Cintrón, Dahima

Orexin A (OxA) is a hypothalamic neuropeptide involved in regulation of feeding behavior, metabolism, sleep‐wakefulness and emotion. Plasma levels of this peptide increase with age in both men and women. However, little is known about changes in circulating OxA levels during age‐associated, sex‐ specific hormonal changes, such as menopause, or the effect of menopausal hormone therapy (MHT) on OxA levels. No studies have assessed changes of OxA levels after discontinuation of MHT. The objective of this study was to assess plasma OxA during and three years after cessation of either oral conjugated equine estrogen (o‐CEE, n = 17), transdermal 17β‐estradiol (t‐E2; n= 20), or placebo pills and patches (n = 22) in healthy recently menopausal women (> 6 months < 3 years from their menses) who participated in the Kronos Early Estrogen Prevention Study. The plasma OxA was measured by enzyme‐linked immune absorbent assay prior to randomization to treatment (Baseline) and at 12 months, 24 months, 36 months, 48 months after randomization and at 36 months after cessation of study MHT. Data are presented as median with 25 th and 75 th percentile. Baseline plasma levels of OxA did not differ among groups (o‐CEE: 3.02 (2.2–4.4) ng/mL, t‐E2=4.09 (3.6–4.5) ng/mL, Placebo= 3.15 (2.5–6.2) ng/mL. During MHT treatment, women randomized to o‐CEE had higher OxA levels when compared to their baseline values at 24, 36 and 48 months of exposure (4.4 ng/mL (2.5–6.3), 4.1 ng/mL(2.5–7.3), 4.2 ng/mL(3.1–6.5), respectively). Changes of OxA levels in the t‐E2 and placebo groups were variable and did not show a consistent trend over the MHT treatment period. Three years after cessation of MHT, only the o‐CEE group showed significantly higher Ox A levels than during the treatment phase of the trial (treatment 3 year discontinuation median – 48 month treatment median =1.369 ng/mL). Our study suggests that the formulation of MHT, in particular o‐CEE (contain metabolites of estrogen) increases plasma OxA. This is the first study to assess Ox A levels for a period of more than 6 months under MHT and after years of discontinuation. If plasma levels of OxA reflect those in the brain, these results may explain in part the beneficial effects of o‐CEE on mood and other menopausal symptoms in women of KEEPS. An increase in OxA driven by o‐CEE could be a mechanism by which MHT helps women regulate energy metabolism and emotional behavior responses. Support or Funding Information This project was supported by the Mayo Clinic Office of Health Disparities Research and NIH AG 44170. In addition DC was supported by the CTSA Grant Number TL1 TR000137 from the National Center for Advancing Translational Science, a component of the National Institutes of Health.

Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle–Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.

Abstract Objective: This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Methods: Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Results: Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change −1.27 [o-CEE] and −1.32 [t-E2]) when compared with PBO (−0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (r s = 0.170, P < 0.001 for hot flashes; r s = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Conclusions: Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women.