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Combination of Testosterone and Vardenafil Increases Female Sexual Functioning in Sub-Primed Rats

Authors

  • Eelke M.S. Snoeren PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
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  • Astrid Bovens BSc,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
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  • Louise K. Refsgaard BSc,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
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  • Koen G.C. Westphal BSc,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
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  • Marcel D. Waldinger MD, PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    2. Department of Psychiatry and Neurosexology, Haga Hospital Leyenburg, The Hague, The Netherlands
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  • Berend Olivier PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    2. Yale University School of Medicine, New Haven, CT, USA
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  • Ronald S. Oosting PhD

    Corresponding author
    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
      Ronald S. Oosting, PhD, Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, Utrecht 3584CA, The Netherlands. Tel: +31 30 253 3730; Fax: +31 30 253 7900; E-mail: r.s.oosting@uu.nl
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Ronald S. Oosting, PhD, Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, Utrecht 3584CA, The Netherlands. Tel: +31 30 253 3730; Fax: +31 30 253 7900; E-mail: r.s.oosting@uu.nl

ABSTRACT

Introduction.  Hypoactive sexual desire disorder (HSDD) is a common problem in women and may have a negative impact on quality of life. A recent clinical study shows an increase in sexual drive of HSDD women after cotreatment of testosterone and vardenafil (phosphodiesterase type 5 inhibitor).

Aim.  In this study, we investigated the effect of testosterone and vardenafil on sexual activity in female rats.

Main Outcome Measures.  Proceptive (darts and hops), receptive (lordosis), and paced-mating (percentages after exits and contact-return latencies) behaviors were quantified.

Methods.  Ovariectomized female rats, sub-primed with only estradiol and fully primed with estradiol and progesterone, were tested in a paced-mating sex test and sexual behaviors were quantified. The sub-primed rats are thought to model HSDD. The effect of testosterone (100 and 300 µg, subcutaneous [SC]) and vardenafil (10 mg/kg, per os [PO]) alone and testosterone (300 µg, SC) in combination with vardenafil (3 and 10 mg/kg, PO) were tested. We also studied the effects of testosterone (300 µg, SC) + intracerebroventricular (ICV) injections of vardenafil (25 and 50 µg) on sexual activity.

Results.  No effect of testosterone and vardenafil alone was found, but cotreatment of testosterone and vardenafil (PO) caused a significant increase in proceptive and receptive behavior in the sub-primed female rats. Testosterone and vardenafil did not affect fully primed females. ICV administration of vardenafil combined with systemic testosterone, on the other hand, had no effect on sexual activity in both sub-primed and fully primed female rats.

Conclusions.  We conclude that cotreatment of subcutaneous testosterone and oral vardenafil increase sexual activity in sub-primed female rats. Our data supports the human finding that combination treatment of testosterone and vardenafil could be used as a new treatment for women with HSDD. Snoeren EMS, Bovens A, Refsgaard LK, Westphal KGC, Waldinger MD, Olivier B, and Oosting RS. Combination of testosterone and vardenafil increases female sexual functioning in sub-primed rats. J Sex Med 2011;8:989–1001.

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