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Determining the Relationship Between Hot Flushes and LH Pulses in Menopausal Women Using Mathematical Modeling

Research output: Contribution to journalArticle

  • Julia K. Prague
  • Margaritis Voliotis
  • Sophie Clarke
  • Alexander N. Comninos
  • Ali Abbara
  • Channa N. Jayasena
  • Rachel E. Roberts
  • Lisa Yang
  • Johannes D. Veldhuis
  • Krasimira Tsaneva-Atanasova
  • Craig A. McArdle
  • Waljit S. Dhillo
Original languageEnglish
Pages (from-to)3628-3636
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
Early online date15 Apr 2019
DateAccepted/In press - 9 Apr 2019
DateE-pub ahead of print - 15 Apr 2019
DatePublished (current) - 1 Sep 2019


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.

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Copyright © 2019 Endocrine Society.

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