Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, doubleblind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/ day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the lowdose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.

Sleep complaints are reported by 40–60 % of menopausal women. Poor sleep is a risk factor for cardiovascular disease, diabetes, and obesity. The effect of menopausal hormone therapy on sleep quality is unclear. A systematic review and meta-analysis were conducted to summarize the efficacy of menopausal hormone therapy on self-reported sleep quality. Electronic databases (PubMed, Scopus, Ovid MEDLINE, EMBASE, EBM Reviews CENTRAL, and Psyclnfo) were searched from 2002 to October 2015. Randomized trials assessing the effect of menopausal hormone therapy with a minimum follow up of 8 weeks were included. Titles, abstracts, and full texts were screened independently and in duplicate. Primary outcome included sleep items within a questionnaire, scale or diary. Standardized mean differences across trials were pooled using random-effects models. The search identified 424 articles, from which 42 trials were included. Seven trials at a moderate to high risk of bias enrolling 15,468 women were pooled in meta-analysis. Menopausal hormone therapy improved sleep quality in women who had vasomotor symptoms at baseline [standardized mean difference −0. 54 (−0. 91 to −0. 18), moderate quality evidence]. No difference was noted when women without such symptoms were analyzed separately or combined. Across 31 sleep quality questionnaires, daytime dysfunction was the most evaluated sleep domain. Menopausal hormone therapy improves sleep in women with concomitant vasomotor symptoms. Heterogeneity of trials regarding study population, formulations, and sleep scales; limit overall certainty in the evidence. Future menopausal hormone therapy trials should include assessment of self-reported sleep quality using standardized scales and adhere to reporting guidelines.

Objective:The goal of this study was to characterize the parkinsonian phenotype in patients with Gaucher disease (GD) who developed parkinsonism in order to evaluate clinical course and prognosis.Methods:This is a retrospective observational study conducted at the Clinical Center of the NIH, Bethesda, MD, over a period of 10 years. The study included 19 patients with GD and parkinsonism. The severity of Gaucher and parkinsonian symptoms was determined from clinical data including physical, neurologic, pathologic, and neurocognitive evaluations, family histories, imaging studies, olfactory testing, and validated questionnaires.Results:We found an earlier age at onset of parkinsonism and evidence of mild cognitive dysfunction in our cohort. Although the clinical course in some patients was similar to that of idiopathic Parkinson disease with a favorable levodopa response, others exhibited features characteristic of dementia with Lewy bodies. When we examined the patients as a group, we did not observe a uniformly aggressive form of parkinsonism after the initial onset of symptoms, contrary to other published reports.Conclusions:Appreciable clinical variation was seen in this cohort with GD and parkinsonism. Although some patients had early onset and prominent cognitive changes, others had a later, slower course, indicating that GBA1 mutations may not be a reliable prognostic indicator in Parkinson disease in clinical settings.