ORAL N-ACETYLCYSTEINE FOR MENSTRUAL PAIN IN ADOLESCENTS: A RANDOMIZED CONTROLLED STUDY OF OXIDATIVE STRESS REDUCTION WITHOUT HORMONAL MODULATION.

BACKGROUND

Primary dysmenorrhea is painful menstruation without recognizable pelvic disease that is extremely frequent in adolescents and managed with NSAIDs or hormonal management. In this age group, however, such treatments are ill-tolerated or inappropriate. There is mounting evidence that oxidative stress may be a cause of menstrual pain, which implies the growing interest in the non-hormonal use of antioxidants.

OBJECTIVE

The aim of the study was to assess the effectiveness and safety of oral N-acetylcysteine (NAC), a glutathione precursor and a potent antioxidant in decreasing menstrual pain and oxidative stress among adolescents with primary dysmenorrhea.

METHODS

50 adolescents aged 13-19 years with moderate to severe dysmenorrhea were randomly assigned to either NAC (600 mg twice daily, five days, starting with menstrual period in three menstrual cycles) or placebo in this randomized, double-blind, placebo-controlled trial. The severity of pain was measured on a 0-10 visual analogue scale (VAS) on a daily basis. Secondary outcomes were NSAID use and urinary concentrations of the oxidative stress marker 8-iso-prostaglandin F₂α adjusted by creatinine.

RESULTS

There were no differences between the two groups in baseline. In the three cycles, NAC group was found to have significantly low mean VAS scores in comparison to the placebo group (4.6±1.3 vs. 5.9±1.1, p<0.001). Use of rescue ibuprofen was also markedly lower with NAC (666.7±445.1 mg vs. 1,299.7±626.6 mg per cycle, p<0.001), along with fewer NSAID-use days per cycle (1.5 vs. 2.4, p=0.004). Urinary 8-iso-PGF₂α levels were significantly reduced in the NAC group as well (0.6±0.2 vs. 0.8±0.2 ng/mg Cr, p=0.010). Multivariate analysis found treatment assignment to be an independent predictor of the pain and oxidative stress reductions.

CONCLUSIONS

Oral NAC during menstruation reduced the intensity of pain, biomarkers of oxidative stress, and NSAID use in adolescents with primary dysmenorrhea significantly. Such results make NAC a safe, non-hormonal, and mechanistically plausible intervention. Further research is required to prove long-term benefit and to directly compare NAC to other antioxidant interventions.