Effects of Raloxifene Combined with Low-dose Conjugated Estrogen on the Endometrium in Menopausal Women at High Risk for Breast Cancer.

OBJECTIVES: To compare the effects of low-dose conjugated estrogen (CE), raloxifene, and the combination thereof on the endometrium of postmenopausal women. METHODS: Postmenopausal women between 45 and 60 years of age, with Gail score≥1.67 and no endometrial disorders, were randomly assigned to receive low-dose CE (0.3 mg), raloxifene (60 mg), or combined therapy for 1 year. Transvaginal ultrasound was performed at baseline and every 3 months; the Kupperman Index was assessed at baseline and every 6 months. Endometrial biopsies were performed if endometrial thickness (ET) was ≥5 mm or if vaginal bleeding occurred. The primary outcome was the occurrence of ET≥5 mm over the one-year period. RESULTS: Seventy-three women were randomly assigned and analyzed on an intent-to-treat basis. Eight, three, and four women in the CE, raloxifene, and combination groups, respectively, exhibited ET≥5 mm. No genital bleeding was reported in the combination group. Endometrial biopsy revealed atrophy or polyps in all groups, with one patient in the CE group exhibiting a proliferative endometrium without atypia. At 6 months, there was a progressive increase in mean ET in the CE group, but not in the other two groups, with statistically significant differences at 6, 9, and 12 months. Mean scores for vasomotor symptoms and Kupperman Index favored the CE and combination groups over raloxifene. CONCLUSION: Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as raloxifene alone on the endometrium.

Effects of raloxifene combined with low-dose conjugated estrogen on the endometrium in menopausal women at high risk for breast cancer

OBJECTIVES: To compare the effects of low-dose conjugated estrogen (CE), raloxifene, and the combination thereof on the endometrium of postmenopausal women. METHODS: Postmenopausal women between 45 and 60 years of age, with Gail score≥1.67 and no endometrial disorders, were randomly assigned to receive low-dose CE (0.3 mg), raloxifene (60 mg), or combined therapy for 1 year. Transvaginal ultrasound was performed at baseline and every 3 months; the Kupperman Index was assessed at baseline and every 6 months. Endometrial biopsies were performed if endometrial thickness (ET) was ≥5 mm or if vaginal bleeding occurred. The primary outcome was the occurrence of ET≥5 mm over the one-year period. RESULTS: Seventy-three women were randomly assigned and analyzed on an intent-to-treat basis. Eight, three, and four women in the CE, raloxifene, and combination groups, respectively, exhibited ET≥5 mm. No genital bleeding was reported in the combination group. Endometrial biopsy revealed atrophy or polyps in all groups, with one patient in the CE group exhibiting a proliferative endometrium without atypia. At 6 months, there was a progressive increase in mean ET in the CE group, but not in the other two groups, with statistically significant differences at 6, 9, and 12 months. Mean scores for vasomotor symptoms and Kupperman Index favored the CE and combination groups over raloxifene. CONCLUSION: Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as raloxifene alone on the endometrium.

O conhecimento da higiene do sono na menopausa / Awareness of sleep hygiene in menopause

Objetivo:Identificar o conhecimento sobre a Higiene do Sono em mulheres que frequentavam um ambulatório de climatério. Método: Os dados foram obtidos pelo preenchimento de questionário sobre a higiene do sono, por 72 mulheres na perimenopausa/pós-menopausa, sendo que 30 eram atendidas pelo ambulatório geral do climatério e 42 pelo ambulatório de ?distúrbios do sono?. Foram realizadas análises estatísticas por frequência simples, diferenciando entre o conhecimento ou não da higiene do sono e comparação entre os subgrupos pelo qui-quadrado. Resultados: No grupo total de mulheres, foi identificado que 79,2% delas não conheciam a expressão higiene do sono, apesar de, muitas vezes, reconhecerem as medidas que induzem a um sono adequado. Conclusão: O artigo sugere a importância da assistência dos profissionais de saúde durante a fase de transição menopáusica e pós-menopausa no que se refere à promoção de conhecimento sobre a importância da qualidade do sono.

To identify the awareness about Sleep Hygiene in women attended at a menopause clinic. Method: The data were obtained from responses to a Sleep Hygiene questionnaire, from 72 women in perimenopause / menopause, with 30 of them being attended by the general climacteric clinic and 42 by the ?sleep disorders? clinic. Statistical analyses were conducted using simple frequency, differentiating between the awareness, or not, of sleep hygiene, and a chi-square comparison between the subgroups. Results: For this group of women, overall, it was ascertained that 79,2% of them were not aware of the term Sleep Hygiene, despite, in many cases, recognizing the steps that lead to adequate sleep. Conclusion: The article suggests the importance of professional health assistance for women during the menopausal and postmenopausal transition phases with regard to promoting an awareness of the importance of the quality of sleep.

Extrato de soja no tratamento dos sintomas vasomotores no período menopausal / Soybean extract in the treatment of vasomotor symptoms in menopausal period

Os sintomas vasomotores, tais como fogachos e sudorese noturna, são comuns no período menopausal. A terapia hormonal permanece como a mais efetiva no alívio desses sintomas. No entanto, desperta preocupações sob o risco de aumentar a ocorrência de doenças diretamente relacionadas ao trato genital e mamas, sendo ainda contraindicada em algumas doenças crônicas. Assim, alguns tratamentos alternativos, baseados em alimentos ou suplementos enriquecidos com fitoestrogênios, produtos químicos presentes em algumas plantas, têm sido utilizados. No entanto, existem divergências quanto a sua eficácia. Assim, realizamos esta revisão a partir de artigos recuperados da base de dados Medical Literature Analysis and Retrieval System on Line (MEDLINE), com o objetivo de tentar esclarecer se o uso das isoflavonas está relacionado à redução dos sintomas vasomotores na menopausa. A partir dos artigos recuperados, pudemos observar que não existem evidências de que o uso de fitoestrogênios por mulheres na pós-menopausa reduzem os sintomas vasomotores. Por outro lado, nenhum dos trabalhos analisados mencionou efeitos prejudiciais no uso dessas substâncias. Entretanto, estudos experimentais em animais evidenciaram, quando administradas em altas doses, a ocorrência de metaplasia endometrial.

Hot flushes and night sweats are common vasomotor symptoms during menopausal period. Hormone therapy is believable to be the most effective treatment for relieving these symptoms. However, such treatment concerns us because its use may be directly related to genital tract and breast diseases. It is also contraindicated in some chronic diseases. Thus, some alternative treatments have been used such as consuming foods or supplements enriched with phytoestrogens, which are chemical compounds present in some plants. Whereas there are disagreements regarding its effectiveness, we conducted this review based on articles retrieved from the Medical Literature Analysis and Retrieval System on Line (MEDLINE) data base. Our aim was to try clarifying whether the use of isoflavones are related to reduction of vasomotor symptoms at menopause. From the articles retrieved, we observed that there is no conclusive evidence that the use of isoflavones by postmenopausal women reduces vasomotor symptoms. On the other hand, none of the consulted articles reported harmful effects on the use of such substances. However, experimental studies in animals have shown endometrial metaplasia when they are administered in high doses.

Estrogens plus raloxifene on endometrial safety and menopausal symptoms--semisystematic review.

OBJECTIVE: The aim of this study was to summarize the evidence of endometrial safety and quality of life assessment in postmenopausal women taking raloxifene (RLX) + estrogens (E). METHODS: Clinical studies reporting RLX + E were identified using Medline and LILACS and through reviewing reference lists of highly significant publications. Articles published in Portuguese, Spanish, and English from the past 10 years were considered. RESULTS: Six corresponding clinical trials were identified. Different estrogen formulations, doses, and routes were used. The primary outcome of the selected studies also differed. Most of the studies found a benefit profile on RLX + E on women's quality of life, satisfaction with the treatment, and vaginal dryness. Some studies showed an increased endometrial thickness after 3 months of treatment. Most biopsies revealed benign endometrial proliferation; only two women experienced endometrial hyperplasia, both of them after 24 weeks of treatment. CONCLUSIONS: There are only a few clinical trials that evaluated endometrial safety and quality of life with RLX + E in postmenopausal women. The benefits shown on quality of life and endometrial safety are not certified. Larger studies are deemed necessary to define the better estrogen form and to evaluate the safety and efficacy of long-term use of RLX + E.

[Effects of high doses of genistein on mammary gland of female rat]. / Efeitos de altas doses de genisteína sobre o epitélio mamário de ratas.

PURPOSE: to evaluate the effects of high doses of genistein on the mammary glands of adult female rats. METHODS: Twenty-eight days after oophorectomy, 50 adult female rats were divided into five groups, as follows: a control group (Ctrl), three rats that received genistein (GEN) at the doses of 46 mg/kg (GEN46;), 125 mg/kg (GEN125) and 250 mg/kg (GEN250); one group received conjugated equine estrogen at the dose of 50 µg/g (ECE50). The substances were administered daily for 30 consecutive days by gavage and in the last week of the period of treatment, colpocytological exams were carried out for seven consecutive days. After treatment, the animals were anesthetized, blood samples were collected for estradiol and progesterone determination and the first pair of inguinal mammary glands was removed and processed for histomorphometric analysis. Collected data were subjected to analysis of variance supplemented by the Tukey-Kramer test (p<0.05). RESULTS: the ctrl group and the ones treated with different doses of GEN showed atrophic mammary glands, whereas the glands were more developed in the ECE group, where numerous mammary ducts and alveoli were observed. Morphometry showed a larger area of mammary parenchyma in the ECE group (98.870.1 ± 550.4 µm²* per mm²; p<0.05) compared with other groups (Ctrl=36.875.6 ± 443.4; GEN46=37.001.7 ± 557.4; GEN125=36.480.8 ± 658.3 and GEN250=37.502.8 ± 669.3). The same occurred in the number of alveoli in the ECE group (33.2 ± 6.9* per mm²; p<0.05) compared to the other groups (Ctrl=10.4 ± 2.1, GEN46=11.2 ± 3.1; GEN125=11.6 ± 2.1 and GEN250=12.3 ± 2.3). The estradiol level was higher in the ECE group compared to the other groups (9.4 ± 1.7 pg/mL; p<0.05), whereas serum levels of progesterone were similar in all groups. CONCLUSION: the administration of genistein at high doses had no trophic effect on the mammary glands of rats.

Efeitos de altas doses de genisteína sobre o epitélio mamário de ratas / Effects of high doses of genistein on mammary gland of female rat

OBJETIVO: avaliar os efeitos de altas doses de genisteína sobre o epitélio mamário de ratas adultas. MÉTODOS: após 28 dias da ooforectomia, cinquenta ratas adultas foram divididas em cinco grupos, a saber: um controle (Ctrl), três que receberam genisteína (GEN) nas doses de 46 mg/kg (GEN46), 125 mg/kg (GEN125) e 250 mg/kg (GEN250), e um que recebeu estrogênios conjugados equinos na dose de 50 µg/kg (ECE). As substâncias foram administradas diariamente durante 30 dias consecutivos por gavagem e na última semana de tratamento foi efetuado exame colpocitológico durante sete dias consecutivos. Após o tratamento, os animais foram anestesiados, amostras de sangue foram retiradas para determinação do estradiol e da progesterona, e o primeiro par de mamas inguinais retirado e processado para análise histomorfométrica. Os dados obtidos foram submetidos à análise de variância complementada pelo teste de Tukey-Kramer (p<0,05). RESULTADOS: nos grupos Ctrl e tratados com as diferentes doses de GEN as mamas apresentaram-se atróficas, no entanto mostraram-se desenvolvidas no grupo ECE, onde se notou a presença de inúmeros ductos e alvéolos mamários contendo material eosinófilo em seu interior. A morfometria mostrou maior área de parênquima mamário no grupo ECE (98.870,1±550,4 µm²* por mm²; p<0,05) comparado aos outros grupos (Ctrl=36.875,6±443,4; GEN46=37.001,7±557,4; GEN125=36.480,8±658,3 e GEN250=37.502,8±669,3). O mesmo ocorreu em relação ao número de alvéolos e ductos mamários no grupo ECE (33,2±6,9* por mm²; p<0,05) em relação aos outros grupos (Ctrl=10,4±2,1, GEN 46=11,2±3,1; GEN 125=11,6±2,1 e GEN 250=12,3±2,3). Os níveis de estradiol mostraram-se aumentados no grupo ECE em relação aos outros grupos (9,4±1,7 pg/mL; p<0,05), sendo que os níveis séricos de progesterona mostraram-se semelhantes em todos os grupos de estudo. CONCLUSÃO: a administração de genisteína em altas doses não apresentou efeito proliferativo no tecido mamário de ratas.

PURPOSE: to evaluate the effects of high doses of genistein on the mammary glands of adult female rats. METHODS: Twenty-eight days after oophorectomy, 50 adult female rats were divided into five groups, as follows: a control group (Ctrl), three rats that received genistein (GEN) at the doses of 46 mg/kg (GEN46;), 125 mg/kg (GEN125) and 250 mg/kg (GEN250); one group received conjugated equine estrogen at the dose of 50 µg/g (ECE50). The substances were administered daily for 30 consecutive days by gavage and in the last week of the period of treatment, colpocytological exams were carried out for seven consecutive days. After treatment, the animals were anesthetized, blood samples were collected for estradiol and progesterone determination and the first pair of inguinal mammary glands was removed and processed for histomorphometric analysis. Collected data were subjected to analysis of variance supplemented by the Tukey-Kramer test (p<0.05). RESULTS: the ctrl group and the ones treated with different doses of GEN showed atrophic mammary glands, whereas the glands were more developed in the ECE group, where numerous mammary ducts and alveoli were observed. Morphometry showed a larger area of mammary parenchyma in the ECE group (98.870.1±550.4 µm²* per mm²; p<0.05) compared with other groups (Ctrl=36.875.6±443.4; GEN46=37.001.7±557.4; GEN125=36.480.8±658.3 and GEN250=37.502.8±669.3). The same occurred in the number of alveoli in the ECE group (33.2±6.9* per mm²; p<0.05) compared to the other groups (Ctrl=10.4±2.1, GEN46=11.2±3.1; GEN125=11.6±2.1 and GEN250=12.3±2.3). The estradiol level was higher in the ECE group compared to the other groups (9.4±1.7 pg/mL; p<0.05), whereas serum levels of progesterone were similar in all groups. CONCLUSION: the administration of genistein at high doses had no trophic effect on the mammary glands of rats.

Involvement of GDF-9, leptin, and IGF1 receptors associated with adipose tissue transplantation on fertility restoration in obese anovulatory mice.

The aim was to analyze the effect of adipose tissue transplantation on growth differentiation factor-9 (GDF-9), insulin growth factor 1 receptor (IGF1R), and leptin receptor (LEPR) protein expression in ovaries of obese anovulatory mice. Leptin-deficient female (ob/ob) and wild-type mice were divided into untreated ob/ob mice and gonadal white adipose tissue transplanted ob/ob mice, with evaluation after 7, 15, and 45 days and compared to control wild-type mice. The corporal weight and glycemia levels increased in the obese group concomitant with polymicrocyst formation and abundant estrone, mimicking anovulatory disease. In the treated group after 45 days, glycemia, weight, ovarian size, and number of follicles were decreased and corpora lutea were decreased. The analysis of GDF-9 revealed that, whereas control ovaries presented follicular localization, the obese ovary lacked this protein. On the other hand, obese ovaries showed elevated expression of IGF1R that was normalized after the transplantation. Finally, LEPR was reduced in obese ovaries, and adipose tissue transplantation was efficient in returning it to normal levels. In conclusion, the adipose tissue transplantation, especially after 45 days, seems to stimulate ovulation, supported by the fact that several proteins involved in ovulation returned to basal levels.

Efetividade do dispositivo intrauterino liberador de levonorgestrel (Mirena®) para a terapia de reposição hormonal na perimenopausa e pós-menopausa. / The effectiveness of the levonorgestrel-releasing intrauterine system (Mirena®) for hormone replacement therapy in the peri- and postmenopausal women

A utilização do dispositivo intrauterino (DIU) hormonal para a contracepção é uma constante no consultório de ginecologia da atualidade. Entretanto, outras indicações como o tratamento de algumas patologias ginecológicas benignas, e mais recentemente, o uso para terapia de reposição hormonal (TRH) no climatério têm chamado a atenção. Esta revisão tem como objetivo demonstrar os achados dos artigos publicados, desde 2001, sobre a avaliação do DIU de levonorgestrel (LNG) durante esta fase de turbulência hormonal feminina. No período do climatério, a mulher com útero intacto ganha vários benefícios com essa nova modalidade terapêutica associada ao estrogênio nas suas diversas formas de apresentação. Pode-se concluir que o DIU com LNG na mulher da perimenopausa e pós-menopausa pode ser utilizado para contracepção, alívio de sintomas vasomotores quando associado à terapia com estrogênio e alta resolutividade nos quadros de menorragia que frequentemente acometem a mulher durante esta fase da vida

There is a wide use of the levonorgestrel-releasing intrauterine system (LNG IUS) in recent years for hormonal contraception. However, other indications, as the treatment of some benign gynecological diseases and, more recently, for hormone replacement therapy in peri and postmenopausal women have happened. This review aimed to demonstrate the findings of articles published since 2001 on the use of the LNG IUS in the women's climacteric period. During this phase of life, women with intact uterus benefit of using this new modality of therapy associated with estrogen in their several forms of presentation. It can be concluded that LNG IUS in the peri and postmenopausal women can be used as a contraceptive method, to abbreviate hot flashes symptoms when associated with estrogen therapy and to solve menorrhagia that is a very common finding in this period

Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens.

OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. DESIGN: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 microg/kg; GE0.5mg, group receiving CEE at 500 microg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10% formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.

Effects of melatonin on the endometrial morphology and embryo implantation in rats.

OBJECTIVE: To determine the effects of melatonin on rat endometrium morphology and embryo implantation. DESIGN: Experimental study. SETTING: Federal University of São Paulo, Brazil. ANIMAL(S): Forty female rats. INTERVENTION(S): GI: control, GII: sham-operated, GIII: pinealectomized, and GIV: pinealectomized rats that received melatonin during 3 months. The GI, GII, and GIII groups received the vehicle of melatonin (NaCl + ethanol). At the end of the treatment, the animals were killed during the estrous phase; the uterus was removed for morphometric analysis. Urine was collected for 6-sulfatoxymelatonin. Blood was collected for estrogen (E) and progesterone (P) level determinations. In a second experiment, female rats were used to evaluate the endometrial embryo implantation. MAIN OUTCOME MEASURE(S): Endometrial morphology and embryo implantation. RESULT(S): GIII presented the highest values for endometrial area and thickness index, number of endometrial glands, and eosinophils. The number of vessels of groups I, II, and IV was fewer than that of GIII. The highest number of eosinophils was detected in GIII in comparison to other groups. The implantation rate in GIII was the lowest of all groups. This implantation rate was significantly increased and restored toward normal in GIV. CONCLUSION(S): Our data suggested that, in nonphotoperiodic animals such as rats, melatonin may positively affect the endometrial morphology and improve embryo implantation.

Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens

OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 µg/kg; GE0.5mg, group receiving CEE at 500 µg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10 percent formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.

Estrogen therapy reduces nocturnal periodic limb movements.

It is believed that periodic limb movement (PLM) and more specifically, restless leg syndrome (RLS), are a common cause of insomnia. And one study in the literature examined PLM when associated to the use of estrogens. Polo-Kantola et al. [Polo-Kantola P, Rauhala E, Erkkola R, Irjala K, Polo O. Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial. Obstet Gynecol 2001;97(4):548-54] observed that estrogen therapy improved subjective sleep quality regardless of periodic limb movements or related arousals. Herein is a case of a symptomatic postmenopausal patient with high PLM index who complained of insomnia and leg pain. Given that the patient had hot flashes and a high Kupperman Menopausal Index (which evaluates climacteric symptoms), we decided to administer transdermal ESTRADOT 25 microg (Novartis, Brazil) twice-a-week. Our patient experienced a significant decrease in PLM as well as a great increase in REM and a slight increase in slow wave sleep (stages 3 and 4), as shown in the polysomnography. The patient reported an overall improvement in her condition.

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women.

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 microg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

Transplante de tecido ovariano / Ovarian tissue transplant

O congelamento de tecido ovariano para ser transplantado é um procedimento que pode reservar a função reprodutiva e endócrina desse órgão no futuro. Constitui uma alternativa para pacientes jovens com câncer e submetidas a quimioterapia, sem prole constituída, que desejam engravidar. Embora a lesão celular e as modificações moleculares possam ocorrer em decorrência do processo de congelamento e de descongelamento, há relatos de transplantes bem sucedidos tanto em animais quanto em seres humanos. A técnica de congelamento pode ter aplicações nos programas de Reprodução Humana, além de poder ser útil para evitar eventuais repercussões do hipoestrogenismo em mulheres que foram ooforectomizadas precocemente devido ao tratamento de neoplasias.

Efeitos da isoflavona e dos estrogênios conjugados eqüinos sobre a qualidade de vida na pós-menopausa / Effects of isoflavone and conjugated equine estrogen on the postmenopausal quality of life

OBJETIVO: analisar os efeitos da isoflavona e do estrogênio sobre a qualidade de vida de mulheres na pós-menopausa. MÉTODOS: realizou-se estudo randomizado, duplo-cego, com 79 pacientes, amenorréia de 12 meses, idade superior a 40 anos e índice de massa corporal (IMC) superior a 30 kg/m². As mulheres foram aleatoriamente divididas em dois grupos de tratamento: GECP recebeu duas cápsulas, via oral, de 12/12 horas, uma contendo 0,625 mg de estrogênios conjugados eqüinos e, a outra, placebo (n=33); GECS recebeu duas cápsulas de 150 mg de extrato de soja, com 60 mg de isoflavonas cada (n=32), por seis meses. O Questionário de Qualidade de Vida Específico para Menopausa foi empregado antes e após um, três e seis meses de tratamento. Os parâmetros do risco de câncer ginecológico foram avaliados. Para análise dos dados, aplicaram-se os testes de ANOVA e de Tukey. RESULTADOS: quanto aos parâmetros vasomotores, houve redução nos valores após seis meses de tratamento, 1,6±0,8 e 2,4±1,6, em relação aos valores antes da terapia, 4,0±2,2 e 4,2±2,3, respectivamente, nos GECP e GECS. Os aspectos psicossociais mostraram diminuição dos valores após seis meses de terapia, 2,5±1,2 e 2,9±1,4, em relação aos valores antes da terapia, 3,6±1,6 e 4,1±1,9, respectivamente, nos GECP e GECS. De forma semelhante ocorre no aspecto físico e nos sintomas sexuais. CONCLUSÕES: as isoflavonas agem positivamente na qualidade de vida de mulheres na pós-menopausa, semelhantemente aos estrogênios conjugados eqüinos.

PURPOSE: to analyze the isoflavone and estrogen effects on the postmenopausal quality of life. METHODS: this is a randomized and double-blind study with 79 postmenopausal patients, 12 months of amenorrhea, 40 years old or more and body mass index (BMI) above 30 kg/m². The participants were randomly divided into two treatment groups: GECP received orally two capsules, every 12 hours, one contained 0.625 mg conjugated equine estrogen and another placebo (n=33); GECS received two capsules of 150 mg extract of soy, with 60 mg isoflavone (n=32). Both treatments were administered for six months. The Quality Menopause Specific Questionnaire of Life was applied before and after one, three and six months of treatment. The parameters of gynecological cancer risk were evaluated. ANOVA and the Tukey test were used for data analysis. RESULTS: there was a reduction in the values of the vasomotor parameters after six months of treatment, 1.6±0.8 and 2.4±1.6, compared to before therapy, 4.0±2.2 and 4.2±2.3 in GECP and GECS, respectively. The psychological aspects showed reduction in values after six months of therapy, 2.5±1.2 and 2.9±1.4, compared to before treatment, 3.6±1.6 and 4.1±1.9 in GECP and GECS, respectively. Similar results were obtained on the physical aspects and in the sexual symptoms. CONCLUSIONS: isoflavones may positively act on life quality of postmenopausal women. This effect was similar to conjugated equine estrogen.

The effects of soy extract on the uterus of castrated adult rats.

OBJECTIVE: The aim of this study was to evaluate the effects of different doses of a standardized soy extract on the uterus of castrated rats. METHODS: Fifty-six adult castrated female Wistar rats were randomly divided into seven groups (eight animals in each) that received: GI--drug vehicle (propylene glycol); GII--soy extract 10mg/kg per day; GIII--soy extract 50mg/kg per day; GIV--soy extract 100mg/kg per day; GV--soy extract 300mg/kg per day; GVI--soy extract 600mg/kg per day; GVII-conjugated equine estrogens (CEE) 200microg/kg per day. After 21 days of treatment, all animals were sacrificed and fragments of the uterine horns were immediately removed, fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The endometrial cell proliferation index was determined with the PCNA antibody PC-10 and expressed as the percentuals of the PCNA-positive nuclei relative to the total countings. Other fragments were immediately frozen in liquid nitrogen for RNA extraction and VEGF analysis using RT-PCR technique. RESULTS: The minimal dose of soy extract that produced a significant increase of the morphometric parameters was 100mg/kg (GIV). The maximum effects on endometrial and myometrial morphometry were detected in the groups treated with 300 and 600mg/kg of soy extract (groups V and VI) and CEE (GVII). The expression of PCNA in the endometrial epithelium and stroma was increased by treatment with 100-600mg/kg per day of soy extract (groups IV-VI) or with CCE (group VII). Doses equal to or higher than 50mg/kg of soy extract (groups III-VI) and CEE stimulated the expression of VEGF. CONCLUSION: The treatment of adult castrated rats during 21 days with doses of 100mg/kg per day or higher of soy extract may determine significant proliferation in the endometrium and myometrium.

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida.

Efeitos das isoflavonas sobre o assoalho pélvico e a vascularização peri-uretral de mulheres na pós-menopausa / Effects of isoflavones on the pelvic floor and the periurethral vascularization of postmenopausal women

OBJETIVO: avaliar a força muscular do assoalho pélvico e os vasos periuretrais de mulheres na pós-menopausa, antes e após seis meses de uso contínuo de extrato de soja. MÉTODOS: estudo prospectivo com 30 mulheres na pós-menopausa antes e após o uso de extrato de soja (100 mg/dia) durante seis meses consecutivos. Foram investigadas a perda urinária e a força muscular do assoalho pélvico por perineômetro digital e avaliação funcional. Avaliou-se ainda o número de vasos da região peri-uretral pela dopplervelocimetria. Para comparar os resultados antes e após tratamento, utilizou-se o teste pareado t de Student. RESULTADOS: das 30 mulheres analisadas, 20 referiram alguma forma de perda urinária no inicio do experimento. A melhora deste sintoma ocorreu em 15 (75 por cento) mulheres após o tratamento. A medida da pressão vaginal (força muscular do assoalho pélvico) foi 12,9±1,7 e 15,8±1,8 Sauers, respectivamente, antes e após o tratamento (p<0,001). Observou-se aumento da pressão em 22 (73,3 por cento) mulheres no final do estudo. Na avaliação funcional, verificou-se que 12 mulheres não sofreram alteração da função muscular do assoalho pélvico, ou seja, 18 (60 por cento) tiveram aumento da força muscular. Pelo exame ultra-sonográfico (Doppler) obtivemos no início do experimento 2,20±0,15 vasos sanguíneos/campo, passando para 3,4±0,2 vasos sanguíneos/campo ao final do experimento (p<0,001). Em 21 mulheres (70 por cento) registrou-se aumento do número dos vasos peri-uretrais após os seis meses de tratamento. CONCLUSÃO: ressalta-se que são resultados preliminares, havendo necessidade de outras investigações com número maior de participantes em estudo duplo-cego, randomizado e controlado por placebo. Contudo, o tratamento com extrato de soja, por seis meses consecutivos, determinaria aumento da força muscular do assoalho pélvico e do número de vasos peri-uretrais em mulheres na pós-menopausa.

PURPOSE: to evaluate muscular strength of the pelvic floor and the periurethral vessels of postmenopausal women before and after six months of soybean extract treatment. METHODS: the study was conducted on 30 postmenopausal women before and after six consecutive months of soyabean extract (100 mg/day) administration. Urinary loss and muscular strength of the pelvic floor were investigated through digital perineometer and functional evaluation. Digital color Doppler in the periurethral region was used to count the number of vessels. For statistical analysis, the paired Student t test was applied to compare the results before and after the treatment. RESULTS: twenty women reported urinary incontinence before the treatment period. The amelioration of this symptom was observed in 15 (75 percent) women after the treatment. Vaginal pressure (muscular strength of the pelvic floor) was 12.95±1.73 and 15.86±1.86 Sauers, before and after the treatment, respectively (p<0.001). Twenty-two women (73.3 percent) presented an increase in the pressure at the end of this study. In relation to the function evaluation, 18 (60 percent) had improvement in muscular strength and 12 women did not present any change. On ultrasonography (Doppler), the number of vessels was 2.20±0.15 blood vessels/field in the beginning of this study and 3.46±0.25 blood vessels/field at the end of the treatment (p<0.001). An increase in the number of periurethral vessels was detected in 21 women (70 percent). CONCLUSION: it is important to emphasize that these are preliminary results. A double blind randomized and placebo-controlled clinical trial with a high number of participants is necessary. However, the treatment with concentrated soybean extract (100 mg per day) for six consecutive months may determine an improvement in pelvic floor muscular strength and an increase in the number of periurethral vessels in postmenopausal women.

Effect of conjugated equine estrogens and tamoxifen administration on thyroid gland histomorphology of the rat.

OBJECTIVE: The aim of this study was to evaluate the action of the conjugated equine estrogens and tamoxifen on the morphology of thyroid gland in ovariectomized (OVx) rats. METHODS: Conjugated equine estrogens (CEE), clinically used as estrogen therapy, is a complex formulation containing multiple estrogens that decrease menopausal symptoms. Thirty ovariectomized rats were randomly divided into 3 treatment groups: GI, vehicle (propylene glycol); GII, CEE 200 microg/kg per day; and GIII, tamoxifen 1 mg/kg per day. Another group of 10 rats with intact ovaries (GIV) was included, treated with the vehicle, and sacrificed during estrous. All animals were treated by gavage for 50 days, after which they were sacrificed. Blood samples were collected, and the thyroid was removed for morphological analysis and PCNA evaluation through immunohistochemical study. RESULTS: The thyroid follicular cell height was increased in animals treated with CEE (14.90 +/- 0.20 microm), with TAM (14.90 +/- 0.10 microm), and in rats with intact ovaries (15.10 +/- 0.50 microm) in comparison to that of the vehicle group (9.90 +/- 0.20 microm) (P < 0.001). The follicular area was larger in the CEE (2,225 +/- 51 microm2) and TAM (2,127 +/- 67 microm2) groups compared to that of the vehicle group (5,016 +/- 53 microm2). The levels of T4 and T3 in rats treated with CEE, with Tamoxifen and in rats with intact ovaries, were higher than those those in the vehicle group (P < 0.001). The PCNA index in the vehicle group was lower than in other groups. CONCLUSION: Our data suggest that estrogen and tamoxifen administration has a proliferative effect on the thyroid.