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Sex, drugs, and trial design: sex influences the heart and drug responses.

Authors
  • Murphy, Elizabeth
  • Steenbergen, Charles
Type
Published Article
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Publication Date
Jun 01, 2014
Volume
124
Issue
6
Pages
2375–2377
Identifiers
DOI: 10.1172/JCI76262
PMID: 24837428
Source
Medline
License
Unknown

Abstract

Preclinical studies indicate that the phosphodiesterase 5 (PDE5) inhibitor sildenafil is protective against hypertrophy-induced cardiac remodeling. Despite an initial clinical study demonstrating sildenafil-dependent amelioration of pathological remodeling, the cardioprotective effect of this drug was not significant in a large placebo-controlled clinical trail. In this issue, Sasaki and colleagues reveal that the efficacy of PDE5 inhibition in female mice requires estrogen. Induction of cardiac stress in male and intact female mice resulted in increased activation of protein kinase G (PKG) signaling, which was further enhanced by sildenafil. PKG activity was not enhanced in ovariectomized (OVX) female mice as a result of cardiac stress, but administration of estrogen restored PKG activation and enhancement by sildenafil. These data highlight the importance of considering sex-specific differences and drug responses in clinical trial design.

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