Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II

Background:

• 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.
• 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

• Histological evidence of CIN I and II
• Transformation zone and lesion margins fully visible
• Compliant subject
• Safe contraception
• Negative pregnancy test

Exclusion criteria

Lesion related

• CIN III, (micro)-Invasive Cancer
• Endocervical lesion, upper margin of lesion not visible on colposcopy
• Non-compliance of patient
• PAP V

Drug related

• Age > 60
• Hypersensitivity to progesterone or any component of the formulation
• Thrombophlebitis
• Undiagnosed vaginal bleeding
• Carcinoma of the breast
• Cerebral apoplexy
• Severe liver dysfunction
• Pregnancy
• Depression
• Diabetes
• Epilepsy
• Migraine
• Renal dysfunction
• Asthma
• HIV infection
• Hepatitis B or C
• Concurrent use of anticoagulants
• Uncontrolled hypertension (> 160/90 mmHg)
• Breast cancer in personal history
• Concurrent hormonal therapy including OC

Clinical laboratory related

• Hemoglobin < 11 g/dl
• Leukocytes < 4,0 x 109/L
• Platelet count < 100 x 109/L
• Serum bilirubin > 2 x above upper cut-off value
• Serum GOT > 2 x above upper cut-off value
• Serum GPT > 2 x above upper cut-off value
• Serum alkaline phosphatase > 2 x above upper cut-off value
• Serum creatinine > 2 x above cut-off value