Efficacy of Sildenafil in the Treatment of Female Sexual Dysfunction Due to Multiple Sclerosis

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How Does Viagra Affect Women?
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How It Works

Precaution	Rationale	Advice
Medical consultation	To rule out contraindications	Always consult prior to use
Avoid Nitrates	Risk of severe hypotension in combination	Do not combine with nitrates
Monitoring Blood Pressure	Possible hypotensive effects	Check BP regularly
Use under medical supervision	For dosage and safety guidance	Essential for off-label use

The study, published in Obstetrics & Gynecology, found that women using sildenafil cream experienced significant improvements in sexual arousal sensation compared to those using a placebo.

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Topical sildenafil cream is effective for improving outcomes in women with female sexual arousal disorder, according to a recent study published in Obstetrics & Gynecology.1 Topical sildenafil cream has shown promising results in improving sexual arousal outcomes for women with female sexual arousal disorder. The study, published in Obstetrics & Gynecology, found that women using sildenafil cream experienced significant improvements in sexual arousal sensation compared to those using a placebo. Phase 1 and phase 2 studies indicated that sildenafil cream is safe, well-tolerated, and effective for treating female sexual arousal disorder. Significant improvements were observed in the SFQ28 Desire domain scores at week 8, especially in women with only female sexual desire disorder. Researchers suggest future studies should include a more diverse population by removing restrictions on enrolling sexual partners, to better evaluate the cream's efficacy.

Comparison table

Female sexual arousal disorder, presenting in approximately 20% of US women, refers to the inability to attain or maintain sexual arousal and often leads to distress and interpersonal difficulty. Currently, no pharmacologic treatments have received FDA approval for managing this condition in the United States. While oral sildenafil has shown little efficacy compared to placebo and high rates of side effects, topical sildenafil cream 3.6% (sildenafil cream) is another method of managing female sexual arousal disorder symptoms. Topical administration of sildenafil may also reduce side effects and provide a more immediate biological efficacy response. Sildenafil cream is an investigational proprietary topical formulation designed for the treatment of female sexual arousal disorder.2 Phase 1 and phase 2 studies have indicated safety, tolerance, and efficacy from sildenafil cream use. Phase 1 and phase 2 studies indicated that sildenafil cream is safe, well-tolerated, and effective for treating female sexual arousal disorder. Significant improvements were observed in the SFQ28 Desire domain scores at week 8, especially in women with only female sexual desire disorder. Researchers suggest future studies should include a more diverse population by removing restrictions on enrolling sexual partners, to better evaluate the cream's efficacy. Female sexual arousal disorder, presenting in approximately 20% of US women, refers to the inability to attain or maintain sexual arousal and often leads to distress and interpersonal difficulty. Currently, no pharmacologic treatments have received FDA approval for managing this condition in the United States. While oral sildenafil has shown little efficacy compared to placebo and high rates of side effects, topical sildenafil cream 3.6% (sildenafil cream) is another method of managing female sexual arousal disorder symptoms. Topical administration of sildenafil may also reduce side effects and provide a more immediate biological efficacy response. Sildenafil cream is an investigational proprietary topical formulation designed for the treatment of female sexual arousal disorder.2 Phase 1 and phase 2 studies have indicated safety, tolerance, and efficacy from sildenafil cream use. Investigators conducted a clinical trial to evaluate the safety and efficacy of sildenafil cream among women with female sexual arousal disorder.1 Participants included healthy premenopausal women aged at least 18 years and their sexual partners. Female sexual arousal disorder outcomes were assessed using the Arousal Sensation domain of the Sexual Function Questionnaire (SFQ38) and question 14 of the Female Sexual Distress Scale—Desire, Arousal, Orgasm (FSDS-DAO). Changes from baseline to week 12 were measured.1 A female sexual arousal disorder diagnosis and status as the woman’s primary sexual dysfunction concern were determined through a 1-on-1 clinical interview.

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Participants underwent a no-drug run-in period for 28 days, with eligibility determined by compliance with recorded sexual and adverse events.

How Does Viagra Affect Women?

Key Findings

Following the no-drug run-in period, eligible participants were randomized 1:1 to receive sildenafil cream or placebo cream for a 12-week double-blind period. Baseline scores included responses and electronic diary data at the end of the run-in period, and double-blind visits occurred at weeks 4, 8, and 12. During double-blind visits, patients completed 1-month recall SFQ28 and FSDS-DAO surveys. Within 24 hours of a sexual event, participants recorded data in an electronic diary. Participants’ response to the question “Did you consider sexual activity satisfactory for you?” in the electronic diary after a sexual event was the secondary outcome of the analysis, measured as the changes in the number and proportion of satisfying events from baseline to week 12. There were 200 participants included in the final analysis, 101 of whom received sildenafil cream and 99 placebo cream.

What special precautions should I follow?

Investigators conducted a clinical trial to evaluate the safety and efficacy of sildenafil cream among women with female sexual arousal disorder.1 Participants included healthy premenopausal women aged at least 18 years and their sexual partners. Female sexual arousal disorder outcomes were assessed using the Arousal Sensation domain of the Sexual Function Questionnaire (SFQ38) and question 14 of the Female Sexual Distress Scale—Desire, Arousal, Orgasm (FSDS-DAO). Changes from baseline to week 12 were measured.1 A female sexual arousal disorder diagnosis and status as the woman’s primary sexual dysfunction concern were determined through a 1-on-1 clinical interview. Participants underwent a no-drug run-in period for 28 days, with eligibility determined by compliance with recorded sexual and adverse events. Following the no-drug run-in period, eligible participants were randomized 1:1 to receive sildenafil cream or placebo cream for a 12-week double-blind period.

Physiology of female sexual function: Animal models

Baseline scores included responses and electronic diary data at the end of the run-in period, and double-blind visits occurred at weeks 4, 8, and 12. During double-blind visits, patients completed 1-month recall SFQ28 and FSDS-DAO surveys. Within 24 hours of a sexual event, participants recorded data in an electronic diary. Participants’ response to the question “Did you consider sexual activity satisfactory for you?” in the electronic diary after a sexual event was the secondary outcome of the analysis, measured as the changes in the number and proportion of satisfying events from baseline to week 12. There were 200 participants included in the final analysis, 101 of whom received sildenafil cream and 99 placebo cream. Of participants, 99 and 94, respectively, were in the intention-to-treat (ITT) analysis and 90 and 84, respectively, completed all study visits.1 When measuring outcomes based on the SFQ28 Arousal Sensation domain, increased efficacy was reported for the sildenafil cream group vs the placebo cream group. However, statistically significant improvements were not observed for either coprimary endpoint during the double-blind period, pfizer sildenafil 100 nor were the number of satisfying events improved. In the ITT population, patients in the sildenafil cream group had significantly improved SFQ28 Desire domain scores at week 8, which was considered an exploratory endpoint. Women with female sexual arousal disorder with concomitant orgasmic dysfunction had lessened treatment benefits at week 12 vs those with other sexual dysfunction diagnoses.1 The largest 12-week improvements in sexual dysfunction from sildenafil cream were observed among women with only female sexual desire disorder as their sexual dysfunction. These patients had significant improvements in the SFQ28 Arousal Sensation domain, SFQ28 Desire domain, and SFQ28 Orgasm domain vs placebo users. These results indicated improved outcomes from sildenafil cream among women with female sexual arousal disorder.

More about sildenafil

Of participants, 99 and 94, respectively, were in the intention-to-treat (ITT) analysis and 90 and 84, respectively, completed all study visits.1 When measuring outcomes based on the SFQ28 Arousal Sensation domain, increased efficacy was reported for the sildenafil cream group vs the placebo cream group. However, statistically significant improvements were not observed for either coprimary endpoint during the double-blind period, pfizer sildenafil 100 nor were the number of satisfying events improved. In the ITT population, patients in the sildenafil cream group had significantly improved SFQ28 Desire domain scores at week 8, which was considered an exploratory endpoint. Women with female sexual arousal disorder with concomitant orgasmic dysfunction had lessened treatment benefits at week 12 vs those with other sexual dysfunction diagnoses.1 The largest 12-week improvements in sexual dysfunction from sildenafil cream were observed among women with only female sexual desire disorder as their sexual dysfunction. These patients had significant improvements in the SFQ28 Arousal Sensation domain, SFQ28 Desire domain, and SFQ28 Orgasm domain vs placebo users.

Inclusion Criteria

These results indicated improved outcomes from sildenafil cream among women with female sexual arousal disorder. Investigators recommended removing the restrictions to enroll sexual partners in future studies to evaluate a more diverse study population.1 Johnson I, Thurman A, Cornell K, et al. Preliminary efficacy of topical sildenafil cream for the treatment of female sexual arousal disorder: A randomized controlled trial. Potential first-in-category therapy for female sexual arousal disorder. Sildenafil (Viagra, Revatio) reduced antidepressant-associated sexual dysfunction in women in a randomized controlled trial, which investigators characterize as the first conducted in women with this adverse drug effect. Investigators recommended removing the restrictions to enroll sexual partners in future studies to evaluate a more diverse study population.1 Johnson I, Thurman A, Cornell K, et al. Preliminary efficacy of topical sildenafil cream for the treatment of female sexual arousal disorder: A randomized controlled trial.

Sildenafil is primarily approved for erectile dysfunction in men.
Some studies explore its potential to treat female arousal disorder.
Its use for women remains off-label in many regions.
Long-term safety data for women is limited.

Potential first-in-category therapy for female sexual arousal disorder. Sildenafil (Viagra, Revatio) reduced antidepressant-associated sexual dysfunction in women in a randomized controlled trial, which investigators characterize as the first conducted in women with this adverse drug effect. The study, recently published in JAMA, was conducted by George Nurnberg, MD, of the department of psychiatry, University of New Mexico, and colleagues.1 This group's 2003 study, also published in JAMA, demonstrated sildenafil's benefit in men with this complaint.2 That study was a departure from the anecdotal or open-label reports that served as an evidence base for a myriad of proposed remedies.3 Although the association between sexual dysfunction and antidepressant therapy has been recognized since the introduction of tricyclics, the incidence of this adverse effect has increased since the advent of serotonin reuptake inhibitors (SRIs). Sexual dysfunction has also played a role in reducing patient adherence to the prescribed medication. Consequently, Nurnberg commented to Psychiatric Times, "treatments have been driven more by opinion than by solid data." Nurnberg and colleagues emphasize this concern in their latest study, warning that "without evidence-based data to treat sexual function associated sildenafil pick up with SRIs in women, clinicians may lack the confidence to manage it effectively, which leaves patients exposed to excess random pharmacology." The investigators employed a design and protocol similar to those in their study with men. The data for women indicated that sildenafil reduced adverse sexual effects, specifically including delayed orgasm responses and inadequate lubrication. Nurnberg commented on the relative sparsity of research on the effect of sildenafil on orgasm function, despite the fact that delayed or unachieved orgasm is "the central factor of SRI antidepressant-associated sexual dysfunction." He attributed this to the FDA-approved indication and marketing focus for male erectile dysfunction and to the more complex measures needed to assess orgasm function in women than sexual arousal in men. In addition, he noted, the initial studies of sildenafil had not shown benefit in women with sexual arousal disorder unrelated to antidepressant medication. Nevertheless, there was good reason to evaluate the effects of a selective phosphodiesterase type 5 inhibitor such as sildenafil in women experiencing sexual dysfunction from antidepressant medication, according to Nurnberg. The initial studies of sildenafil for women with sexual arousal disorder may not have adequately controlled for hormonal factors or level of sexual interest, or measured efficacy in the varied facets of sexual response.

User Name	Reported Effects	Side Effects Experienced	Usage Frequency	Overall Satisfaction
Jenny	Noticed increased sensitivity but mild headaches	Headache, flushes	Weekly	Moderately satisfied
Maria	Felt more aroused, no side effects	None	Occasionally	Satisfied
Lisa	No significant effect	Nausea, dizziness	Rarely	Dissatisfied
Karen	Improved orgasm intensity	Flushing, mild headache	Regular	Satisfied

Later, more focused studies yielded favorable results. In addition, Nurnberg noted, nitric oxide synthase isoforms, nitric oxide, and phos- phodiesterase type 5 inhibitors are present in female genital tissue. Phosphodiesterase type 5 inhibitor enhancement of nitric oxide–cyclic guanosine monophosphate signaling occurs in both women and men. Studying Drug Treatment of Adverse Drug EffectWomen in the Nurnberg study had to have reported good sexual interest and activity before the onset of depression and antidepressant treatment.

Strategy	Description	Notes
Low-dose initial	Starting with 25 mg, titrating up as needed	To minimize side effects
Maximum dose	Up to 100 mg, under medical supervision	To maximize effect, risk side effects
As-needed use	Taken before anticipated sexual activity	Short-term use
Daily use	Continuous daily dosing for sustained effect	Experimental, under doctor's guidance

Their episodes of sexual dysfunction had to be associated with antidepressant treatment and needed to have remitted with improvement of depression and discontinuation of medication.

Does Viagra help women?

Secondary outcome instruments were the Sexual Function Questionnaire, the Arizona Sexual Experience scale–female version, and the University of New Mexico Sexual Function Inventory–female version. Patients maintained logs that were reviewed for the frequency and percentage of successful intercourse attempts and the number of satisfactory attempts at orgasm. In the intention-to-treat analysis, women receiving sildenafil had a statistically significant higher mean score improvement from baseline of 1.9 on the CGI than the 1.1 mean improved score for those receiving placebo.

Curr. Psychiatry Rep.

Baseline endocrine values were obtained in these women to later analyze for possible correlations with treatment response. This analysis indicated that women whose sexual function improved after receiving sildenafil or placebo had higher mean levels of free testosterone and thyroxine. Ninety-eight women of 145 screened were randomized to receive either sildenafil in a 50-mg starting dosage or matching placebo. They were instructed to take the study medication approximately 1 to 2 hours before anticipated sexual activity but not more than once daily. They were asked to attempt to have sexual activity twice weekly, but not less than once weekly throughout the 8-week trial. Treatment efficacy was measured with 4 validated instruments. The primary outcome measure was the mean improvement on the Clinical Global Impression Scale (CGI) adapted for sexual function.

Ethics declarations

Phosphodiesterase type 5 inhibitor enhancement of nitric oxide–cyclic guanosine monophosphate signaling occurs in both women and men. Studying Drug Treatment of Adverse Drug EffectWomen in the Nurnberg study had to have reported good sexual interest and activity before the onset of depression and antidepressant treatment. Their episodes of sexual dysfunction had to be associated with antidepressant treatment and needed to have remitted with improvement of depression and discontinuation of medication. Baseline endocrine values were obtained in these women to later analyze for possible correlations with treatment response. This analysis indicated that women whose sexual function improved after receiving sildenafil or placebo had higher mean levels of free testosterone and thyroxine.

Research on Sildenafil Citrate for Women

Ninety-eight women of 145 screened were randomized to receive either sildenafil in a 50-mg starting dosage or matching placebo. They were instructed to take the study medication approximately 1 to 2 hours before anticipated sexual activity but not more than once daily. They were asked to attempt to have sexual activity twice weekly, but not less than once weekly throughout the 8-week trial. Treatment efficacy was measured with 4 validated instruments. The primary outcome measure was the mean improvement on the Clinical Global Impression Scale (CGI) adapted for sexual function. Secondary outcome instruments were the Sexual Function Questionnaire, the Arizona Sexual Experience scale–female version, and the University of New Mexico Sexual Function Inventory–female version.

The use of sildenafil in women is still under scientific investigation.
Some women report benefits, but evidence is not definitive.
Potential risks must be carefully weighed against benefits.
Proper medical guidance is essential for safe use.

Patients maintained logs that were reviewed for the frequency and percentage of successful intercourse attempts and the number of satisfactory attempts at orgasm. In the intention-to-treat analysis, women receiving sildenafil had a statistically significant higher mean score improvement from baseline of 1.9 on the CGI than the 1.1 mean improved score for those receiving placebo.

How It Works

The study, recently published in JAMA, was conducted by George Nurnberg, MD, of the department of psychiatry, University of New Mexico, and colleagues.1 This group's 2003 study, also published in JAMA, demonstrated sildenafil's benefit in men with this complaint.2 That study was a departure from the anecdotal or open-label reports that served as an evidence base for a myriad of proposed remedies.3 Although the association between sexual dysfunction and antidepressant therapy has been recognized since the introduction of tricyclics, the incidence of this adverse effect has increased since the advent of serotonin reuptake inhibitors (SRIs). Sexual dysfunction has also played a role in reducing patient adherence to the prescribed medication. Consequently, Nurnberg commented to Psychiatric Times, "treatments have been driven more by opinion than by solid data." Nurnberg and colleagues emphasize this concern in their latest study, warning that "without evidence-based data to treat sexual function associated sildenafil pick up with SRIs in women, clinicians may lack the confidence to manage it effectively, which leaves patients exposed to excess random pharmacology." The investigators employed a design and protocol similar to those in their study with men. The data for women indicated that sildenafil reduced adverse sexual effects, specifically including delayed orgasm responses and inadequate lubrication. Nurnberg commented on the relative sparsity of research on the effect of sildenafil on orgasm function, despite the fact that delayed or unachieved orgasm is "the central factor of SRI antidepressant-associated sexual dysfunction." He attributed this to the FDA-approved indication and marketing focus for male erectile dysfunction and to the more complex measures needed to assess orgasm function in women than sexual arousal in men.

Sexual Health in the Neurogenic Patient

In addition, he noted, the initial studies of sildenafil had not shown benefit in women with sexual arousal disorder unrelated to antidepressant medication. Nevertheless, there was good reason to evaluate the effects of a selective phosphodiesterase type 5 inhibitor such as sildenafil in women experiencing sexual dysfunction from antidepressant medication, according to Nurnberg. The initial studies of sildenafil for women with sexual arousal disorder may not have adequately controlled for hormonal factors or level of sexual interest, or measured efficacy in the varied facets of sexual response. Later, more focused studies yielded favorable results. In addition, Nurnberg noted, nitric oxide synthase isoforms, nitric oxide, and phos- phodiesterase type 5 inhibitors are present in female genital tissue.