The earliest physiological sign of puberty in both boys and girls is an augmentation of the pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH). This augmentation initially occurs only during sleep. We hypothesize that the hypoxic episodes and arousals which disrupt sleep in children with obstructive sleep apnea (OSA) will disrupt the nocturnal GnRH/LH secretory pattern of children with OSA in the early stages of puberty. Specifically, we expect children with OSA in early puberty to have decreased LH pulse frequency and amplitude proportional to the severity of their sleep apnea. To investigate this hypothesis, we will enroll 15 children in early puberty with OSA treated with a continuous positive airway pressure (CPAP) machine. Each child will undergo two studies consisting of a polysomnographic sleep study with simultaneous frequent blood sampling to detect LH pulses with or without CPAP in random order such that each child serves as his own control to determine whether LH pulse frequency and amplitude are decreased in the absence of CPAP. We will then investigate whether EEG arousals in the absence of hypoxia can produce a decrement in LH pulse frequency and amplitude. We will enroll another 15 children, and each child will undergo two polysomnographic sleep studies with frequent blood sampling. CPAP will be used in both studies during one of which auditory stimuli will be used to induce EEG arousals. The order of the studies will be randomized. These protocols will also allow us to analyze the connection between sleep stage and GnRH/LH pulses during puberty. Given the high prevalence of OSA in children (1-4%), there is a potentially large population of children at risk for reproductive dysfunction in the form of failure to progress or delayed progression through puberty. These studies will allow us to define this risk as well as to provide greater insights into the basic physiology which ties GnRH/LH pulses to sleep.

Public Health Relevance

This research will determine if the relatively large population of children with OSA is at risk for failure to progress or delayed progression through puberty and would therefore benefit from the close supervision of a pediatric endocrinologist.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F06-E (20))
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Winer, Karen
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Massachusetts General Hospital
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