Non-steroidal anti-inflammatory drug induces luteinized unruptured follicle syndrome in young female juvenile idiopathic arthritis patients.
Level 3 - non-randomized controlled study
Prospective non-randomized comparative cohort study
PubMed 30003441 · doi:10.1007/s10067-018-4208-x
What was done
Pelvic ultrasound monitoring, urinary luteinizing hormone (LH), and luteal-phase serum progesterone were prospectively evaluated across one menstrual cycle in 23 adolescent and young adult female patients with juvenile idiopathic arthritis (JIA; 8 receiving NSAIDs, 15 not receiving NSAIDs) and 11 healthy female controls. The primary outcome was luteinized unruptured follicle (LUF) syndrome, defined as a dominant ovarian follicle without rupture despite elevated luteal progesterone and urinary LH surge. Ovarian reserve markers and baseline hormone levels were also compared.
What was found
LUF syndrome occurred in 2 of 8 (25%) JIA patients on NSAIDs versus 0 of 15 (0%) JIA patients without NSAIDs and 0 of 11 (0%) healthy controls (p = 0.049). Both affected patients were taking naproxen 500 mg twice daily. No statistically significant differences were observed across the three groups for anti-Müllerian hormone (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), antral follicle count (p = 0.240), or ovarian volume (p = 0.363). Disease duration between JIA patients with and without NSAIDs was comparable (19.8 vs. 13 years, p = 0.232).
Why it matters
This study shows that NSAID therapy (such as naproxen) may cause reversible ovulatory failure via LUF syndrome in young JIA patients, even in the presence of normal menstrual cycles and normal ovarian reserve markers.
Limits
The sample size was very small (total n = 34, with only 8 patients taking NSAIDs), yielding only two observed events. The study evaluated only a single menstrual cycle, lacked a prospective medication discontinuation and rechallenge protocol to prove reversibility, and did not assess long-term pregnancy outcomes.
Cited by
- supports Taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen around the time of ovulation can inhibit the acute inflammatory cascade and prevent the ovarian follicle from rupturing.