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Dive into the research topics where Deborah Papadopoulou is active.

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Featured researches published by Deborah Papadopoulou.


The Lancet | 2017

Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: A phase 2, randomised, double-blind, placebo-controlled trial

Julia K. Prague; Rachel Roberts; Alexander Comninos; Sophie Clarke; Channa N. Jayasena; Zachary Nash; Chedie Doyle; Deborah Papadopoulou; Stephen R. Bloom; Pharis Mohideen; Nicholas Panay; Myra Hunter; Johannes D. Veldhuis; Lorraine Webber; Les Huson; Waljit S. Dhillo

Summary Background Hot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes. Methods This phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. Eligible participants were healthy women aged 40–62 years, having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome, who had not had a menstrual period for at least 12 months, and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks. Participants received 4 weeks of MLE4901 (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. Randomisation was completed by a central computer, and participants were allocated to treatment number in numerical order. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. All analyses were prespecified in the study protocol. The trial is registered at ClinicalTrials.gov, number NCT02668185. Findings 68 women were screened between Feb 3 and Oct 10, 2016, of which 37 were randomly assigned and included in an intention-to-treat analysis. 28 participants completed the trial and were included in a per-protocol analysis. MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22–67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 [95% CI 40·81–58·56] vs MLE4901 19·35 [15·99–23·42]; adjusted estimate of difference 29·66 [17·39–42·87], p<0·0001). Treatment was well tolerated. Three participants developed a transaminase rise (alanine aminotransferase 4·5–5·9 times the upper limit of normal) with a normal bilirubin 28 days after starting MLE4901, which normalised within 90 days. Interpretation Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure. Larger scale studies of longer duration are now indicated. Funding UK Medical Research Council and National Institute for Health Research.


The Journal of Clinical Endocrinology and Metabolism | 2016

Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men

Shakunthala Narayanaswamy; Julia K. Prague; Channa N. Jayasena; Deborah Papadopoulou; Maria Mizamtsidi; Amar Shah; Paul Bassett; Alexander Comninos; Ali Abbara; Stephen R. Bloom; Johannes D. Veldhuis; Waljit S. Dhillo

Context: A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits. Objective: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. Design, Setting, and Participants: This was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. Intervention and Main Outcome Measure: After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. Results: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle). Conclusions: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.


Clinical Endocrinology | 2016

Subcutaneous infusion of kisspeptin‐54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels

Shakunthala Narayanaswamy; Channa N. Jayasena; Noel Ng; Risheka Ratnasabapathy; Julia K. Prague; Deborah Papadopoulou; Ali Abbara; Alexander Comninos; Paul Bassett; Stephen R. Bloom; Johannes D. Veldhuis; Waljit S. Dhillo

Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin‐54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin.


Neuroendocrinology | 2018

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men

Ali Abbara; Shakunthala Narayanaswamy; Chioma Izzi-Engbeaya; Alexander Comninos; Sophie Clarke; Zainab Malik; Deborah Papadopoulou; Ailish Clobentz; Zubair Sarang; Paul Bassett; Channa N. Jayasena; Waljit S. Dhillo

Background: Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men. Methods: Following 1 h of baseline sampling, healthy older men (n = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (n = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m2) who underwent the same protocol. Results: Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (p < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (p = 0.003) response was observed in older men. The follicle-stimulating hormone (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-54 (p ≤ 0.009) were reduced in older men. Conclusions: Our data suggest that healthy older men without late-onset hypogonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH.


Diabetes, Obesity and Metabolism | 2018

The Effects of Kisspeptin on β-cell Function, Serum Metabolites and Appetite in Humans.

Chioma Izzi-Engbeaya; Alexander Comninos; Sophie Clarke; Anne Jomard; Lisa Yang; S. C. P. Jones; Ali Abbara; Shakunthala Narayanaswamy; Pei Chia Eng; Deborah Papadopoulou; Julia K. Prague; Paul Bech; Ian F. Godsland; Paul Bassett; Caroline Sands; Stephane Camuzeaux; María Gómez-Romero; Jake T. M. Pearce; Matthew R. Lewis; Elaine Holmes; Jeremy K. Nicholson; Tricia Tan; Risheka Ratnasabapathy; Ming Hu; Gaelle Carrat; Lorenzo Piemonti; Marco Bugliani; Piero Marchetti; Paul Johnson; Stephen J. Hughes

To investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.


Human Reproduction | 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

Ali Abbara; Sophie Clarke; Rumana Islam; Julia K. Prague; Alexander Comninos; Shakunthala Narayanaswamy; Deborah Papadopoulou; Rachel Roberts; Chioma Izzi-Engbeaya; Risheka Ratnasabapathy; Alexander Nesbitt; Sunitha Vimalesvaran; R. Salim; Stuart Lavery; Stephen R. Bloom; Les Huson; Geoffrey Trew; Waljit S. Dhillo


Human Reproduction | 2018

Reply: Clinical trial registry alone is not adequate: on the perception of possible endpoint switching and P-hacking

Ali Abbara; Sophie Clarke; Rumana Islam; Julia K. Prague; Alexander Comninos; Shakunthala Narayanaswamy; Deborah Papadopoulou; Rachel Roberts; Chioma Izzi-Engbeaya; Risheka Ratnasabapathy; Alexander Nesbitt; Sunitha Vimalesvaran; R. Salim; Stuart Lavery; Stephen R. Bloom; Les Huson; Geoffrey Trew; Waljit S. Dhillo


Society for Endocrinology BES 2017 | 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

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


Society for Endocrinology BES 2017 | 2017

Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels

Shakunthala Narayanaswamy; Channa N. Jayasena; Noel Ng; Risheka Ratnasabapathy; Julia K. Prague; Deborah Papadopoulou; Ali Abbara; Alexander Comninos; Paul Bassett; Stephen R. Bloom; Johannes D. Veldhuis; Waljit S. Dhillo


Maturitas | 2017

Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: A phase 2, randomised, double-blind, placebo controlled trial

Julia K. Prague; Rachel Roberts; Alexander Comninos; Sophie Clarke; Channa N. Jayasena; Zachary Nash; Chedie Doyle; Deborah Papadopoulou; Stephen R. Bloom; Pharis Mohideen; Nicholas Panay; Myra Hunter; Johannes D. Veldhuis; Lorraine Webber; Les Huson; Waljit S. Dhillo

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Ali Abbara

Imperial College London

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Les Huson

Imperial College London

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