The Effectiveness of Short-Term Sequential Combined Hormonal Replacement Therapy Augmentation of Selective Serotonin Reuptake Inhibitor in Postmenopausal Women with Depression: Pilot Study

Lee, Moon Soo; Yang, Jae Won; Ko, Young Hoon; Joe, Sook Haeng

Abstract

OBJECTIVES
Estrogen may be useful to manage depression. Some studies have suggested that treatment using antidepressant medications augmented with estrogen can be more effective than using antidepressant medication alone. However, data about the estrogen augmentation of selective serotonin reuptake inhibitor (SSRI) medication is insufficient. We investigated the effect of hormonal replacement treatment (HRT) as an augmentation in postmenopausal women with depression who were already being treated with SSRIs.
METHODS
This was an 8-week prospective, open trial study. The subjects were 13 patients who met the DSM-IV criteria for major depressive disorder or dysthymia. The menses of all subjects had ceased for at least one year, and all subjects had serum levels of follicular stimulating hormone (FSH) greater than 40 mIU/mL. All subjects were already taking sertraline (50-150 mg) or paroxetine (20-30 mg); during the study they received sequential combined hormone replacement treatment (1.25 mg estrogen +5 mg medroxyprogesterone). Subjects continued their SSRI medication at their original dosages throughout the 8-week study. Mood and anxiety symptoms were measured with the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Menopause-related symptoms were assessed using the Women's Health Questionnaire (WHQ). Overall clinical symptoms were also assessed using the Symptom Checklist 90-Revised (SCL-90-R). Serum levels of luteinizing hormone (LH), FSH, prolactin, estradiol, and progesterone were measured. Measurements were conducted at three times: baseline, four weeks, and endpoint.
RESULTS
The subjects' mean age was 53.54+/-5.38 years and mean postmenopausal duration was 4.46+/-3.67 years. During the HRT, BDI and Trait Anxiety Inventory scores decreased significantly. On the WHQ subscales, scores for somatic symptoms, vasomotor symptoms, sexual behavior, and sleep problems were significantly improved. Hormonal levels of LH, FSH, and estradiol changed significantly. Menopausal duration was significantly correlated with changes in each assessment: somatic symptoms (r=-0.583, p=0.037), anxiety symptoms (r=-0.623, 0.023), WHQ depressive symptoms (r=-0.586, p=0.035), depression (r=-0.584, p=0.036), global severity index (r=-0.642, p=0.018), and positive symptom distress index (r=-0.592, p=0.033) of SCL-90-R. CONCLUSION: The results suggest that HRT may augment the antidepressant response to SSRIs in postmenopausal women with depression. The treatment effect of augmentation by HRT seems to be influenced by menopausal duration. Therefore, further controlled studies should be conducted to test estrogen augmentation of antidepressants, dependent on the duration of menopause.