Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II
Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II
The investigators want to test whether treatment with a natural progesterone intravaginally
 increases the cure rate of cervical intraepithelial neoplasia grade I and II.
Background:

 1. The development of cervical intraepithelial neoplasia (CIN) was linked to a decreased
 local immune response as evidenced by a decrease of Langerhans' cell (LC) count in the
 cervical epithelium. Preliminary studies show that vaginally administered progesterone
 locally increases the number of LCs.

 2. There is no accepted treatment strategy of low grade CIN, i.e., CIN I and II, than await
 spontaneous regression.

 Thus, vaginal progesterone is expected to increase the regression rate of cervical dysplasia
 grade I and II.

 Outcome parameters:

 Primary outcome parameters:

 To evaluate whether or not a treatment with vaginal progesterone increases regression and
 remission rates of CIN I and II during a 6-month treatment period.

 Secondary outcome parameters:

 Change of immunohistochemically detected expression of LCs in CIN.

 Methods:

 Prospective phase II trial with vaginal progesterone as treatment of CIN I and II. 60
 patients receive vaginal micronized progesterone 400mg 1x daily for 10 days/month from
 menstrual cycle day 16-25 for 6 months. After 3 and 6 months patients are examined for
 possible regression, persistence, or progression of disease and treated accordingly.
 Treatment of patients with progressing CIN is being discontinued after 3 months. Follow-up of
 patients is ensured based on current clinical practice, i.e., regular outpatient visits every
 3 months, until the lesion completely regresses.

 Diagnosis and main inclusion criteria:

 CIN I and II diagnosed by punch biopsy, lesion fully visible, otherwise healthy subjects < 60
 years, no history of breast cancer, patient's compliance

 Medication:

 Micronized progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16-25

 Duration of treatment:

 6 months
Inclusion Criteria:

 1. Histological evidence of CIN I and II

 2. Transformation zone and lesion margins fully visible

 3. Compliant subject

 4. Safe contraception

 5. Negative pregnancy test

 Exclusion Criteria:

 Lesion related

 1. CIN III, (micro)-Invasive Cancer

 2. Endocervical lesion, upper margin of lesion not visible on colposcopy

 3. Non-compliance of patient

 4. PAP V

 Drug related

 1. Age > 60

 2. Hypersensitivity to progesterone or any component of the formulation

 3. Thrombophlebitis

 4. Undiagnosed vaginal bleeding

 5. Carcinoma of the breast

 6. Cerebral apoplexy

 7. Severe liver dysfunction

 8. Pregnancy

 9. Depression

 10. Diabetes

 11. Epilepsy

 12. Migraine

 13. Renal dysfunction

 14. Asthma

 15. HIV infection

 16. Hepatitis B or C

 17. Concurrent use of anticoagulants

 18. Uncontrolled hypertension (> 160/90 mmHg)

 19. Breast cancer in personal history

 20. Concurrent hormonal therapy including OC

 Clinical laboratory related

 1. Hemoglobin < 11 g/dl

 2. Leukocytes < 4,0 x 109/L

 3. Platelet count < 100 x 109/L

 4. Serum bilirubin > 2 x above upper cut-off value

 5. Serum GOT > 2 x above upper cut-off value

 6. Serum GPT > 2 x above upper cut-off value

 7. Serum alkaline phosphatase > 2 x above upper cut-off value

 8. Serum creatinine > 2 x above cut-off value