Evaluation of different add-back estradiol and progesterone treatments to gonadotropin- releasing hormone agonist treatment in patients with premenstrual.

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Evaluation of different add-back estradiol and progesterone treatments to gonadotropin- releasing hormone agonist treatment in patients with premenstrual dysphoric disorder Birgitta Segebladh, MD, Anna Borgström, MSc, Sigrid Nyberg, PhD, Marie Bixo, MD, PhD, Inger Sundström-Poromaa, MD, PhD American Journal of Obstetrics & Gynecology Volume 201, Issue 2, Pages 139.e1-139.e8 (August 2009) DOI: 10.1016/j.ajog.2009.03.016 Copyright © 2009 Mosby, Inc. Terms and Conditions

FIGURE 1 Flow-chart of the study PMDD, premenstrual dysphoric disorder. Segebladh. Evaluation of add-back treatments for patients with PMDD. Am J Obstet Gynecol 2009. American Journal of Obstetrics & Gynecology 2009 201, 139.e1-139.e8DOI: (10.1016/j.ajog.2009.03.016) Copyright © 2009 Mosby, Inc. Terms and Conditions

FIGURE 2 Schematic diagram of the study design GnRH, gonadotropin-releasing hormone; HRT, hormone replacement therapy. Segebladh. Evaluation of add-back treatments for patients with PMDD. Am J Obstet Gynecol 2009. American Journal of Obstetrics & Gynecology 2009 201, 139.e1-139.e8DOI: (10.1016/j.ajog.2009.03.016) Copyright © 2009 Mosby, Inc. Terms and Conditions

FIGURE 3 Negative mood during add-back hormone replacement therapy to GnRH agonist Mean ± SEM daily symptom ratings on a 9-point cyclicity diagnoser (CD) scale of irritability, anxiety, depressed moods, and impact on daily life during the last 10 days of each treatment cycle in 27 patients with PMDD. Treatments consisted of leuprolide acetate only, leuprolide acetate with add-back of 1.5E2P, 0.5E2P, and 1.5E2-only, respectively. During the first treatment cycle, the 2-way analysis of variance revealed significant differences between the add-back hormone replacement therapy regimens (premenstrual irritability scores, F[3,26] = 5.69 [P < .001]; anxiety scores, F[3,26] = 4.50; [P < .01]; depression, F[3,26] = 6.00 [P < .001]; mood swings, F[3,26] = 3.72 [P < .05]; and impact on daily life scores, [F3,26] = 3.64 [P < .05]). Post-hoc analyses are given in the Figure. Triple asterisks denote P < .001, Tukey Honestly Significance Test. GnRH, gonadotropin-releasing hormone. Segebladh. Evaluation of add-back treatments for patients with PMDD. Am J Obstet Gynecol 2009. American Journal of Obstetrics & Gynecology 2009 201, 139.e1-139.e8DOI: (10.1016/j.ajog.2009.03.016) Copyright © 2009 Mosby, Inc. Terms and Conditions

FIGURE 4 Cross-over effects that depended on the first used add-back treatment Summarized negative mood symptoms throughout the study course, depending on with which treatment the subjects started. Each point represents the group mean ± SEM of the last 10 days of each treatment cycle. Patients with premenstrual dysphoric disorder who started with 1.5E2P continued to display higher negative mood ratings throughout the study, compared with subjects who started with 1.5E2-only (F[2,26] = 5.73; P < .01). During the gonadotropin-releasing hormone (GnRH) cycle, there was no difference between groups in summarized negative mood symptoms. CD, cyclicity diagnoser. Segebladh. Evaluation of add-back treatments for patients with PMDD. Am J Obstet Gynecol 2009. American Journal of Obstetrics & Gynecology 2009 201, 139.e1-139.e8DOI: (10.1016/j.ajog.2009.03.016) Copyright © 2009 Mosby, Inc. Terms and Conditions

FIGURE 5 Physical symptoms during add-back hormone replacement therapy to GnRH agonist Mean ± SEM daily symptom ratings on a 9-point cyclicity diagnoser (CD) scale of bloating and breast tenderness during the last 10 days of each treatment cycle in 27 patients with premenstrual dysphoric disorder. Treatments consisted of leuprolide acetate only, leuprolide acetate with add-back of 1.5E2P, 0.5E2P, and 1.5E2-only, respectively. The 2-way analysis of variance revealed significant differences between add-back hormone replacement therapy regimens in breast tenderness (F[3,26] = 7.67; P < .001) and bloating (F[3,26] = 13.30; P < .001). Post-hoc analyses are given. The single asterisk denotes P < .05, Tukey Honestly Significance Test; the triple asterisks denote P < .001, Tukey Honestly Significance Test. GnRH, gonadotropin-releasing hormone. Segebladh. Evaluation of add-back treatments for patients with PMDD. Am J Obstet Gynecol 2009. American Journal of Obstetrics & Gynecology 2009 201, 139.e1-139.e8DOI: (10.1016/j.ajog.2009.03.016) Copyright © 2009 Mosby, Inc. Terms and Conditions