MARIA CANDIDA PINHEIRO BARACAT REZENDE
Projetos de Pesquisa
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LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Androgens and breast(2017) FLORENCIO‐SILVA, R.; SASSO, G. R. D. S.; GIRAO, J. H. C.; BARACAT, M. C. P.; SIMOES, R. S.Breast cancer (BCAA) is one of the most frequent malignancies in women in several countries, which excessive exposure to oestrogens is one of the main risk factors. The ovaries are the main source of endogenous estrogen production; however, at menopause this production sessate and extra‐gonadal synthesis, especially in ectomesenchymal cells from adipose tissue, turns the main source of estrogen production, since these cells express aromatase, an enzyme that converts androgens to estrogens. Supported by strong clinical evidence androgen replacement has been recommended for the relief of symptoms caused by female syndrome of androgen insufficiency, such as fatigue, mood swings and depression; Furthermore, experimental studies have suggested the possibility of protection of androgen replacement against BCA. In these studies, acting through their receptors, testosterone showed antiproliferative, proapoptotic and inhibited the activity of estrogen receptors and growth of mammary tumors; Clinical evidence also support the protective role of androgens in the breast. However, studies indicate that this protective role depends on the level of aromatase activity; for instance, testosterone can exert a direct inhibitory effect on tumor growth by binding to its receptor, but have an indirect effect by stimulating its conversion to oestrogens by aromatase. Obesity and insulin, as well as multiple other factors, some of which are independent risk factors for BCA, may result in overexpression of aromatase, resulting in increased localized production of estrogens, which are inducible factors of BCA. Studies on the administration of testosterone in women are scarce and controversial, and there are no studies that provide data in terms of long‐term use of safety. Thus, in this review we intend to show how androgens act in the breast. Given the current evidence, the use of androgens in women with risk factors for breast cancer is not recommended. © 2017 Sociedade Brasileira de Reprodução Humana
- Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome(2023) BARACAT, Maria Candida P.; BARACAT, Edmund C.; SIMOES, Ricardo S.; SIMOES, Manuel J.; MACIEL, Gustavo A. R.; AZZIZ, Ricardo; JR, Jose Maria SoaresHormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day x 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.
- Association of intrauterine synechiae with pituitary gonadotrophin pulse patterns: A pilot study(2023) GIANFALDONI, Arlete; ROA, Cristiane; SIMOES, Ricardo dos Santos; BARACAT, Maria Candida P.; FONSECA, Angela Maggio da; BAGNOLI, Vicente Renato; SOPRESO, Isabel Cristina Esposito; RIVAS, Fernando Wladimir Silva; MONTELEONE, Pedro; BARACAT, Edmund C.; JR, Jose Maria SoaresBackgroundIntrauterine synechiae (IS) is an acquired uterine condition that occurs when scar tissues (adhesions) form within the uterus and/or cervix, causing menstrual disturbance. However, approximately 50% of patients with IS are refractory to treatment. Therefore, other endocrine disturbances, such as gonadotropin disturbance, may affect treatment success.Study aimTo analyze gonadotropin levels in women with and without IS.MethodsTen women with refractory IS experiencing amenorrhea since at least 6 months and nine with normal menstrual cycles (control group) were included in this study. Blood sample were collected every 10 minutes during a 4-h period. The serial ultrasound was performed in both groups for evaluating the cycle phase. Blood was collected when the follicles size was between 5-10 mm. Serum LH, FSH, progesterone and estradiol concentrations were measured. To detect LH and FSH pulses, the technique proposed by Santen and Bardin was adopted; therefore, one pulse was defined as a 20% increase in the concentrations as to the preceding point, followed by an important decrease.ResultsNo differences were observed between the study groups at baseline. Estradiol levels were lower in the IS group than in the control group, but the difference was not statistically significant. During the first hour of monitoring, cumulative FSH pulsatile frequency of IS group was lower than one of control.ConclusionOur data suggest that the estradiol levels of IS participants are lower than those of women with normal menstrual cycle. The role of this finding in the physiology of uterine synechiae requires further investigation.
- Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?(2023) URBANETZ, Lorena Ana Mercedes Lara; JR, Jose Maria Soares; MACIEL, Gustavo Arantes Rosa; SIMOES, Ricardo dos Santos; BARACAT, Maria Candida Pinheiro; BARACAT, Edmund ChadaPCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ER alpha or Er beta, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.
- Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats(2023) MENEZESDASILVA, Glaucia Mara; VEIGA, Eduardo Carvalho de Arruda; SIMOES, Manuel Jesus; SIMOES, Ricardo Santos; SHIROMA, Marcos Eiji; BARACAT, Maria Candida Pinheiro; CAVALCANTI, Givanna Santos; SOARES JUNIOR, Jose Maria; BARACAT, Edmund ChadaIntroduction: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement ther-apy may attenuate the reduction. Objectives: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats.Methods: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 mu g/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solu-tion. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 +/- 0.026 mu/m2) and the early raloxifene (0.437 +/- 0.012 mu/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 +/- 0.038 mu/m2 and 0.277 +/- 0.015 mu/m2 respectively).Conclusions: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.