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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-17112023-131207
Document
Author
Full name
Daniela Mencaroni Rodrigues Lourenço
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Brentani, Alexandra Valeria Maria (President)
Gormezano, Natali Weniger Spelling
Kozu, Katia Tomie
Sallum, Adriana Maluf Elias
Title in Portuguese
Avaliação da esteroidogênese adrenal e ovariana em mulheres adultas com lúpus eritematoso sistêmico juvenil
Keywords in Portuguese
Fertilidade
Hormônios
Lúpus eritematoso sistêmico
Prednisona
Reserva ovariana
Abstract in Portuguese
Objetivo: Avaliar a esteroidogênese adrenal mineralocorticoide, glicocorticoide e androgênica em pacientes adultos que apresentaram lúpus eritematoso sistêmico de início juvenil (LESj) e o possível efeito da prednisona sobre os hormônios adrenais e a reserva ovariana. Métodos: Cinquenta e um adultos que apresentaram LESj (critérios do Colégio Americano de Reumatologia) e 23 controles saudáveis foram avaliados para esteroidogênese adrenal, incluindo os mineralocorticoides (progesterona, desoxicorticosterona, aldosterona), glicocorticóide (17-OHprogesterona, 11-desoxicortisol, cortisol) e androgênio (androstenediona, sulfato de dehidroepiandrosterona, testosterona total e dihidrotestosterona). A avaliação da reserva ovariana incluiu hormônio folículo estimulante (FSH), estradiol, hormônio anti-Mülleriano, volumes ovarianos e contagem de folículos antrais. Resultados: A mediana da idade atual [29,11 (19-39,8) vs. 30,8 (19,6-42,1) anos, p=0,502] foi semelhante em adultos LESJ e controles. Em relação aos hormônios mineralocorticoide e glicocorticoide, as medianas da progesterona (p=0,003), 17-OH progesterona (p<0,001) e 11-desoxicortisol (p=0,036) foram significantemente menores nos pacientes em comparação aos controles. Todos os hormônios da esteroidogênese androgênica foram reduzidos no primeiro grupo [sulfato de deidroepiandrosterona (p<0,001), androstenediona (p=0,001), testosterona total (p=0,005) e diidrotestosterona (p<0,001)]. Comparações adicionais de pacientes com e sem uso atual de prednisona e controles revelaram um impacto predominante sobre os glicocorticóides adrenais e esteroidogênese androgênica, pacientes sob este medicamento apresentaram níveis reduzidos de 17-OH progesterona [0,17 (0-0,5) vs. 0,27 (0,1-2,9) vs. 0,33 ( 0,1-0,8) ng/mL, p<0,001], sulfato de dehidroepiandrosterona [0,155 (0-0,6) vs. 0,49 (0,1-1,6) vs. 1,11 (0,1-2,6) mg /mL,p<0,001], androstenediona [0,56 (0,2-4,4) vs. 1,7 (0,5-4,5) vs. 2,33 (0,3-3,8) ng/mL, p<0,001], testosterona total [12 (12-167) vs. 16 (12-28) vs.(16,5 (0-50) ng/dL, p=0,002] e di-hidrotestosterona [92,68 (11,8-198,5) vs. 160,62 (37,9-842,1) vs. 188,3 (71,3-543,9) pg/ml, p<0,001. Além disso, os pacientes em uso de prednisona também tiveram volumes ovarianos medianos reduzidos [4,14 (2-12) vs. 7,13 (2-25,7) vs. 5,18 (2,4-17,3) cm3, p=0,028) o que não foi associado com dose cumulativa de ciclofosfamida (p>0,05). A dose mediana de prednisona foi 15/mg/dia (2,5-40). Conclusão: Fornecemos novas evidências de que os pacientes com LESJ apresentam um comprometimento da esteroidogênese adrenal em relação ao grupo controle. Além disso, o uso de prednisona baixo/moderado parece estar subjacente a essas anormalidades e pode afetar adversamente a produção dos hormônios da suprarrenal e a reserva ovariana, independentemente do uso de outros imunossupressores
Title in English
Adrenal steroidogenesis and ovarian reserve in adult childhood-onset systemic lupus erytematosus patients
Keywords in English
Fertility
Hormones
Ovarian reserve
Prednisone
Systemic lupus erythematosus
Abstract in English
Objective: To assess overall adrenal mineralocorticoid, glucocorticoid and androgen steroidogenesis in juvenile systemic lupus erythematosus (jSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. Methods: Fifty-one adult jSLE (American College of Rheumatology criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count. Results: The median of current age [29.11 (19-39.8) vs. 30.8 (19.6-42.1) years, p=0.502] was similar in adult jSLE and controls. Regarding mineralocorticoid and glucocorticoid, the median of progesterone (p=0.003), 17-OH progesterone (p<0.001), and 11-desoxycortisol (p=0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p<0.001), androstenedione (p=0.001), total testosterone (p=0.005), and dihydrotestosterone (p<0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0-0.5) vs. 0.27 (0.1-2.9) vs. 0.33 (0.1-0.8) ng/mL, p<0.001], dehydroepiandrosterone-sulfate [0.155 (0-0.6) vs. 0.49 (0.1-1.6) vs. 1.11 (0.1-2.6) g/mL, p<0.001], androstenedione [0.56 (0.2-4.4) vs. 1.7 (0.5-4.5) vs. 2.33 (0.3-3.8) ng/mL, p<0.001], total testosterone [12 (12-167) vs. 16 (12-28) vs. (16.5 (0-50) ng/d, p=0.002], and dihydrotestosterone [92.68 (11.8-198.5) vs. 160.62 (37.9-842.1) vs. 188.3 (71.3-543.9) pg/ml, p<0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2-12) vs. 7.13 (2-25.7) vs. 5.18 (2.4-17.3) cm3, p=0.028) that was not associated with cyclophosphamide cumulative dose (p>0.05). The median prednisone dose was 15/mg/day (2.5-40). Conclusions: We provided novel evidence that jSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants
 
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Publishing Date
2023-11-24
 
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