Publications
359 results found
Clarke SA, Phylactou M, Patel B, et al., 2023, Letter to the Editor of Clinical Endocrinology: Assessment of adrenal function in patients who survive COVID‐19, Clinical Endocrinology, Vol: 98, Pages: 270-272, ISSN: 0300-0664
It is widely recognised that the effects of COVID-19 extend beyond the respiratory system. Moreover, there are an estimated 1.3 million people living with Long COVID (symptoms persisting beyond 12 weeks after infection) in the UK alone.
Koysombat K, Abbara A, Dhillo WS, 2023, Current pharmacotherapy and future directions for neuroendocrine causes of female infertility, EXPERT OPINION ON PHARMACOTHERAPY, Vol: 24, Pages: 37-47, ISSN: 1465-6566
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- Citations: 2
Grant B, Pradeep A, Minhas S, et al., 2023, Survey of endocrinologists managing recovery from anabolic androgenic steroid induced hypogonadism, Reproduction and Fertility, Vol: 4, Pages: 1-3, ISSN: 2633-8386
Anabolic steroids (also known as ‘steroids’) are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.
Jasuja R, Pencina KM, Spencer DJ, et al., 2023, Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure, ANDROLOGY, Vol: 11, Pages: 125-133, ISSN: 2047-2919
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- Citations: 1
Lo Y, Liang S, Dhillo WS, et al., 2023, Robotic APTamer-Enabled Electrochemical Reader (RAPTER) System for Automated Aptamer-Mediated Electrochemical Analysis., Methods Mol Biol, Vol: 2570, Pages: 271-280
Electrochemical aptamer-based (E-AB) sensors using conformational change-induced electron transfer kinetics are sensitive, reagent-less, and cost-effective tools for molecular sensing. Current advances in this technology can allow continuous drug pharmacokinetic monitoring in living animals (Dauphin-Ducharme et al., ACS Sens 4(10):2832-2837, 2019; Idili et al., Chem Sci 10(35):8164-8170, 2019), as well as automated analysis of hormone pulsatility (Liang et al., Nat Commun 10(1):852, 2019). In this chapter, we provide the methodology for an automated E-AB conformational change-based robotic sensing platform. By using an open-source programmable robotic system, this method can be adapted to a wide range of experimental scenarios.
Abbara A, Patel B, Parekh I, et al., 2022, Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Introduction: Ovarian Hyperstimulation Syndrome (OHSS) is a life-threatening iatrogenic complication of In vitro fertilisation (IVF). This study aimed to quantify rates of Ovarian Hyperstimulation Syndrome (OHSS) requiring intensive care unit (ICU) admission and assess whether trends have changed between 1996-2020 commensurate with the introduction of safer IVF practices.Methods: Data regarding Intensive Care Unit (ICU) admission across England, Wales and Northern Ireland was gathered retrospectively from the Intensive Care National Audit and Research Centre (ICNARC) database. 38,957 female patients aged between 18-55 years were admitted to ICU for OHSS or related conditions between 1996-2020. The primary outcome was the rate of OHSS requiring ICU admission expressed as a proportion of the number of fresh IVF cycles conducted in that year according to Human Fertility and Embryology Authority (HFEA) records. Baseline characteristics (for example, age, ethnicity, BMI), biochemical parameters (such as renal function, serum electrolytes), length of ICU stay and duration and need for organ support, were also compared between ICU patients with ‘confirmed OHSS’ and those ‘without OHSS’.Results: There were 238 cases of ‘confirmed OHSS’ requiring ICU admission recorded between 1996-2020. Rates of OHSS requiring ICU admission declined over the study period (P=0.006); the annual rate of severe OHSS requiring intensive care admission halved when comparing those occurring between 1996-2007 and 2008-2020 (OR=0.37, 95% CI 0.37-0.45; P<0.0001). Patients spent a mean of 3.5 days in the ICU, with 86.3% of patients with ‘confirmed OHSS’ requiring at least 2 days of higher level (i.e., level 2 or 3) care. Patients with ‘confirmed OHSS’ required a shorter duration of renal, advanced cardiovascular, and advanced respiratory support than patients ‘without OHSS’ (P<0.0001 for all comparisons). There was no signif
Voliotis M, Hanassab S, Abbara A, et al., 2022, Quantitative approaches in clinical reproductive endocrinology, Current Opinion in Endocrine and Metabolic Research, Vol: 27, ISSN: 2451-9650
Understanding the human hypothalamic-pituitary-gonadal (HPG) axis presents a major challenge for medical science. Dysregulation of the HPG axis is linked to infertility and a thorough understanding of its dynamic behaviour is necessary to both aid diagnosis and to identify the most appropriate hormonal interventions. Here, we review how quantitative models are being used in the context of clinical reproductive endocrinology to: 1. analyse the secretory patterns of reproductive hormones; 2. evaluate the effect of drugs in fertility treatment; 3. aid in the personalization of assisted reproductive technology (ART). In this review, we demonstrate that quantitative models are indispensable tools enabling us to describe the complex dynamic behaviour of the reproductive axis, refine the treatment of fertility disorders, and predict clinical intervention outcomes.
Tsoutsouki J, Abbara A, Dhillo W, 2022, Novel therapeutic avenues for kisspeptin, CURRENT OPINION IN PHARMACOLOGY, Vol: 67, ISSN: 1471-4892
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- Citations: 2
Abbara A, Koysombat K, Phylactou M, et al., 2022, Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH.Materials and methods: Retrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured.Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB.Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54.Results: Median INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating
Thurston L, Hunjan T, Ertl N, et al., 2022, Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial, Jama Network Open, Vol: 5, Pages: 1-14, ISSN: 2574-3805
Importance: The absence or deficiency of sexual desire leading to distress or interpersonal difficultydefines ‘hypoactive sexual desire disorder’ (HSDD). Despite being the most common female sexualhealth complaint worldwide, current treatment options for HSDD are limited in their safety andeffectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonalaxis with additional emerging roles in sexual and emotional behavior, however, its effects in womenwith HSDD are unknown.Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing inwomen with HSDD.Design: A randomized, double-blind, two-way crossover, placebo-controlled clinical trial. Functionalneuroimaging, psychometric and hormonal analyses were employed to investigate the effects ofkisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facialattraction (face images of varying attractiveness).Setting: The trial was conducted in a university research setting from October 2020 to April 2021. Datawere analyzed from May to December 2021.Participants: 32 premenopausal women with HSDD for at least 6 months’ duration.Interventions: 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rateplacebo infusion.Main Outcome and Measures: Blood oxygen level–dependent responses across the whole brain andregions of interest during kisspeptin vs placebo administration, in response to erotic and facialattraction stimuli.Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin andplacebo visits, and the mean (SEM) age was 29.2 (1.2) years. Kisspeptin administration resulted inmodulations in sexual and facial attraction brain processing (all P<.05). Furthermore, positivecorrelations were observed between kisspeptin-enhanced hippocampal activity in response to eroticvideos, and baseline distress relating to sexual function (P<.01). In additio
Thurston L, Hunjan T, Mills E, et al., 2022, Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder, Journal of Clinical Investigation, Vol: 132, Pages: 1-12, ISSN: 0021-9738
BACKGROUND. Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODS. Using psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTS. MC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSION. These data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATION. ClinicalTrials.gov NCT04179734.FUNDING. This is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (C
Mills EG, Dhillo WS, 2022, Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health, Journal of Neuroendocrinology, Vol: 34, ISSN: 0953-8194
The reproductive neuropeptide kisspeptin has emerged as the master regulator of mammalian reproduction due to its key roles in the initiation of puberty and the control of fertility. Alongside the tachykinin neurokinin B and the endogenous opioid dynorphin, these peptides are central to the hormonal control of reproduction. Building on the expanding body of experimental animal models, interest has flourished with human studies revealing that kisspeptin administration stimulates physiological reproductive hormone secretion in both healthy men and women, as well as patients with common reproductive disorders. In addition, emerging therapeutic roles based on neurokinin B for the management of menopausal flushing, endometriosis and uterine fibroids are increasingly recognised. In this review, we focus on kisspeptin and neurokinin B and their potential application as novel clinical strategies for the management of reproductive disorders.
Sharma B, Koysombat K, Dhillo W, et al., 2022, Use of kisspeptin to trigger oocyte maturation during in vitro fertilisation (IVF) treatment, Frontiers in Endocrinology, Vol: 13, Pages: 1-9, ISSN: 1664-2392
Infertility is a major global health issue and is associated with significant psychological distress for afflicted couples. In vitrofertilisation (IVF) utilises supra-physiological doses of stimulatory hormones to induce the growth of multiple ovarian follicles toenable surgical retrieval of several oocytes for subsequent fertilisation and implantation into the maternal endometrium. Thesupra-physiological degree of ovarian stimulation can lead to potential risks during IVF treatment, including ovarianhyperstimulation syndrome (OHSS) and multiple pregnancy.The choice of oocyte maturation trigger, such as human chorionic gonadotrophin (hCG) or gonadotrophin releasing hormoneagonist (GnRHa), can impact both the efficacy of IVF treatment with a bearing on luteal phase hormonal dynamics and thus thedegree of luteal phase support required to maintain optimal pregnancy rates, as well as on safety of treatment with particularrespect to the risk of OHSS. Kisspeptin regulates gonadotrophin releasing hormone (GnRH) release and is therefore a key regulatorof the hypothalamo-pituitary-gonadal (HPG) axis. Kisspeptin has been shown to be requisite for the occurrence of the physiologicalovulatory luteinising hormone (LH) surge. In this review, we discuss the potential use of kisspeptin as a novel trigger of oocytematuration.
Izzi-Engbeaya C, Dhillo WS, 2022, Gut hormones and reproduction, ANNALES D ENDOCRINOLOGIE, Vol: 83, Pages: 254-257, ISSN: 0003-4266
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- Citations: 1
Garg A, Patel B, Abbara A, et al., 2022, Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS), CLINICAL ENDOCRINOLOGY, Vol: 97, Pages: 156-164, ISSN: 0300-0664
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- Citations: 12
Tsoutsouki J, Patel B, Dhillo W, et al., 2022, Kisspeptin in the prediction of pregnancy complications, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Kisspeptin and its receptor are central to reproductive health acting as key regulators of the reproductive endocrine axis in humans. Kisspeptin is most widely recognised as a regulator of gonadotrophin releasing hormone (GnRH) neuronal function. However, recent evidence has demonstrated that kisspeptin and its receptor also play a fundamental role during pregnancy in the regulation of placentation. Kisspeptin is abundantly expressed in syncytiotrophoblasts, and its receptor in both cyto- and syncytio-trophoblasts. Circulating levels of kisspeptin rise dramatically during healthy pregnancy, which have been proposed as having potential as a biomarker of placental function. Indeed, alterations in kisspeptin levels are associated with an increased risk of adverse maternal and foetal complications. This review summarises data evaluating kisspeptin’s role as a putative biomarker of pregnancy complications including miscarriage, ectopic pregnancy (EP), preterm birth (PTB), foetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), gestational diabetes mellitus (GDM), and gestational trophoblastic disease (GTD).
Farahani L, Mowla S, Tharakan T, et al., 2022, Next generation sequencing analysis of the seminal microbiome in male partners of women with idiopathic recurrent pregnancy loss: results of a prospective cohort study, Publisher: OXFORD UNIV PRESS, Pages: I149-I149, ISSN: 0268-1161
Papanikolaou N, Coulden A, Parker N, et al., 2022, Pituitary functioning gonadotroph adenomas (FGA)-induced ovarian hyperstimulation syndrome (OHSS): results from tertiary neuroendocrine centres in the UK, 38th Hybrid Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: I518-I518, ISSN: 0268-1161
Mills E, Yang L, Abbara A, et al., 2022, Current perspectives on kisspeptins role in behaviour, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
The neuropeptide kisspeptin is now well-established as the master regulator of the mammalian reproductive axis. Beyond the hypothalamus, kisspeptin and its cognate receptor are also extensively distributed in extra-hypothalamic brain regions. An expanding pool of animal and human data demonstrates that kisspeptin sits within an extensive neuroanatomical and functional framework through which it can integrate a range of internal and external cues with appropriate neuroendocrine and behavioural responses. In keeping with this, recent studies reveal wide-reaching effects of kisspeptin on key behaviours such as olfactory-mediated partner preference, sexual motivation, copulatory behaviour, bonding, mood, and emotions. In this review, we provide a comprehensive update on the current animal and human literature highlighting the far-reaching behaviour and mood-altering roles of kisspeptin. A comprehensive understanding of this important area in kisspeptin biology is key to the escalating development of kisspeptin-based therapies for common reproductive and related psychological and psychosexual disorders.
Hunjan T, Thurston L, Ertl N, et al., 2022, Kisspeptin modulates sexual brain processing in women with low sexual desire, Publisher: WILEY, Pages: 200-200, ISSN: 1470-0328
Hudson J, Cruickshank M, Quinton R, et al., 2022, Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis., The Lancet Healthy Longevity, Vol: 3, Pages: e381-e393, ISSN: 2666-7568
Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225
Guzman S, Dragan M, Kwon H, et al., 2022, Targeting hepatic kisspeptin receptor ameliorates non-alcoholic fatty liver disease in a mouse model., Journal of Clinical Investigation, Vol: 132, Pages: 1-20, ISSN: 0021-9738
Nonalcoholic fatty liver disease (NAFLD), the most common liver disease has become a silent worldwide pandemic. The incidence of NAFLD correlates with the rise in obesity, type 2 diabetes and metabolic syndrome. A hallmark feature of NAFLD is excessive hepatic fat accumulation or steatosis, due to dysregulated hepatic fat metabolism which can progress to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Currently, there are no approved pharmacotherapies to treat this disease. Here we have identified that activation of the kisspeptin receptor (KISS1R) signaling pathway has therapeutic effects in NAFLD. Using high fat diet-fed mice, we demonstrated that a deletion of hepatic Kiss1r exacerbated hepatic steatosis. In contrast, enhanced stimulation of KISS1R protected against steatosis in wild-type C57BL/6J mice and decreased fibrosis using a diet-induced mouse model of NASH. Mechanistically, we found that hepatic KISS1R signaling activates the master energy regulator, AMPK, to thereby decrease lipogenesis and progression to NASH. In NAFLD patients and in HFD-fed mice, hepatic KISS1/KISS1R expression and plasma kisspeptin levels were elevated, suggesting a compensatory mechanism to reduce triglyceride synthesis. These findings establish KISS1R as a therapeutic target to treat NASH.
Hunjan T, Thurston L, Mills E, et al., 2022, MELANOCORTIN-4 RECEPTOR AGONISM MODULATES SEXUAL BRAIN PROCESSING IN WOMEN WITH LOW SEXUAL DESIRE, Publisher: ELSEVIER SCI LTD, Pages: S123-S123, ISSN: 1743-6095
Patel B, S Dhillo W, 2022, Menopause review: Emerging treatments for menopausal symptoms., Best Pract Res Clin Obstet Gynaecol, Vol: 81, Pages: 134-144
Vasomotor symptoms (VMS) affect 2 out of 3 women during menopause and are highly disruptive and intolerable. They exert a negative impact on a woman's physical and mental well-being and are considered a high clinical priority requiring effective treatment. Although hormone therapy remains the gold-standard treatment for hot flushes, it is associated with several side effects and contraindications. Furthermore, alternative treatments for VMS are currently less efficacious and have limited availability; therefore, a new medication to treat VMS would benefit millions of women worldwide. Neurokinin 3 receptor (NK3R) antagonists have recently been developed as novel therapeutic agents for the amelioration of VMS through their action on NK3 receptors within the hypothalamus and consequent regulation of the thermoregulatory centre. So far, three NK3R antagonists have been studied in menopausal women, which have demonstrated significant reductions in VMS frequency and severity and have shown their ability to transform patients' quality of life.
Jayasena CN, Dhillo WS, 2022, Secondary amplification of sperm DNA fragmentation for male infertility: hope for improved and affordable fertility testing in affected couples, Clinical Chemistry, Vol: 68, Pages: 489-490, ISSN: 0009-9147
Comninos AN, Hansen MS, Courtney A, et al., 2022, Acute effects of kisspeptin administration on bone metabolism in healthy men, Journal of Clinical Endocrinology and Metabolism, Vol: 107, ISSN: 0021-972X
CONTEXT: Osteoporosis results from disturbances in bone formation and resorption. Recent non-human data suggests that the reproductive hormone, kisspeptin, directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. OBJECTIVE: To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. DESIGN: In vitro study: Mono- and co-cultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, two-way crossover clinical study in twenty-six men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. PARTICIPANTS: In vitro study: Twelve male blood donors and eight patients undergoing hip replacement surgery. Clinical Study: Twenty-six healthy eugonadal men (age 26.8±5.8 years). INTERVENTION: Kisspeptin (versus placebo). MAIN OUTCOME MEASURES: Changes in bone parameters and turnover markers. RESULTS: Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P=0.0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P<0.0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P=0.021) and 24.3% maximal increase in carboxylated osteocalcin levels (P=0.014). CONCLUSIONS: Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex-steroid levels. Kisspeptin could therefore have clinical thera
Sharma A, Jayasena CN, Dhillo WS, 2022, Regulation of the hypothalamic-pituitary-testicular axis: pathophysiology of hypogonadism, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: 29-45, ISSN: 0889-8529
Clarke S, Phylactou M, Patel B, et al., 2022, Preserved C-peptide in survivors of COVID-19: post-hoc analysis, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 24, Pages: 570-574, ISSN: 1462-8902
Izzi-Engbeaya C, Dhillo WS, 2022, Emerging roles for kisspeptin in metabolism, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 1079-1088, ISSN: 0022-3751
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- Citations: 9
Sharma A, Ul-Haq Z, Sindi E, et al., 2022, Clinical characteristics and comorbidities associated with testosterone prescribing in men, CLINICAL ENDOCRINOLOGY, Vol: 96, Pages: 227-235, ISSN: 0300-0664
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- Citations: 1
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