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

Elizabeth Murphy, Charles Steenbergen

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2375-2377
Number of pages3
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 2 2014

ASJC Scopus subject areas

  • General Medicine


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