Endometrial pathology and its relation to estrogen therapy in patients with hypogonadism

From this study, it appears that total lifetime dose, duration of therapy, and estrogen dose at the time of examination were important factors influencing endometrial histology in patients receiving exogenous estrogens. Our patients were shown to be at statistically greater risk for abnormal endometrial biopsy findings if (1) they had received a lifetime dose of conjugated estrogens ≥2,500 mg, (2) the duration of their estrogen therapy was more than seven years, and (3) their dose of conjugated estrogens at the time of biopsy was > 1.25 mg/day. Almost all of our patients had recieved sequential estrogen-progesterone therapy. The progestational agent given at the dose and in the fashion described above did not appear to protect the patients from development of endometrial pathology. Control groups of patients receiving unopposed estrogens are lacking, and therefore we cannot speculate on whether the incidence of endometrial changes was decreased by the progestational agent. The total lifetime dose of progestational agent was not significantly different in the three grades of endometrial histology despite the fact that the estrogen dose was almost twice as high in the hyperplasia group (grade III) than in groups with normal endometrium (grades I and II). Although both the dose of estrogens and the duration of therapy were found to be statistically important factors increasing risk of endometrial pathology, it remains to be shown whether patients receiving low doses of estrogen for long durations are at risk of developing endometrial abnormalities. On the basis of these data, we would like to suggest that estrogen therapy should be maintained at the lowest possible therapeutic dose level (the level that will maintain regular cyclic bleeding). Further, patients receiving estrogen-progesterone therapy should have endometrial biopsy periodically to determine if there is a silent endometrial abnormality.