Objective To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. Design Series of randomised, placebo controlled n-of-1 trials. Setting Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. Participants 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Interventions Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo. Main outcome measures At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods. Results 151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo −0.11, 95% confidence interval −0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins. Conclusions No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment. Trial registration ISRCTN30952488 , EUDRACT 2016-000141-31, NCT02781064 .

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Recent reports have indicated that analysis of changes in the staining characteristics of gonadotropin-releasing hormone (GnRH) neurons and characterization of morphological plasticity of the related structural framework may help to elucidate the physiological mechanisms involved in neuroendocrine control of mammalian reproduction. Whether comparative studies will facilitate this process or simply elucidate species-specific mechanisms is not yet clear. The present study was performed in order to begin analysis of GnRH neurons in a seasonally breeding species that exhibits an unusually long ovulatory luteinizing hormone (LH) surge. To this end, light microscopy and image analysis were used to characterize distribution and morphology of GnRH neurons in 15 adult male and female ponies. Samples were collected in the middle of the normal ovulatory season. Unipolar, bipolar, and multipolar GnRH neurons were organized in a loosely defined continuum that extended from the medial septum to tuberoinfundibular areas in the medical basal hypothalamus (MBH). Most cells were bipolar, and the majority of neurons were located in the MBH. Fiber projections to the median eminence included presumptive pathways similar to those previously described in other species. Image analysis of cell size indicated that cells in the MBH were larger than those in preoptic areas and GnRH neurons in both of these locations were larger than neurons in rostral areas of the medial septum. Results from this experiment suggest that the large population of MBH GnRH neurons in the equine species is likely to be of primary importance to reproductive function, whereas cells in other areas are fewer and smaller. Further work is needed to characterize morphological characteristics that may be related to physiological fluctuations in reproductive function of the equine species.