Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate Wulf H Utian, M.D.,

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Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate Wulf H Utian, M.D., Ph.D., Donna Shoupe, M.D., Gloria Bachmann, M.D., Joanne V Pinkerton, M.D., James H Pickar, M.D. Fertility and Sterility Volume 75, Issue 6, Pages 1065-1079 (June 2001) DOI: 10.1016/S0015-0282(01)01791-5

Figure 1 Mean daily number of hot flushes by week are shown for the eight treatment groups. (A), The placebo and the CEE alone groups. (B), The placebo and the CEE/MPA groups. Data are adjusted for baseline. All values for mean number of hot flushes (unadjusted) were significantly less than baseline (P<.05), except CEE 0.3/MPA 1.5 at week 1. ∗Difference from placebo was significant (P<.05) from weeks 2 through 12. †Difference from placebo was significant (P<.05) from weeks 3 through 12. ‡Difference between CEE 0.45 and CEE 0.45/MPA 2.5 was significant (P<.05) at weeks 3, 4, 5 and 9. §Difference between CEE 0.625 and CEE 0.45 was significant (P<.05) from weeks 2 through 12. ∥Difference between CEE 0.625 and CEE 0.3 was significant (P<.05) at weeks 4, 5, 6, 9, 10, and 12. Utian. Lower HRT doses. Fertil Steril 2001. Fertility and Sterility 2001 75, 1065-1079DOI: (10.1016/S0015-0282(01)01791-5)

Figure 2 Mean daily number of hot flushes by cycle are shown for the eight treatment groups. (A), The placebo and the CEE alone groups. (B), The placebo and the CEE/MPA groups. Data are adjusted for baseline. All values for mean number of hot flushes (unadjusted) were significantly less than baseline (P<.05) in all groups. ∗Difference from placebo was significant (P<.05) for all cycles. †Difference from placebo was significant (P<.05) for all cycles except cycle 1. ‡Difference from placebo was significant (P<.05) for all cycles except cycle 6. §Difference between CEE 0.625 and CEE 0.45 was significant (P<.05) at cycles 1 through 3 and 9 through 13. ∥Difference between CEE 0.625 and CEE 0.3 was significant (P<.05) at cycles 3, 5, and 6. ¶Difference between CEE 0.45 and CEE 0.45/MPA 2.5 was significant (P<.05) at cycles 2 and 3. #Difference between CEE 0.3 and CEE 0.3/MPA 1.5 was significant (P<.05) at cycle 5. Utian. Lower HRT doses. Fertil Steril 2001. Fertility and Sterility 2001 75, 1065-1079DOI: (10.1016/S0015-0282(01)01791-5)

Figure 3 Mean daily severity of hot flushes by week for the eight treatment groups. (A), The placebo and the CEE alone groups. (B), The placebo and the CEE/MPA groups. Data are adjusted for baseline. All values for mean severity of hot flushes (unadjusted) were significantly less than baseline (P<.05), except CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5 at weeks 1 and 2, and placebo at weeks 1, 2, and 4. ∗Difference from placebo was significant (P<.05) from weeks 2 through 12. †Difference from placebo was significant (P<.05) from weeks 3 through 12. ‡Difference between CEE 0.625 and MPA 0.45 was significant (P<.05) at weeks 3 through 5 and 8 through 12. §Difference between CEE 0.45 and CEE 0.45/MPA 2.5 was significant (P<.05) at week 5 and weeks 8 through 12. ∥Difference between CEE 0.625 and CEE 0.3 was significant (P<.05) at weeks 4 through 7 and 9 through 12. ¶Difference between CEE 0.625/MPA 2.5 and CEE 0.3/MPA 1.5 was significant (P<.05) at weeks 4 and 9. #Difference between CEE 0.45/MPA 2.5 and CEE 0.3/MPA 1.5 was significant (P<.05) at weeks 4 through 6 and weeks 8 and 9. Utian. Lower HRT doses. Fertil Steril 2001. Fertility and Sterility 2001 75, 1065-1079DOI: (10.1016/S0015-0282(01)01791-5)

Figure 4 Mean daily severity of hot flushes by cycle for the eight treatment groups. (A), The placebo and the CEE alone groups. (B), The placebo and the CEE/MPA groups. Data are adjusted for baseline. All values for mean severity of hot flushes (unadjusted) were significantly less than baseline (P<.05) for all cycles. ∗Difference from placebo was significant (P<.05) from cycles 1 through 13. †Difference between CEE 0.625 and CEE 0.45 was significant (P<.05) at all cycles. ‡Difference between CEE 0.625 and CEE 0.3 was significant (P<.05) from cycles 2 through 13. §Difference between CEE 0.45 and CEE 0.45/MPA 2.5 was significant (P<.05) at cycles 2, 3, 5, and 9. ∥Difference between CEE 0.3 and CEE 0.3/MPA 1.5 was significant (P<.05) at cycles 4 through 7 and 9 through 13. ¶Difference between CEE 0.45/MPA 2.5 and CEE 0.3/MPA 1.5 was significant (P<.05) at cycle 2. Utian. Lower HRT doses. Fertil Steril 2001. Fertility and Sterility 2001 75, 1065-1079DOI: (10.1016/S0015-0282(01)01791-5)

Figure 5 Box and whisker plots of median change from baseline in VMI for superficial cells (%) at cycle 13. For each treatment group, the box shows the distance between the 75th and 25th percentiles, with the median marked as a line, and the “whiskers” show the maximum (top) and minimum (bottom) values. ∗Significantly different from CEE 0.625, P<.001. †Significantly different from CEE 0.625, P<.05. ‡Significantly different from CEE 0.3/MPA 1.5, P<.05. Utian. Lower HRT doses. Fertil Steril 2001. Fertility and Sterility 2001 75, 1065-1079DOI: (10.1016/S0015-0282(01)01791-5)