vardenafil-dihydrochloride and Sexual-Dysfunction--Physiological

Phosphodiesterase type 5 inhibitors (PDE5), such as sildenafil, tadalafil, and vardenafil, have revolutionized the treatment of erectile dysfunction. Few successes, in contrast, have been reported for the use of these agents in treatment of sexual arousal problems in women.. To review research examining efficacy of PDE5 in women, critique the methods and models employed, and integrate the findings within a broader, gender-specific understanding of female sexual response.. A conceptual and methodological review of all published studies examining PDE5 efficacy in female samples.. Study methods, populations, outcome measures, study results.. A total of 16 studies were reviewed. Studies using self-reported measures of sexual functioning showed mixed results whereas studies examining physiological effects of PDE5 on genital vasocongestion consistently report significant effects on genital sexual response.. The lack of efficacy of PDE5 treatment in women is likely attributable to gender differences in the concordance between physiological and psychological components of sexual response. Discordance between genital and subjective measures of sexual response in women may be augmented by PDE5 effects on genital vasocongestion in some populations, rendering successful treatment unlikely via pharmacological treatment alone.

Topics: Animals; Carbolines; Clitoris; Female; Humans; Imidazoles; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sex Factors; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vagina; Vardenafil Dihydrochloride; Women's Health

To date, there is no FDA-approved therapy for premature ejaculation (PE). Recently, phosphodiesterase 5 inhibitors (PDE5-Is) have been demonstrated to have encouraging results in the treatment of PE by a few studies. The aim of this review was to assess the updated manuscripts and thereafter present the practical recommendations and possible mechanisms concerning PDE5-Is for treating PE. Using MEDLINE, we searched and assessed the peer manuscripts published from 1 January 1996 to 1 September 2005 about PDE5-Is for treating PE. The results show that the number of patients in all the reports is very few and most of the studies do not employ double-blinded and placebo-controlled tests, though they are prospective and randomized. Therefore, the results and conclusions might be biased. PDE5-Is are suggested to be used in PE with old age or associated with erectile dysfunction (ED), or to be employed alone or in combination with selective-serotonin reuptake inhibitors (SSRIs) when SSRIs fail to treat PE; behavioural therapy is proposed to be used for preventing the recurrence of PE following withdrawal of PDE5-Is. In addition, for the PE patient with a definite aetiological cause, the aetiology should be cured first, if PE still exists, followed by PDE-Is prescription. Possible mechanisms that are involved include relaxing the smooth muscles of vas deferens, seminal vesicle, prostate and urethra; decreasing the central sympathetic output; inducing peripheral analgesia; prolonging the duration of erection; and increasing confidence, the perception of ejaculatory control, overall sexual satisfaction, and decreasing the post-orgasmic refractory time to achieve a second erection after ejaculation. Well-designed multicentre studies are urgently warranted to further elucidate the efficacies and safety as well as mechanisms of PDE5-Is in the treatment of PE.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Ejaculation; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Several authors have reported their experience with PDE5 inhibitors alone or in combination with selective serotonin re-uptake inhibitors for treating premature ejaculation. However, to our knowledge, this is the first laboratory design study to evaluate the effects of three PDE5 inhibitors throughout the ejaculation process in men with lifelong premature ejaculation. In this laboratory setting study PDE5 inhibitors seem to prolong ELT but the difference from placebo is significant only in vardenafil. The quality of penile rigidity is better with PDE5 inhibitors in the post-ejaculatory period but the difference is significant only in sildenafil and vardenafil.. • To evaluate the effects of three phosphodiesterase type 5 (PDE5) inhibitors on the ejaculation process in men with lifelong premature ejaculation using a double-blind laboratory setting.. • Eighty men with lifelong premature ejaculation, 20 in each group, received placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double-blind study design. Placebo or PDE5 inhibitor was ingested after at least 2 h fasting and non-smoking. The subjects were placed in a silent room immediately and real-time penile rigidity and tumescence was monitored. • Subjects read some magazines or newspapers without any sexually stimulating material for 1.5 h. At the end of this period audiovisual sexual stimulation began with a video film and after the 8th minute the subject began vibratory stimulation to the frenular area. • At the beginning of ejaculation the patient stopped stimulation. When the patient began and stopped stimulation, the light near the observer turned on and off and the observer calculated the ejaculation period with a chronometer. The elapsed time was the ejaculation latency time (ELT) in seconds. • There was no interaction between subjects and observer during the test. The ELT, and the qualities of base and tip rigidities during ELT and after ejaculation were calculated.. • Median age of patients was 29 (range 22-39) years and median duration of premature ejaculation was 60 (range 7-180) months and there was no significant difference between groups. Median duration of vibratory stimulation (ELT) of subjects who received placebo was 48.5 s: 53.5 s for sildenafil, 70.0 s for tadalafil and 82.5 s for vardenafil. Compared with the placebo group, ELT was significantly longer only in subjects receiving vardenafil (P = 0.019). • In the post-ejaculatory refractory period, times to last recorded base rigidities were significantly longer than placebo in vardenafil and sildenafil groups with better erection quality (P < 0.01 for each).. • The PDE5 inhibitors seem to prolong ELT and the quality of penile rigidity is better with PDE5 inhibitors in post-ejaculatory period. • These findings suggest that PDE5 inhibitors might have some beneficial effects in men with lifelong premature ejaculation.

Topics: Administration, Oral; Adult; Carbolines; Dose-Response Relationship, Drug; Ejaculation; Follow-Up Studies; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Young Adult

The aim of this study is to measure the ejaculation latency time (ELT) and to evaluate the effects of vardenafil on ELT and rigidity parameters of patients with lifelong premature ejaculation (PE) in a laboratory setting.. Double-blind, placebo-controlled, cross-over laboratory study was performed with 40 males with lifelong PE. As the subject ingested the placebo or vardenafil, real-time penile tumescence and rigidity monitoring began. Audiovisual sexual stimulation (AVSS) was performed 45 min later. The patient began vibratory stimulation to the frenular area at 8th minute of AVSS till ejaculation. A button has been placed under the cover where the patient presses to operate the vibrator. ELT was calculated in seconds with a chronometer. Following ejaculation, AVSS was stopped. The test was repeated with second medication in 7-15 days.. Among 40 patients, the results of 17 could be evaluated. When the patient took placebo and vardenafil, mean ELTs were 62.7 and 189.5 s, respectively. When compared with placebo, vardenafil improved ELT significantly (P = 0.04). After the beginning of AVSS, time to first recorded base or tip rigidities was shorter and time to last recorded tip or base rigidities following ejaculation was longer than placebo; however, these differences were not significant (P > 0.05 for each).. This laboratory design might be used to evaluate the effects of drugs on patients with ejaculation disorders. In this laboratory setting study, vardenafil exerted a threefold increase in ejaculation delay outside the vagina in patients with lifelong PE.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Ejaculation; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Sexual Dysfunction, Physiological; Sulfones; Time Factors; Triazines; Vardenafil Dihydrochloride

Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function.. To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods. In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital-physiological and subjective reactions.. A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used.. In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning.. In women suffering from low sexual desire-associated with low attention for sexual cues-the combination of testosterone and vardenafil may be a promising new treatment.

Topics: Adult; Affect; Attention; Cognition; Cross-Over Studies; Cues; Double-Blind Method; Erotica; Female; Genitalia, Female; Humans; Imidazoles; Motion Pictures; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Sexual Behavior; Sexual Dysfunction, Physiological; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED).. One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners' sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment.. A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED>6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner).. Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI).. Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners' FSFI total and individual domain scores.. Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners' sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sexual Partners; Sexuality; Sulfones; Surveys and Questionnaires; Triazines; Vardenafil Dihydrochloride

Topics: Aged; Antihypertensive Agents; Ejaculation; Female; Health Knowledge, Attitudes, Practice; Health Status; Humans; Imidazoles; Male; Patient Education as Topic; Piperazines; Sexual Dysfunction, Physiological; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Drug Synergism; Enzyme Inhibitors; Finasteride; Humans; Imidazoles; Male; Piperazines; Prostatic Hyperplasia; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Administration of serotonin reuptake inhibitors (SRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) relieves depressive symptoms but may cause sexual dysfunction in women and men.. The aim of the present study was to evaluate the effects of the phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, on inhibition of genital vascular responses (GVR) induced by SRI or SNRI administration in female rabbits.. Vaginal and clitoral vasodilatory responses to pelvic nerve electrical stimulation were measured by laser Doppler flow needle probes.. GVR were significantly potentiated by vardenafil even at the low dose of 0.1 mg/kg, in clitoris and vagina (181 +/- 22% and 180 +/- 31% of control, in vagina and clitoris, respectively, at 8 Hz). The selective SRI, paroxetine (5 mg/kg), significantly inhibited GVR in female rabbits (54 +/- 5% and 48 +/- 6% of control). GVR were also significantly inhibited by the SNRIs, venlafaxine (5 mg/kg) (57 +/- 3% and 32 +/- 11%) and duloxetine (1 mg/kg) (40 +/- 7% and 28 +/- 5%). Treatment with vardenafil (0.1 and 0.3 mg/kg) completely reversed the inhibition of GVR induced by paroxetine, venlafaxine, or duloxetine.. Potentiation of the nitric oxide (NO) pathway by vardenafil improves vascular sexual responses in female rabbits and overcomes the inhibitory effects of acutely administered antidepressants on GVR, irrespective of the underlying pathophysiologic mechanism, i.e., disruption of the NO pathway or enhancement of alpha-adrenergic mechanisms. PDE5 inhibition may represent a reasonable approach to treat SRI- or SRNI-induced female sexual dysfunction, in particular, arousal disorders.

Topics: Animals; Antidepressive Agents; Blood Vessels; Electric Stimulation; Female; Imidazoles; Laser-Doppler Flowmetry; Phosphodiesterase Inhibitors; Piperazines; Rabbits; Regional Blood Flow; Sexual Dysfunction, Physiological; Sulfones; Triazines; Vagina; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents

Topics: Adult; Antidepressive Agents; Depression; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sertraline; Sexual Dysfunction, Physiological; Sulfones; Triazines; Vardenafil Dihydrochloride