Importance: Perimenopause is accompanied by an increased risk of new and recurrent @entity308 . The coincidence of declining ovarian function with the onset of @entity308 led to the inference that "withdrawal" from physiologic @entity53 levels underpinned @entity308 in perimenopause. To our knowledge, this is the first controlled systematic study to directly test the @entity172 withdrawal theory of @entity308 ( @entity308 ). Objective: To examine the role of @entity53 withdrawal in @entity308 . Design, Setting, and @entity1 : Initial open-label treatment with @entity53 followed by randomized, double-blind, placebo-controlled, parallel-design evaluation of continued @entity53 treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center. An intent-to-treat analysis was performed between October 2003 and July 2012. @entity1 included asymptomatic postmenopausal @entity1 with past @entity308 responsive to hormone therapy (n   =   26) and asymptomatic postmenopausal @entity1 with no history of @entity308 (n   =   30) matched for age, body mass index, and reproductive status who served as controls. Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance. Interventions: After 3 weeks of open-label administration of transdermal @entity53 (100   g/d), @entity1 were randomized to a parallel design to receive either @entity53 (100   g/d; 27 @entity1 ) or matched placebo skin patches (29 @entity1 ) for 3 additional weeks under double-blind conditions. Main Outcomes and Measures: Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale (completed by raters blind to diagnosis and randomization status), self-administered visual analog symptom ratings, and blood hormone levels obtained at weekly clinic visits. Results: None of the @entity1 reported @entity308 symptoms during open-label use of @entity53 . @entity1 with past @entity308 who were crossed over from @entity53 to placebo experienced a significant increase in @entity308 symptom severity demonstrated using the Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale, with mean (SD) scores increasing from @entity53 (ie, 2.4 [2.0] and 3.0 [2.5]) to placebo (8.8 [4.9] and 6.6 [4.5], respectively [P   =   .0004 for both]). @entity1 with past @entity308 who continued @entity53 therapy and all @entity1 in the control group remained asymptomatic. @entity1 in both groups had similar hot-flush severity and plasma @entity53 levels during use of placebo. Conclusions and Relevance: In @entity1 with past @entity308 that was previously responsive to hormone therapy, the recurrence of @entity308 symptoms during blinded hormone withdrawal suggests that normal changes in ovarian @entity53 secretion can trigger an abnormal behavioral state in these susceptible @entity1 . @entity1 with a history of @entity308 should be alert to the risk of recurrent @entity308 when discontinuing hormone therapy. Trial Registration: clinicaltrials.gov Identifier: NCT00060736.

Effects of @entity53 Withdrawal on Mood in XXXX With Past Perimenopausal Depression: A Randomized Clinical Trial.

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity1 :: ('9606', 'Species') :: ['participants', 'women', 'Women', 'Participants'] @entity308 :: ('MESH:D003866', 'Disease') :: ['depression', 'perimenopausal depression', 'depressive', 'PMD'] @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol']
@entity1 :: (9606,Species) :: ['Women']
