OR11-4 Determining the Relationship between Hot Flushes and LH Pulses in Menopausal Women Using Mathematical Modelling

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 8hr study where they self‐reported HF and underwent peripheral blood sampling every 10mins. LH pulsatility was determined using two mathematical models. Firstly, blinded deconvolution analysis was used to identify LH peaks and the likelihood that they coincide with self‐reported hot flushes. Secondly Bayesian spectrum analysis was used to determine the probability distribution for LH pulse intervals and the probability of a match between the LH peak and self‐reported hot flush intervals. 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. For both methods (BSA and blinded deconvolution analysis) the probability of a match for the intervals between the LH pulses and hot flushes varied greatly between participants (lowest P=0.062 to highest P=0.816, where P=1 reflects a perfect match). For the majority of participants (8/11) the probability of a match was <0.5 suggesting a weak association between the occurrence of the hot flush and the LH pulse in the majority of menopausal women. 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: Using two independent and established mathematical models we have demonstrated that in the majority of menopausal women in this study there was no clear association between LH pulse and hot flush interval. Our data challenges the widely accepted dogma that HF consistently synchronise with an LH pulse. This suggests that hypothalamic KNDy neurones regulate LH pulsatility and HF by different pathways, and so has clinically important therapeutic and mechanistic implications. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.