Graded sequential therapy in the menopause: A double-blind study

A sequential formulation of estrogen and progestogen was graded in dosage to mimic the natural ovarian cycle and tested in menopausal patients. Three preparations, one containing 1,400 mcg. of mestranol in a 28 day cycle, one containing 700 mcg. of mestranol in a 28 day cycle, one containing only a placebo, and all three looking exactly alike, were compared with the use of a carefully controlled double-blind technique. This innovative and logical approach to estrogen relacement therapy was found to be effective in relieving vasomotor symptoms and was well tolerated. The lower-dosage formulation and nervousness. The higher dosage caused a significant in relieving hot flushes and nervousness. The higher dosage caused a significant increase in breast soreness. Withdrawal bleeding simulated normal menstruation with both dosage levels. Breakthrough bleeding was rare in both. Although the two regimens increased corticosteroid-binding globulin, the effect on this plasma protein was slight with the lower estrogen level. Our lower-dosage, graded, sequential estrogen-progestogen formulation seems acceptable for physiologic replacement therapy in the menopausal woman.