Background/Purpose: Juvenile idiopathic arthritis (JIA) may be active during reproductive age, therefore ovarian function and future fertility are relevant issues for its female population. Nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility inducing luteinized unruptured follicle syndrome (LUF) in adults rheumatoid arthritis patients however there is no study evaluating this condition in female adolescent and young adults with JIA. Thus, our objective was to assess LUF in three groups: JIA patients with NSAIDs vs. JIA without NSAIDs vs. healthy controls.

Methods: Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 healthy females were studied by pelvic ultrasound repeated 2 to 3 times monitoring for follicular development and ovulation in one menstrual cycle. Exclusion criteria included: presence of current gestation or lactation; hypothalamic-pituitary-ovarian axis dysfunction; end-stage renal disease; contraindication or refusal to suspend the use of hormonal contraceptives for at least 6 months; thyroid diseases; history of surgery or pelvic irradiation or neoplasia; use of gonadotrophin releasing hormone analogs; obesity in virgin patients due to the difficulty of performing the abdominal ultrasonography; polycystic ovarian syndrome; amenorrhea; and presence of another systemic autoimmune disease. JIA patients and healthy controls were systematically assessed for menstrual flow duration and cycle length. LUF syndrome was defined by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of progesterone in blood sample in the luteal phase of the menstrual cycle and LH detected in the urine.

Results: Comparison between JIA patients with (n=8) vs. JIA without NSAIDs (n=15) and healthy controls (n=11) revealed that the frequency of LUF syndrome was significantly higher in the former group [2(25%) vs. 0% vs. 0%, p=0.049)]. Of note, the two patients with LUF syndrome had normal menstrual cycles and used naproxen 500 mg bid. Further comparison between JIA patients with and without NSAIDs, and healthy controls showed similar mean in three groups regarding levels of Anti-Mülerian hormone (AMH) [3.4 (0.47-5.0) vs. 3.4 (0.6-13.9) vs. 3.3 (0.49-10.6) ng/mL, p=0.909], estradiol [43 (32.7-160) vs. 47 (25.8-119) vs. 41.5 (18.9-61) pg/mL, p=0.436], FSH [6.3 (5-10) vs. 6.4 (5-12) vs. 6.8 (4-10), p=0.662], LH [8 (6.3-9.6) vs. 7.7 (4.1-28.7) vs. 7.6 (4.4-14.4) IU/L, p=0.686], antral follicle count [15.5 (8-19) vs. 19 (6-40) vs. 22 (7-33), p=0.240] and ovarian volume mL [6.1 (3.2-7.8) vs. 4.5 (2-15.8) vs. 4.6 (2.8-7.4), p=0.363]. No differences were evidenced in three groups regarding white race, body mass index, duration and length of menstrual cycles (p>0.05). The frequencies of prednisone, methotrexate and biological agents were similar in two JIA groups (p>0.05).

Conclusion: The present study identified an increased incidence of LUF syndrome in JIA patients using NSAIDs. We further demonstrated that reduced ovarian reserve does not seem to contribute to this condition.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/luteinized-unruptured-follicle-syndrome-in-young-female-with-juvenile-idiopathic-arthritis/