III) TRAITEMENTS HORMONAUX DE LA MENOPAUSE : IMPLICATION DE L’ESTRADIOL
6) Conclusion générale et perspectives cliniques
La ménopause est une transition dans la vie de la femme qui s’accompagne par une plus forte incidence de troubles variés, dont des désordres respiratoires du sommeil (Krystal et al., 1998).
Les remplacements hormonaux avaient rapporté des effets bénéfiques sur la qualité du sommeil
(Hays et al., 2003) et les désordres respiratoires associés (Shahar et al., 2003) Toutefois la « Women Health Initiative » rapporte que les bénéfices ne sont pas suffisants par rapport aux effets secondaires pour recommander une thérapie hormonale substitutive chez toutes les femmes (Rossouw et al., 2002). Même si ces conclusions ont été critiquées par la communauté scientifique, rapportant que leurs études contenaient de nombreux biais (Klaiber et al., 2005; van der Mooren and Kenemans, 2004b), les thérapies hormonales substitutives de la ménopause ont été arrêtées.
L’alternative la plus crédible est l’utilisation des SERMs, dont le tamoxifène, le raloxifène et le bazédoxifène (BZA) sont les plus connues (Komm and Mirkin, 2014). Le BZA associé l’estradiol conjugué a été étudié dans 5 essais cliniques randomisés et contrôlés, dénommés SMART pour « Selective estrogens, Menopause, and Response to Therapy » (Parish and Gillespie, 2017). Ces essais ont enrôlé plus de 7500 femmes en santé ménopausées avec ou sans symptômes de la ménopause. La sélection du BZA par rapport aux autres SERMs est basée sur le fait que l’association avec l’estradiol conjugué n’induit pas de stimulation de l’endométriome ou l’apparition de cancers de l’utérus et des ovaires (Pinkerton et al., 2009; Stovall et al., 2007). De plus, la densité mammaire n’est pas affectée par ce traitement au
141 contraire du traitement estradiol conjugué/médroxyprogestérone (Harvey et al., 2013; Pinkerton et al., 2013).
Concernant le sommeil, le traitement estradiol conjugué/BZA améliore significativement les problèmes de sommeil tels que la somnolence diurne, les ronflements et la qualité du sommeil
(Utian et al., 2009). Toutefois, l’indice d’apnées/hypopnées n’a pas été évalué dans cette étude, tout comme les conséquences associées au SAOS.
On peut tout de même suggérer au vu de nos résultats sur les effets protecteurs de l’estradiol dans un modèle animal et l’absence d’effets secondaires rapportés jusqu’à présent de l’estradiol associé au BZA chez les femmes ménopausées que ce traitement peut être une thérapie efficace contre l’apnée du sommeil et ses conséquences chez les femmes ménopausées. Seul l’avenir et des études supplémentaires nous le dira.
142
Partie V
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