Title:Current Perspectives for the use of Gonane Progesteronergic Drugs in the Treatment of Central Hypoventilation Syndromes
Volume: 16
Issue: 10
Author(s): Camille Loiseau, Florence Cayetanot, Fanny Joubert, Anne-Sophie Perrin-Terrin, Philippe Cardot, Marie-Noëlle Fiamma, Alain Frugiere, Christian Straus and Laurence Bodineau*
Affiliation:
- Sorbonne Universites, UPMC Univ Paris 06, INSERM, UMR_S1158 Neurophysiologie Respiratoire Experimentale et Clinique, F-75013, Paris,France
Keywords:
Central congenital hypoventilation syndrome, desogestrel, etonogestrel, Ondine’s curse syndrome, gonane, progesterone,
respiratory control.
Abstract: Background: Central alveolar hypoventilation syndromes (CHS) encompass neurorespiratory
diseases resulting from congenital or acquired neurological disorders. Hypercapnia, acidosis,
and hypoxemia resulting from CHS negatively affect physiological functions and can be lifethreatening.
To date, the absence of pharmacological treatment implies that the patients must receive
assisted ventilation throughout their lives.
Objective: To highlight the relevance of determining conditions in which using gonane synthetic
progestins could be of potential clinical interest for the treatment of CHS.
Methods: The mechanisms by which gonanes modulate the respiratory drive were put into the context
of those established for natural progesterone and other synthetic progestins.
Results: The clinical benefits of synthetic progestins to treat respiratory diseases are mixed with
either positive outcomes or no improvement. A benefit for CHS patients has only recently been
proposed. We incidentally observed restoration of CO2 chemosensitivity, the functional deficit of
this disease, in two adult CHS women by desogestrel, a gonane progestin, used for contraception.
This effect was not observed by another group, studying a single patient. These contradictory findings
are probably due to the complex nature of the action of desogestrel on breathing and led us to
carry out mechanistic studies in rodents. Our results show that desogestrel influences the respiratory
command by modulating the GABAA and NMDA signaling in the respiratory network, medullary
serotoninergic systems, and supramedullary areas.
Conclusion: Gonanes show promise for improving ventilation of CHS patients, although the conditions
of their use need to be better understood.
