Publications
358 results found
Dhillo WS, 2019, Kisspeptin, Neurokinin B and New Players in Reproduction Preface, SEMINARS IN REPRODUCTIVE MEDICINE, Vol: 37, Pages: 153-153, ISSN: 1526-8004
- Author Web Link
- Cite
- Citations: 2
Behary P, Tharakan G, Alexiadou K, et al., 2019, Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Glycaemia and Body Weight in Obesity and Type 2 Diabetes: A Randomized, Single-Blinded Study, 79th Scientific Sessions of the American-Diabetes-Association (ADA), Publisher: AMER DIABETES ASSOC, ISSN: 0012-1797
Hunjan T, Abbara A, Patel A, et al., 2019, FSH requirements for follicle growth during controlled ovarian stimulation in IVF cycles, Publisher: WILEY, Pages: 193-194, ISSN: 1470-0328
Modi M, Dhillo WS, 2019, Neurokinin B and Neurokinin-3 Receptor Signaling: Promising Developments in the Management of Menopausal Hot Flushes, SEMINARS IN REPRODUCTIVE MEDICINE, Vol: 37, Pages: 125-129, ISSN: 1526-8004
- Author Web Link
- Cite
- Citations: 6
Dhillo WS, 2019, Kisspeptin, Neurokinin B and New Players in Reproduction Preface, SEMINARS IN REPRODUCTIVE MEDICINE, Vol: 37, Pages: 107-107, ISSN: 1526-8004
- Author Web Link
- Cite
- Citations: 1
Prague JK, Roberts RE, Comninos AN, et al., 2019, Neurokinin 3 Receptor Antagonism Rapidly Improves Vasomotor Symptoms With Sustained Duration of Action, Obstetrical & Gynecological Survey, Vol: 74, Pages: 221-222, ISSN: 0029-7828
Jayasena CN, Alkaabi FM, Liebers CS, et al., 2019, A systematic review of randomised controlled trials investigating the efficacy and safety of testosterone therapy for female sexual dysfunction in postmenopausal women, Clinical Endocrinology, Vol: 90, Pages: 391-414, ISSN: 1365-2265
The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomised, placebo-controlled clinical trials suggest that testosterone therapy improves sexual function in post-menopausal women. Some studies suggest that testosterone therapy has additional effects which include increased bone mineral density and decreased serum high density lipoprotein (HDL) cholesterol. Furthermore, the long-term safety profile of testosterone therapy in post-menopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating post-menopausal women. This article is protected by copyright. All rights reserved.
Dhillo WS, 2019, Kisspeptin, Neurokinin B and New Players in Reproduction Preface, SEMINARS IN REPRODUCTIVE MEDICINE, Vol: 37, Pages: 45-45, ISSN: 1526-8004
Liang S, Kinghorn AB, Voliotis M, et al., 2019, Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader, Nature Communications, Vol: 10, Pages: 1-10, ISSN: 2041-1723
Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility. Through selective evolution of ligands by exponential enrichment (SELEX), we identify DNA aptamers that bind specifically to LH and not to related hormones. The aptamers are integrated into electrochemical aptamer-based (E-AB) sensors on a robotic platform. E-AB enables rapid, sensitive and repeatable determination of LH concentration profiles. Bayesian Spectrum Analysis is applied to determine LH pulsatility in three distinct patient cohorts. This technology has the potential to transform the clinical care of patients with reproductive disorders and could be developed to allow real-time in vivo hormone monitoring.
Romero-Ruiz A, Avendaño MS, Dominguez F, et al., 2019, Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications, American Journal of Obstetrics and Gynecology, Vol: 220, Pages: 480.e1-480.e17, ISSN: 0002-9378
BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN: A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue
Jayasena CN, Radia UK, Figueiredo M, et al., 2019, Reduced testicular steroidogenesis and increased semen oxidative stress in male partners as novel markers of recurrent miscarriage, Clinical Chemistry, Vol: 65, Pages: 161-169, ISSN: 1530-8561
BACKGROUND: Recurrent pregnancy loss, (RPL) affecting 1%–2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm quality is reduced in male partners of women with RPL, but the reasons underlying this lower quality are unclear. We hypothesized that these men may have underlying impairments of reproductive endocrine and metabolic function that cause reductions in sperm quality.METHODS: After ethical approval, reproductive parameters were compared between healthy controls and male partners of women with RPL. Semen reactive oxygen species (ROS) were measured with a validated inhouse chemiluminescent assay. DNA fragmentation was measured with the validated Halosperm method.RESULTS: Total sperm motility, progressive sperm motility, and normal morphology were all reduced in the RPL group vs controls. Mean ±SE morning serum testosterone (nmol/L) was 15% lower in RPL than in controls (controls, 19.0 ± 1.0; RPL, 16.0 ± 0.8; P < 0.05). Mean ±SE serum estradiol (pmol/L) was 16% lower in RPL than in controls (controls, 103.1 ± 5.7; RPL, 86.5 ± 3.4; P < 0.01). Serum luteinizing hormone and follicle-stimulating hormone were similar between groups. Mean ±SE ROS (RLU/sec/106 sperm) were 4-fold higher in RPL than in controls (controls, 2.0 ± 0.6; RPL, 9.1 ± 4.1; P < 0.01). Mean ±SE sperm DNA fragmentation (%) was 2-fold higher in RPL than in controls (controls, 7.3 ± 1.0; RPL, 16.4 ± 1.5; P < 0.0001).CONCLUSIONS: Our data suggest that male partners of women with RPL have impaired reproductive endocrine function, increased levels of semen ROS, and sperm DNA fragmentation. Routine reproductive assessment of the male partners may be beneficial in RPL.
Modi M, Dhillo WS, 2019, Neurokinin 3 Receptor Antagonism: A Novel Treatment for Menopausal Hot Flushes, NEUROENDOCRINOLOGY, Vol: 109, Pages: 242-248, ISSN: 0028-3835
- Author Web Link
- Cite
- Citations: 26
Jayasena CN, Luo R, Dimakopoulou A, et al., 2018, Prevalence of abnormal semen analysis and levels of adherence with fertility preservation in men undergoing therapy for newly diagnosed cancer: A retrospective study in 2906 patients, Clinical Endocrinology, Vol: 89, Pages: 798-804, ISSN: 1365-2265
BACKGROUND: Sperm cryopreservation (freezing) should be offered to all men with cancer due to risk of infertility. However, many men with cancer already have impaired spermatogenesis prior to sperm cryopreservation. Furthermore, physical ill-health may hinder attendance of freeze visits. Investigating both the distribution of sperm functions and freeze attendance rates in men with newly diagnosed cancer, may identify patients benefiting from targeted reproductive fertility support. METHODS: We performed a retrospective study of 2906 male patients undergoing sperm cryopreservation prior to cancer therapy at a single UK tertiary centre between 1989 and 2013; all patients were asked to attend three hospital semen collection visits prior to cancer therapy. RESULTS: Fifteen per cent (433/2906) of men with newly diagnosed cancer had severely impaired semen quality (i.e., sperm total motile count, TMC < 1 million) during the first semen collection visit. However, patients with severely impaired semen quality had the poorest attendance of subsequent semen collection visits despite being requested to do so (non-attendance in TMC < 1 million: 43.4%; TMC < 1-30 million: 35.7%, P < 0.05 vs. <1 million; TMC > 30 million: 33.2%, P < 0.01 vs. <1 million). CONCLUSIONS: This study expands understanding of the semen quality of men with newly diagnosed cancer, and their ability to adhere to fertility preservation recommendations. Our data suggest that patients with the poorest semen quality paradoxically suffer the poorest attendance rates of sperm cryopreservation appointments prior to commencing cancer therapy. We suggest that additional support may be of clinical benefit to men with newly diagnosed cancer and TMC < 1 million sperm.
Izzi-Engbeaya CN, Comninos AN, Clarke S, et al., 2018, The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans, Diabetes, Obesity and Metabolism, Vol: 20, Pages: 2800-2810, ISSN: 1462-8902
AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.
Comninos A, Demetriou L, Wall M, et al., 2018, Modulations of human resting brain connectivity by Kisspeptin enhance sexual and emotional Functions, JCI insight, Vol: 3, Pages: 1-11, ISSN: 2379-3708
BACKGROUND. Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.METHODS. We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.RESULTS. Kisspeptin’s modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin’s DMN modulation was greater in men with less reward drive (r = –0.489, P = 0.008) and predicted reduced sexual aversion (r = –0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus–globus pallidus (all P < 0.05). Consistent with this, kisspeptin’s enhancement of hippocampus–globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]).CONCLUSION. Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind.
Abbara A, Clarke S, Eng PC, et al., 2018, A SINGLE BOLUS OF THE KISSPEPTIN ANALOGUE, MVT-602, INDUCES A MORE PROLONGED LH SURGE THAN KISSPEPTIN-54 DURING THE FOLLICULAR PHASE OF HEALTHY WOMEN, 74th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM), Publisher: ELSEVIER SCIENCE INC, Pages: E103-E103, ISSN: 0015-0282
Abbara A, Clarke S, Eng PC, et al., 2018, Clinical and biochemical characteristics of patients presenting with pituitary apoplexy, Endocrine Connections, Vol: 7, Pages: 1058-1066, ISSN: 2049-3614
PurposeTo review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre.MethodsWe retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 and 2015.ResultsWe identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5–57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100 nmol/L was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient.ConclusionsIn conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.
Mills EGA, Dhillo WS, Comninos AN, 2018, Kisspeptin and the control of emotions, mood and reproductive behaviour, J Endocrinol, Vol: 239, Pages: R1-R12
Reproduction is fundamental for the survival of all species and requires meticulous synchronisation of a diverse complement of neural, endocrine and related behaviours. The reproductive hormone kisspeptin (encoded by the KISS1/Kiss1 gene) is now a well-established orchestrator of reproductive hormones, acting upstream of gonadotrophin-releasing hormone (GnRH) at the apex of the hypothalamic–pituitary–gonadal (HPG) reproductive axis. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network implicated in sexual and emotional behaviours. We are now forming a more comprehensive appreciation of extra-hypothalamic kisspeptin signalling and the complex role of kisspeptin as an upstream mediator of reproductive behaviours, including olfactory-driven partner preference, copulatory behaviour, audition, mood and emotion. An increasing body of research from zebrafish to humans has implicated kisspeptin in the integration of reproductive hormones with an overall positive influence on these reproductive behaviours. In this review, we critically appraise the current literature regarding kisspeptin and its control of reproductive behaviour. Collectively, these data significantly enhance our understanding of the integration of reproductive hormones and behaviour and provide the foundation for kisspeptin-based therapies to treat related disorders of body and mind.
Mills EG, Dhillo WS, Comninos AN, 2018, Kisspeptin and the control of emotions, mood and reproductive behaviour, Journal of Endocrinology, Vol: 239, Pages: R1-R12, ISSN: 1479-6805
Reproduction is fundamental for the survival of all species and requires meticulous synchronisation of a diverse complement of neural, endocrine and related behaviours. The reproductive hormone kisspeptin (encoded by the KISS1/kiss1 gene), is now a well-established orchestrator of reproductive hormones, acting upstream of gonadotrophin releasing hormone (GnRH) at the apex of the hypothalamic-pituitary-gonadal (HPG) reproductive axis. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network implicated in sexual and emotional behaviours. We are now forming a more comprehensive appreciation of extra-hypothalamic kisspeptin signalling and the complex role of kisspeptin as an upstream mediator of reproductive behaviours, including olfactory-driven partner preference, copulatory behaviour, audition, mood and emotion. An increasing body of research from zebrafish to humans has implicated kisspeptin in the integration of reproductive hormones with an overall positive influence on these reproductive behaviours. In this review, we critically appraise the current literature regarding kisspeptin and its control of reproductive behaviour. Collectively, these data significantly enhance our understanding of the integration of reproductive hormones and behaviour and provide the foundation for kisspeptin-based therapies to treat related disorders of body and mind.
Abbara A, Clarke S, Nesbitt A, et al., 2018, Interpretation of serum gonadotropin levels in hyperprolactinemia, Neuroendocrinology, Vol: 107, Pages: 105-113, ISSN: 0028-3835
Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. Methods: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). Results: In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. Conclusion: The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.
Gardiner JV, Ma Y, Ratnasabapathy R, et al., 2018, Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis, Diabetes, Obesity and Metabolism, Vol: 20, Pages: 2246-2254, ISSN: 1462-8902
AimsGlucokinase (GK) serves as a glucose sensor in several tissues including glucose‐sensitive neurons of the arcuate nucleus within the hypothalamus. We have previously demonstrated a role for arcuate GK in the regulation of food and glucose intake. However, its role in the regulation of glucose homeostasis is less clear. We therefore sought to investigate the role of arcuate GK in the regulation of glucose homeostasis.Materials and MethodsRecombinant adeno‐associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus. GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A. The effect of altered arcuate nucleus GK activity on glucose homeostasis was subsequently investigated using glucose and insulin tolerance tests.ResultsIncreased GK activity specifically within the arcuate nucleus increased insulin secretion and improved glucose tolerance in rats during oral glucose tolerance tests. Decreased GK activity in this nucleus reduced insulin secretion and increased glucose levels during the same tests. Insulin sensitivity was not affected in either case. The effect of arcuate nucleus glucokinase was maintained in a model of type 2 diabetes.ConclusionsThese results demonstrate a role for arcuate nucleus GK in systemic glucose homeostasis.
Abbara A, Clarke SA, Dhillo WS, 2018, Novel concepts for inducing final oocyte maturation in IVF (In Vitro Fertilization) Treatment., Endocr Rev
Infertility affects 1 in 6 of the population and increasingly couples require treatment with assisted reproductive techniques (ART). In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotrophin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication 'ovarian hyperstimulation syndrome' (OHSS), which can cause significant morbidity and rarely even mortality in otherwise healthy women. The use of GnRH agonists (GnRHa) has been pioneered over the last two decades to provide a safer option to induce final oocyte maturation. More recently, the neuropeptide kisspeptin, a hypothalamic regulator of GnRH release, has been investigated as a novel inductor of oocyte maturation.The hormonal stimulus used to induce oocyte maturation has a major impact on the success (retrieval of oocytes and chance of implantation) and safety (risk of OHSS) of IVF treatment. This review aims to appraise experimental and clinical data of hormonal approaches used to induce final oocyte maturation by either hCG, GnRHa, both GnRHa and hCG administered in combination, recombinant LH, or kisspeptin. We also examine evidence for the timing of administration of the inductor of final oocyte maturation in relation to parameters of follicular growth and the subsequent interval to oocyte retrieval.In summary, we review data on the efficacy and safety of the major hormonal approaches used to induce final oocyte maturation in clinical practice, as well as some novel approaches that may offer fresh alternatives in future.
Yang L, Comninos AN, Dhillo WS, 2018, Author Correcdtion: Intrinsic links among sex, emotion, and reproduction, Cellular and Molecular Life Sciences, Vol: 75, Pages: 2489-2489, ISSN: 1420-682X
Author Correction: Cellular and Molecular Life Sciences https://doi.org/10.1007/s00018-018-2802-3The original version of this article unfortunately contained a mistake. The text below the section head “Kisspeptin’s role in sex and emotion” was incorrectly stated as “The first evidence for kisspeptin’s role in sexual behaviour came from Keller et al., who show that peripheral administration of kisspeptin stimulates the lordosis reflex in female mice [30]”. Later, Kauffman and colleagues, demonstrate that testosterone-replaced Kiss1r knock-out male mice lack”.The correct text should read as follows “Evidence for kisspeptin’s role in female sexual behaviour comes from Hellier et al., who show that peripheral administration of kisspeptin affects mate preference and copulatory behaviour in female mice [30]. Kauffman and colleagues demonstrate that testosterone-replaced Kiss1r knock-out male mice lack”.
Abbara A, Islam R, Clarke S, et al., 2018, Clinical parameters of ovarian hyperstimulation syndrome (OHSS) following different hormonal triggers of oocyte maturation in IVF treatment', Clinical Endocrinology, Vol: 88, Pages: 920-927, ISSN: 1365-2265
ObjectiveOvarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to the hormone used to induce oocyte maturation during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently been demonstrated to safely trigger final oocyte maturation during IVF treatment even in women at high risk of OHSS. However, to date, the safety of kisspeptin has not been compared to current hormonal triggers of oocyte maturation.DesignWe conducted a retrospective single‐centre cohort study investigating symptoms and clinical parameters of early OHSS in women at high risk of OHSS (antral follicle count or total number of follicles on day of trigger ≥23) triggered with human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99) or kisspeptin (n = 122) at Hammersmith Hospital IVF unit, London, UK (2013‐2016).ResultsClinical Parameters of OHSS: Median ovarian volume was larger following hCG (138 ml) than GnRHa (73 ml; P < .0001), and in turn kisspeptin (44 ml; P < .0001). Median ovarian volume remained enlarged 20‐fold following hCG, 8‐fold following GnRHa and 5‐fold following kisspeptin compared to prestimulation ovarian volumes. Mean (±SD) ascitic volumes were lesser following GnRHa (9 ± 44 ml) and kisspeptin (5 ± 8 ml) than hCG (62 ± 84 ml; P < .0001). Symptoms of OHSS were most frequent following hCG and least frequent following kisspeptin. Diagnosis of OHSS: The odds ratio for OHSS diagnosis was 33.6 (CI 12.6‐89.5) following hCG and 3.6 (CI 1.8‐7.1) following GnRHa, when compared to kisspeptin.ConclusionTriggering oocyte maturation by inducing endogenous gonadotrophin release is preferable to the use of exogenous hCG in women at high risk of OHSS.
Yang L, Comninos AN, Dhillo WS, 2018, Intrinsic links among sex, emotion, and reproduction, Cellular and Molecular Life Sciences, Vol: 75, Pages: 2197-2210, ISSN: 1420-682X
Species survival is dependent on successful reproduction. This begins with a desire to mate, followed by selection of a partner, copulation and in monogamous mammals including humans, requires emotions and behaviours necessary to maintain partner bonds for the benefit of rearing young. Hormones are integral to all of these stages and not only mediate physiological and endocrine processes involved in reproduction, but also act as neuromodulators within limbic brain centres to facilitate the expression of innate emotions and behaviours required for reproduction. A significant body of work is unravelling the roles of several key hormones in the modulation of mood states and sexual behaviours; however, a full understanding of the integration of these intrinsic links among sexual and emotional brain circuits still eludes us. This review summarises the evidence to date and postulates future directions to identify potential psycho-neuroendocrine frameworks linking sexual and emotional brain processes with reproduction.
Takacs S, Bardoczi Z, Skrapits K, et al., 2018, <i>Post mortem</i> single-cell labeling with DiI and immunoelectron microscopy unveil the fine structure of kisspeptin neurons in humans, BRAIN STRUCTURE & FUNCTION, Vol: 223, Pages: 2143-2156, ISSN: 1863-2653
- Author Web Link
- Cite
- Citations: 4
Comninos A, Yang L, Abbara A, et al., 2018, Frequent falls and confusion: recurrent hypoglycaemia in a patient with tuberous sclerosis complex, Clinical Case Reports, Vol: 6, Pages: 904-909, ISSN: 2050-0904
Recurrent hypoglycaemia is common, but its presentation is often insidious resulting in delays in diagnosis and significant morbidity. We describe a case of an insulinoma presenting with falls and confusion in a patient with Tuberous Sclerosis, demonstrating the importance of early hypoglycaemia identification and a potential shared molecular pathogenesis.
Abbara A, Narayanaswamy S, Izzi-Engbeaya C, et al., 2018, Hypothalamic response to kisspeptin and pituitary response to GnRH are preserved in healthy older men, Neuroendocrinology, Vol: 106, ISSN: 0028-3835
Background: Male testosterone levels decline by 1% per year from the age of 40yrs. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin and the pituitary response to GnRH of older men with those of young men. Methods: Following 1 hour of baseline sampling, healthy older men (n=5, mean age 59.3±2.9yrs) received a 3 hour intravenous infusion (IVI) of either: vehicle, kisspeptin-54 0.1, 0.3, 1.0nmol/kg/h, or GnRH 0.1nmol/kg/h on 5 different study days. Serum gonadotropins and total testosterone were measured every 10 minutes and compared to young men (n=5/group) (mean age 28.9±2.0yrs) with a similar BMI (24 kg/m2) who underwent the same protocol. Results: Kisspeptin and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (P<0.001 for all groups). Gonadotropin response to kisspeptin was at least preserved in older men when compared with young men. At the highest dose of kisspeptin (1.0nmol/kg/h), a significantly greater LH (P=0.003) response was observed in older men. The FSH response to GnRH was increased in older men (P=0.002), but the LH response was similar (P=0.38). Serum testosterone rises following all doses of kisspeptin (P≤0.009) were reduced in older men. Conclusions: Our data suggests that healthy older men without late onset hypogonadism (LOH) have preserved hypothalamic response to kisspeptin and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin to identify hypothalamic deficits in men with LOH.
Owens L, Abbara A, Lerner A, et al., 2018, The in vivo and in vitro effects of kisspeptin on human ovarian function, Publisher: SPRINGER LONDON LTD, Pages: S181-S182, ISSN: 0021-1265
Lehman MN, Coolen LM, Steiner RA, et al., 2018, The 3rd World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond": Unresolved questions, challenges and future directions for the field, Journal of Neuroendocrinology, Vol: 30, ISSN: 0953-8194
The 3rd World Conference on Kisspeptin, “Kisspeptin 2017: Brain and Beyond” was held on 30-31 March at the Rosen Centre Hotel in Orlando, Florida, providing an international forum for multidisciplinary scientists to meet and share cutting-edge research on kisspeptin biology and its relevance to human health and disease. The meeting built upon previous world conferences focused on the role of kisspeptin and associated peptides in the control of gonadotrophin-releasing hormone (GnRH) secretion and reproduction. Based on recent discoveries, the scope of this meeting was expanded to include functions of kisspeptin and related peptides in other physiological systems, including energy homeostasis, pregnancy, ovarian and uterine function, and thermoregulation. In addition, discussions addressed the translation of basic knowledge of kisspeptin biology to the treatment of disease, with the goal of seeking consensus about the best approaches to improve human health. The 2-day meeting featured a nontraditional structure, with each day starting with poster sessions followed by lunch discussions and facilitated large-group sessions with short presentations to maximise the exchange of new, unpublished data. Topics were identified by a survey prior to the meeting, and focused on major unresolved questions, important controversies and future directions in the field. Finally, career development activities provided mentoring for trainees and junior investigators, as well as networking opportunities for those individuals with established researchers in the field. Overall, the meeting was rated as a success by attendees and covered a wide range of lively and provocative discussion topics on the changing nature of the field of “kisspeptinology” and its future.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.