Determining the relationship between hot flushes and LH pulses in menopausal women using mathematical modelling
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Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2019-09
Date Acceptance
2019-04-09
Citation
Journal of Clinical Endocrinology and Metabolism, 2019, 104 (9), pp.3628-3636
ISSN
0021-972X
Publisher
Oxford University Press (OUP)
Start Page
3628
End Page
3636
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism
Volume
104
Issue
9
Copyright Statement
© 2019 Endocrine Society. 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).
License URL
Sponsor
National Institute for Health Research
Medical Research Council (MRC)
Grant Number
CDF-2009-02-05
MR/M024954/1
Subjects
Endocrinology & Metabolism
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Publication Status
Published
Date Publish Online
2019-04-15