolona teve peso corporal inferior (p<0,001) ao longo do experimento, alcançando peso médio final de 215,6±9,3 versus 243,6±6,4 g no Grupo Controle. Com relação ao perfil lipídico, o Grupo Tibolona apresentou valores inferiores de colesterol total em comparação ao Grupo Controle (30,3 versus 78,6 mg/dL) mostrando diferença significativa (p<0,001). A dosagem de HDL-c também mostrou diferença significativa (p<0,001), com o Grupo Tibolona apresentando níveis inferiores ao Controle (9,0 versus 52,0 mg/dL). Quanto aos demais parâmetros bioquímicos analisados (LDL-c, VLDL-c e triglicerídeos), não houve diferença entre os grupos. CONCLUSÕES: A tibolona causa redução de HDL-c e colesterol total e tem efeito deletério sobre o peso corporal de ratas ooforectomizadas, que pode estar relacionado ao menor consumo ...

PURPOSE: to evaluate the effect of the prolonged use of a high dose of tibolone on the body weight variation and lipid profile of oophorectomized female rats. METHODS: 15 Wistar rats weighing 250 g were randomly divided into two groups. The Experimental Group (n=9) received 1 mg/day of oral tibolone. The Control Group (n=6) received daily 0.5 mL of 0.5 percent carboxymethylcellulose by gavage. Bilateral oophorectomy was performed 30 days before the beginning of the experiment. On day 0 of the experiment, the animals began to receive the respective treatment for 20 weeks. Body weight was controlled every seven days and food consumption was measured every three to four days along the experiment, in order to establish the daily mean consumption per animal. The results were compared by the Student's t-test, with the significance level set at p<0.05. RESULTS: the daily food consumption of the Tibolone Group was significantly lower (12.7±1.2 g, p<0.001) compared to the Control Group (14.5±1.4 g). This difference was also significant when the body weight was compared between the Tibolone and Control Groups (p<0.001), with the Tibolone Group having lower weight along the experiment. At the end of the experiment, the mean body weight was 215.6±9.3 g in the Tibolone Group and 243.6±6.4 g in the Control Group. Regarding the lipid profile, the Tibolone Group had significantly (p<0.001) lower total cholesterol compared to the Control Group (30.3 versus 78.6 mg/dL). The level of HDL-c was also significantly different (p<0.001), with the Tibolone Group showing lower levels than the Control Group (9.0 versus 52.0 mg/dL). No significant difference between the groups was registered in the other biochemical parameters examined (LDL-c, VLDL-c and triglycerides). CONCLUSIONS: tibolone causes a significant reduction of HDL-c and total cholesterol and has a deleterious effect on the body weight of oophorectomized rats, which may be related to the lower food ...

[Effect of tibolone on endometrium of castrated rats]. / Efeito da tibolona sobre o endométrio de ratas castradas.

PURPOSE: to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometrium of castrated female rats. METHODS: fifteen female Wistar rats, aged eight weeks and weighting about 250 g were used. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9) received 1 mg of tibolone/day orally; the Control Group (n=6) received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were sedated and sacrificed by cervical dislocation. The uterus was removed and fixated in 10% buffer formaldehyde. Both uterine horns were divided in three regions (proximal, medial and distal) and processed to be included in paraffin. Histological sections, stained with hematoxylin-eosin were submitted to morphological and morphometrical analysis. The following parameters have been analyzed: thickness of the endometrial superficial epithelium, thickness of the endometrium stroma, endometrial area, absolute number of endometrial glands and number of glands/endometrial area. The data obtained were compared by the t-Student test. RESULTS: in the Tibolone Group, the uteri were well developed and there was a significant increase (p<0.01) of all the histomorphometric parameters. In some cases, the cylindrical epithelium became stratified, pavimentous and covered the internal portions of the glands, as well as of the endometrium cavity. Rats from the Control Group presented uterine atrophy. There were few tubular-like glands and scarce intercellular substance. Glands were covered by cubic epithelium which extended itself to the endometrial cavity. CONCLUSIONS: high doses of tibolone, given for long periods of time to castrated female rats, have an estrogenic effect which can be dose-dependent, causing proliferation in the endometrium and causing changes in the cell differentiation (squamous metaplasia), but do not lead to hyperplasia.

Efeito da tibolona sobre o endométrio de ratas castradas / Effect of tibolone on endometrium of castrated rats

OBJETIVO: avaliar o efeito do uso prolongado de alta dose de tibolona na morfologia do endométrio em ratascastradas. MÉTODOS: foram utilizadas 15 ratas Wistar, fêmeas, com idade de oito semanas e peso médio de 250 g.Todas as ratas foram submetidas à ooforectomia bilateral e 30 dias depois foi coletada citologia vaginal, verificandose o status de menopausa. As ratas foram divididas aleatoriamente em dois grupos: o tratado (n=9) recebeu via oral 1 mg tibolona/dia; o controle (n=6) recebeu apenas solução do veículo carboximetilcelulose. Após 20 semanas de tratamento, todos os animais foram sedados e sacrificados por deslocamento cervical. Os úteros foram retirados e fixados em formol 10% tamponado. Ambos os cornos uterinos foram clivados em três regiões (proximal, medial, distal) e processados para inclusão em parafina. Cortes histológicos corados com hematoxilina-eosina foram submetidos à análise morfológica e morfométrica. Foram avaliados os seguintes parâmetros: espessura do epitélio superficialendometrial, espessura do estroma endometrial, área endometrial, número absoluto de glândulas endometriais e número de glândulas/área endometrial. Os dados obtidos foram comparados mediante o teste t de Student. RESULTADOS: no Grupo Tibolona os úteros se apresentaram bem desenvolvidos e houve aumento significativo (p��0,01) de todos osparâmetros histomorfométricos. Por vezes, o epitélio cilíndrico tornava-se estratificado pavimentoso e recobria porções internas das glândulas bem como a cavidade endometrial. As ratas do Grupo Controle apresentaram útero atrofiado. Havia poucas glândulas de padrão tubular e escassa substância intercelular. As glândulas eram revestidas de epitélio cúbico que se estendia à cavidade endometrial...

PURPOSE: to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometriumof castrated female rats. METHODS: fifteen female Wistar rats, aged eight weeks and weighting about 250 g wereused. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9) received 1 mg of tibolone/day orally; the Control Group (n=6) received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were sedated and sacrificed by cervical dislocation. The uterus was removed and fixated in 10% buffer formaldehyde. Both uterine horns were divided in three regions (proximal,medial and distal) and processed to be included in paraffin. Histological sections, stained with hematoxylin-eosin were submitted to morphological and morphometrical analysis. The following parameters have been analyzed: thickness of the endometrial superficial epithelium, thickness of the endometrium stroma, endometrial area, absolute number of endometrial glands and number of glands/endometrial area. The data obtained were compared by the t-Student test. RESULTS: in the Tibolone Group, the uteri were well developed and there was a significant increase (p<0.01) of all the histomorphometric parameters. In some cases, the cylindrical epithelium became stratified, pavimentous and coveredthe internal portions of the glands, as well as of the endometrium cavity. Rats from the Control Group presented uterineatrophy. There were few tubular-like glands and scarce intercellular substance. Glands were covered by cubic epithelium which extended itself to the endometrial cavity...