Ultradian Rhythms in Heart Rate Variability and Distal Body Temperature Anticipate the Luteinizing Hormone Surge Onset

Abstract

The human menstrual cycle is characterized by predictable patterns of physiological change across timescales, yet non-invasive anticipation of key events is not yet possible at individual resolution. Although patterns of reproductive hormones across the menstrual cycle have been well characterized, monitoring these measures repeatedly to anticipate the preovulatory luteinizing hormone (LH) surge is not practical for fertility awareness. In the present study, we explored whether non-invasive and high frequency measures of 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 across the menstrual cycle. Cycles were examined from both pre- (n=45 cycles) and perimenopausal (n=10 cycles) women using days of supra-surge threshold LH and dates of menstruation for all cycles. For a subset of cycles, urinary estradiol and progesterone metabolites were measured daily around the time of the LH surge. Wavelet analysis revealed a consistent inflection point of ultradian rhythm (2-5 h) power of DBT and HRV that enabled anticipation of the LH surge at least 2 days prior to its onset in 100% of individuals. In contrast, the power of ultradian rhythms in heart rate, circadian rhythms in body temperature, and metrics of sleep duration and sleep timing were not predictive of the LH surge. Together, the present findings reveal fluctuations in distal body temperature and heart rate variability that consistently anticipate the LH surge and may aid in fertility awareness.

Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives

“…However, from the time of rise in fE2 (a defining marker of pubertal onset), CBT UR power retained the same mean value but commenced a 4-day, ovulatory cycle-associated pattern. Four day cycles in URs are consistent with data collected on URs in adult rodents(10,147,148) and humans (at a longer time scale)(139). Four-day patterning was not present in ovariectomized or E2-replaced animals, consistent with dependence on the ovarian cycle.…”

“…Conversely, CRs increase in magnitude and stability in early adolescence, are not significantly impacted by the phase of OR, and are impacted by ovariectomy. These results support the notion that ultradian and ovulatory systems are tightly coupled and reflected in CBT, and that circadian effects on the ovulatory cycle may be unidirectional(22, 139). Ovariectomy, E2 replacement, and pubertal contraceptive administration have a number of effects on rhythmic dynamics at each timescale, overall indicating that ‘intact’ dynamics are not easily recapitulated and that exogenous sex steroids can have enduring impact.…”

“…This property permits frequency strength calculation at a given position. In the present analyses we use a Morse wavelet with a low number of oscillations (defined by β=5 and γ=3, the frequencies of the two waves superimposed to create the wavelet(138)), similar to wavelets used in many circadian and ultradian applications(9,10,136–139). Additional values of β (3–8) and γ (2–5) did not alter the findings (data not shown).…”

“…Continuous measures of activity have been used for rhythmic monitoring(52), but this measure is not as closely tied to high-frequency changes driven by hormonal systems(9, 10) and does not appear to predict individual health events with comparable specificity(9,10,103). In contrast, CBT exhibits clear URs, CRs, and ORs that reflect underlying hormonal changes(6,61,104), including ultradian rhythmic CBT patterns that mirror LH(21, 105) and estradiol(21) prior to ovulation. Likewise, CBT is a reliable phase marker for circadian rhythmicity(106, 107).…”

“…Subsequent formation of the corpus luteum leads to a brief rise in circulating progesterone prior to beginning the next cycle. As with URs and CRs, ORs manifest as changes in a number of systems, including metabolic hormones, cardiac output, and thermoregulation(61–63). Although it is clear that ORs emerge at puberty, the continuous patterns of commencement and stabilization are poorly understood.…”