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  • Title: Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep.
    Author: Chowdhuri S, Bascom A, Mohan D, Diamond MP, Badr MS.
    Journal: Sleep; 2013 Dec 01; 36(12):1793-8. PubMed ID: 24293753.
    Abstract:
    STUDY OBJECTIVES: Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. DESIGN: Randomization to oral finasteride vs. sham, single-center study. SETTING: Sleep research laboratory. PARTICIPANTS: Fourteen healthy young males without sleep apnea. INTERVENTION: Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. MEASUREMENTS AND RESULTS: The apnea threshold (AT) was defined as the end-tidal CO₂(P(ET)CO₂) that demarcated the central apnea closest to the eupneic P(ET)CO₂. The CO₂ reserve was defined as the difference in P(ET)CO₂ between eupnea and AT. The apneic threshold and CO₂ reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO₂ reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. CONCLUSIONS: Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations.
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