Quantitation of the estrogenic effects of mestranol on human endometrium and vaginal mucosa

Abstract

The responses of the vaginal and uterine mucosa to mestranol (MEE) were defined by establishing the karyopyknotic index (KI) and the degrees of endometrial proliferation in 6 menopausal women. Each woman received 3 dosages of MEE (5, 20, and 80 mcg. daily) during consecutive treatment courses lasting 14 days, with a 6 week rest period between courses. A change in the KI occurred between the 5 and 20 mcg. dosage with a rise from a mean of 6.6 to a mean of 42.2. The daily dosage of 80 mcg. caused a further slight rise of the KI, although the maximum proliferation of the vaginal mucosa was not achieved with a mean KI of only 5.38. The 5 mcg. MEE dosage did not induce endometrial proliferation; moderate proliferation occurred with the 20 mcg. dosage; late proliferation to mild hyperplasia was observed with the 80 mcg. dosage. More advanced degrees of proliferation did not occur with the dosages studied. Withdrawal bleeding occurred after the 80 mcg. dosage; only spotting occurred after 20 mcg., and occasional bleeding after the 5 mcg. dosage was caused by the biopsy. The prompt reaction of the KI to a specific dosage makes vaginal cytology suitable for detecting the “threshold” dosage for estrogens. Endometrial changes can be graded more precisely, thus enabling the establishment of a dose-related response.