Síndrome dos ovários policísticos: particularidades no manejo da infertilidade / Polycystic ovary syndrome: particularities in the management of infertility

A síndrome dos ovários policísticos (SOP) é responsável por cerca de 80% dos casos de infertilidade anovulatória. Não há na literatura evidências suficientes para a definição do tratamento ideal da infertilidade na SOP, mas repete-se que deve ser iniciado por mudanças no estilo de vida, e frequentemente envolve a indução farmacológica da ovulação e, em casos selecionados, as técnicas de reprodução assistida e o drilling ovariano laparoscópico. Este texto pretende reunir informações atuais sobre o manejo da infertilidade em mulheres com SOP e, dessa forma, permitir ao ginecologista a escolha da melhor abordagem, de forma Individualizada e baseada nas melhores evidências disponíveis.(AU)

PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression / 부인종양

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%–48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1–3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8–11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.

Sangrado y terapia hormonal en la menopausia (THM) / Bleeding during menopause hormone therapy (MHT)

La definición de sangrado ginecológico anormal durante terapia hormonal de la menopausia es aquel sangrado no programado durante el uso de la terapia. Este artículo es un pauteo que describe: 1) cuándo diagnosticar unsangrado anormal, ya que difiere según el tipo de esquema hormonal utilizado; 2) eldiagnóstico diferencial del origen del sangrado anormal; 3) los métodos de evaluación para diagnosticar el origen del sangrado. Se destacan los aspectos principales para el diagnóstico diferencial entre patología orgánica versus disrupción endometrial debida al tratamiento hormonal. Además, se describen los ajustes posibles para resolver el sangrado cuando éste se debe a disrupción del endometrio.

Abnormal bleeding related to menopausal hormone therapy is defined as unscheduled bleeding during the use of the therapy. This article outlines when to diagnose an abnormal bleeding -as this differs according to the type of hormonal scheme used-, the differential diagnosis of the origin of abnormal bleeding, and the methods of evaluation to assess the origin of the bleeding. The main aspects are highlighted on the differentiation of organic pathology versus disruption of the endometrium due to treatment. Also, treatment adjustments to resolve bleeding when it is due to disruption of the endometrium are outlined.

Histopathological and immunohistochemical changes induced by Bisphenol A in reproductive tissues of female rat

Background: Bisphenol A [BPA] is an environmental chemical that has been widely used in the manufacture of polycarbonate plastics and epoxy resins for many years. Due to its major applications in the production of plastic food or beverage containers and the coating of food cans, people of different ages are inevitably exposed to BPA in daily life. It is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells

Aim of the work: the present study was designated to evaluate the histopathological and immunohistochemical effect of BPA on the histoarchitecture of pituitary ,adrenal, ovarian and uterine axis of female albino rats and the ameliorative effect of antiestrogen drug and stem enhance

Experimental model and methods: 20 female albino rats weighing 100 - 120 g. were kept under observation for about 15 days before the onset of the experiment for adaptation, then the rats were classified into 4 groups 5 rats for each , the first group was left without any treatment for 30 days as negative control group , the second group was administered with 20 mg/kg.bw of BPA for 15 consecutive days as positive control, the third group administered with 20 mg/kg.bw of BPA for 15 consecutive days and then treated with antiestrogen drug as 0.1 mg/100gm.bw for 15 day, the fourth group administered with the same dose for the same period and the treated with stem enhance [4.5 mg/100.bw] for 15 days. All rats are scarified and organs were histologically examined after processing

Results: The results showed that PA has a histopathological effects on vital organs [pituitary, adrenal, ovary, oviduct and uterus] even for a short period with minimal ameliorative effect of antiestrogen drug and stem enhance

Role of Ovarian Function Suppression in Premenopausal Women with Early Breast Cancer / 한국유방암학회지

Historically, endocrine therapy for breast cancer began with ovarian ablation (OA) for the treatment of premenopausal patients. After the identification of estrogen receptors and the development of many antiestrogens, tamoxifen has been approved and used as the standard endocrine therapy for hormonal receptor (HR)-positive premenopausal patients to date. With the development of luteinizing hormone-releasing hormone agonists, the paradigm of endocrine therapy for premenopausal women with HR-positive breast cancer began to change from OA to ovarian function suppression (OFS). To date, the indication for OFS was limited to those premenopausal patients with HR-positive breast cancer who were unable to use tamoxifen as the primary adjuvant endocrine therapy. However, following the definitive demonstration of the therapeutic role of OFS added to tamoxifen or aromatase inhibitor after chemotherapy in large randomized trials, such as Tamoxifen and Exemestane Trial or Suppression of Ovarian Function Trial, the American Society of Clinical Oncology guidelines for the use of endocrine therapy in premenopausal HR-positive breast cancer were recently updated to recommend OFS in high-risk patients who required adjuvant chemotherapy. In contrast, the role of OFS to protect ovarian function during chemotherapy in premenopausal women has remained controversial, and some evidence showing the protective effect of OFS on the ovaries during chemotherapy as well as its therapeutic effect for breast cancer in premenopausal women with HR-negative breast cancer was recently published. Further evaluation is necessary to determine its exact role. In conclusion, the role of OA or OFS has been evolving, not only to improve the efficacy of breast cancer treatment, but also to preserve ovary function. OFS remains a main strategy for premenopausal women with HR-positive early breast cancer, though its exact role should be determined in further studies.

Efeitos da tibolona sobre o parênquima mamário: estudo experimental / Effects of tibolone on the breast parenchyma: experimental study

OBJETIVO: Avaliar o efeito da terapia hormonal com tibolona, em três períodos de tempo diferentes, sobre o tecido mamário de ratas castradas. MÉTODO: Foram utilizadas 60 ratas Wistar adultas e virgens, submetidas à ooforectomia. Após 21 dias de pós-operatório (PO), confirmado o hipoestrogenismo, os animais foram divididos aleatoriamente em 6 grupos: tibolona 1 (n=10) recebeu tibolona 1 mg/dia por 23 dias, tibolona 2 (n=10), por 59 dias, tibolona 3 (n=10), por 118 dias; os subgrupos controle 1 (n=8), controle 2 (n=7) e controle 3 (n=10) receberam a água destilada por 23, 59 e 118 dias, respectivamente. Após o tratamento, foram ressecados seis pares de mamas, destinados à análise histológica pela coloração de hematoxilina e eosina (HE); o procedimento seguiu de eutanásia. Os parâmetros histológicos avaliados foram: hiperplasia epitelial e atividade secretora (AS). As variáveis foram submetidas à análise estatística, adotando-se como significante p<0,05. RESULTADOS: Foram observadas alterações histológicas em 20/55 ratas, sendo: hiperplasia epitelial leve (HEB1) em 7/55, hiperplasia epitelial moderada (HEB2) em 5/55, hiperplasia alvéolo-nodular (HAN) em 7/55, atipia sem proliferação epitelial em 1/55, não sendo encontrada hiperplasia severa (HEB3). Encontrou-se AS em 31/55 das ratas. A AS foi significativamente maior no grupo tibolona (T), em todos os tempos avaliados (p=0,001). As alterações histológicas analisadas não foram significantes comparando (p>0,05) os grupos controle (C) e T. A variável tempo de exposição à droga não apresentou significância, quando comparados os três períodos avaliados. CONCLUSÃO: Não foi verificada relação entre as alterações histológicas e a terapêutica com tibolona em curto, médio e longo prazo. .

OBJECTIVE: To assess the effect of tibolone on mammary tissue of castrated rats over 3 different periods of time. METHODS: Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days after surgery, with hypoestrogenism confirmed, the experimental rats were randomly assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days, tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for 23, 59 and 118 days, respectively. After treatment, all six pairs of mammary glands were removed and stained with hematoxylin and eosin (HE) for histological analysis after euthanasia. The histological parameters evaluated were: epithelial cell proliferation and secretory activity. The variables were analyzed statistically, with the level of significance set at 0.05. RESULTS: Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in 7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in 7/55, atypia without epithelial proliferation in 1/55, and no cases of severe epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats. The secretory activity was significantly higher in the tibolone groups compared to control at all the time points assessed (p=0,001). The histological changes were did not show significance when the control and tibolone groups were compared. The time of exposure to tibolone did not show significance when the three different periods of evaluation were compared. CONCLUSION: No relation between histological modification and tibolone treatment was verified after short-, medium- and long-term treatment. .

MR Imaging Findings of Tamoxifen-associated Uterine Adenosarcoma: Report of Two Cases

Adenosarcoma of the uterus is a rare biphasic tumor containing benign glandular epithelial and malignant mesenchymal components. The tumor has been reported to be associated with antiestrogen therapy, particularly tamoxifen, but there have been a few case reports with MRI. We present two cases of MRI findings of uterine adenosarcoma after antiestrogen therapy, tamoxifen and toremifene in breast cancer patients. The tumor presents as a large polypoid mass occupying the endometrial cavity, and may protrude into the vagina. On MRI, the tumor typically shows solid components with scattered small cysts and heterogeneous enhancement. These findings are not significantly different from conventional adenosarcoma.

Factors Influencing the Background Parenchymal Enhancement in Follow-Up Breast MRI after Adjuvant Endocrine Therapy

PURPOSE: To investigate factors influencing the evaluation of background parenchymal enhancement (BPE) at follow-up breast magnetic resonance imaging (MRI) after adjuvant endocrine therapy. MATERIALS AND METHODS: One hundred twelve women with breast cancer and MRI of the contralateral unaffected breast before and after endocrine therapy were identified. Two readers in consensus performed blinded side-by-side comparison of BPE (minimal, mild, moderate, and marked) before and after therapy with categorical scales. Age, body mass index, menopausal status, treatment regimen (selective estrogen receptor modulator or aromatase inhibitor), chemotherapy, follow-up duration, BPE at baseline MRI, MRI field strength before and after therapy, and recurrence were analyzed for their influences on decreased BPE. RESULTS: Younger age, premenopausal status, treatment with selective estrogen receptor modulator, MRI field strength, and moderate or marked baseline BPE were significantly associated with decreased BPE. In multivariate analysis, MRI field strength and baseline BPE showed a significant association. CONCLUSION: MRI field strength and baseline BPE before and after therapy were associated with decreased BPE at post-therapy, follow-up MRI.

A 14-Day Repeated Dose Toxicity of Epimedii Herba Aqueous Extract Administered by Oral Gavage in F344 Rats

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

Pattern Alopecia during Hormonal Anticancer Therapy in Patients with Breast Cancer

We report five cases of pattern alopecia in female patients who are undergoing hormonal anticancer therapy for the prevention of recurrence of breast cancer after surgery. Three patients demonstrated male pattern alopecia with receding frontal hairlines, and two patients demonstrated female pattern alopecia without receding hairlines. The detailed clinical history showed that the pattern alopecia of the patients developed after the full recovery of global hair loss of the entire scalp due to previous cytotoxic chemotherapy. All of the adjuvant hormonal anticancer drugs that were used in the patients are antiestrogenic agents, either aromatase inhibitors or selective estrogen receptor modulators. Considering androgen effect on the hair follicles of the fronto-parietal scalp, the androgen-estrogen imbalance caused by the drugs was thought to be the reason for the onset of pattern alopecia in the patients. In general, alopecia that develops during cytotoxic chemotherapy is well known to both physicians and patients; however, the diagnosis of pattern alopecia during hormonal anticancer therapy in breast cancer patients seems to be overlooked.

Effect of carnosol against proliferative activity of breast cancer cells and its estrogen receptor subtype's mediation and regulation mechanisms / 中国中药杂志

Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERβ expressions of T47D cells, and remarkably increase ERα/ERβ ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERβ pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERβ.

Leptin as a Potential Target for Estrogen Receptor-Positive Breast Cancer / 한국유방암학회지

PURPOSE: Leptin is a potent adipokine that plays a significant role in tumor development and the progression of breast cancer. The aim of this study was to evaluate whether leptin affects the response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cells. METHODS: Leptin, leptin receptor (Ob-R), and activation of signaling pathways were studied by Western immunoblotting. The effects of leptin on tamoxifen-dependent growth inhibition were studied in MCF-7 and T-47D cells. RESULTS: Leptin was expressed in MCF-7 and T-47D and had a proliferative effect on MCF-7 cells. Leptin significantly inhibited the antiestrogenic effect of tamoxifen in both cells only under beta-estradiol (E2) (20 nM) conditions. In MCF-7, the inhibitory effect against tamoxifen was a result from the activation of the ERK1/2 and STAT3 signal transduction pathway. CONCLUSION: Leptin interferes with the effects of tamoxifen under E2 stimulated conditions in ER-positive breast cancer cells. These results imply that inhibition of leptin is expected to enhance the response to tamoxifen in ER-positive breast cancer cells, and, therefore, could be a promising way to overcome endocrine resistance.

Osteoporose no climatério II: prevenção e tratamento / Osteoporosis in postmenopausal II: prevention and treatment

A osteoporose é uma doença que pode acarretar um enorme prejuízo na qualidade de vida dos pacientes em função das alterações no tecido ósseo, levando à fragilidade mecânica e consequente predisposição a fraturas e dor. Hoje, dispomos de medidas preventivas, do uso de suplementos e de várias drogas aprovadas para terapia farmacológica da osteoporose, no período pós-menopausa, revisadas neste artigo. Essas drogas apresentam características antirreabsortivas (bisfosfonatos, terapia estrogênica, agonistas seletivos dos receptores de estrogênio - SERM -, calcitonina e denozumabe), anabólicas (teriparatida - PTH) ou ambas, simultaneamente (ranelato de estrôncio). A terapia estrogênica (TE) e a terapia com os bisfosfonatos compreendem as primeiras linhas de medicamentos utilizadas para prevenção e tratamento da osteoporose no climatério. Os medicamentos de segunda linha ficam reservados aos casos com evolução desfavorável com uso de TE e/ou bisfosfonatos, ou quando essas pacientes apresentem alguma enfermidade óssea associada (osteoporose secundária), necessitando de tratamento específico. Na falha ou impossibilidade da utilização dos medicamentos de segunda linha podemos utilizar o ranelato de estrôncio ou o denozumabe, pesando que os riscos dessas drogas precisam ser mais bem estudados

Osteoporosis is a disease that can cause a great loss of quality of life of patients according to the changes in bone tissue leading to mechanical fragility and consequent susceptibility to fractures and pain. Today, we offer preventive measures, the use of supplements and several drugs approved for pharmacologic therapy for osteoporosis in postmenopausal, reviewed in this article. These drugs have anti resorptive characteristics (bisphosphonates, estrogen, selective estrogen receptor modulators - SERM -, calcitonin and denozumab), anabolic (teriparatide - PTH) or both, simultaneously (strontium ranelate). Estrogen therapy (ET) and therapy with bisphosphonates comprise the first line drugs used for prevention and treatment of osteoporosis in the climacteric. The second-line drugs are reserved to cases with unfavorable outcome with the use of TE and/or bisphosphonates, or when these patients have a disease associated with bone (secondary osteoporosis), requiring specific treatment. In the failure or inability of use of second-line drugs, we can use the strontium ranelate or denozumab, weighing the risks of these drugs that need to be further studied

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.

Survey on the Consumption of the Phytoestrogen Isoflavone in Postmenopausal Korean Women / 대한폐경학회지

OBJECTIVES: Isoflavone is a plant-derived compound, abundant in soy food, and its character is mixed estrogenic and antiestrogenic action, so it is highlighted as an alternative to hormone replacement therapy (HRT) in postmenopausal women. The purpose of this study is to establish a foundation for isoflavone study in the future, by estimating isoflavone intake in postmenopausal women and by recommending proper isoflavone intake. METHODS: Isoflavone intake was estimated in a total of 189 Korean postmenopausal women over 50 years old, by using a food frequency questionnaire (FFQ). Data were statistically analyzed by t-test, and one-way ANOVA with Turkey's test. RESULTS: The daily average isoflavone intake level was 21.94 +/- 19.96 mg. There is no significant difference in isoflavone intake according to age. About 60 percentile of postmenopausal women intake isoflavone under 20 mg a day, and 2 percentile of postmenopausal women intake about 80 mg isoflavone. CONCLUSION: There was no definite precise amount of isoflavone for reliving postmenopausal symptom and health. But through this study, most postmenopausal women did not intake enough isoflavone, so they have to intake more isoflavone.

Endocrine Disrupting Chemicals and Pubertal Development

During the past decades, advancement in pubertal onset especially in girls has been noticed worldwide. Genetic factors and increasing prevalence of adiposity may contribute, however ubiquitous presence of endocrine disrupting chemicals (EDCs) is suspected to be involved in the trend of earlier pubertal onset. Most of known EDCs have estrogenic and/or anti-androgenic actions and few have androgenic or anti-estrogenic effects. Some studies reported earlier age at menarche after exposure to polycholorinated biphenyls (PCBs), polybrominated biphenyls, dicholordiphenyltrichloroethane, phthalate esters, while several other studies found no effect of these compounds on Tanner stages or age at menarche in girls. Limited studies reported an association of delayed puberty in boys and exposure to PCBs or the pesticide endosulfan. However, epidemiological research on the effects of EDCs on sexual maturation is hampered by many pitfalls, such as the mixture of many chemicals with different effects in environment, unidentified critical window of exposure, and limited knowledge about the time lag between exposure and effect. In this paper, we reviewed possible mode of actions of different chemical compounds, and summarized animal/human studies shown the effects of EDCs on the pubertal development.

Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2 / Genetic predisposition for breast cancer: BRCA1 and BRCA2 genes

El descubrimiento de los genes BRCA1 y BRCA2 ha llevado a la introducción de pruebas genéticas cada vez más sofisticadas para medir el riesgo de cáncer de mama de origen hereditario, entre otras cosas. En el presente artículo exploramos los criterios a seguir para realizar pruebas para estos genes, así como las implicaciones en el tratamiento para los pacientes en caso de identificarlos.

The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.

Effect of plumbagin free alcohol extract of Plumbago zeylanica Linn. root on reproductive system of female Wistar rats

OBJECTIVE@#To assess the effect of plumbagin-free alcohol extract (PFAE) of Plumbago zeylanica Linn. (Plumbaginaceae) (P. zeylanica) root, on female reproductive system and fertility of adult female wistar rats.@*METHODS@#After the oral acute toxicity study, the PFAE was administered at two dose levels to perform the estrous cycle study, anti-implantation and abortifacient activity and hormonal analysis. However, the estrogenic/antiestrogenic activity was evaluated at only one most effective dose.@*RESULTS@#LD(50) cut-off was 5,000 mg/kg body weight. The extract exhibited significant anti-implantation and abortifacient activity at the tested dose levels (300 and 500 mg/kg, p.o.) (P<0.01). The extract dose-dependently decreased the levels of serum progesterone, follicle stimulating hormone and luteinizing hormone, while a dose-dependent increase was observed in the concentration of serum prolactin. The extract did not show any significant changes in structure and function of uterus when given alone, but when given along with ethinyl estradiol, it exhibited significant antiestrogenic activity in immature overiectomized female rats(P<0.001). Biochemical parameters in the serum/blood and haematological parameters did not show appreciable changes throughout and after the course of investigation. However, all the altered parameters returned to normalcy within 30 days following withdrawal of treatment.@*CONCLUSIONS@#All findings suggest that the antifertility activity of extract could possibly be through the changes in the implantation site, altered hormonal levels, prolonged estrous cycle and anti-estrogenic activity. Hence, the extract possesses reversible antifertility activity without adverse toxicity in female rats.

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 ...