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Objective: To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. Methods: Fifty-one adult cSLE (ACR 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 cSLE and controls. Regarding mineralocorticoid/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) μg/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 cSLE 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. Key Points • cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. • Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants. [ABSTRACT FROM AUTHOR]