Adverse Endometrial Effects of Long-Cycle Estrogen and Progestogen Replacement Therapy

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Abstract
Treatment with unopposed estrogen is known to increase the risk of endometrial hyperplasia, atypia, and carcinoma, and therefore the administration of a progestogen during hormone-replacement therapy is recommended.1,2 The addition of a progestogen may cause unwanted monthly bleeding, changes in mood, and other side effects.3 To improve compliance during hormone-replacement therapy, various long-cycle regimens of progestogen therapy are used in clinical practice. However, there are few controlled studies of the safety of such treatment as regards the endometrium, and only one study has been carried out for more than two years.4,5 We present here preliminary data from the Scandinavian LongCycle Study, which was recently discontinued because of the unsatisfactory safety profile of the long-cycle hormone-replacement regimen.