The Relationship Between Estrogen and the Decline in Delta Power During Adolescence

Abstract

Study objectives: During adolescence, there is a precipitous decrease in slow-wave sleep (SWS) and its spectral correlate, delta power, which may reflect cortical reorganization. The temporal association between the decrease in delta power and puberty suggests that sex steroids may initiate these changes. This association has not been previously investigated.

Methods: To determine whether estrogen triggers the adolescent decline in delta power, we compared delta power in 14 girls with central precocious puberty (CPP) and 6 age-matched, prepubertal controls. Five CPP participants were re-studied 7-14 months after pubertal suppression to determine if the changes in delta power are reversible after restoring a prepubertal hormonal milieu. The change in delta power was also compared between CPP participants and five historic controls from a longitudinal polysomnographic study.

Results: CPP participants (6.7-10.5 years) spent 30% of the night in SWS. Delta power (3.7 × 106 ± 2.7 × 105 µV2) predominated in the first 2 non-rapid eye movement episodes and decayed exponentially (tau 0.006 minutes). Age-matched controls demonstrated similar sleep staging (24% SWS) and delta dynamics (3.3 × 106 ± 5.1 × 105 µV2, tau 0.004 minutes). Four out of 5 CPP participants had a significant decrease (26%) in delta power after hormone suppression (p < .05), similar to historic controls.

Conclusion: Using an innovative model of girls with CPP studied before and after estrogen suppression, the effects of puberty on the decline in delta power were dissociated from those of chronologic age. The current studies suggest that increased estrogen does not cause the adolescent decline in delta power and indicate that neurodevelopmental changes per se or other factors associated with puberty drive these sleep changes.

Keywords: central precocious puberty; sex steroids; slow-wave activity; slow-wave sleep.

Figure 1

Pubertal milestones and GnRH agonist treatment in relation to sleep study visits in 14 girls with central precocious puberty (CPP). Age at all sleep study visits is given for study controls (n = 6) and historic NDAR controls (n = 5). All participants underwent at least one sleep study visit. Seven CPP participants were studied before (o) and after (▼) treatment with a GnRH agonist (—) to suppress sex steroid production. Time of last contact is denoted by (I), thelarche by (●) and menarche by (M).

Figure 2

Average percent distribution of sleep staging during the sleep opportunity for the control, central precocious puberty before treatment (CPP Pre-TX) and central precocious puberty after treatment (CPP Post-TX) groups. WASO = Wake after sleep onset; REM = Rapid Eye Movement; N3 = Non-REM stage 3; N2 = Non-REM stage 2; and N1 = Non-REM stage 1. There were no significant differences between percent of time spent in each sleep stage between conditions (control vs. CPP Pre-TX or CPP Post-TX) or visits (CPP Pre-TX vs. CPP Post-TX, all p > .05).

Figure 3

Delta power across the entire sleep opportunity (A) and in the first 2 NREM episodes (B) for the study controls, central precocious puberty subjects before treatment (CPP Pre-TX) and central precocious puberty subjects after treatment (CPP Post-TX). The percent change in delta power between study visits for CPP subjects and NDAR historic controls is shown in (C). Subject-level data is connected by a line and the off-set black squares indicate mean ± SEM. Asterisks denote significant differences between groups (p < .05).

Figure 4

Decay of slow-wave activity across the sleep opportunity for the control (▪), central precocious puberty before treatment (CPP Pre-TX, o) and central precocious puberty after treatment (CPP Post-TX, ▲) groups. Data are plotted on the x-axis as the midpoint of each non-REM (NREM) episode and on the y-axis as percent of the average SWA in stages NREM 2 and 3 across the entire sleep episode. Lines represent the exponential decay function for control (−), CPP Pre-TX (- - -), and CPP Post-TX (. . . . .) groups. There were no significant differences in decay rates between groups (p > .05).