Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep

Susmita Chowdhuri, Amy Bascom, David Mohan, Michael P. Diamond, M. Safwan Badr

Research output: Contribution to journalArticle

11 Scopus citations

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 ETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 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.

Original languageEnglish (US)
Pages (from-to)1793-1798
Number of pages6
JournalSleep
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • 5α-reductase blockade
  • Apneic threshold
  • CO reserve
  • Central sleep apnea
  • Chemoresponsiveness
  • Dihydrotestosterone
  • Finasteride
  • Testosterone

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep'. Together they form a unique fingerprint.

  • Cite this