Efeito da combinação enantato de estradiol e algestona acetofenida sobre os parâmetros de função renal de ratos
Data
2021-12-16
Orientadores
Gomes, Guiomar Nascimento 
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As formulações contendo estrogênio e progestina têm sido amplamente utilizadas no auxílio de modificações corporais durante a transição do gênero masculino para o feminino no Brasil e no mundo. Grande parte do uso destes hormônios ocorre por automedicação e poucos estudos avaliam as repercussões destas formulações sobre os diversos sistemas do organismo. Objetivo: avaliar os efeitos da administração crônica da combinação de estrogênio e progestina em ratos sobre a pressão arterial e parâmetros de função renal. Métodos: ratos Wistar machos, com dois meses de idade, obtidos do CEDEME-UNIFESP, foram alojados em gaiolas ventiladas, em sala com temperatura fixa (22° C) e ciclo de luz (alternando o ciclo a cada 12h, iniciando o período de iluminação às 7h), e tiveram acesso livre a ração (para roedores - Purina) e água durante todo o protocolo experimental. Os animais foram inicialmente submetidos à orquiectomia (OQX) ou a cirurgia simulada (Sham) e a seguir foram distribuídos em quatro grupos experimentais: S+G - Sham tratado com veículo (óleo de gergelim), S+H - Sham tratado com a combinação de hormônios: algestona acetofenida e enantato de estradiol (AAEE), O+G - OQX tratado com veículo, O+H - OQX tratado com AAEE. Tanto o óleo de gergelim como o AAEE foram administrados i.m., a cada 10 dias durante 5 meses. Após o tratamento, amostras de urina foram coletadas em gaiolas metabólicas a o sangue foi colhido por punção da artéria aorta abdominal. Parâmetros avaliados: pressão arterial (PA), peso corporal (PC), comprimento nasoanal (CNA), ingestão de ração (IR) e hídrica (IH), perfil lipídico (triglicerídeos, LDL, HDL), perfil ácido básico (valores sanguíneos de pH, pCO2 e bicarbonato), concentrações plasmáticas de ureia (URpl) e creatinina (Crpl), volume urinário (V24h), excreção de sódio (UNa+), potássio (UK+), amônio, acidez titulável (AT), e proteinúria. Os resultados estão expressos como média ± ep. A análise estatística foi feita com ANOVA seguida de teste de Tukey. O nível de significância foi estabelecido em 5% (p ≤ 0,05). Estudo aprovado pelo CEUA/UNIFESP nº 0573101218. Resultados: Verificamos que o tratamento hormonal reduziu significativamente o peso corporal [S+G: 462,8 ± 24,4; S+H: 324,5 ± 31,1*; O+G: 423,4 ± 78,01; O+H: 291,7 ± 41,3* (g)] e o comprimento nasoanal [S+G: 27,5 ± 0,7; S+H: 24,5 ± 0,4*; O+G: 27,7 ± 0,7; O+H: 24,6 ± 1,0* (cm)], sem alterar os valores de pressão arterial [S+G: 126 ± 6,5; S+H: 129 ± 7,6; O+G: 123 ± 4,0; O+H: 131 ±4,2 (mmHg)]. Os valores de concentração plasmática de ureia [S+G: 40,4 ± 9,6; S+H: 55,0 ± 4,8*; O+G: 42,1 ± 6,7; O+H: 42,5 ± 8,8$ (mg/dL)] e creatinina [S+G: 0,35±0,05; S+H: 0,47±0,05*; O+G: 0,38±0,04; O+H: 0,46±0,04* (mg/dL)] foram alterados pelo tratamento sem no entanto alterar o clearance de creatinina [S+G: 6,2 ± 1,2; S+H: 5,8 ± 1,1; O+G: 5,3 ± 0,7; O+H: 5,5 ± 1,4 (ml/min/kg)]. Houve aumento significativo da carga excretada de sódio [S+G: 1,7 ± 0,5; S+H: 3,1 ± 0,8*; O+G: 1,6 ± 0,4; O+H: 3,3 ± 0,4* (µEq/min/kg)], potássio [S+G: 0,53 ± 0,15; S+H: 0,91 ± 0,22*; O+G: 0,51 ± 0,09; O+H: 0,94 ± 0,22* (µEq/min/kg)] e do volume urinário [S+G: 10,9 ± 2,1; S+H: 15,5 ± 2,1*; O+G: 10,4 ±2,3; O+H: 16,4 ± 2,9* (ml/24h)]. Não foram observadas alterações no perfil lipídico e nos valores sanguíneos de pH, pCO2 e bicarbonato. Conclusões: A terapia hormonal cruzada em ratos Wistar machos alterou significativamente as características físicas do animal em consequência da redução do ritmo de crescimento, repercutindo no peso corporal e o comprimento nasoanal. O tratamento com AAEE também aumentou o volume urinário e a excreção de sódio e potássio, provavelmente pelas adaptações renais, e sem repercussão sobre a pressão arterial. O aumento das concentrações plasmáticas de ureia e creatinina pode indicar o início de uma disfunção renal, porém mais avaliações em longo prazo são necessárias para a compreensão das repercussões deste tratamento hormonal sobre a função renal.
The use of hormonal combinations by trans people has been a useful tool for bodily changes during the process of gender transition. The use of these hormones usually occurs through self-medication and few studies assessed the impact of this procedure on the body's systems. OBJECTIVES: this work aimed to evaluate the effects of the chronic administration of a combination of estrogen and progestin, in rats, on blood pressure and renal function parameters. METHODS: Two-month-old male Wistar rats, obtained from CEDEME-UNIFESP, were housed in ventilated cages, in a room with fixed temperature (22°C) and light cycle (alternating the cycle every 12h, starting the period lighting at 7 am), and had free access to food (for rodents - Purina) and water throughout the experimental protocol. The animals were initially submitted to orchiectomy (OQX) or sham surgery (Sham) and then were divided into four experimental groups: S+G - Sham treated with vehicle (sesame oil), S+H - Sham treated with algestone acetofenide and estradiol enanthate (AAEE), O+G - OQX which was treated with vehicle, O+H - OQX which was treated with AAEE. Both sesame oil (G) and AAEE (P) were administered i.m., every 10 days for 5 months. After the treatment, urine samples were collected in metabolic cages and blood samples were collected by puncturing the abdominal aorta. The parameters evaluated were: blood pressure (BP), body weight (BW), nasoanal length (NAL), food (FI) and water intake (WI), lipid profile (triglycerides, LDL, HDL), blood values of pH, pCO2 and bicarbonate, plasma concentrations of urea (URpl) and creatinine (Crpl), urinary volume (V24h), sodium (UNa+) and potassium (UK+) excretion, ammonium, titratable acidity (TA), and proteinuria. Results are expressed as mean±epm. Statistical analysis was performed using ANOVA followed by Tukey's test. The level of significance was set at 5% (p ≤ 0.05). Study approved by CEUA/UNIFESP nº 0573101218. RESULTS: We observed that hormonal treatment significantly reduced body weight [S+G: 462.8 ± 24.4 ; S+H: 324.5 ± 31.1*; O+G: 423.4 ± 78.01; O+H: 291.7 ± 41.3* (g)] and the nasoanal length [S+G: 27.5 ± 0.7; S+H: 24.5 ± 0.4*; O+G: 27.7 ± 0.7; O+H: 24.6 ± 1.0* (cm)], without changing blood pressure values S+G: 126 ± 6.5; S+H: 129 ± 7.6; O+G: 123 ± 4.0; O+H: 131 ±4.2 (mmHg)]. The values of plasma urea concentration [S+G: 40.4 ± 9.6; S+H: 55.0 ± 4.8*; O+G: 42.1 ± 6.7; O+H: 42.5 ± 8.8% (mg/dL)] and creatinine [S+G: 0.35 ± 0.05; S+H: 0.47±0.05*; O+G: 0.38±0.04; O+H: 0.46±0.04* (mg/dL)] were increased, however, without changing the creatinine clearance [S+G: 6.2 ± 1.2; S+H: 5.8 ± 1.1; O+G: 5.3 ± 0.7; O+H: 5.5 ± 1.4 (ml/min/kg)]. There was a significant increase in the excreted load of sodium [S+G: 1.7 ± 0.5; S+H: 3.1 ± 0.8*; O+G: 1.6 ± 0.4; O+H: 3.3 ± 0.4* (μEq/min/kg)], potassium [S+G: 0.53 ± 0.15; S+H: 0.91 ± 0.22*; O+G: 0.51 ± 0.09; O+H: 0.94 ± 0.22* (μEq/min/kg)] and urinary volume [S+G: 10.9 ± 2.1; S+H: 15.5 ± 2.1*; O+G: 10.4 ±2.3; O+H: 16.4 ± 2.9* (ml/24h)]. No changes were observed x in the lipid profile and in the blood pH, pCO2 and bicarbonate values. CONCLUSIONS: Cross-hormone therapy in male Wistar rats significantly impacted the animal's physical characteristics as a result of the reduction in the growth rate affecting body weight and nasal-anal length. The treatment also increased urinary volume and sodium and potassium excretion, probably due to renal adaptations. There was no repercussion on blood pressure. Increased plasma urea and creatinine concentrations may indicate the onset of renal dysfunction, but further evaluations are needed to understand the repercussions of this hormonal treatment on renal function.
The use of hormonal combinations by trans people has been a useful tool for bodily changes during the process of gender transition. The use of these hormones usually occurs through self-medication and few studies assessed the impact of this procedure on the body's systems. OBJECTIVES: this work aimed to evaluate the effects of the chronic administration of a combination of estrogen and progestin, in rats, on blood pressure and renal function parameters. METHODS: Two-month-old male Wistar rats, obtained from CEDEME-UNIFESP, were housed in ventilated cages, in a room with fixed temperature (22°C) and light cycle (alternating the cycle every 12h, starting the period lighting at 7 am), and had free access to food (for rodents - Purina) and water throughout the experimental protocol. The animals were initially submitted to orchiectomy (OQX) or sham surgery (Sham) and then were divided into four experimental groups: S+G - Sham treated with vehicle (sesame oil), S+H - Sham treated with algestone acetofenide and estradiol enanthate (AAEE), O+G - OQX which was treated with vehicle, O+H - OQX which was treated with AAEE. Both sesame oil (G) and AAEE (P) were administered i.m., every 10 days for 5 months. After the treatment, urine samples were collected in metabolic cages and blood samples were collected by puncturing the abdominal aorta. The parameters evaluated were: blood pressure (BP), body weight (BW), nasoanal length (NAL), food (FI) and water intake (WI), lipid profile (triglycerides, LDL, HDL), blood values of pH, pCO2 and bicarbonate, plasma concentrations of urea (URpl) and creatinine (Crpl), urinary volume (V24h), sodium (UNa+) and potassium (UK+) excretion, ammonium, titratable acidity (TA), and proteinuria. Results are expressed as mean±epm. Statistical analysis was performed using ANOVA followed by Tukey's test. The level of significance was set at 5% (p ≤ 0.05). Study approved by CEUA/UNIFESP nº 0573101218. RESULTS: We observed that hormonal treatment significantly reduced body weight [S+G: 462.8 ± 24.4 ; S+H: 324.5 ± 31.1*; O+G: 423.4 ± 78.01; O+H: 291.7 ± 41.3* (g)] and the nasoanal length [S+G: 27.5 ± 0.7; S+H: 24.5 ± 0.4*; O+G: 27.7 ± 0.7; O+H: 24.6 ± 1.0* (cm)], without changing blood pressure values S+G: 126 ± 6.5; S+H: 129 ± 7.6; O+G: 123 ± 4.0; O+H: 131 ±4.2 (mmHg)]. The values of plasma urea concentration [S+G: 40.4 ± 9.6; S+H: 55.0 ± 4.8*; O+G: 42.1 ± 6.7; O+H: 42.5 ± 8.8% (mg/dL)] and creatinine [S+G: 0.35 ± 0.05; S+H: 0.47±0.05*; O+G: 0.38±0.04; O+H: 0.46±0.04* (mg/dL)] were increased, however, without changing the creatinine clearance [S+G: 6.2 ± 1.2; S+H: 5.8 ± 1.1; O+G: 5.3 ± 0.7; O+H: 5.5 ± 1.4 (ml/min/kg)]. There was a significant increase in the excreted load of sodium [S+G: 1.7 ± 0.5; S+H: 3.1 ± 0.8*; O+G: 1.6 ± 0.4; O+H: 3.3 ± 0.4* (μEq/min/kg)], potassium [S+G: 0.53 ± 0.15; S+H: 0.91 ± 0.22*; O+G: 0.51 ± 0.09; O+H: 0.94 ± 0.22* (μEq/min/kg)] and urinary volume [S+G: 10.9 ± 2.1; S+H: 15.5 ± 2.1*; O+G: 10.4 ±2.3; O+H: 16.4 ± 2.9* (ml/24h)]. No changes were observed x in the lipid profile and in the blood pH, pCO2 and bicarbonate values. CONCLUSIONS: Cross-hormone therapy in male Wistar rats significantly impacted the animal's physical characteristics as a result of the reduction in the growth rate affecting body weight and nasal-anal length. The treatment also increased urinary volume and sodium and potassium excretion, probably due to renal adaptations. There was no repercussion on blood pressure. Increased plasma urea and creatinine concentrations may indicate the onset of renal dysfunction, but further evaluations are needed to understand the repercussions of this hormonal treatment on renal function.