Chronic Intermittent Hypoxia Advances Hormonal Aging: Implications for Parkinson’s Related Sexual Dysfunction

Purpose: Chronic intermittent hypoxia (CIH) is an established model for sleep apnea and a common comorbidity in Parkinson’s disease (PD). Further, CIH is a known inducer of oxidative stress (OS), which is a key characteristic of PD and aging. Interestingly, in men both sleep apnea and PD are strongly linked with sexual dysfunction. However, it is unknown if CIH induces sexual dysfunction. Therefore, we examined the role of CIH on steroid hormones, sex behaviors, neuropeptides associated with social behaviors, and OS generation in young and old rats. Methods: Young (3-months) and old (12-months) male F344/BNF1 rats, were exposed to either mild CIH or normoxic conditions. CIH consisted of cycling oxygen levels from 21% to 10% over a span of 6 minutes during the rat’s sleep phase for a total of ten days. Sex behavioral tests were conducted to examine the influence of CIH. Specifically, the frequency and latencies of mounts, intromissions, and ejaculations were quantified. At the end of testing, plasma was collected and assayed for testosterone (T), corticosterone (C), vasopressin (AVP), oxytocin (OXY), and advanced oxidation protein products (AOPP). Results: Old rats had impaired sex behaviors compared to young rats. However, CIH induced sexual dysfunction in young rats, consistent with behaviors in old rats. Accordingly, in young rats CIH decreased T, increased C, and increased OS, as indicated by AOPP. CIH did not alter OXY and AVP in young rats. Interestingly, in old rats CIH had no effect on sexual behavior, T, C, OXY, or AVP, indicating that age may have a ceiling effect. Conclusions: Results show that mild CIH advances hormonal aging. Hormonal aging is an understudied phenomenon in PD and in sleep apnea. Therefore, PD progression may be halted by examining the influence of sleep apnea induced hormonal aging.