A First-of-its-Kind Female Arousal Cream

Dr. Brainard's practice received funding from Daré Bioscience for study specific activities. Dr. Goldstein also reported receiving payments from Nuvig, Ipsen, and AbbVie. This is a phase 2b study of topical sildenafil cream 3.6%, which is being developed clinically for the treatment of female sexual arousal disorder. The study was conducted under a U.S. Food and Drug Administration–approved investigational new drug application. Each author has confirmed compliance with the journal's requirements for authorship. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited.

• Clinical research into sildenafil for women includes various dosage trials.
• Women using sildenafil should monitor blood pressure to avoid adverse effects.
• The safety profile of sildenafil in women is less documented than in men.
• Sildenafil’s impact on female sexual desire is still under scientific investigation.
• Women should avoid sildenafil if pregnant or breastfeeding unless prescribed.
• Alternative therapies for female sexual dysfunction include counseling and hormone therapy.

The work cannot be changed in any way or used commercially without permission from the journal. To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder. We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale—Desire, Arousal, Orgasm). Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P=.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores.

• 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.

This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P≤.04). Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction.

• 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.

In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress. Topical sildenafil cream 3.6% improved outcomes among women with female sexual arousal disorder, particularly an exploratory subset of women with female sexual arousal disorder with or without concomitant decreased desire. Female sexual arousal disorder is a persistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement that causes marked distress or interpersonal difficulty.1,2 Despite the high prevalence of female sexual arousal disorder (about 20% of U.S. women3–5), to date there are no U.S. Food and Drug Administration (FDA)–approved pharmacologic treatments for female sexual arousal disorder.

What is Viagra, and how does it work?

Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P=.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores. This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P≤.04). Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction.

How should sildenafil for women be used?

In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress. Topical sildenafil cream 3.6% improved outcomes among women with female sexual arousal disorder, particularly an exploratory subset of women with female sexual arousal disorder with or without concomitant decreased desire. Female sexual arousal disorder is a persistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement that causes marked distress or interpersonal difficulty.1,2 Despite the high prevalence of female sexual arousal disorder (about 20% of U.S. women3–5), to date there are no U.S. Food and Drug Administration (FDA)–approved pharmacologic treatments for female sexual arousal disorder.

Ospemifene (Osphena)

Female sexual arousal disorder is clinically analogous to male erectile dysfunction, characterized by impaired blood flow to genital tissues. Oral sildenafil citrate (Viagra) was approved in 1998 for sildenafil syrup the treatment of erectile dysfunction. Published placebo-controlled trials of oral sildenafil administered in premenopausal and postmenopausal women afflicted with broad-spectrum female sexual dysfunction (eg, hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, dyspareunia) demonstrated marginal efficacy compared with placebo6–9 with high incidences of intolerable side effects. Topical sildenafil cream 3.6% (sildenafil cream) has been developed for the treatment of female sexual arousal disorder. We hypothesized that by delivering sildenafil citrate topically with a fast-absorbing delivery technology specifically targeting genital anatomy central to the vascular arousal response,10 there would be less systemic exposure, fewer systemic side effects, and a more immediate biological efficacy response. Female sexual arousal disorder is clinically analogous to male erectile dysfunction, characterized by impaired blood flow to genital tissues. Oral sildenafil citrate (Viagra) was approved in 1998 for sildenafil syrup the treatment of erectile dysfunction. Published placebo-controlled trials of oral sildenafil administered in premenopausal and postmenopausal women afflicted with broad-spectrum female sexual dysfunction (eg, hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, dyspareunia) demonstrated marginal efficacy compared with placebo6–9 with high incidences of intolerable side effects.

• The legality of women using sildenafil varies by country and local regulations.
• Lifestyle modifications can complement medication for better sexual health outcomes.
• Women with diabetes may have different responses to sildenafil therapy.
• The stigma surrounding female sexual dysfunction can hinder treatment seeking.
• Advances in research are aimed at developing female-specific ED medications.
• Open discussions with physicians are essential for safe and effective treatments.

Topical sildenafil cream 3.6% (sildenafil cream) has been developed for the treatment of female sexual arousal disorder. We hypothesized that by delivering sildenafil citrate topically with a fast-absorbing delivery technology specifically targeting genital anatomy central to the vascular arousal response,10 there would be less systemic exposure, fewer systemic side effects, and a more immediate biological efficacy response. Before the start of the study, we conducted a qualitative content validity study among women with female sexual arousal disorder to ensure that the efficacy endpoints, which were patient-reported outcome measures, were fit for purpose and valid for this specific population.11 This clinical trial was conducted at 49 sites in the United States, approved by the Advarra IRB (Pro00049161), and registered at ClinicalTrials.gov (NCT04948151).

Healthy premenopausal women aged 18 years or older and their sexual partners were screened for the study. Volunteers and their sexual partners provided written informed consent before the performance of any study-related procedures. Women at risk of pregnancy used effective contraception during the study (eg, hormonal contraception). Male condoms could be used for sexually transmitted infection prevention.

The coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ38 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale—Desire, Arousal, Orgasm). A one-on-one clinical interview was conducted with each potential participant, using interviewers who were not employees of the study sponsor and who were recognized experts in the field, to establish the diagnosis of female sexual arousal disorder and to verify that female sexual arousal disorder was the woman's main sexual dysfunction concern if other concomitant sexual dysfunction diagnoses or symptoms existed. The clinical interview documented those concomitant diagnoses or symptoms for exploratory post hoc analyses based on sexual dysfunction diagnoses or symptoms at enrollment. The first screening occurred in July 2021, and the last participant visit was in April 2023. Appendix 1, available online at outlines the schedule of efficacy evaluations.

In brief, volunteers underwent informed consent and screening safety procedures at visit 1. A major barrier to recruitment was the requirement for sexual partners to be consented and involved in adverse event reporting because many volunteers did not want to disclose their female sexual arousal disorder symptoms to their sexual partners.

What special dietary instructions should I follow?

Before the start of the study, we conducted a qualitative content validity study among women with female sexual arousal disorder to ensure that the efficacy endpoints, which were patient-reported outcome measures, were fit for purpose and valid for this specific population.11 This clinical trial was conducted at 49 sites in the United States, approved by the Advarra IRB (Pro00049161), and registered at ClinicalTrials.gov (NCT04948151). Healthy premenopausal women aged 18 years or older and their sexual partners were screened for the study. Volunteers and their sexual partners provided written informed consent before the performance of any study-related procedures. Women at risk of pregnancy used effective contraception during the study (eg, hormonal contraception). Male condoms could be used for sexually transmitted infection prevention.

Can Viagra make a woman wet?

The coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ38 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale—Desire, Arousal, Orgasm). A one-on-one clinical interview was conducted with each potential participant, using interviewers who were not employees of the study sponsor and who were recognized experts in the field, to establish the diagnosis of female sexual arousal disorder and to verify that female sexual arousal disorder was the woman's main sexual dysfunction concern if other concomitant sexual dysfunction diagnoses or symptoms existed. The clinical interview documented those concomitant diagnoses or symptoms for exploratory post hoc analyses based on sexual dysfunction diagnoses or symptoms at enrollment. The first screening occurred in July 2021, and the last participant visit was in April 2023. Appendix 1, available online at outlines the schedule of efficacy evaluations.

Knowledge Gaps in Urologic Care of Female Spinal Cord Injury Patients

In brief, volunteers underwent informed consent and screening safety procedures at visit 1. A major barrier to recruitment was the requirement for sexual partners to be consented and involved in adverse event reporting because many volunteers did not want to disclose their female sexual arousal disorder symptoms to their sexual partners. Therefore, amendment 3 of the protocol allowed women to enroll in the trial if they did not have a sexual partner or if their sexual partner did not want to participate in the informed consent and safety monitoring process. In this latter case, investigational product was used only for unpartnered sexual events. As shown in Appendix 1 ( the study included a 28-day no-drug run-in period starting at visit 2, followed by a 28-day single-blind placebo run-in period beginning at visit 3. Therefore, amendment 3 of the protocol allowed women to enroll in the trial if they did not have a sexual partner or if their sexual partner did not want to participate in the informed consent and safety monitoring process. In this latter case, investigational product was used only for unpartnered sexual events. As shown in Appendix 1 ( the study included a 28-day no-drug run-in period starting at visit 2, followed by a 28-day single-blind placebo run-in period beginning at visit 3.

The Sexy Science Behind Dare to Play

Participants were screen failed during these 2 months if they were not compliant with recording sexual events, adverse events, or concomitant medications in the daily electronic diary or if they had a predetermined placebo response during the single-blind run-in period. Eligible participants were randomized at visit 4 in a 1:1 manner to sildenafil cream or placebo cream. The double-blind dosing period lasted 12 weeks, and responses at visit 4 and electronic diary data from the single-blind placebo run-in period were baseline scores. Participants were seen monthly during the double-blind dosing period at weeks 4 (visit 5), 8 (visit 6), and 12 (visit 7) and answered the 1-month recall SFQ28 and FSDS-DAO surveys. Participants recorded data in the electronic diary within 24 hours of a sexual event between monthly appointments.

Though you cannot place an order quite yet...

Participants were randomized with a concealed, interactive response technology system, after the single-blind run-in period, to either sildenafil cream or placebo cream in a 1:1 ratio. The allocation was blinded, and there were no allocation errors. The placebo cream contained the same ingredients as the sildenafil cream but without the active ingredient, sildenafil citrate. Each month, the investigational product was dispensed in a 30-g tube, along with nine 2-g dosing cards. Participants were instructed to apply no more than one 2-g application of product per calendar day and no more than 9 applications per month.

Flibanserin (Addyi)

Participants applied the investigational product about 10–20 minutes before the sexual event. One gram was applied externally to the anterior labial commissure, prepuce of the clitoris, glans, frenulum, vestibule, and labia minora. The other gram was applied to the anterior distal vagina to an approximate depth of 0–3 cm or about halfway between the distal and proximal interphalangeal joints, targeting the distal, lower one-third of the vagina. Participants were instructed to wash off the cream and have their partner wash off the cream, if relevant, after the sexual experience. The Arousal Sensation domain of the SFQ28 questionnaire is made up of questions 6 through 9 (Appendix 2, available online at These four questions were answered using a Likert scale ranging from 1–5, with 1 being no sensation and 5 being a very strong sensation. Participants were screen failed during these 2 months if they were not compliant with recording sexual events, adverse events, or concomitant medications in the daily electronic diary or if they had a predetermined placebo response during the single-blind run-in period.

Adverse effects

Dr. Brainard's practice received funding from Daré Bioscience for study specific activities. Dr. Goldstein also reported receiving payments from Nuvig, Ipsen, and AbbVie. This is a phase 2b study of topical sildenafil cream 3.6%, which is being developed clinically for the treatment of female sexual arousal disorder.

What special precautions should I follow?

The study was conducted under a U.S. Food and Drug Administration–approved investigational new drug application. Each author has confirmed compliance with the journal's requirements for authorship. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Related medical questions

To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder. We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale—Desire, Arousal, Orgasm). Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Eligible participants were randomized at visit 4 in a 1:1 manner to sildenafil cream or placebo cream. The double-blind dosing period lasted 12 weeks, and responses at visit 4 and electronic diary data from the single-blind placebo run-in period were baseline scores.

Detection in biological fluids

The range of scores for the Arousal Sensation domain is 4–20, with higher scores indicating higher sexual function. The FSDS-DAO survey includes 15 questions, each of which began with the phrase, “How often in the past 30 days did you feel,” with responses of 0–4, with 0 indicating never feeling this way and 4 indicating always feeling this way (Appendix 2, Question 14 asks, “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?” The range of scores for question 14 of the FSDS-DAO is 0–4, with lower scores indicating decreased levels of sexual distress. Participants were seen monthly during the double-blind dosing period at weeks 4 (visit 5), 8 (visit 6), and 12 (visit 7) and answered the 1-month recall SFQ28 and FSDS-DAO surveys. Participants recorded data in the electronic diary within 24 hours of a sexual event between monthly appointments. Participants were randomized with a concealed, interactive response technology system, after the single-blind run-in period, to either sildenafil cream or placebo cream in a 1:1 ratio. The allocation was blinded, and there were no allocation errors. The placebo cream contained the same ingredients as the sildenafil cream but without the active ingredient, sildenafil citrate. Each month, the investigational product was dispensed in a 30-g tube, along with nine 2-g dosing cards. Participants were instructed to apply no more than one 2-g application of product per calendar day and no more than 9 applications per month. Participants applied the investigational product about 10–20 minutes before the sexual event. One gram was applied externally to the anterior labial commissure, prepuce of the clitoris, glans, frenulum, vestibule, and labia minora. The other gram was applied to the anterior distal vagina to an approximate depth of 0–3 cm or about halfway between the distal and proximal interphalangeal joints, targeting the distal, lower one-third of the vagina. Participants were instructed to wash off the cream and have their partner wash off the cream, if relevant, after the sexual experience. The Arousal Sensation domain of the SFQ28 questionnaire is made up of questions 6 through 9 (Appendix 2, available online at These four questions were answered using a Likert scale ranging from 1–5, with 1 being no sensation and 5 being a very strong sensation. The range of scores for the Arousal Sensation domain is 4–20, with higher scores indicating higher sexual function. The FSDS-DAO survey includes 15 questions, each of which began with the phrase, “How often in the past 30 days did you feel,” with responses of 0–4, with 0 indicating never feeling this way and 4 indicating always feeling this way (Appendix 2, Question 14 asks, “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?” The range of scores for question 14 of the FSDS-DAO is 0–4, with lower scores indicating decreased levels of sexual distress.