Kisspeptins are a group of peptide fragments encoded by the KISS1 gene in humans. They bind to kisspeptin receptors with equal efficacy. Kisspeptins and their receptors are expressed by neurons in the arcuate and anteroventral periventricular nuclei of the hypothalamus. Oestrogen mediates negative feedback of gonadotrophin-releasing hormone secretion via the arcuate nucleus. Conversely, it exerts positive feedback via the anteroventral periventricular nucleus. The sexual dimorphism of these nuclei accounts for the differential behaviour of the hypothalamic-pituitary-gonadal axis between genders. Kisspeptins are essential for reproductive function. Puberty is regulated by the maturation of kisspeptin neurons and by interactions between kisspeptins and leptin. Hence, kisspeptins have potential diagnostic and therapeutic applications. Kisspeptin agonists may be used to localise lesions in cases of hypothalamic-pituitary-gonadal axis dysfunction and evaluate the gonadotrophic potential of subfertile individuals. Kisspeptin antagonists may be useful as contraceptives in women, through the prevention of premature luteinisation during in vitro fertilisation, and in the treatment of sex steroid-dependent diseases and metastatic cancers.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the benefits and harms of different treatments of hepatorenal syndrome in people with decompensated liver cirrhosis. B A C K G R O U N D Description of the condition Liver cirrhosis 1 Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis (Protocol)

Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH.

Background: Evidence on the efficacy and safety of anticoagulation in preventing stroke and thromboembolic events in people with thyrotoxic atrial fibrillation is scarce. Objective: We evaluated the efficacy and safety of anticoagulation in people with thyrotoxic atrial fibrillation. Methods: Our study protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42020222782). Four databases and two systematic review registers were searched through 25 November 2020 for interventional and observational studies comparing anticoagulation therapy with active comparators, placebo, or no treatment in people with thyrotoxic atrial fibrillation. Random-effects meta-analysis and sensitivity analysis were performed. Quality of evidence was described using the GRADE framework. Results: 23,145 records were retrieved. 1 randomized controlled trial and 8 cohort studies were ultimately included. Effect estimates on the efficacy and safety of anticoagulation were extracted. Meta-analysis using the inverse variance and random-effects methods was conducted on 4 cohort studies with 3443 participants and 277 events. Anticoagulation in people with thyrotoxic atrial fibrillation reduced the risk of ischemic stroke and systemic thromboembolism by 3% (95% confidence interval (CI): 1 – 6%). Warfarin may prevent ischemic stroke in people with thyrotoxic atrial fibrillation if the CHA2DS2-VASc score exceeds 1 and when atrial fibrillation persists beyond 7 days. Direct oral anticoagulants may be associated with fewer bleeding events than warfarin. Conclusions: Anticoagulation prevents ischemic stroke and systemic thromboembolism in people with thyrotoxic atrial fibrillation. Direct oral anticoagulants may be associated with fewer bleeding events.