Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives

Forty-seven young women with mild or moderate dysplasia of the uterine cervix (cervical intraepithelial neoplasia) diagnosed by cervical smears, received oral supplements of folic acid, 10 mg, or a placebo (ascorbic acid, 10 mg) daily for 3 months under double-blind conditions. All had used a combination-type oral contraceptive agent for at least 6 months and continued it while returning monthly for follow-up examinations. All smears and a biopsy obtained at the end of the trial period were classified by a single observer without knowledge of treatment status using an arbitrary scoring system (1 normal, 2 mild, 3 moderate, 4 severe, 5 carcinoma in situe). Mean biopsy scores from folate supplemented subjects were significantly better than in folate-unsupplemented subjects (2.28 versus 2.92, respectively; p less than 0.05). Final versus initial cytology scores were also significantly better in supplemented subjects (1.95 versus 2.32, respectively; p less than 0.05), unchanged in patients receiving the placebo (2.27 versus 2.30, respectively). Before treatment the mean red cell folate concentration was lower among oral contraceptive agent users than nonusers (189 versus 269 ng/ml, respectively; p less than 0.01) and even lower among users with dysplasia (161 versus 269 ng/ml, respectively; p less than 0.001). Morphological features of megaloblastosis were associated with dysplasia and also improved in folate supplemented subjects. These studies indicate that either a reversible, localized derangement in folate metabolism may sometimes be misdiagnosed as cervical dysplasia, or else such a derangement is an integral component of the dysplastic process that may be arrested or in some cases reversed by oral folic acid supplementation.