FRI408 Metabolic Hormone- And Energy-related-factors Are Associated With The Pulsatile LH Secretion Response To Short-term Energy Restriction In Healthy Women
Authors: Shekhar Skand , Tonleu Joselyne Tessa , Brown Ethan Devin , Okigbo Chinelo , Helen Leka , Kim Anne E , Purse Bona , Zaccaro Daniel , Soldin Steven John , Hirsch Katie , Smith-Ryan Abbie , Hall Janet Elizabeth 
Published: October 2023

Disclosure: S. Shekhar: None. J. Tessa Tonleu: None. E.D. Brown: None. C. Okigbo: None. L. Helen: None. A.E. Kim: None. B. Purse: None. D. Zaccaro: None. S.J. Soldin: None. K. Hirsch: None. A. Smith-Ryan: None. J.E. Hall: None.

Introduction: Functional hypothalamic amenorrhea is characterized by reproductive dysfunction in a deficient energy state mediated through suppressed secretion of pulsatile GnRH. We investigated the relationship between metabolic, appetite, energy, body composition and attitude variables with LH pulse frequency responses.

Methods: Two 5-day dietary interventions were administered to nineteen regularly cycling, healthy women (mean age (SD): 23.36 (2.08) y) with unchanged exercise in the early follicular phases of two menstrual cycles. The neutral energy availability diet (NEA, 45 kCal/kg*LBM/d, ±0%) was followed by a deficient energy availability (DEA, -55%) intervention. On enrollment, we administered the following questionnaires: almost perfect, perceived stress, dysfunctional attitude, eating attitudes, exercise (IPAQ), appetite, and palatability. Resting energy expenditure (REE), maximum oxygen uptake (VO2 max) and body composition were assessed at baseline. After each intervention, blood was sampled every 10 min for LH and metabolic hormones (thyroid hormones, GH, cortisol, glucose, insulin, leptin, and orexin) was measured at varying intervals (0800 — 1600hrs). Outcomes included 1) DEA LH pulse frequency expressed as an absolute number (LHPF), 2) change from NEA (αLHPF) and 3) % change from NEA (%αLHPF). Principal components (PC) analysis tested the association between predictor variables separated into relevant domains. As expected from the degree of energy restriction, LHPF decreased in response to DEA in ∼53% of women (‘responders’, n=10) for whom PC analysis was separately performed.

Results: For the entire group, the PC for energy expenditure domain highlighted VO2 max and REE and was significantly associated with αLHPF (p=0.04) and %αLHPF (p=0.05). There was no relationship between metabolic or thyroid hormone, or body composition domains with DEA LHPF, αLHPF and %αLHPF. In responders, the fasting metabolic domain primarily consisted of insulin and leptin and was associated with αLHPF (p=0.008) and %αLHPF (p=0.08). The thyroid domain, which was a primary composite of T3, reverse T3 and T4 had a trend of association with DEA LHPF (p=0.06) and %αLHPF (p=0.05). The metabolic domain primarily consisted of samples from the across-the-day growth hormone and cortisol and was associated with αLHPF (p=0.05) and %αLHPF (p=0.049). There was no association between attitude, anthropometry, or energy domains and outcome variables in this subgroup.

Conclusion: Our data suggest that in normal women higher resting energy expenditure and a greater degree of fitness predict a greater inhibitory effect of energy restriction on the reproductive axis. In those who demonstrate this inhibition, the degree of response to ER can be predicted by the fasting metabolic (insulin and leptin) and thyroid domains.

Presentation: Friday, June 16, 2023