Determining the relationship between hot flushes and LH pulses in menopausal women using mathematical modelling
dc.contributor.author | Prague, JK | |
dc.contributor.author | Voliotis, M | |
dc.contributor.author | Clarke, S | |
dc.contributor.author | Comninos, AN | |
dc.contributor.author | Abbara, A | |
dc.contributor.author | Jayasena, CN | |
dc.contributor.author | Roberts, RE | |
dc.contributor.author | Yang, L | |
dc.contributor.author | Veldhuis, JD | |
dc.contributor.author | Tsaneva-Atanasova, K | |
dc.contributor.author | Mc Ardle, CA | |
dc.contributor.author | Dhillo, WS | |
dc.date.accessioned | 2019-04-23T14:57:22Z | |
dc.date.issued | 2019-04-15 | |
dc.description.abstract | Background Hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurones regulate LH pulsatility. It is widely accepted that the menopausal hot flush (HF) consistently synchronises with the LH pulse. This suggests that the hypothalamic KNDy neurones are implicated in generating LH pulsatility and HF. Using a modern immunoassay and mathematical modelling we investigated if the HF and LH pulse was consistently synchronised in menopausal women. Methods Eleven menopausal women (51-62yrs experiencing ≥7 HF/24hrs) attended for an 8 hour study where they self-reported HF and underwent peripheral blood sampling every 10 mins. LH pulsatility was determined using two mathematical models: blinded deconvolution analysis and Bayesian spectrum analysis. The probability that the LH pulse and HF event intervals matched was estimated using the interval distributions observed in our data. Results Ninety-six HF were self-reported, and 82 LH pulses were identified by blinded deconvolution analysis. Using both models, the probability that the two event intervals matched was low in the majority of participants (mean P=0.24 (P=1 reflects perfect association)). Interpretation Our data challenges the widely accepted dogma that HF consistently synchronise with an LH pulse, and so has clinically important therapeutic and mechanistic implications. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Engineering and Physical Sciences Research Council (EPSRC) | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.identifier.citation | Published online 15 April 2019 | en_GB |
dc.identifier.doi | 10.1210/jc.2018-02797 | |
dc.identifier.grantnumber | MR/M024954/1 | en_GB |
dc.identifier.grantnumber | EP/N014391/1 | en_GB |
dc.identifier.grantnumber | RP-2014-05-001 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/36887 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press | en_GB |
dc.rights | Copyright © 2019 Endocrine Society. Open access. This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). | en_GB |
dc.title | Determining the relationship between hot flushes and LH pulses in menopausal women using mathematical modelling | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-04-23T14:57:22Z | |
dc.identifier.issn | 0021-972X | |
dc.description | This is the final version. Available on open access from Oxford University Press via the DOI in this record. | en_GB |
dc.identifier.journal | Journal of Clinical Endocrinology & Metabolism | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-04-09 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-04-09 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-04-23T14:52:06Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-07-23T13:45:49Z | |
refterms.panel | B | en_GB |
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Except where otherwise noted, this item's licence is described as Copyright © 2019 Endocrine Society. Open access.
This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).