Assistência ginecológica aos transgênero / Gynecological care for transgenders

Transgênero (trans) é um termo que alberga toda a diversidade de gênero. A incongruência de gênero faz parte desse espectro e refere-se à pessoa cuja identidade de gênero é oposta ao sexo que lhe foi atribuído no nascimento. A terapia hormonal de afirmação de gênero, bem como a cirurgia de afirmação de gênero, é necessária para adequar o corpo ao gênero ao qual a pessoa se identifica. Os homens trans necessitam da terapia com testosterona, que visa reduzir as concentrações de estradiol e incrementar a testosterona circulante para níveis fisiológicos masculinos, resultando em masculinização. A mulher trans receberá o estradiol, associado ou não a um antiandrogênico, visando reduzir a testosterona e incrementar o estrogênio para níveis femininos, resultando em feminização. A cirurgia de afirmação de gênero é, frequentemente, requerida para completar as modificações fenotípicas para o homem e a mulher trans. O ginecologista e obstetra tem um papel crucial no provimento de cuidados a essa população. O presente artigo visa sistematizar algumas ações que o ginecologista e obstetra pode oferecer e que têm potencial para melhorar a qualidade de vida dos homens e mulheres trans. (AU)

Transgenero (trans) is an umbrella term that encompasses all gender diversity. Gender Incongruity is part of this spectrum and refers to the person whose gender identity is opposed to the sex assigned to them at birth. Gender-affirming hormone therapy as well as gender-affirming surgery are necessary to adapt the body to the gender to which the person identifies. Trans men require testosterone therapy to reduce estradiol concentrations and increase circulating testosterone to male physiological levels resulting in masculinization. Trans women will receive estradiol associated or not with an antiandrogenic to reduce testosterone and increase estrogen to female levels resulting in feminization. gender-affirming surgery is often required to complete phenotypic modifications for trans men and women. The gynecologist and obstetrician plays a crucial role in to provide care to this population. This article aims to systematize some actions that the gynecologist and obstetrician can offer to improve the quality of life of trans men and women. (AU)

CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice

Eosinophils are abundant in the reproductive tract, contributing to the remodeling and successful implantation of the embryo. However, the mechanisms by which eosinophils migrate into the uterus and their relationship to edema are still not entirely clear, since there are a variety of chemotactic factors that can cause migration of these cells. Therefore, to evaluate the role of CCR3 in eosinophil migration, ovariectomized C57BL/6 mice were treated with CCR3 antagonist SB 328437 and 17β-estradiol. The hypothesis that the CCR3 receptor plays an important role in eosinophil migration to the mouse uterus was confirmed, because we observed reduction in eosinophil peroxidase activity in these antagonist-treated uteruses. The antagonist also influenced uterine hypertrophy, inhibiting edema formation. Finally, histological analysis of the orcein-stained uteruses showed that the antagonist reduced eosinophil migration together with edema. These data showed that the CCR3 receptor is an important target for studies that seek to clarify the functions of these cells in uterine physiology.

Is the expression of the components of the carotid matrix of rats influenced by estrogen, progestin and tibolone? / A expressão dos componentes da matriz carotídea de ratos é influenciada pelo estrogênio, progestagênio e tibolona?

Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.

Effect of injectable progesterone on follicular development in lactating beef cows treated with estradiol plus a low-concentration progesterone device / Efeito da progesterona injetável no desenvolvimento folicular em vacas de corte lactantes tratadas com estradiol e dispositivo de progesterona de baixa concentração

The effect of injectable progesterone was evaluated along with estradiol benzoate (EB) on the fate of the dominant follicle (DF) present in the ovary at the beginning of low progesterone-based TAI protocol. All cattle were given 500 µg cloprostenol im (PGF; Schering-Plough Animal Health for Estrumate, Pointe-Claire, QC, Canada) twice, 11 d apart, and allocated into two groups: Estradiol group (E group, n = 11) and Estradiol-Progesterone group (EP group, n = 11). Ten days after the second PGF (Day 0), all cattle were given an intravaginal progesterone device with half progesterone concentration (Cue-Mate with a single pod containing 0.78 g progesterone). Concurrently, all cattle were given 1.5 mg im of estradiol benzoate in 3 mL of canola oil and PGF im on Day 0 of the protocol in a crossover design, in which each cow received both treatments. Cows in the EP group also received 100 mg im progesterone (Sigma) in 2 mL of canola oil. On Day 8, progesterone devices were removed and all cattle were given PGF im. All statistical analyses were performed with SAS 9.0. The DF present on Day 0 ovulated in 76% (16/21) of cows from E group and 28.6% (6/21) of cows from EP group (P = 0.002). After progesterone device removal, the size of ovulatory follicle did not differ between groups (E group, 15.5 ± 0.43 mm vs EP group, 15.8 ± 0.98 mm; P = 0.82). These follicles ovulated in 81.3 ± 3.1 h in E group and 71.0 ± 6.1 h in EP group (P = 0.13). In conclusion, injectable progesterone reduced the proportion of cows that ovulate the dominant follicle present in the ovary at the beginning of estradiol-progesterone-based protocols. However, no difference was detected on time of ovulation after progesterone device removal between groups.(AU)

Foi avaliado o efeito da progesterona injetável e do benzoato de estradiol (BE) no destino do olículo dominante (FD) presente no ovário no início do protocolo de IATF. Todas as vacas receberam duas injeções de 500 µg de cloprostenol im (PGF; Schering-Plough Animal Health for Estrumate, Pointe-Claire, QC, Canadá) em um intervalo de onze dias e foram alocadas em dois grupos: Estradiol (grupo E, n = 11) e Estradiol-Progesterona (grupo EP, n = 11). Dez dias após a segunda injeção de PGF (Dia 0), elas receberam um implante intravaginal de progesterona com metade da concentração hormonal (Cue-Mate com apenas uma haste contendo 0,78 g de progesterona). Além disso, todas vacas receberam 1,5 mg im de BE dissolvido em óleo de canola e PGF im no Dia 0 do protocolo, em um delineamento em crossover no qual cada vaca recebeu ambos tratamentos. Vacas do grupo EP ainda receberam uma injeção de 100 mg im de progesterona (Sigma) em 2 mL de óleo de canola no Dia 0. No Dia 8, os dispositivos de progesterona foram removidos e todas as vacas receberam PGF im. A análise estatística foi realizada por meio do pacote estatístico SAS 9.0. O FD presente no Dia 0 ovulou em 76% (16/21) das vacas do grupo E e em 28,6% (6/21) das vacas do grupo EP (P = 0,002). Após a remoção do dispositivo de progesterona, o diâmetro do folículo ovulatório não apresentou qualquer diferença entre os grupos (grupo E, 15,5 ± 0,43 mm; grupo EP, 15,8 ± 0,98 mm; P = 0,82). Esses folículos ovularam em 81,3 ± 3,1 h no grupo E e em 71,0 ± 6,1 h no grupo EP (P = 0,13). A conclusão obtida foi que o uso de progesterona injetável reduziu a proporção de vacas que ovularam o folículo dominante presente no ovário no início do protocolo à base de estradiol e progesterona. No entanto, entre os grupos não houve diferença no momento da ovulação após a remoção do dispositivo de progesterona.(AU)

Changes of the uterine tissue in rats with polycystic ovary syndrome induced by estradiol valerate

Background: Polycystic ovary syndrome [PCOS] is one of the most common hormonal disorders that can lead to irregular menstrual cycles and hyperandrogenism. Reduced levels of progesterone and increased estrogen in these women can perpetually stimulate the endometrial tissue of the uterus. In this study, we assess the effect of PCOS induction by estradiol valerate [EV] in a rat model

Materials and Methods: In this experimental study, adult female Wistar rats that weighed approximately 200 g were divided into control, sham, and experimental groups [n=6 per group]. The experimental group received subcutaneous injections of 2 mg EV for induction of PCOS. We confirmed the presence of PCOS in the experimental group rats. Rats from all groups were subsequently killed, after which their uteri were removed and fixed for histological and cytological analyses. The uterine tissue sections were stained with hematoxylin and eosin [H and E] and iron hematoxylin [iron-H]. We examined epithelium height, thickness of the uterus wall, and frequency of the mitotic cells. The data were assessed at alpha=0.05

Results: Uterine tissue findings from the experimental group showed significant increases in the height of the uterus luminal epithelium, the thickness of the uterus wall, and the frequency of eosinophils in the endometrial stroma. We observed an increased frequency of mitotic cells in the experimental group in both luminal and glandular epithelia of the uterus. An increased rate of the glandular epithelium region was noticeable and significant

Conclusion: Induction of PCOS by EV could change the proliferation rate in the endometrial tissue of the uterus

Resistance training and hormone replacement increase MMP-2 activity, quality and quantity of bone in ovariectomized rats

AIMS: The aim of the present study was to investigate the influence of resistance training (RT) and hormone replacement (HR) on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX) rats. METHODS: Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group): sham-operated sedentary (SHAM Sed), ovariectomized sedentary (OVX Sed), sham-operated resistance training (SHAM RT), ovariectomized resistance training (OVX RT), ovariectomized sedentary hormone replacement (OVX Sed-HR), and ovariectomized resistance training hormone replacement (OVX RT-HR). HR groups received implanted silastic capsules with a 5% solution of 17ß-estradiol (50 mg 17ß-estradiol/ml of sunflower oil). In a 12-week RT period (27 sessions; 4-9 climbs) the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. RESULTS: Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load) demonstrated better bone tissue quality in the RT associated with HR. CONCLUSION: The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.(AU)

Effect of estrogen administration on middle cerebral arterial viscoelastic properties in aged female rats

ABSTRACT PURPOSE: To develop a model for studying cerebrovascular disease prevention in elderly women. METHODS: Sixty 18-month-old Sprague Dawley (SD) rats were randomly divided into an estrogen administration group (EA, n=30) and a non-administration group (NA, n=30); thirty 4-month-old SD rats were allocated to a control group. The EA group received estradiol benzoate starting on the 5th day of a 34-day breeding period, and the serum levels of estradiol (E2), estrogen receptor (ER), and malondialdehyde (MDA) were measured. The MCA of each group was then sampled for viscoelastic experiments. RESULTS: The serum levels of E2 and MDA in the EA group showed significant differences compared to those in the control group (p<0.05), while the difference in ER between the EA and control groups was not significant (p>0.05). The decrease in MCA stress at 7,200 s and the increase in strain at 7,200 s in the EA group showed no significant differences compared to the control group (p>0.05). CONCLUSION: Estradiol administration inhibited the formation of lipid peroxidation products and restored middle cerebral arterial viscoelasticity in aged female rats.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus. .

The effects of maternal low protein and estrogen on sexual behavior and testicular maturation in male rats / Efectos de niveles maternos bajos de estrógeno y proteína sobre el comportamiento sexual y maduración testicular en ratas macho

In recent years, disorders related to the development and function of the male reproductive tract has increased, thus generating a surprising decrease in semen volume and sperm count. We examined the effects of low protein and estrogen on sexual behavior and testicular maturation in male rats. We also examined FSH, LH and testosterone levels and histological damage of testis tissue. The male rats were subjected to standard long-term treatment with estradiol by oral and paranteral delivery. The number of mounts, copulatory efficiency and ejaculation latencies for the paranteral protein diet (PPD) group was significantly lower than those in a group nourished with a low protein diet (LPD) and oral protein diet (OPD) groups (P<0.05). Testes and epididymis sections were examined by four grades, according to the level of damage of epithelium in the testes and epididymis. Higher histological damage was also detected in the PPD group. In conclusion, the present study confirmed that unwanted estrogen effects were higher in the paranteral administered group on examination of sexual behavior and histological damage of epithelium in the testes and epididymis of male rats.

En los últimos años, los trastornos relacionados con el desarrollo y la función del tracto reproductivo masculino han aumentado, lo que genera una disminución importante en el volumen de semen y el conteo de espermatozoides. Se examinaron los efectos de niveles bajos en proteínas y estrógeno en el comportamiento sexual y la maduración testicular en ratas macho. También se examinaron FSH, LH y los niveles de testosterona y el daño histológico de tejido testicular. Las ratas macho fueron sometidas al tratamiento y administración estándar a largo plazo con estradiol por vias oral y parenteral. El número de montajes, eficiencia de copulación y latencias de eyaculación para el grupo de dieta de proteínas parenteral (DPP) fue significativamente menor que los del grupo con una dieta baja en proteínas (PBD) y de proteína oral baja (POB) grupos (P<0,05). Fueron examinados los testículos y epidídimo de acuerdo a cuatro grados, en relación al nivel de daño del epitelio en los testículos y epidídimo. También se detectó un mayor daño histológico en el grupo DPP. En conclusión, se confirma que los efectos no deseados del estrógeno fueron mayores en el grupo con administración parenteral en el examen de conducta sexual y en el daño histológico del epitelio en los testículos y el epidídimo de ratas macho.

What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels. .

Development of a subcutaneous endometriosis rat model

PURPOSE: To present a rat model of subcutaneous endometriosis for the study of pathophysiology and the effects of drugs. METHODS: Fifty three-month-old female Wistar rats (Rattus norvergicus) were distributed into one control group and four treatment groups: estradiol (2.5; 5; 10mg/kg sc), medroxyprogesterone acetate (0.5; 2; 5mg/kg sc), triptorelin pamoate (0.18; 0.56mg/kg sc) and acetylsalicylic acid (3mg/kg per os). The animals were autoimplanted subcutaneously with 4x4-mm uterine fragments to induce endometriosis. The endometriomas were measured on days 1, 7, 14 and 21. The relative dry and wet weights of the endometrioma were used to evaluate response to the drug. Endometrial -like tissue was confirmed by histology. The greatest weight gain was observed on day 14 (relative wet weight: 29.1 ± 6.7mg%, relative dry weight: 5.3 ± 0.9mg %). Treatments were administered between day 5 and day 14. RESULTS: The relative wet weight of the hemiuterus in the 10mg/kg estradiol group differed significantly from control and the other two estradiol groups (p=0.0001). In the medroxyprogesterone acetate group the weight decreased significantly but this decrease was not dose-dependent. Weight reduction was also significant in the triptorelin pamoate and the acetylsalicylic acid groups. CONCLUSION: The model of subcutaneous endometriosis is reproducible, low-cost and easy to perform, and suitable for the study of pathophysiology and the effects of drugs. .

A influencia da administracao de estradiol nos receptores de estrogeno da mucosa nasal: estudo experimental em cobaias / Influence of estradiol administration on estrogen receptors of nasal mucosa: an experimental study on guinea pigs

Introdução: A literatura indica uma correlação entre estrogênio elevado no soro e sintomas nasais ou alterações inflamatórias na mucosa nasal. Os receptores de estrogênio tendem a ser controlados por retroalimentação negativa, para evitar um estímulo nocivo sobre as diversas funções corporais em períodos de hiperestrogenismo. Propomos uma hipótese em que os mecanismos que regulam a expressão de receptores de estradiol na mucosa nasal estão ausentes em alguns pacientes, e a sua concentração permanece estável mesmo em períodos de elevada concentração sérica hormonal, o que pode conduzir a sintomas locais na mucosa nasal. Desenho do estudo: Estudo prospectivo experimental. Objetivo: Determinar se altos níveis de estrogênio induzem à redução no número de receptores de estrogênio na mucosa nasal. Material e método: Trinta cobaias foram submetidas à biópsia da concha nasal, recebendo 0,5 ml de cipionato de estradiol por via intraperitoneal por trinta dias consecutivos. Em seguida foram obtidas amostras da concha nasal contralateral. As análises imuno-histoquímicas dos receptores de estrógeno foram realizadas antes e depois da hormonioterapia. Resultados: O grupo pós-tratamento mostrou uma redução da expressão dos receptores (p = 5,2726-5). Conclusão: Redução na expressão do receptor de estrogênio nasal foi encontrada após trinta dias de administração de estradiol. .

Introduction: Some clinical trials revealed a correlation between increased serum estrogen and nasal symptoms or inflammatory changes in nasal mucosa. Estrogen receptors tend to be controlled by a negative feedback, to avoid a deleterious stimulus over several body functions while in hyperestrogenic periods. This study proposes a hypothesis where mechanisms regulating expression of estradiol receptors in nasal mucosa are absent in some patients, and their concentration remains steady even in periods of high serum hormonal concentration, potentially leading to local estrogenic symptoms in nasal mucosa. Study design: This was an experimental prospective study. Aim: To determine whether estrogen levels induce the reduction of the number of estrogen receptors in the nasal mucosa. Methods: In the present study, 30 adult male guinea pigs were subjected to a biopsy of the middle nasal turbinate and received 0.5 mL of estradiol cypionate intraperitoneally for 30 consecutive days. Afterwards, samples from contralateral middle turbinate were obtained. Immunohistochemical analysis of estrogen receptors were performed pre- and post-treatment. Results: The post-treatment group showed reduction of receptor expression when compared to the pre-treatment group. (p = 5.2726-5). Conclusion: A reduction in the expression of the nasal estrogen receptor was observed after 30 days of estradiol administration. .

Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats / Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg) for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001). In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001). In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA) concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001). It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg) por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001). No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001). Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA) for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001). Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo naqueles animais.

Efeitos do estradiol sobre a função endotelial, sensibilidade insulínica e viscosidade sanguínea em mulheres na pós-menopausa com excesso de peso / Effects of estradiol on endothelial function, insulin sensitivity and blood viscosity in overweight postmenopausal women

A ação que o estrogênio desempenha sobre o endotélio depende da integridade deste e consequentemente das características clínicas de cada indivíduo. O uso da terapia hormonal da menopausa (THM) em mulheres com baixo risco cardiovascular geralmente resulta em efeitos benéficos, desde que iniciado em um período próximo da menopausa. Em contrapartida, o seu uso em mulheres com alto risco cardiovascular, como diabéticas ou portadoras de lesões ateroscleróticas já estabelecidas, e ainda naquelas com início da THM em um período superior a dez anos da menopausa geralmente resulta em efeitos maléficos. Nosso objetivo é avaliar os efeitos do estrogênio sobre a função endotelial em mulheres com sobrepeso ou obesidade, ou seja, indivíduos com risco cardiovascular intermediário. Para isso, 44 mulheres na pós-menopausa com idade entre 47 a 55 anos e índice de massa corporal (IMC) de 27,5 a 34,9kg/m², foram randomizadas nos grupos placebo (P) e estrogênio transdérmico (ET). A intervenção consistiu no uso transdérmico de estradiol, 1mg por dia, por um período de três meses. As participantes realizaram avaliação da reatividade endotelial em repouso e após isquemia [pletismografia por oclusão venosa (POV), com medidas do fluxo sanguíneo do antebraço (FSA) e videocapilaroscopia dinâmica do leito periungueal (VCLP), com medidas da velocidade de deslocamento das hemácias (VDH)], dosagens de moléculas de adesão [E-selectina, molécula de adesão intercelular (ICAM-1) e molécula de adesão vascular (VCAM-1)], aferição da sensibilidade insulínica [através do homeostatic model assessment of insulin resistance (HOMA-IR) e área sob a curva (AUC) da insulina durante o teste oral de tolerância à glicose (TOTG)] e mensurações das viscosidades sanguínea e plasmática. As participantes apresentaram idade de 51,77 ± 2,3 anos, IMC de 31,52 ± 2,54 kg/m² e tempo de menopausa de 3 [2-5] anos. O grupo P não apresentou nenhuma mudança significativa em qualquer variável. Após a intervenção, o grupo ...

The action that estrogen plays on the endothelium depends on its integrity and consequently on the clinical characteristics of each individual. The use of menopausal hormone therapy (MHT) in women with low cardiovascular risk usually results in beneficial effects, since it is started in a period close to menopause. In contrast, its use often results in harmful effects in women at high cardiovascular risk, such as diabetic ones or those with established atherosclerotic lesions, and even in those that the beginning of MHT exceeds ten years from menopause. Our goal is to evaluate the effects of estrogen on endothelial function in overweight women, ie, individuals at intermediate cardiovascular risk. For this purpose, 44 postmenopausal women, aged 47-55 years with body mass index (BMI) from 27.5 to 34.9 kg / m², were randomized into placebo (P) and transdermal estrogen (TE) groups. The intervention consisted of using transdermal estradiol 1mg per day for a period of three months. Participants underwent endothelial reactivity assessment at rest and after ischemia [by venous occlusion plethysmography (VOP), with assessment of forearm blood flow (FBF) and dynamic nailfold videocapillaroscopy (DNV), with assessment of red blood cell velocity (RBCV)], measurements of soluble adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1)], measurement of insulin sensitivity [by homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) of insulin during the oral glucose tolerance test (OGTT)] and measurements of blood and plasma viscosities. The participants aged 51.77 ± 2.3 years, BMI 31.52 ± 2.54 kg/m² and had a time since menopause of 3 [2-5] years. P group showed no significant change in any variable. After intervention, the TE group compared to the baseline presented in DNV lower time taken to reach RBCV during post-occlusive reactive hyperemia (PORH) (4,0 [3,25-5,0] vs. 5,0 ...

Comparison between two progesterone sources and two oestradiol formulations in a Heatsynch protocol for postpartum cycling dairy cows in pasture

To compare an injectable progesterone (MAD-4) with an intravaginal device (IPD), and natural O17 with synthetic oestradiol (OB) in a synchronisation protocol, 51 cows were divided into four groups. Each group was treated with one of the two sources of progesterone and one of the two oestradiol formulations. Oestrus behaviour, follicle diameter, and pregnancy rates were evaluated. Oestrus behaviour (p = 0.902), numbers of cows in oestrus (p = 0.917), follicle diameter (p = 0.416), and pregnancy rates (p = 0.873) were similar among the four groups. More cows in the group treated with the IPD and OB scored > 200 oestrus behaviour points compared to the other groups (p = 0.038). A longer interval between the end of treatment and oestrus was observed among cows treated with MAD-4 than cows given the IPD (p = 0.030), but no differences were found between animals receiving the two oestradiol formulations (OB and O17). While the use of MAD-4 requires further testing, similar responses to natural oestradiol observed in the present study could allow the use of this formulation in reproductive protocols because it is not associated with the potential human health risks of OB.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol / Níveis diminuídos de óxido nítrico no hipocampo podem ser importantes nos déficits de aprendizado e de memória em ratas ooforectomizadas tratadas com alta dose de estradiol

The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1) than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively). Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001). These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

Os efeitos de uma alta dose de estradiol na memória e nos metabólitos do óxido nítrico de tecidos hipocampais foram estudados. Os Grupos Sham-Est e OVX-Est foram tratados com 4 mg/kg de valerato de estradiol por 12 semanas. O tempo de latência e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX, respectivamente (p<0,001). Os animais dos Grupos Sham-Est e OVX-Est passaram menos tempo na meta do quadrante (Q1) do que aqueles dos Grupos Sham e OVX durante o teste inicial (p<0,05 e <0,001, respectivamente). Níveis significativamente menores de metabólitos do óxido nítrico foram observados nos hipocampos dos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX (p<0,001). Esses resultados sugerem que os níveis diminuídos de óxido nítrico no hipocampo podem ter um papel nos déficits de aprendizado e de memória, que são observados após tratamento com alta dose de estradiol, embora os mecanismos específicos envolvidos nestes achados ainda precisam ser elucidados.

Topical estradiol does not interfere with the expression of the metalloproteinase-1 enzyme in photo exposed skin cells / Estradiol tópico não interfere na expressão da enzima metaloproteinase-1 em células da pele fotoexposta

BACKGROUND: In postmenopausal women there is a rapid destruction of dermal collagen, resulting in accelerated skin ageing, which is manifested by cutaneous atrophy, increased number and depth of wrinkles and sagging. This accelerated catabolism of the collagen is due to estrogen deficiency and increased synthesis of the metalloproteinase-1 enzyme, which degrades the dermal collagen. OBJECTIVES: To assess whether the use of topical estradiol 0.05% cream on photo exposed skin can inhibit the expression of the metalloproteinase-1 enzyme on the dermis and subsequently the rapid loss of collagen in women after menopause. METHODS: We included 40 postmenopausal women without hormone replacement therapy. Information about lifestyle, lipid profile, blood glucose level, thyroid hormones, mammography, Pap smear and transvaginal ultrasound were obtained to rule out associated diseases. Skin biopsy of the right preauricular region was performed before and after treatment with topical estradiol 0.05% for 30 days. The biopsy specimens were subjected to immunohistochemistry to identify the expression of the metalloproteinase-1 enzyme. RESULTS: There was no statistically significant difference on the expression of the metalloproteinase-1 enzyme in keratinocytes, fibroblasts and endothelial cells before and after treatment with topical estradiol for 30 days. CONCLUSION: Treatment with estradiol 0.05% cream, in photo exposed skin for 30 days, does not inhibit the production of metalloproteinase-1.

FUNDAMENTOS: Na pós-menopausa, ocorre rápida destruição do colágeno dérmico, com consequente envelhecimento acelerado da pele, que se expressa com atrofia cutânea, aumento do número e da profundidade das rugas e flacidez. Esse catabolismo acelerado do colágeno ocorre por deficiência estrogênica e aumento na síntese da enzima metaloproteinase-1, que degrada o colágeno dérmico. OBJETIVOS: Avaliar se o uso de estradiol tópico a 0,05% em creme na pele fotoexposta pode inibir a expressão da enzima metaloproteinase-1 na derme e, consequentemente, a perda acelerada do colágeno em mulheres na pósmenopausa. MÉTODOS: Foram incluídas 40 mulheres na pós-menopausa sem terapia de reposição hormonal. Informações sobre hábitos de vida, perfil lipídico, níveis glicêmicos, hormônios tireoidianos, mamografia, colpocitologia oncótica e ultrassom transvaginal foram obtidas para excluir doenças associadas. Biópsia de pele da região pré-auricular direita foi realizada antes e após tratamento com estradiol tópico a 0,05% por 30 dias. Os espécimes de biópsia foram submetidos à reação imunoistoquímica para identificar a expressão da enzima metaloproteinase-1. RESULTADOS: Não foi observada diferença estatisticamente significativa na expressão da enzima metaloproteinase-1 em queratinócitos, células endoteliais e fibroblastos da pele antes e após tratamento com estradiol tópico por 30 dias. CONCLUSÃO: O tratamento com creme contendo estradiol a 0,05% em pele fotoexposta por 30 dias não inibe a produção da enzima metaloproteinase-1.

Promestrieno no tratamento da atrofia vulvovaginal: revisão sistemática / Promestriene for treatment of vulvovaginal atrophy: a systematic review

Os sintomas decorrentes da atrofia vulvovaginal são muito comuns no climatério. Os estrogênios aplicados localmente na vagina se mostram eficazes no alívio de tais manifestações; no entanto, os estrogênios conjugados na forma de creme vaginal apresentam efeitos sistêmicos e o estriol aplicado localmente pode ser absorvido sistemicamente também. O promestrieno é um estrogênio cuja absorção sistêmica é desprezível quando empregado topicamente, porém a falta de revisão sistemática sobre o tema suscitou a realização da presente revisão. Foram incluídos 16 estudos publicados entre 1976 e 2009, que avaliaram eficácia do promestrieno no alívio dos sintomas decorrentes da atrofia vulvovaginal, ou que investigaram seus efeitos na citologia vaginal, e também aqueles que avaliaram a absorção da substância quando empregada topicamente. As evidências encontradas confirmaram a eficácia do promestrieno, utilizado localmente no tratamento das afecções atróficas genitais femininas decorrentes do hipoestrogenismo, aliada a absorção sistêmica desprezível

The symptoms resulting from vulvovaginal atrophy are very common during climacteric. Estrogens applied locally in the vagina are effective in relieving these manifestations, however, conjugated estrogens as vaginal cream have systemic effects and locally applied estriol may be systemically absorbed. Promestriene is an estrogen without systemic absorption when applied topically, but the lack of a systematic review on the substance motivated the idea to make this review. Sixteen studies published between 1976 and 2009 which evaluated the effectiveness of promestriene on the relief of symptoms resulting from vulvovaginal atrophy or which investigated its effects on vaginal cytology and those which evaluated the absorption of the substance when used locally were included. The found evidences confirmed the effectiveness of locally applied promestriene in the treatment of female genital atrophic disorders due to low estrogen levels coupled with negligible systemic absorption