Estrogen Replacement Therapy - 1

Abstract

To the Editor: I read with interest the article on hormone replacement therapy by Evans and colleagues, which was published in the August 1995 issue of the Mayo Clinic Proceedings (pages 800 to 805). They stated that, in women with a past history of endometrial cancer, estrogen replacement therapy may be indicated to decrease morbidity and mortality from atherosclerosis and osteoporosis. A more cautious viewpoint of estrogen replacement therapy is that postmenopausal women with a prior history of endometrial cancer may represent a subset of women who require no exogenous estrogens. Postmenopausal obese women represent the major group at risk for endometrial cancer.1Wynder EL Escher GC Mantel N An epidemiological investigation of cancer of the endometrium.Cancer. 1966; 19: 489-520Crossref PubMed Scopus (236) Google Scholar Unopposed estrogen excess due to endogenous conversion of adrenal androgens to estrogens by adipose tissue aromatase is the pathophysiologic event responsible for the development of endometrial cancer. The amount of estrogen production correlates with the degree of obesity. These women are not estrogen deficient and may have sufficient levels of estrogen to prevent atherosclerosis and osteoporosis. Pettersson and associates2Pettersson B Bergstrom R Johansson ED Serum estrogens and androgens in women with endometrial carcinoma.Gynecol Oncol. 1986; 25: 223-233Crossref PubMed Scopus (29) Google Scholar compared 52 postmenopausal women in whom endometrial cancer had been recently diagnosed with 58 postmenopausal age-matched control subjects. The patients with endometrial cancer had significantly higher estradiol levels and lower follicle-stimulating hormone levels; levels of steroid hormone-binding globulin also tended to be lower in these patients. Ovariectomy, a component of the therapy for endometrial cancer, does not decrease baseline preoperative estrogen levels in postmenopausal patients. Judd and coworkers3Judd HL Lucas WE Yen SS Serum 17 beta-estradiol and estrone levels in postmenopausal women with and without endometrial cancer.J Clin Endocrinol Metab. 1976; 43: 272-278Crossref PubMed Scopus (137) Google Scholar described 16 postmenopausal women with endometrial cancer before and after ovariectomy; estradiol (13.5 versus 14.1 pg/mL, respectively) and estrone (33.8 versus 39.5 pg/mL, respectively) levels were not significantly different. Patients with endometrial cancer ultimately have a decreased risk for the development of osteoporosis and fracture. Laufer and colleagues4Laufer LR Davidson BJ Ross RK Lagasse LD Siiteri PK Judd HL Physical characteristics and sex hormone levels in patients with osteoporotic hip fractures or endometrial cancer.Am J Obstet Gynecol. 1983; 145: 585-590PubMed Scopus (25) Google Scholar described significant differences in the following factors that favored patients with endometrial cancer (N = 25) in comparison with patients who had hip fractures (N = 25): weight, estrone and estradiol levels, free estradiol levels, and sex hormone-binding globulin levels. A population-based cohort5Persson I Naessen T Adami HO Bergstrom R Lagrelius A Mollerstrom G et al.Reduced risk of hip fracture in women with endometrial cancer.Int J Epidemiol. 1992; 21: 636-642Crossref PubMed Scopus (16) Google Scholar of 2,111 women diagnosed with endometrial cancer demonstrated a reduced relative risk (standardized incidence ratio, 0.6; 95% confidence interval, 0.5 to 0.8) of hip fracture; a case-control analysis within this cohort suggested that a trend of higher weight provided a more protective effect than lower weight. Protection for these women seemed to persist into advanced age. Careful assessment of symptoms (for example, vasomotor symptoms) and signs (for example, vaginal atrophy) is an important strategy for determining the individual need for estrogen replacement therapy in women with a history of endometrial cancer. The issue is whether these women need estrogen replacement therapy based on the endocrine pathogenesis of the disease.