British Journal of Obstetrics and Gynaecology
Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study
Introduction
Among sexual dysfunctions, female sexual arousal disorder is a highly prevalent problem1. According to the DSM-IV2 and the WHO'ICD-103, sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, expressed as a lack of genital lubrication or swelling response. Both nosological and diagnostic classifications are founded on the model described by Masters and Johnson4., 5.. This work was later expanded by Kaplan6 for the human sexual response, in which sexual arousal disorder may cause sexual desire disorder, with persistent or recurrent deficiency of sexual fantasies and desire for sexual activity, and/or orgasmic disorder. The potential role of vascular mechanisms in the pathophysiology of female sexual arousal disorder has led to studies of the effects of drugs, such as ephedrine7 or phentolamine8, that are used to facilitate the initial stages of sexual arousal in women. Magnetic resonance imaging has shown that during female sexual arousal changes occur in the anterior vaginal wall, through gradual filling of the bladder, and involving the clitoris9. Systems designed to model pathophysiologies in clitoral function have been limited10. It is accepted that the human clitoris plays a functional role during sexual arousal11., 12., 13.. There is a growing body of evidence that women with sexual dysfunction commonly will have physiologic abnormalities, such as vasculogenic female sexual dysfunction, contributing to their overall sexual health problems14.
Clitoral erection, a key component of female sexual arousal, develops as a result of haemodynamic changes within the clitoral cavernous erectile tissue15., 16., 17., 18., 19.. During intercourse the anterior vaginal wall transmits the effect of penile introduction into the vagina to the clitoris by stretching the two ligaments around its base9., 20.. Although the clitoris is an embryological homologue of the penis15., 16., 17., there are anatomical differences between penis and clitoris, including the absence in the clitoris of the subalbugineal layer between the erectile tissue and the tunica albuginea21., 22.. The absence of the venous plexus in the clitoris suggests that this organ achieves tumescence but not rigidity during sexual arousal.
In the human corpus cavernousum, release of nitric oxide from the non-adrenergic non-cholinergic nerves and/or the endothelium activates guanylyl cyclase and increases intracellular cGMP levels. cGMP modulates intracellular calcium and, in turn, regulates smooth muscle contractility and erectile function23. Phosphodiesterase type 5 (PDE5) plays an important physiological role by regulating the intracellular levels of cyclic nucleotides. Sildenafil, a selective PDE5 inhibitor, taken orally, promotes penile erection through increased intracellular cGMP in response to sexual stimulation, potentiating smooth muscle relaxation24. However, sildenafil is able to inhibit cGMP hydrolysis by high-affinity selective PDE5 inhibition in intact cells and in soluble extracts of human clitoral corpus cavernousum smooth muscle cells25. Clinical trials suggest that sildenafil could be an effective treatment for iatrogenic sexual dysfunction26., 27.. On the basis of these observations that human clitoral corpus cavernousum smooth muscle tone may be regulated by synthesis and releases of nitric oxide28 and that this pathway is dependent on PDE5 activity, we hypothesised that sildenafil could have beneficial clinical effects on women affected by sexual arousal disorders.
Section snippets
Methods
The Institutional Review Board of our Department approved the study. Based on results of differences between placebo and sildenafil 25 mg of 0.9 in male erectile dysfunction score29, with α (two-sided) = 0.05 and 1-β=0.8, sample size for independent two sample t test was calculated as 18 subjects for each arm. Thus, a total of 53 consecutive subjects were recruited for the study. The sample consisted of volunteer women aged 22-38 years, with a mean (SD) of 29 (4.8) years with subjectively
Results
Of the 53 women who started treatment, 51 provided follow up information to include in the analyses. One woman with a homosexual relationship and another with more than one sexual partner were excluded from study.
Each woman was available for follow up once monthly for three months. Mean (SD) usage of sildenafil 25 mg, sildenafil 50 mg, and placebo was, respectively; 2.8 (0.8), 2.7 (1.3), and 2.8 (1.6) times weekly. The Personal Experiences Questionnaire detected changes in global sexuality
Discussion
This is the first study on the use sildenafil in premenopausal women with sexual arousal disorder. We used a series of subjective measures to assess its effects. The three period cross-over study design allowed us to obtain outcomes from each individual woman during treatment with: 1. placebo; 2. low dose sildenafil; and 3. high dose sildenafil. Each woman had requested consultation for lack of clitoral sensation, lack of vaginal lubrication, or for being “slow to respond”. Therefore the
Conclusion
Our results demonstrate that sildenafil may directly improve female arousal disorder and thus other sexual qualitative functions such as enjoyment and orgasm, and it may possibly have an indirect therapeutic role in quantitative aspects of sexual functioning such as the frequency of sexual fantasies and thoughts, and the frequency of sexual intercourse. We believe that psychosexual and pharmacological approaches should be used together in these cases. PDE type 5 inhibitors could be useful in
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