A long-term study of regression of precancerous lesions under oral progestin medication: observations on the prevalence of carcinoma in situ and dysplasia in private versus planned parenthood groups.

PIP: This study is concerned with the relationship of the oral progestins to cancer of the cervix and endometrium and to establish the effect of long-term use of the pill on lesions of carcinoma in situ or dysplasia. A screening study was made of 1696 women attending the Nassau County Planned Parenthood Clinic. Patients with negative cytology were advised to have a routine check in 6 to 12 months. Those with positive cytology who were also found to have advanced or progressive lesions were referred for surgical treatment. Patients showing cells of moderate dysplasia or carcinoma in situ were referred to the Cancer Prevention Clinic where they could elect immediate surgical treatment or experimental treatment with an oral contraceptive. Almost all, 68 in number, chose to defer surgery. They visited the clinic at 4 to 6 week intervals when an examination, a Paanicolaou smear and fluorescent microscopic DNA of nuclear patterna were done. While under study no premalignant lesion progressed to a stage of infiltration. Clinically none showed lesions suggestive of early cancer. Of this group 45 showed no alteration in growth, of cells while 21 had signs of regression, some to a normal morphology. Progression occurred in 2 patients. Of these 1 followed a 4 month interval without oral progestin medication. The greater prevalence of positive findings in patients attending Planned Parenthood Clinics as compared with those being treated by private practitioners is attributed to the types of patients being tested. The clinics see mostly patients of lower socioeconomic status, those who have been more sexually active and those who have begun sexual activities at an early age with more sexual partners. These findings are consistent with the theory of viral transmission of cancer of the cervix by sexual intercourse. After over 8 years of study the authors conclude that the pill does not initiate or accelerate precancerous growth but that the oral progestins at high dose levels show some cancer-inhibiting or regressive influences, often dramatic. Al so they think that the existence of dysplasia or cancer in situ in women attending clinics antedates the taking of the pill, perhaps by several years.^ieng

Influence of norethynodrel and mestranol upon cervical dysplasia and carcinoma in situ.

PIP: A 3-year progress investigation of the results of continuing serial cytologic, cytochemical, colposcopic, histologic, and clinical studies i nvolving 782 women is reported. These patients were selected from 60,00 0 women by a cytodiagnostic screening group before medication was given. The drug used was the steroid contraceptive Enovid, a combination of 9.85 mg norethynodrel with .15 mg mestranol. The usual daily dose of Enovid was 2, 5, or 10 mg orally. Tablets were taken in 20 doses from D ay 5 to Day 24 of the menstrual cycles. In some, continuous therapy was given at the same dosage for 60-240 days. Response was not related to dosage. Medication was begun after a cell-diagnosis was made. Frequent periodic examinations were made of cells scraped from the squamo-columnal junction of the cervix. This method was considered much more accurate than smears from the vaginal area. Some were followed for 3-4 years. No case was found in which a lesion progressed to a stage of infiltration. In the 654 women found to have normal cytology, Enovid therapy appeared to have exerted no unfavorable influence. Of the 66 women who had preexisting inflammatory lesions with precancerous tendencies, slight progression was noted in 2 (6%) and remission in 20 (30%). In 42 (64%) no change was found after Enovid medication. Of 60 patients having marked dysplasia of cells or with beginning carcinoma in situ, 3 (5%) showed remission, 15 (25%) showed fluctuation of findings, and 42 (70%) showed unaltered expected progression. Cytochemical investigations included continuing fluorescent microscopic studies to evaluate changing levels of DNA and RNA, glycogen studies, and micropolysaccharide evaluations. It is concluded that Enovid showed no carcinogenic influence even in preexisting premalignant dysplasia or carcinoma in situ of the cervix. However, periodic examinations with cervical cytologic studies are recommended for those under Enovid medication.^ieng