Searchable abstracts of presentations at key conferences in endocrinology

ea0032p887 | Pituitary – Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2013

Gender determines ACTH recovery after experimental hypercortisolemia in older individuals

Sharma Animesh , Aoun Paul , Wigham Jean , Weist Sue , Veldhuis Johannes

Introduction: Available clinical literature raises the possibility that stress-responsive mechanisms differ by gender, especially in older individuals; however the accompanying evidence is both limited and discrepant. We hypothesize that gender determines the degree of ACTH inhibition by and recovery after an experimental cortisol clamp in older subjects.Subjects and design: We conducted a prospectively randomized, double-blind, placebo-controlled, cross...

ea0043oc12 | Cardiovascular Outcome Studies | WCTD2016

Interleukins 6 and 8 and abdominal fat depots are distinct correlates of lipid moieties in healthy pre- and postmenopausal women

Veldhuis Johannes , Dyer Roy , Trushin Sergey , Bondar Olga , Singh Ravinder , Klee George

Purpose: Available data associate lipids concentrations in men with BMI, anabolic steroids, age, and certain cytokines. Data are less clear in women, especially across the full adult lifespan, and when segmented by pre- and postmenopausal status.Methods: Subjects: 120 healthy women in Olmsted County, MN, USA, a stable well studied clinical population. Dependent variables: measurements of 10-hr fasting high-density lipoprotein cholesterol (HDL-C), total c...

ea0028oc1.1 | Young Endocrinologists prize session | SFEBES2012

Functional characterisation and translational clinical applications of kisspeptin-10

George Jyothis , Quinton Richard , Young Jacques , Veldhuis Johannes , Millar Robert , Anderson Richard

Hypothesis: Exogenous kisspeptin-10 (Kp10) enhances pulsatile LH. Research strategy: A first-in-man dosing study of kp10 was first performed. Healthy volunteers and hypogonadal patients were subsequently infused with kp10. Dose titration study Rapid increases in LH with clear dose-dependency (P<0.0001) were observed in healthy men (n=6), with the 0.3 and 1 µg/kg doses being maximally stimulatory (P<0.01). Effect of sex-steroid milieu: LH respo...

ea0034yep1.2 | SfE Young Endocrinologists' prize lectures | SFEBES2014

Clinical effects of kisspeptin on reproductive hormone secretion, LH pulsatility and oocyte maturation

Jayasena Channa , Abbara Ali , Comninos Alexander , Nijher Gurjinder , Veldhuis Johannes , Carby Anna , Trew Geoffrey , Ghatei Mohammad , Bloom Stephen , Dhillo Waljit

A decade ago, genetic disruption of the kisspeptin signalling pathway was observed to cause hypogonadotrophic hypogonadism. Hypothalamic kisspeptin acts by stimulating secretion of endogenous GnRH. Our research has investigated the physiological effects of kisspeptin in women, with the overarching aim of determining if kisspeptin could be used to treat women with infertility.We initially observed that s.c. bolus injection of kisspeptin acutely stimulated...

ea0014p231 | (1) | ECE2007

Pioglitazone treatment significantly decreases 5-alpha reductase activity and improves metabolic risk factors in PCOS

Glintborg Dorte , Hermann Anne Pernille , Hagen Claus , Veldhuis Johannes , Schmedes Anne , Frystyk Jan , Flyvbjerg Allan , Andersen Marianne

Objective: To investigate the effect of pioglitazone on cortisol metabolism in PCOS.Design: Thirty insulin resistant PCOS patients were randomized to either 16 weeks of pioglitazone (30 mg/day) or placebo treatment. Before and after intervention, patients underwent 24 h 20 min.-integrated blood sampling for measurement of cortisol and 24 h excretion of cortisol, cortisone and steroid metabolites (cortisol, corticosteron, androgen, and 17-hydroxyprogester...

ea0038oc1.1 | Early Career Oral Communications | SFEBES2015

A novel pharmacological approach to target LH and testosterone hypersecretion in women with polycystic ovary syndrome: a randomised, double-blind, placebo-controlled multi-centre randomised clinical trial of the neurokinin B receptor antagonist AZD4901

George Jyothis , Kakkar Rahul , Marshall Jayne , Scott Martin , Finkelman Richard , Ho Tony , McIntosh Stuart , Veldhuis Johannes , Skorupskaite Karolina , Anderson Richard , Webber Lorraine

LH hyper-secretion, driven by increased GnRH pulsatility, underpins excess testosterone secretion – a key clinical feature of PCOS.The kisspeptin-neurokinin B (NKB)-GnRH pathway has emerged as the pivotal regulator of reproduction. We hypothesised that pharmacologic blockade of NKB may address the central pathophysiology of LH hyper-secretion and hyperandrogenism in PCOS. We undertook a randomised, double blind, placebo-controlled multi-centre Phase...

ea0035oc3.1 | Neuroendocrinology &amp; Signalling | ECE2014

Constant intravenous infusion of kisspeptin-54 restores LH pulsatility in women with hypothalamic amenorrhoea

Jayasena Channa , Abbara Ali , Comninos Alexander , Veldhuis Johannes , Nihjer Gurjinder , Ganiyu-Dada Zainab , Mehta Amrish , Todd Catriona , Ghatei Mohammad , Bloom Stephen , Dhillo Waljit

Background: Women with hypothalamic amenorrhoea (HA) have reduced LH pulsatility causing amenorrhea and infertility. Estrogen supplementation provides symptomatic relief for women with HA, but does not restore the pulsatile pattern of LH secretion which necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulates GNRH secretion within the hypothalamus. The effect of exogenous kisspeptin-54 administration on LH pulsatility in women with HA ...

ea0031oc1.8 | Young Endocrinologists prize session | SFEBES2013

Kisspeptin advances ovulation in healthy women

Comninos Alexander , Jayasena Channa , Nijher Monica , Abbara Ali , De Silva Akila , Veldhuis Johannes , Ratnasabapathy Risheka , Izzi-Engbeaya Chioma , Lim Adrian , Patel Daksha , Ghatei Mohammad , Bloom Steve , Dhillo Waljit

Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to profound tachyphylaxis in women with hypothalamic amenorrhoea. It is not known whether exogenous kisspeptin can alter the m...

ea0050oc1.1 | Early Career Oral Communications | SFEBES2017

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

Prague Julia , Roberts Rachel , Comninos Alexander , Clarke Sophie , Jayasena Channa , Nash Zachary , Doyle Chedie , Papadopoulou Deborah , Bloom Stephen , Mohideen Pharis , Lin Vivian , Stern Theresa , Panay Nicholas , Hunter Myra , Veldhuis Johannes , Webber Lorraine , Huson Les , Dhillo Waljit

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...