Exogenous estrogens and endometrial carcinoma: review and comments for the clinician

It is justifiable to have reservations about the significance of the data available at this time on a possible increase in the risk of a patient's developing endometrial cancer if estrogen replacement therapy has been prescribed for her. Hopefully, additional studies currently being conducted will help to clarify the issue further. In the meantime, clinicians need guidelines on the use of estrogen replacement therapy. Estrogen is indicated in the premenopausal woman who has had surgical or radiation castration for treatment of disease. Menopausal women with severe vasomotor instability or atrophic vaginitis should also be considered for estrogen replacement therapy. In the latter situation, topical administration may be adequate. Contraindications to estrogen replacement include undiagnosed vaginal bleeding, breast cancer history of thromboembolic disease, liver disease, uterine leiomyomata, hypertension, diabetes, migraine headaches or gall bladder disease. In patients for whom estrogens are contraindicated, atrophic vaginitis can be treated with local estrogens and vasomotor symptoms with sedatives such as phenobarbital and belladonna. Before estrogen treatment is begun, a medical history and physical examination that look for possible contraindications are required. Obviously, any woman with abnormal uterine bleeding in the menopausal age group requires a procedure that provides tissue for histopathologic examination. Although postmenopausal women taking estrogen may have uterine bleeding related to the hormone, such bleeding cannot be assumed to be due to the therapy and always requires evaluation. The lowest dose effective in controlling a patient's symptoms should be administered, preferably in cyclic fashion. Whether the addition of a progestational compound at cyclic intervals has a beneficial effect on the endometrium is a matter of conjecture at this time. Requirement for continuing therapy should be reevaluated at least on an annual basis and preferably more often. In conclusion, a quote from Graber and Barber is appropriate: "The entire picture of routine postmenopausal estrogen therapy is in a state of complete confusion. We must proceed with circumspection and caution. We need less passion, fewer hypotheses, and more facts."