Treatment with vaginal progesterone in women with low-grade cervical dysplasia: a phase II trial.

BACKGROUND The development of low-grade cervical dysplasia (CIN I) has been linked to a decrease of apoptosis and Langerhans cell (LC) count in the cervical epithelium and to an increase in the expression of various adhesion molecules. Vaginally administered progesterone locally increases apoptosis and the number of LCs, and reduces the expression of various adhesion molecules. We hypothesized that vaginal progesterone would increase the regression rate in women with CIN I. MATERIALS AND METHODS A non-randomized, open phase II trial with vaginal progesterone as treatment of CIN I was performed. Forty women were treated with vaginal micronized progesterone at 400 mg daily for 10 days/month from menstrual cycle day 16-25 for 6 months. The control group consisted of 96 consecutive women with CIN I treated prior and after the study period. After 3 and 6 months, all women were examined for regression, persistence, or progression of disease. Women were treated according to standard clinical protocols. In cases of progressive disease, a large loop excision of the transformation zone (LLETZ) was performed. RESULTS The mean (standard deviation) age of women in the treatment and control groups was 32.0 (7.6) and 32.6 (8.5) years, respectively. A total of 30% and 38.3% of CIN I regressed in the treatment and control group, respectively. In a multivariate model, a higher number of children, a higher lifetime number of sexual partners, a lower age at first intercourse, non-use of condoms as contraception, current smoking, and treatment with vaginal progesterone were associated with a higher probability of having persistent or progressive CIN. Current smoking and treatment with vaginal progesterone were associated with a higher probability of undergoing LLETZ. CONCLUSION Treatment with vaginal progesterone is associated with a lower rate of disease regression and a higher rate of surgical interventions in women with CIN I. We suggest that vaginal progesterone treatment should not be applied in women with known dysplasia.