Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial

Double-blind, randomized, placebo-controlled trial in women with low-grade cervical cytological abnormalities (borderline changes or mild dyskaryosis) identified through the Cervical Screening Wales program. Participants aged 19–65 (mean ~36). Randomization 2:1 to DIM vs placebo; 603 women randomized between Oct 2004 and Dec 2007; follow-up included colposcopy at 6 months.

Diindolylmethane (BioResponse DIM), 150 mg daily for 6 months; taken orally in capsules.

DIM did not significantly reduce CIN2+ at 6 months (8.8% vs 12.4%; RR 0.70, 95% CI 0.4–1.2). CIN3+ 4.6% vs 5.1% (RR 0.9, 95% CI 0.4–2.0). Negative cytology/colposcopy/HPV at 6 months: 27.3% vs 34.3% (RR 0.8, 95% CI 0.6–1.0). Among baseline HPV-positive women, 69% remained HPV-positive with DIM vs 61% with placebo (RR 1.1, 95% CI 0.9–1.4). DIM was generally well tolerated; darkening of urine more common. Short-term DIM (150 mg daily) is well tolerated but unlikely to affect cytology or HPV infection, with inconclusive impact on CIN2+.

Main limitation is lack of power for the primary endpoint CIN2+ due to under-recruitment (603 randomized; ~30% power). Early stopping for funding; substantial loss to follow-up/missing 6-month data; heterogeneity from pragmatic design; no baseline biopsy performed to avoid altering standard care.