201 results found
Abbara A, Clarke S, Islam R, et al., 2018, Reply: Clinical trial registry alone is not adequate: on the perception of possible endpoint switching and P-hacking, HUMAN REPRODUCTION, Vol: 33, Pages: 342-344, ISSN: 0268-1161
Abbara A, Clarke SA, Nesbitt A, et al., 2018, Interpretation of serum gonadotropin levels in hyperprolactinemia., Neuroendocrinology
<br>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of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology.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.<br>.
Abbara A, Islam R, Clarke SA, et al., 2018, Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment, CLINICAL ENDOCRINOLOGY, Vol: 88, Pages: 920-927, ISSN: 0300-0664
Abbara A, Narayanaswamy S, Izzi-Engbeaya C, et al., 2018, Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men, NEUROENDOCRINOLOGY, Vol: 106, Pages: 401-410, ISSN: 0028-3835
Abbara A, Vuong LN, Ho VNA, et al., 2018, Follicle Size on Day of Trigger Most likely to Yield a Mature Oocyte, FRONTIERS IN ENDOCRINOLOGY, Vol: 9, ISSN: 1664-2392
Algeffari M, Jayasena CN, MacKeith P, et al., 2018, Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials, DIABETIC MEDICINE, Vol: 35, Pages: 195-202, ISSN: 0742-3071
Cassatella D, Howard SR, Acierno JS, et al., 2018, Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures, EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol: 178, Pages: 377-388, ISSN: 0804-4643
Comninos AN, Dhillo WS, 2018, Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing, NEUROENDOCRINOLOGY, Vol: 106, Pages: 195-202, ISSN: 0028-3835
Comninos AN, Yang L, Abbara A, et al., 2018, Frequent falls and confusion: recurrent hypoglycemia in a patient with tuberous sclerosis complex, CLINICAL CASE REPORTS, Vol: 6, Pages: 904-909, ISSN: 2050-0904
Law J, Morris DE, Izzi-Engbeaya C, et al., 2018, Thermal Imaging Is a Noninvasive Alternative to PET/CT for Measurement of Brown Adipose Tissue Activity in Humans, JOURNAL OF NUCLEAR MEDICINE, Vol: 59, Pages: 516-522, ISSN: 0161-5505
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., J Neuroendocrinol
The 3rd World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond" was held March 30-31 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 gonadotropin-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 two-day meeting featured a non-traditional structure, with each day starting with poster sessions followed by lunch discussions and facilitated large-group sessions with short presentations to maximize 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, and 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 article is protected by copyright. All rights reserved.
Ma Y, Ratnasabapathy R, Izzi-Engbeaya C, et al., 2018, Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis., Diabetes Obes Metab
AIMS: To investigate the role of arcuate glucokinase (GK) in the regulation of glucose homeostasis. MATERIALS AND METHODS: A recombinant adeno-associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus (arc). GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A. The effect of altered arc GK activity on glucose homeostasis was subsequently investigated using glucose and insulin tolerance tests. RESULTS: Increased GK activity specifically within the arc 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 arc GK was maintained in a model of type 2 diabetes. CONCLUSIONS: These results demonstrate a role for arc GK in systemic glucose homeostasis.
Owens LA, Abbara A, Lerner A, et al., 2018, The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function, HUMAN REPRODUCTION, Vol: 33, Pages: 292-302, ISSN: 0268-1161
Prague JK, Roberts RE, Comninos AN, et al., 2018, Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action., Menopause
OBJECTIVE: Seventy percent of postmenopausal women experience vasomotor symptoms, which can be highly disruptive and persist for years. Hormone therapy and other treatments have variable efficacy and/or side effects. Neurokinin B signaling increases in response to estrogen deficiency and has been implicated in hot flash (HF) etiology. We recently reported that a neurokinin 3 receptor (NK3R) antagonist reduces HF in postmenopausal women after 4 weeks of treatment. In this article we report novel data from that study, which shows the detailed time course of this effect. METHODS: Randomized, double-blind, placebo-controlled, single-center, crossover trial of an oral NK3R antagonist (MLE4901) for vasomotor symptoms in women aged 40 to 62 years, experiencing ≥7 HF/24 hours some of which were reported as bothersome or severe (Clinicaltrials.gov NCT02668185). Thirty-seven women were randomized and included in an intention-to-treat analysis. To ascertain the therapeutic profile of MLE4901, a post hoc time course analysis was completed. RESULTS: By day 3 of treatment with MLE4901, HF frequency reduced by 72% (95% CI, -81.3 to -63.3%) compared with baseline (51 percentage point reduction compared with placebo, P < 0.0001); this effect size persisted throughout the 4-week dosing period. HF severity reduced by 38% compared with baseline by day 3 (95% CI, -46.1 to -29.1%) (P < 0.0001 compared with placebo), bother by 39% (95% CI, -47.5 to -30.1%) (P < 0.0001 compared with placebo), and interference by 61% (95% CI, -79.1 to -43.0%) (P = 0.0006 compared with placebo); all continued to improve throughout the 4-week dosing period (to -44%, -50%, and -70%, respectively by day 28, all P < 0.0001 compared with placebo). CONCLUSIONS: NK3R antagonism rapidly relieves vasomotor symptoms without the need for estrogen exposure.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND)
Takacs S, Bardoczi Z, Skrapits K, et al., 2018, Post mortem 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
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
Yang L, Comninos AN, Dhillo WS, 2018, Intrinsic links among sex, emotion, and reproduction (vol 75, pg 2197, 2018), CELLULAR AND MOLECULAR LIFE SCIENCES, Vol: 75, Pages: 2489-2489, ISSN: 1420-682X
de Tassigny XD, Jayasena CN, Murphy KG, et al., 2018, Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo (vol 12, e0176821, 2017), PLOS ONE, Vol: 13, ISSN: 1932-6203
Abbara A, Clarke S, Islam R, et al., 2017, A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial, HUMAN REPRODUCTION, Vol: 32, Pages: 1915-1924, ISSN: 0268-1161
Bhatt PS, Dhillo WS, Salem V, 2017, Human brown adipose tissue - function and therapeutic potential in metabolic disease, CURRENT OPINION IN PHARMACOLOGY, Vol: 37, Pages: 1-9, ISSN: 1471-4892
Comninos AN, Wall MB, Demetriou L, et al., 2017, Kisspeptin modulates sexual and emotional brain processing in humans, JOURNAL OF CLINICAL INVESTIGATION, Vol: 127, Pages: 709-719, ISSN: 0021-9738
Hameed S, Patterson M, Dhillo WS, et al., 2017, Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight, CELL REPORTS, Vol: 19, Pages: 2202-2209, ISSN: 2211-1247
Katugampola H, King PJ, Chatterjee S, et al., 2017, Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 102, Pages: 3349-3359, ISSN: 0021-972X
Prague JK, Dhillo WS, 2017, Neurokinin 3 receptor antagonism - the magic bullet for hot flushes?, CLIMACTERIC, Vol: 20, Pages: 505-509, ISSN: 1369-7137
Prague JK, Dhillo WS, 2017, Treating hot flushes with a neurokinin 3 receptor antagonist, ONCOTARGET, Vol: 8, Pages: 106153-106154, ISSN: 1949-2553
Prague JK, Roberts RE, Comninos AN, et al., 2017, Neurokinin 3 receptor antagonism is a highly effective, novel treatment for menopausal hot flushes with rapid onset: a phase 2, randomised, double-blind, placebo-controlled trial, 28th Annual Meeting of the North-American-Menopause-Society, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1429-1430, ISSN: 1072-3714
Prague JK, Roberts RE, Comninos AN, et al., 2017, Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial, LANCET, Vol: 389, Pages: 1809-1820, ISSN: 0140-6736
Vimalesvaran S, Narayanaswamy S, Yang L, et al., 2017, Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea., Endocrinol Diabetes Metab Case Rep, Vol: 2017, ISSN: 2052-0573
SUMMARY: Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. LEARNING POINTS: Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a
Wernig F, Jayasena CN, Dhillo WS, 2017, Carcinoid syndrome and neuroendocrine tumours, Medicine (United Kingdom), Vol: 45, Pages: 543-546, ISSN: 1357-3039
© 2017 Neuroendocrine tumours (NETs) arise from the gastrointestinal tract, pancreas, bronchi or other rare primary sites and comprise a variety of different tumour types. Carcinoid tumours are the most common. NETs can be associated with a variety of clinical syndromes. For instance, classic symptoms of carcinoid syndrome, such as flushing and diarrhoea, occur because of the release of hormones, including serotonin, tachykinins and peptide hormones. However, most NETs are non-secretory in nature and are detected incidentally or through compression of surrounding structures. Liver metastasis has usually already occurred at the time of diagnosis. Surgery can be curative if disease is entirely localized. Injections of somatostatin analogues such as octreotide are the mainstay of non-surgical treatment for NETs. Surgical debulking and embolization techniques are useful to reduce tumour bulk in patients who remain symptomatic despite medical treatment. Peptide receptor radionucleotide therapy using radiolabelled somatostatin analogues has recently been shown to prolong progression-free survival. Furthermore, several novel agents, such as everolimus, have emerged in the treatment of patients with metastatic disease. This article aims to summarize the pathophysiology and clinical features of NETs, with a focus on carcinoid syndrome. It also discusses recent advances in clinical management of NETs.
de Tassigny XD, Jayasena C, Murphy KG, et al., 2017, Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo, PLOS ONE, Vol: 12, ISSN: 1932-6203
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