Obstructive Sleep Apnea (OSA) in Preadolescent Girls is Associated with Delayed Breast Development Compared to Girls without OSA

Abstract

The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is a prospective cohort study of 6-to 11-year-old children with and without OSA followed over a 4-to 5-year period to investigate the predictors and neurocognitive and physiological sequelae of OSA. As pubertal stage was one of the measures obtained at follow-up, this study represents a unique opportunity to examine the effect of OSA on the pace of pubertal development in otherwise healthy children. Based Study Objective: Adults with obstructive sleep apnea (OSA) have lower sex steroid levels than controls. We sought to determine whether OSA also interferes with reproductive hormones in adolescence by tracking the pace of pubertal development. Methods: One hundred seventy-two children in the Tucson Children's Assessment of Sleep Apnea study (TuCASA) underwent two home polysomnographic studies, spaced 4-5 years apart. Height and weight were measured at both visits, and Tanner staging of breasts/genitals and pubic hair were selfassessed by a pictorial questionnaire at follow-up. Results: Eighty-seven girls and 85 boys, age 8.9 ± 1.6 years (mean ± SD) at baseline and 13.4 ± 1.6 years at follow-up, participated. Twenty-seven percent of participants were overweight or obese at baseline, and the majority remained so at follow-up. Twenty-six percent of girls and 28% of boys met criteria for OSA, defi ned as a respiratory disturbance index (RDI) ≥ 1/h associated with a 3% desaturation (RDI 3%), at baseline. There was an inverse relationship between baseline log RDI 3% and Tanner breast stage at follow-up (coeffi cient -1.3, p = 0.02) in girls after adjusting for age (p < 0.001), body mass index (p < 0.005), and ethnicity. Girls with OSA at baseline were more than 1 Tanner breast stage behind girls without OSA at follow-up. OSA did not affect genital development in boys or pubic hair development in either sex. Conclusions: OSA in preadolescent girls predicts delayed breast development relative to girls without OSA. Sleep fragmentation and/or hypoxia seen in OSA may interfere with reproductive development in girls. keywords: Obstructive sleep apnea, puberty, adolescence, sex steroids, lung Citation: Shaw ND; Goodwin JL; Silva GE; Hall JE; Quan SF; Malhotra A. Obstructive sleep apnea (OSA) in preadolescent girls is associated with delayed breast development compared to girls without OSA. J Clin Sleep Med 2013;9(8):813-818.http://dx.doi.org/10.5664/jcsm.2928 S C I E N T I F I C I N V E S T I G A T I O N SS leep is an important modulator of reproductive hormone secretion. During the early stages of puberty, there is an increase in hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH) secretion in both girls and boys that initially occurs only during sleep. The results of sleep-wake reversal studies, during which subjects remain awake at night and sleep during the day, indicate that LH secretion is related to sleep per se rather than to time of day.2 The sleep-related augmentation of GnRH/LH secretion is responsible for the incr...

A Multi-Oscillatory Circadian System Times Female Reproduction

“…In addition to the effect of circadian dysregulation, it should be kept in mind that shift work-related alterations in other daily functions, particularly food intake and sleep, may indirectly impact female reproduction. Thus, obesity, which is often associated with shift work, has a strong impact on reproductive performance ( 180 ) and sleep disturbance in prepubertal girls can alter estradiol-dependent pubertal development ( 181 ).…”

Hypoxia causes transgenerational impairments in reproduction of fish

“…Both laboratory and field studies have demonstrated that hypoxia can affect specific genes along the brain-pituitary-gonad axis, disrupt the synthesis and balance of sex hormones and lead to reproductive impairments and sex alteration in several fish species 4 5 6 . Notably, hypoxia can also cause similar endocrine disruption and reproductive impairments in rhesus monkeys and humans living at high altitudes 7 8 9 , and men suffering from hypoxia as a consequence of sleep apnoea exhibit lower levels of male and female sex hormones as well as reduced sex drive 10 11 12 , showing that hypoxic responses are highly conserved in vertebrates.…”

Hypoxia delays steroid-induced developmental maturation inDrosophilaby suppressing EGF signaling

“…Hypoxia suppression of EGF signaling is conserved in other organisms (Deygas et al, 2018;Maxeiner et al, 2019), and altered expression of EGFR signaling components has been reported both in human populations living in high altitudes (Jha et al, 2016) and in Drosophila populations which have undergone multiple generations of selection for hypoxia tolerance (Zhou et al, 2008). Also, hypoxia can modulate steroidogenesis and steroid functions in many animals (Bera et al, 2020;Oyedokun et al, 2023;Wang et al, 2008;Yao et al, 2021), and diseases that can result in reduced systemic oxygen levels in humans -such as chronic obstructive pulmonary disease, sleep apnea or asthma -can impact steroid-induced development and sexual maturation (Drosdzol et al, 2007;Gaudino et al, 2021;Shaw et al, 2013). Thus, the mechanisms that we describe here in Drosophila may reflect more general mechanisms by which low oxygen can affect animal development.…”