Ultradian rhythms in heart rate variability and distal body temperature anticipate onset of the luteinizing hormone surge

Abstract

The menstrual cycle is characterized by predictable patterns of physiological change across timescales. Although patterns of reproductive hormones across the menstrual cycle, particularly ultradian rhythms, are well described, monitoring these measures repeatedly to predict the preovulatory luteinizing hormone (LH) surge is not practical. In the present study, we explored whether non-invasive measures coupled to the reproductive system: high frequency distal body temperature (DBT), sleeping heart rate (HR), sleeping heart rate variability (HRV), and sleep timing, could be used to anticipate the preovulatory LH surge in women. To test this possibility, we used signal processing to examine these measures in 45 premenopausal and 10 perimenopausal cycles alongside dates of supra-surge threshold LH and menstruation. Additionally, urinary estradiol and progesterone metabolites were measured daily surrounding the LH surge in 20 cycles. Wavelet analysis revealed a consistent pattern of DBT and HRV ultradian rhythm (2–5 h) power that uniquely enabled anticipation of the LH surge at least 2 days prior to its onset in 100% of individuals. Together, the present findings reveal fluctuations in distal body temperature and heart rate variability that consistently anticipate the LH surge, suggesting that automated ultradian rhythm monitoring may provide a novel and convenient method for non-invasive fertility assessment.

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Naturalistic Conditions

“…If the features described here have analogous counterparts in human populations, as has recently been shown for continuous temperature for female LH surge anticipation (Grant et al, 2020;Webster and Smarr, 2020), pregnancy , and fever (Smarr et al, 2020); then this approach can be applied to develop powerful tools to further understand key developmental events. At present, children in developed nations begin puberty at an earlier age than in past decades, attributed to body fat and stress-related factors (Bellis et al, 2006, p. 12;Chittwar et al, 2012;Delemarre-van de Waal et al, 2002;Herbison, 2016;Parent et al, 2003).…”

“…Peripheral measurements of temperature, such as those from the iButton (Hasselberg et al, 2013) or Oura Ring (Grant et al, 2020;Maijala et al, 2019), could be sufficient for peripubertal detection of temperature and ultradian power rises (Grant et al, 2020), and could be used to develop a population-wide database characterizing features associated with pubertal onset and development. Indeed, rhythmic features of body temperature have already formed the basis of methods for monitoring reproductive health, including pubertal onset and contraceptive use in a laboratory setting , adult fertility in controlled and real world conditions (Grant et al, 2020;Prendergast et al, 2012;Sanchez-Alavez et al, 2011;Smarr et al, 2017), and pregnancy in the laboratory and in small, retrospective cohorts Smarr et al, 2016;Wang et al, 2014). Such tools could be informative and empowering to young people during puberty, potentially anticipating first onset of menses (Fowler et al, 2020;Wartella et al, 2016), impending growth spurts, or for identifying adverse reactions to disruptive behavior (Asimes et al, 2018;Logan et al, 2018) and medication (Apter, 2018).…”

“…Clinical or self-assessment(Elchuri and Momen, 2020) of pubertal status is typically conducted via observation of external characteristics (e.g., Tanner Scale, developed in the late 1960’s)(Rueda-Quijano et al, 2019; Shirtcliff et al, 2009), menstrual cycle tracking in girls(Fowler et al, 2020), or costly hormone measurement(Klein et al, 2017). Today, relatively inexpensive wearable sensors can capture metrics that are closely influenced by reproductive hormones and metabolism, such as body temperature(Grant et al, 2020; Smarr et al, 2020). These sensors may provide a convenient method to monitor pubertal development in real-world settings.…”

“…Biological rhythms in core body temperature (CBT) change markedly across adolescence in rodents, enabling unobtrusive monitoring of this trajectory in a laboratory setting(Grant et al, 2021; Hagenauer et al, 2011; Zuloaga et al, 2009). These rhythms are coupled across physiological systems(Goh et al, 2019; Grant et al, 2020, 2018; Mohawk et al, 2012) and at multiple timescales, including within-a-day (ultradian rhythms; URs)(Bourguignon, 1988) and daily (circadian rhythms; CRs)(Garcia et al, 2001; MacKinnon et al, 1978) in both sexes, and multi-day ovulatory cycles in females (ovulatory rhythms; ORs)(Vidal, 2017). Rhythmicity serves numerous functions, including coordination of reproductive development(Albertsson-Wikland et al, 1997; Ankarberg and Norjavaara, 1999; Hagenauer et al, 2011; Norjavaara et al, 1996) and synchronization of internal systems to variation in the environment(Daan and Slopsema, 1978; Hoogenboom et al, 1984; Lewis and Curtis, 2016).…”

“…Rhythmicity serves numerous functions, including coordination of reproductive development(Albertsson-Wikland et al, 1997; Ankarberg and Norjavaara, 1999; Hagenauer et al, 2011; Norjavaara et al, 1996) and synchronization of internal systems to variation in the environment(Daan and Slopsema, 1978; Hoogenboom et al, 1984; Lewis and Curtis, 2016). Features of biological rhythmicity can provide clinically-relevant diagnostic information(Akin and Elstein, 1975; Bhavani et al, 2019; Grant et al, 2020; Smarr et al, 2020). We recently applied this approach to monitor female adolescent development in rats under controlled laboratory conditions(Grant et al, 2021).…”