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Grant MD, Marbella A, Wang AT, et al. Menopausal Symptoms: Comparative Effectiveness of Therapies [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Mar. (Comparative Effectiveness Reviews, No. 147.)

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Menopausal Symptoms: Comparative Effectiveness of Therapies [Internet].

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Appendix FVasomotor Symptom Supplemental Tables and Plots

Figure F-1 is a forest plot for the pairwise comparison of high dose estrogens compared with placebo (N=9 trials) for vasomotor symptoms, Key Question 1. All nine trials showed significant improvements individually, with a pooled SMD of -0.50 (95% CI: -0.61 to -0.39).

Figure F-1

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (high dose) compared with placebo.

Figure F-2 is a forest plot for the pairwise comparison of standard dose estrogens compared with placebo (N=39 trials) for vasomotor symptoms, Key Question 1. Three trials had 95% confidence intervals including zero, with the remaining 36 trials showing significant improvements in vasomotor symptoms with standard dose estrogen. The pooled SMD is -0.64 (95% CI: -0.74 to -0.53).

Figure F-2

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (standard dose) compared with placebo.

Figure F-3 is a forest plot for the pairwise comparison of low/ultralow dose estrogens compared with placebo (N=53 trials) for vasomotor symptoms, Key Question 1. Seven trials had 95% confidence intervals including zero, with the remaining 46 trials showing significant improvements in vasomotor symptoms with low/ultra low dose estrogen. The pooled SMD is -0.66 (95% CI: -0.81 to -0.48).

Figure F-3

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (low/ultralow dose) compared with placebo.

Figure F-4 is a forest plot for the pairwise comparison of SSRIs or SNRIs compared with placebo (N=13 trials) for vasomotor symptoms, Key Question 1. One point estimate is zero, with one additional trial having a 95% confidence interval including zero. The remaining 11 trials showed significant improvements in vasomotor symptoms with SSRIs or SNRIs. The pooled SMD is -0.35 (95% CI: -0.46 to -0.24).

Figure F-4

Vasomotor symptoms forest plot of pairwise comparisons—SSRIs or SNRIs compared with placebo.

Figure F-B415 is a forest plot for the pairwise comparison of isoflavones compared with placebo (N=35 trials) for vasomotor symptoms, Key Question 1. Eight trials had point estimates larger than zero, and an additional 11 trials had 95% confidence intervals including zero. The remaining 16 trials showed significant improvements in vasomotor symptoms with isoflavones. The pooled SMD is -0.31 (95% CI: -0.41 to -0.22).

Figure F-5

Vasomotor symptoms forest plot of pairwise comparisons—isoflavones compared with placebo.

Figure F-6 is a forest plot for the pairwise comparison of gabpentin compared with placebo (N=5 trials) for vasomotor symptoms, Key Question 1. All five trials reported significant improvements in vasomotor symptoms with gabapentin. The pooled SMD is -0.28 (95% CI: -0.38 to -0.19).

Figure F-6

Vasomotor symptoms forest plot of pairwise comparisons—gabapentin compared with placebo.

Figure F-7 is a forest plot for the pairwise comparison of black cohosh compared with placebo (N=4 trials) for vasomotor symptoms, Key Question 1. Two of the four trials have 95% confidence intervals including zero. The largest trial showed significant improvement in vasomotor symptoms. The pooled SMD is -0.31 (95% CI: -0.46 to -0.15).

Figure F-7

Vasomotor symptoms forest plot of pairwise comparisons—black cohosh compared with placebo.

Figure F-8 is a forest plot for the pairwise comparison of high dose estrogen compared with standard dose estrogen (N=12 trials) for vasomotor symptoms, Key Question 1. All of the trials showed that high dose and standard dose estrogen were equally effective in relieving vasomotor symptoms. The pooled SMD is -0.03 (95% CUI: -0.14 to 0.09).

Figure F-8

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (high dose) compared with estrogen (standard dose).

Figure F-9 is a forest plot for the pairwise comparison of high dose estrogen compared with low/ultra low dose estrogen (N=5 trials) for vasomotor symptoms, Key Question 1. All of the trials showed that high dose and low/ultra low dose estrogens were equally effective in relieving vasomotor symptoms. The pooled SMD is -0.02 (95% CUI: -0.17 to 0.13).

Figure F-9

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (high dose) compared with estrogen (low/ultralow dose).

Figure F-10 is a forest plot for the pairwise comparison of standard dose estrogen compared with low/ultra low dose estrogen (N=24 trials) for vasomotor symptoms, Key Question 1. Five trials showed standard dose estrogens significantly more effective compared with low/ultralow dose estrogens, but the remaining trials showed no difference. The pooled SMD is -0.14 (95% CUI: -0.23 to 0.05).

Figure F-10

Vasomotor symptoms forest plot of pairwise comparisons—estrogen (standard dose) compared with estrogen (low/ultralow dose).

Figure F-11 is a forest plot for the pairwise comparison of ginseng compared with placebo (N=3 trials) for vasomotor symptoms, Key Question 1. Two of the three trials have 95% confidence intervals including zero. The pooled SMD is -0.17 (95% CI: -0.43 to 0.09).

Figure F-11

Vasomotor symptoms forest plot of pairwise comparisons—ginseng compared with placebo.

Figure F-12 is a plot demonstrating consistency within the following closed treatment loops: high estrogen/standard estrogen/ultrlow-low estrogen; high estrogen/standard estrogen/placebo; high estrogen/ultralow-low estrogen/placebo; standard estrogen/ultralow-low estrogen/black cohosh; standard estrogen/ultralow-low estrogen/placebo; standard estrogen/black cohosh/placebo; ultralow-low estrogen/black cohosh/placebo; ultralow-low estrogen/isoflavones/placebo. The plot shows that the only inconsistency among the treatment loops was found in the loop of standard estrogen/ultralow-low estrogen/black cohosh.

Figure F-12

Plot showing consistency of closed loops with letters representing treatments. a: high dose estrogen; b: standard dose estrogen; c: low/ultralow dose estrogen; d: SSRI/SNRI; f: isoflavones; g: black cohosh; I: placebo.

Table F-1. Difference between network result and calculable pairwise effect estimates.

Table F-1

Difference between network result and calculable pairwise effect estimates.

Table F-2. Network analysis including trials (n=134) specifying vasomotor symptoms as a primary outcome and requiring symptoms; SMD and 95% credible interval.

Table F-2

Network analysis including trials (n=134) specifying vasomotor symptoms as a primary outcome and requiring symptoms; SMD and 95% credible interval.

Table F-3. Rankings of comparative efficacy, standard deviations, and 95% credible intervals; trials (n=134) specifying vasomotor symptoms as a primary outcome and requiring symptoms.

Table F-3

Rankings of comparative efficacy, standard deviations, and 95% credible intervals; trials (n=134) specifying vasomotor symptoms as a primary outcome and requiring symptoms.

Table F-4. Network analysis excluding trials judged to have included women without vasomotor symptoms (n=136); SMD and 95% credible interval.

Table F-4

Network analysis excluding trials judged to have included women without vasomotor symptoms (n=136); SMD and 95% credible interval.

Table F-5. Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding trials judged to have included women without vasomotor symptoms.

Table F-5

Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding trials judged to have included women without vasomotor symptoms.

Table F-6. Network analysis excluding black cohosh trials (n=147); SMD and 95% credible interval.

Table F-6

Network analysis excluding black cohosh trials (n=147); SMD and 95% credible interval.

Table F-7. Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding black cohosh trials.

Table F-7

Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding black cohosh trials.

Table F-8. Network analysis including trials rated good or fair quality (n=36); SMD and 95% credible interval.

Table F-8

Network analysis including trials rated good or fair quality (n=36); SMD and 95% credible interval.

Table F-9. Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; including trials rated good or fair quality.

Table F-9

Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; including trials rated good or fair quality.

Table F-10. Network analysis restricted to trials examining moderate to severe hot flush reduction (n=55); SMD and 95% credible interval.

Table F-10

Network analysis restricted to trials examining moderate to severe hot flush reduction (n=55); SMD and 95% credible interval.

Table F-11. Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; trials examining moderate to severe hot flush reduction.

Table F-11

Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; trials examining moderate to severe hot flush reduction.

Table F-12. Network analysis excluding large prevention-focused trials, SMD and 95% credible interval (n=150).

Table F-12

Network analysis excluding large prevention-focused trials, SMD and 95% credible interval (n=150).

Table F-13. Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding large prevention-focused trials.

Table F-13

Vasomotor symptoms rankings of comparative efficacy, standard deviations, and 95% credible intervals; excluding large prevention-focused trials.

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