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  • Title: Exogenous estrogens and endometrial carcinoma: review and comments for the clinician.
    Author: Berger GS, Fowler WC.
    Journal: J Reprod Med; 1977 Apr; 18(4):177-80. PubMed ID: 870690.
    Abstract:
    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." Several published reports on the effect of exogenous estrogen therapy on the development of endometrial carcinoma were reviewed for the conclusiveness of their findings. Smith et.al. from the University of Washington reported in the December 1975 issue of the New England Journal of Medicine that women exposed to estrogen therapy had a 4.5-fold increased risk of developing endometrial cancer. Ziel and Finkle (same issue) from Kaiser Permanente Medical center in Los Angeles calculated a relative risk of 7.6 for women on estrogen therapy. Mack et.al. (June 1976 issue) computed a risk ratio of 8 for women on estrogen therapy. It was suggested that the findings of these three studies were inconclusive because of the elements of bias introduced in the methodologies and interpretative problems encountered during the study. Another published report in the same journal (June 3, 1976 issue) by Weiss et.al. discussed the increased rate of endometrial cancer on selected areas in the United States. Again, it was suggested that the findings were not conclusive because the data used were not reliable. Additional studies are being done on the subject of estrogen therapy and its relation to endometrial cancer. In the meantime, clinicians need guidelines, and caution, on the use of estrogen replacement therapy.
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