Effect of aromatase inhibitors on the endometrium and ovary with their possible role in ovulation in adult albino rats: a histological, immunohistochemical, morphometric, and hormonal assay

Aromatase inhibitors act by inhibiting estrogen synthesis and depletion of its concentrations in the circulation. The aim of the study was to investigate the effect of exemestane and letrozole on the endometrium and ovary with their possible role in ovulation in adult albino rats. Thirty adult female albino rats were used and divided into control and experimental groups. Rats in the experimental group were further divided into subgroup IIA and subgroup IIB. In subgroup IIA each rat was given exemestane at 1 mg/kg/day and in subgroup IIB each rat was given letrozole at 5 mg/kg/day by means of a gastric tube for five consecutive ovarian cycles. Specimens from their ovaries and endometrium were taken and prepared for H and E staining and for immunohistochemical staining for vascular endothelial growth factor study. Morphometric study of endometrial thickness and surface area percentage of immunoreaction in the endometrium was evaluated. Hormonal assay of luteinizing hormone and follicular stimulating hormone was carried out. Significant decrease in endometrial thickness was observed in the exemestane-treated group. The letrozole-treated group revealed significantly thickened endometrium. The exemestane-treated group showed markedly disturbed ovarian architecture in the form of thickened germinal epithelial cell layer and multiple corpora lutea with atretic follicles. The letrozole-treated group revealed an ovarian cortex with multiple stages of follicular development. The vascular endothelial growth factor immunoreaction of the letrozole-treated group showed significant highly positive cytoplasmic reaction. Significant decrease in luteinizing hormone level in the exemestane group and significant increase in the letrozole group were detected. It is concluded that letrozole improved the endometrial thickness and may have a role in ovulation induction. In contrast, exemestane led to disruption of the endometrium and ovary. Therefore, not all aromatase inhibitors help in ovulation

Cortisol basal em asmáticos em uso de duas diferentes doses de propionato de fluticasona / Basal cortisol in asthmatics on two different doses of fluticasone propionate

OBJETIVOS: Avaliar os valores de cortisol basal em asmáticos persistentes em uso de propionato de fluticasona inalatório na dose de 200 ou 300 mcg/dia. MÉTODOS: O diagnóstico e a classificação da gravidade da asma basearam-se nas recomendações do Global Initiative for Asthma. Pacientes menores de 11 anos receberam fluticasona na dose de 200 mcg/dia, e aqueles com mais de 11 anos receberam 300 mcg/dia. Após 10 semanas de tratamento, a dosagem do cortisol foi realizada para avaliação da função adrenal. RESULTADOS: Foram avaliados 41 pacientes (65,9 por cento do sexo masculino) entre 6 e 18 anos. Não houve diferença significativa entre as médias de cortisol basal nos pacientes que receberam 200 mcg/dia de propionato de fluticasona (n = 13) e naqueles que receberam 300 mcg/dia (n = 28). CONCLUSÕES: Os achados mostram que doses baixas a moderadas de propionato de fluticasona não causam supressão adrenal.

OBJECTIVES: To evaluate basal plasma cortisol in persistent asthmatics on inhaled fluticasone propionate 200 mcg/day and 300 mcg/day. METHODS: Asthma diagnosis and classification was based on Global Initiative for Asthma recommendations. Patients aged 11 years old or less received fluticasone propionate 200 mcg/day and those older than 11 years received 300 mcg/day. After 10 weeks of treatment, plasma cortisol levels were monitored to evaluate the hypothalamic-pituitary-adrenal axis. RESULTS: Forty-one patients (65.9 percent males) aged 6 to 18 years old were evaluated. No statistical differences were found between plasma cortisol levels in patients who received 200 mcg/day (n = 13) and those who received 300 mcg/day (n = 28). CONCLUSIONS: Our results show that low and moderate doses of fluticasone propionate do not cause adrenal suppression.

Exemestane: a milestone against breast cancer.

Rapid advances in the treatment of breast cancer, especially in the form of hormone therapy have truly increased the hope of longer and better disease-free survival for these patients. Exemestane, a third generation aromatase inhibitor has been extensively evaluated in metastatic as well as adjuvant therapy of breast cancer. It has also been evaluated for its safety profile, especially on bone and lipids. Exemestane provides hope to the patients with breast cancer both in early and metastatic disease. This review analyzes all the aspects of exemestane therapy.

Efficacy and safety of inhaled steroids in children with asthma: a comparison of fluticasone propionate with beclomethasone

Inhaled corticosteroids are indicated in children who have mild persistent asthma. Fluticasone propionate is a newer corticosteroid agent with higher potency compared with previous generations. However, still few dose-ranging studies have been investigated for optimal dosing of inhaled corticosteroids particularly in children with regard to the tolerability and safety of the drug. The primary purpose of this study was to compare and evaluate the efficacy and safety of fluticasone with beclomethosone in the treatment of childhood asthma unresponsive to non-steroidal medications and also in persistent, moderate and severe asthma. Seventy children, aged 6 to 14 years were enrolled in an open randomized trial with a parallel group design. Fiftytwo children with moderate, severe or persistent asthma received fluticasone 100 micro g twice daily for 12 weeks compared with 18 asthmatic children on beclomethasone 200 micro g daily. The outcome was assessed by data on questionnaires, changes in clinical symptoms, and results of peak flowmetery [PEFR]. Moreover, safety was assessed by 24 hour urinary cortisol measurement at the beginning of the study and comparison of the data with urinary cortisol at the end of 12 weeks. A total of 70 children between 6 to 14 years [33 girls and 37 boys] were randomized to start treatment with fluticasone or beclomethasone. From 70 children 13[18.6%] had a history of contact with pets during their life. At the beginning in beclomethasone group: 88.9% had cough, 88.9% had post exercise cough, 66.7% had dyspnea and 72.2% had wheezing. In Fluticasone group: 75% had cough,76.9% had post exercise cough, 46.2% had dyspnea and 59.6% had wheezing. After 3 months of therapy in beclomethasone group: cough was seen in 16.7%, post exercise cough in 11.1%, dyspnea in 11.1%, wheezing in 16.7% and in fluticasone group: cough in 15.4%, post exercise cough in 11.1%, dyspnea in 1.9% and wheezing in 3.8%.Data showed a better improvement in clinical signs of patients with fluticasone [p < 0.05]. Pulmonary function tests revealed better lung function in fluticasone group [p < 0.05]. In addition, 24 hours urinary cortisol level was measured at the beginning and after 12 weeks of therapy and it was within the normal range for both drugs. Fluticasone produced significantly greater improvement in lung function and control of asthma symptoms compared to beclomethasone and is efficient in the treatment of persistent, moderate and severe asthma in children. In addition these improvements were achieved with no greater degree of cortisol suppression compared with beclomethasone

Inhaled corticosteroids in the treatment of respiratory allergy: safety vs. efficacy

OBJETIVO: Revisar os mecanismos moleculares de ação, eficácia e potenciais efeitos adversos relacionados aos corticosteróides inalados (CEI) em crianças com asma persistente. FONTES DOS DADOS: Artigos de língua inglesa da base de dados MEDLINE. Foram empregados os termos: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, oral candidiasis. Foram selecionados guias de tratamento, artigos de revisão, estudos controlados, meta-análises e revisões sistemáticas que avaliaram a eficácia e os eventos adversos do tratamento com CEI. SíNTESE DOS DADOS: Estudos in vivo e in vitro mostram que os CEI disponíveis apresentam diferentes características farmacocinéticas e farmacodinâmicas que lhes conferem diferentes potenciais de ação. Os CEI também diferem quanto aos efeitos adversos sistêmicos e locais. Salienta-se a biodisponibilidade desses produtos como essencial para determinar a incidência de efeitos colaterais. Em linhas gerais, os CEI são capazes de controlar a asma, reduzindo o número de exacerbações, atendimentos médicos, hospitalizações e a necessidade de pulsos de corticosteróides orais. Também se observa melhora da função pulmonar, sobretudo nos pacientes com asma de início recente. O efeito adversos mais documentado é a desaceleração transitória do ritmo de crescimento. CONCLUSÕES: Os CEI são o principal agente antiinflamatório utilizado no tratamento da asma persistente. Quando administrados em doses baixas, mostram-se seguros e efetivos. O monitoramento dos pacientes permite a detecção precoce de eventuais efeitos adversos associados aos CEI.

OBJECTIVE: Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma. SOURCES: Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected. SUMMARY OF THE FINDINGS: In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate. CONCLUSIONS: ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.