Low Dose Sildenafil (AKA Viagra®) for Women
Flibanserin for premenopausal hypoactive sexual desire disorder: pooled analysis of clinical trials.
Interested, but not quite ready?
At the conclusion of the development program, if successful, Daré intends to leverage the existing safety and efficacy data for sildenafil to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of Sildenafil Cream, 3.6% for the treatment of women in the U.S. DOI: 10.1016/j.sxmr.2016.03.002 Ad Hoc Market Research: FSAD Prevalence Report (Oct 2015) conducted for SST LLC. Based on US Census projections for 2016. We evaluated the efficacy and safety of sildenafil citrate in spontaneously or surgically postmenopausal women with female sexual arousal disorder (FSAD). Sildenafil (a 50 mg dose adjustable to 100 or 25 mg) was evaluated in a 12-week, double-blind, placebo controlled study in 202 postmenopausal women with FSAD who had protocol specified estradiol and free testosterone concentrations, and/or were receiving estrogen and/or androgen replacement therapy.
Raynaud's phenomenon
Patients were excluded if emotional, relationship or historical abuse issues contributed significantly to sexual dysfunction. Primary end points were questions 2 (increased genital sensation during intercourse or stimulation) and 4 (increased satisfaction with intercourse and/or foreplay) from the Female Intervention Efficacy Index (FIEI). Secondary end points were the remaining questions from this index, the Sexual Function Questionnaire and sexual activity event log questions. Significant improvements in FIEI questions 2 (p = 0.017) and 4 (p = 0.015) were noted with sildenafil compared with placebo. For women with FSAD without concomitant hypoactive sexual desire disorder (HSDD) sildenafil was associated with significantly greater improvement in 5 of 6 FIEI items compared with placebo (p <0.02). J Womens Health (Larchmt) 2019;28:769–77. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder.
| Trend | Description | Potential Impact |
|---|---|---|
| Development of women-specific formulations | Customized doses and delivery methods | Improved safety and efficacy |
| Combination therapies | Sildenafil combined with other agents | Potentially enhanced outcomes |
| Non-oral delivery systems | Topicals, patches, or injectables | Increased convenience and quicker onset |
| Personalized medicine approaches | Genetic testing to optimize treatment | Higher success rates with fewer side effects |
| Increased clinical trials in women | More robust evidence for approval | Better guideline development |
Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Female sexual arousal disorder (FSAD) FSAD, as described in the Diagnostic and Statistical Manual 4th Edition (DSM-IV), is a condition characterized as a persistent or recurrent inability to attain or maintain sufficient genital arousal (an adequate lubrication-swelling response) during sexual activity, frequently resulting in distress or interpersonal difficulty. Of the various types of female sexual dysfunction disorders, FSAD is most analogous to erectile dysfunction (ED) in men. There are currently no FDA-approved therapies for FSAD. A meta-analysis of 95 studies from 2000-2014 indicated prevalence of Female Sexual Dysfunction in premenopausal women worldwide is 41%, and difficulty with arousal alone is 23%.1 Market research estimates: 33% of US women aged 21 to 60 (~ 20 million women), experience symptoms of low or no sexual arousal.2,310 million women in the US are considered distressed and actively seeking treatment.2 33% of US women aged 21 to 60 (~ 20 million women), experience symptoms of low or no sexual arousal.2,3 10 million women in the US are considered distressed and actively seeking treatment.2 To put the market opportunity for an FDA-approved FSAD treatment in context, a PDE5 inhibitor utilized in an ED medication for men – Viagra® — peaked at $2.05 billion in sales in 2012.4 Orally administered sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, received FDA approval in 1998 for the treatment of erectile dysfunction in men and is marketed under the brand name Viagra®. Given the underlying pathophysiologic similarities of ED and FSAD, using sildenafil to direct blood to the genitals before sexual activity could provide a potential improvement in genital arousal response and overall sexual experience for women as it does in men. Sildenafil Cream, 3.6% is an investigational proprietary topical formulation of sildenafil being developed as a first-in-category option for women for the treatment of FSAD.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Kamagra Soft Tabs | 100mg | 84 + 4 Pills | 233.05€ 221.95€ | |
| Viagra Generic | 25mg | 120 + 6 Pills | 125.56€ 119.58€ | |
| Viagra Generic | 50mg | 360 + 10 Pills | 225.33€ 214.60€ | |
| Viagra Generic | 100mg | 270 + 10 Pills | 270.47€ 257.59€ | |
| Viagra Generic | 200mg | 30 + 2 Pills | 83.07€ 79.11€ | |
| Kamagra Polo | 100mg | 12 Pills | 60.21€ 57.34€ | |
| Viagra Generic | 100mg | 180 + 8 Pills | 199.37€ 189.88€ | |
| Kamagra | 100mg | 60 + 4 Pills | 201.34€ 191.75€ | |
| Viagra Generic | 100mg | 10 Pills | 28.91€ 27.53€ | |
| Viagra Generic | 200mg | 270 + 10 Pills | 379.76€ 361.68€ | |
| Kamagra Soft Tabs | 100mg | 60 + 4 Pills | 180.59€ 171.99€ | |
| Viagra Generic | 100mg | 360 + 10 Pills | 330.21€ 314.49€ | |
| Viagra Generic | 150mg | 30 + 2 Pills | 72.32€ 68.88€ | |
| Viagra Generic | 150mg | 270 + 10 Pills | 326.61€ 311.06€ |
Unlike the oral formulations of PDE-5 inhibitors, Sildenafil Cream is applied locally to the vaginal tissue and is designed to facilitate vasodilation and increased blood flow directly to the genital tissue to improve the physical arousal response symptoms commonly associated with FSAD while avoiding systemic side effects observed with oral formulations of sildenafil. Phase 1 and Phase 2a Clinical Studies, Previously Completed In a Phase 1 clinical study in 20 healthy post-menopausal women, topical sildenafil cream was safe and well tolerated at clinically relevant doses, and study subjects reported favorable product characteristics: easy to use and readily absorbed. In a Phase 2a study in women with FSAD (15 pre-menopausal and 16 post-menopausal), Sildenafil Cream increased measurable blood flow to the genital tissue compared to placebo cream.
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10 : Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. 11 Guay, A., Munarriz, R., Jacobson, M.A., Talakoub, L., Goldstein, I., Traish, A. et-al: Androgen values in premenopausal women without sexual dysfunction. Presented at International Society for the Study of Women's Sexual Health, Vancouver, British Columbia, Canada, October 10–13, 2002 Google Scholar 13 : Development of a sexual function questionnaire for clinical trials of female sexual dysfunction. J Womens Health Gend Based Med2002; 11: 277.
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14 : The use of the Female Intervention Efficacy Index (FIEI) as an immediate outcome measure of medical intervention to treat female sexual dysfunction. 15 : Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. Further, data from a thermography study in healthy women demonstrated significantly greater increases in genital temperature after administration of Sildenafil Cream compared to placebo cream, indicating a positive impact on genital blood flow during the 30-minute testing session, with statistical separation from placebo within the first 15 minutes after dosing. We also completed a content validity study designed to identify and document the genital arousal symptoms that are the most important and relevant to women with FSAD.
Are there any natural alternatives to Viagra for women?
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The findings of this study helped facilitate alignment with the FDA on acceptable efficacy endpoints for the Phase 2b RESPOND study and a future Phase 3 program.
The bottom line
Flibanserin for premenopausal hypoactive sexual desire disorder: pooled analysis of clinical trials. J Womens Health (Larchmt) 2019;28:769–77. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Female sexual arousal disorder (FSAD) FSAD, as described in the Diagnostic and Statistical Manual 4th Edition (DSM-IV), is a condition characterized as a persistent or recurrent inability to attain or maintain sufficient genital arousal (an adequate lubrication-swelling response) during sexual activity, frequently resulting in distress or interpersonal difficulty.
Recreational use
Of the various types of female sexual dysfunction disorders, FSAD is most analogous to erectile dysfunction (ED) in men. There are currently no FDA-approved therapies for FSAD. A meta-analysis of 95 studies from 2000-2014 indicated prevalence of Female Sexual Dysfunction in premenopausal women worldwide is 41%, and difficulty with arousal alone is 23%.1 Market research estimates: 33% of US women aged 21 to 60 (~ 20 million women), experience symptoms of low or no sexual arousal.2,310 million women in the US are considered distressed and actively seeking treatment.2 33% of US women aged 21 to 60 (~ 20 million women), experience symptoms of low or no sexual arousal.2,3 10 million women in the US are considered distressed and actively seeking treatment.2 To put the market opportunity for an FDA-approved FSAD treatment in context, a PDE5 inhibitor utilized in an ED medication for men – Viagra® — peaked at $2.05 billion in sales in 2012.4 Orally administered sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, received FDA approval in 1998 for the treatment of erectile dysfunction in men and is marketed under the brand name Viagra®. Given the underlying pathophysiologic similarities of ED and FSAD, using sildenafil to direct blood to the genitals before sexual activity could provide a potential improvement in genital arousal response and overall sexual experience for women as it does in men. Sildenafil Cream, 3.6% is an investigational proprietary topical formulation of sildenafil being developed as a first-in-category option for women for the treatment of FSAD. The Phase 2b study was an exploratory study to evaluate a number of primary endpoints and secondary endpoints as well as to identify a target patient population for Sildenafil Cream, 3.6%. The Phase 2b clinical study was designed as a multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of Sildenafil Cream, 3.6% in premenopausal patients with female sexual arousal disorder (FSAD).
- Doctors may prescribe sildenafil off-label for women based on individual assessment.
- Patient education about realistic expectations is essential when using sildenafil.
- Sildenafil’s mechanism involves enhancing nitric oxide signaling in blood vessels.
- Women with liver or kidney problems need careful evaluation before sildenafil use.
- Viagra was initially tested for women before focusing on men’s erectile issues.
- Alternative options like vaginal lubricants are also common for female sexual problems.
Study participants used Sildenafil Cream and placebo cream over 12 weeks in their home setting, following both a non-drug and placebo cream run-in period. All participants had a main diagnosis of FSAD and may have also had concomitant sexual dysfunction diagnoses or symptoms including decreased desire, orgasmic dysfunction, and genital pain. Exploratory Phase 2b clinical study designed to evaluate Sildenafil Cream vs.
- Sildenafil is often known by the brand name Viagra, primarily for men.
- Researchers are exploring other PDE5 inhibitors for women’s sexual health.
- Efficacy of sildenafil in women might depend on underlying health conditions.
- Women with cardiovascular issues should be particularly cautious with sildenafil.
- Some women report increased sexual satisfaction after using sildenafil.
- Medical advice is crucial before women consider sildenafil as a treatment.
placebo over 12 weeks of double-blinded dosing following both a non-drug and placebo run-in period: Compared Sildenafil Cream vs. placebo used lovegra sildenafil in patients’ home setting.
Why is this medicine prescribed?
Unlike the oral formulations of PDE-5 inhibitors, Sildenafil Cream is applied locally to the vaginal tissue and is designed to facilitate vasodilation and increased blood flow directly to the genital tissue to improve the physical arousal response symptoms commonly associated with FSAD while avoiding systemic side effects observed with oral formulations of sildenafil. Phase 1 and Phase 2a Clinical Studies, Previously Completed In a Phase 1 clinical study in 20 healthy post-menopausal women, topical sildenafil cream was safe and well tolerated at clinically relevant doses, and study subjects reported favorable product characteristics: easy to use and readily absorbed. In a Phase 2a study in women with FSAD (15 pre-menopausal and 16 post-menopausal), Sildenafil Cream increased measurable blood flow to the genital tissue compared to placebo cream. Further, data from a thermography study in healthy women demonstrated significantly greater increases in genital temperature after administration of Sildenafil Cream compared to placebo cream, indicating a positive impact on genital blood flow during the 30-minute testing session, with statistical separation from placebo within the first 15 minutes after dosing. We also completed a content validity study designed to identify and document the genital arousal symptoms that are the most important and relevant to women with FSAD.
How should sildenafil for women be used?
The findings of this study helped facilitate alignment with the FDA on acceptable efficacy endpoints for the Phase 2b RESPOND study and a future Phase 3 program. The Phase 2b study was an exploratory study to evaluate a number of primary endpoints and secondary endpoints as well as to identify a target patient population for Sildenafil Cream, 3.6%. The Phase 2b clinical study was designed as a multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of Sildenafil Cream, 3.6% in premenopausal patients with female sexual arousal disorder (FSAD). Study participants used Sildenafil Cream and placebo cream over 12 weeks in their home setting, following both a non-drug and placebo cream run-in period. All participants had a main diagnosis of FSAD and may have also had concomitant sexual dysfunction diagnoses or symptoms including decreased desire, orgasmic dysfunction, and genital pain. Co-primary endpoints: patient reported outcome (PRO) instruments measured improvement in localized genital sensations of arousal (Arousal-Sensation Domain of the Sexual Function Questionnaire) and reduction in FSAD related distress (Female Sexual Distress Scale).
- The market for female sexual enhancement drugs is growing, including sildenafil research.
- Women should be aware of potential drug interactions when using sildenafil.
- Female sexual health involves multiple factors, not just blood flow.
- Sildenafil may not be effective for all women due to physiological differences.
- Regular follow-up with healthcare providers can optimize treatment and safety.
- Lifestyle factors such as stress and hormonal balance influence female libido.
Secondary endpoint: measured change in the number of satisfactory sexual events Exploratory endpoints: Several efficacy endpoints measured and could be candidate endpoints in a Phase 3 study. Efficacy assessments were administered both on an electronic diary to be completed within 24 hours of a sexual event and via 28-day recall assessments. Sildenafil Cream-treated group showed meaningful improvement in the co‑primary endpoint assessment that evaluated change from baseline in the Arousal-Sensation Domain of the Sexual Function Questionnaire, although the endpoint did not achieve statistical significance.1 Post-hoc analyses showed that Sildenafil Cream met the Ph2b co-primary endpoint (SFQ28-arousal domain patient reported outcome (PRO)) and demonstrated clinically meaningful benefit in patients who have FSAD or FSAD with concomitant decreased desire. Secondary and exploratory endpoints saw these patients report meaningful improvement in arousal sensation, desire, orgasm, as well as stress, guilt, and embarrassment about the sexual dysfunction. Read more about the Phase 2b clinical study here. Regulatory Strategy for Sildenafil Cream, 3.6%: Next Steps The Company is working to align with the FDA on the Phase 3 study design. At the conclusion of the development program, if successful, Daré intends to leverage the existing safety and efficacy data for sildenafil to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of Sildenafil Cream, 3.6% for the treatment of women in the U.S. DOI: 10.1016/j.sxmr.2016.03.002 Ad Hoc Market Research: FSAD Prevalence Report (Oct 2015) conducted for SST LLC.
- Some studies suggest sildenafil might help women with sexual arousal disorder.
- The drug's vasodilating effects can have cardiovascular implications in women.
- Women should be cautious of counterfeit or unapproved sildenafil products.
- Combining sildenafil with other ED drugs in women is not recommended without medical advice.
- Psychological support remains an important aspect of treating female sexual dysfunction.
- Ongoing clinical trials aim to establish the safety and efficacy of sildenafil for women.
Based on US Census projections for 2016. We evaluated the efficacy and safety of sildenafil citrate in spontaneously or surgically postmenopausal women with female sexual arousal disorder (FSAD). Sildenafil (a 50 mg dose adjustable to 100 or 25 mg) was evaluated in a 12-week, double-blind, placebo controlled study in 202 postmenopausal women with FSAD who had protocol specified estradiol and free testosterone concentrations, and/or were receiving estrogen and/or androgen replacement therapy. Patients were excluded if emotional, relationship or historical abuse issues contributed significantly to sexual dysfunction.
How should this medicine be used?
No significant improvements were shown for women with concomitant HSDD. Most adverse events were mild to moderate with headache, flushing, rhinitis, nausea and visual symptoms reported most frequently. Sildenafil was effective and well tolerated in postmenopausal women with FSAD without concomitant HSDD or contributory emotional, relationship or historical abuse issues. All patients had protocol specified estradiol and free testosterone concentrations or were receiving sildenafil from canada estrogen and/or androgen replacement therapy. 1 : Report of the International Consensus Development Conference on Female Sexual Dysfunction: definitions and classifications.
Exploratory Phase 2b RESPOND Study, Completed in 2023
2 : Female sexual arousal disorder: new insights. 5 : Development of human and rabbit vaginal smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. 7 : Sildenafil, a novel effective oral therapy for male erectile dysfunction. 8 : Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder. 9 : Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). Primary end points were questions 2 (increased genital sensation during intercourse or stimulation) and 4 (increased satisfaction with intercourse and/or foreplay) from the Female Intervention Efficacy Index (FIEI). Secondary end points were the remaining questions from this index, the Sexual Function Questionnaire and sexual activity event log questions. Significant improvements in FIEI questions 2 (p = 0.017) and 4 (p = 0.015) were noted with sildenafil compared with placebo. For women with FSAD without concomitant hypoactive sexual desire disorder (HSDD) sildenafil was associated with significantly greater improvement in 5 of 6 FIEI items compared with placebo (p <0.02). No significant improvements were shown for women with concomitant HSDD. Most adverse events were mild to moderate with headache, flushing, rhinitis, nausea and visual symptoms reported most frequently. Sildenafil was effective and well tolerated in postmenopausal women with FSAD without concomitant HSDD or contributory emotional, relationship or historical abuse issues. All patients had protocol specified estradiol and free testosterone concentrations or were receiving sildenafil from canada estrogen and/or androgen replacement therapy. 1 : Report of the International Consensus Development Conference on Female Sexual Dysfunction: definitions and classifications. 2 : Female sexual arousal disorder: new insights. 5 : Development of human and rabbit vaginal smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. 7 : Sildenafil, a novel effective oral therapy for male erectile dysfunction. 8 : Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder. 9 : Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i).
| Brand Name | Formulation | Dosage Options | Notes |
|---|---|---|---|
| Viagra Women | Oral tablet | 25 mg, 50 mg | Off-label use, not approved by FDA |
| Female Arousal Gel | Topical gel | N/A | Claimed to enhance blood flow |
| Sildenafil Citrate | Generic oral tablet | 25-100 mg | Widely used off-label in women |
| Custom Compounded | Customized formulations | Variable | Prescribed by special clinics |
10 : Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. 11 Guay, A., Munarriz, R., Jacobson, M.A., Talakoub, L., Goldstein, I., Traish, A. et-al: Androgen values in premenopausal women without sexual dysfunction. Presented at International Society for the Study of Women's Sexual Health, Vancouver, British Columbia, Canada, October 10–13, 2002 Google Scholar 13 : Development of a sexual function questionnaire for clinical trials of female sexual dysfunction.
OUR PRE-FULFILLMENT PRESCRIPTION PERIOD HAS BEGUN.
Exploratory Phase 2b clinical study designed to evaluate Sildenafil Cream vs. placebo over 12 weeks of double-blinded dosing following both a non-drug and placebo run-in period: Compared Sildenafil Cream vs. placebo used lovegra sildenafil in patients’ home setting. Co-primary endpoints: patient reported outcome (PRO) instruments measured improvement in localized genital sensations of arousal (Arousal-Sensation Domain of the Sexual Function Questionnaire) and reduction in FSAD related distress (Female Sexual Distress Scale). Secondary endpoint: measured change in the number of satisfactory sexual events Exploratory endpoints: Several efficacy endpoints measured and could be candidate endpoints in a Phase 3 study.
What side effects can low dose sildenafil cause?
Efficacy assessments were administered both on an electronic diary to be completed within 24 hours of a sexual event and via 28-day recall assessments. Sildenafil Cream-treated group showed meaningful improvement in the co‑primary endpoint assessment that evaluated change from baseline in the Arousal-Sensation Domain of the Sexual Function Questionnaire, although the endpoint did not achieve statistical significance.1 Post-hoc analyses showed that Sildenafil Cream met the Ph2b co-primary endpoint (SFQ28-arousal domain patient reported outcome (PRO)) and demonstrated clinically meaningful benefit in patients who have FSAD or FSAD with concomitant decreased desire. Secondary and exploratory endpoints saw these patients report meaningful improvement in arousal sensation, desire, orgasm, as well as stress, guilt, and embarrassment about the sexual dysfunction. Read more about the Phase 2b clinical study here. Regulatory Strategy for Sildenafil Cream, 3.6%: Next Steps The Company is working to align with the FDA on the Phase 3 study design. J Womens Health Gend Based Med2002; 11: 277. 14 : The use of the Female Intervention Efficacy Index (FIEI) as an immediate outcome measure of medical intervention to treat female sexual dysfunction. 15 : Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder.