title: Combination of testosterone and vardenafil increases female sexual functioning in sub-primed rats.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  In this study, we investigated the effect of testosterone and vardenafil on sexual activity in female rats.
  
  
  METHODS
  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.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
authors.forename: Eelke M S
authors.initials: EM
authors.lastname: Snoeren
authors.forename: Astrid
authors.initials: A
authors.lastname: Bovens
authors.forename: Louise K
authors.initials: LK
authors.lastname: Refsgaard
authors.forename: Koen G C
authors.initials: KG
authors.lastname: Westphal
authors.forename: Marcel D
authors.initials: MD
authors.lastname: Waldinger
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004338:Drug Combinations; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011187:Posture; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000728:Androgens; D004338:Drug Combinations; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D013739:Testosterone; D000069058:Vardenafil Dihydrochloride