A First-of-its-Kind Female Arousal Cream

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.

Why is this medicine prescribed?

As seen in registration trials for hypoactive sexual desire disorder treatments,16,17,31–34 another limitation of our study was the relatively homogeneous population of college-educated White women. We acknowledge that the requirement to enroll sexual partners likely limited enrollment of Hispanic and non-Hispanic Black women and hypothesize that removing this requirement from future studies will result in a more diverse patient population. In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil increased sexual arousal sensation, desire, and orgasm and reduced sexual distress. Will individual participant data be available (including data dictionaries)? What data in particular will be shared?

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When will data be available (start and end dates)? By what access criteria will data be shared (including with whom, for what types of analyses, and by what mechanism)? doi: 10.1016/j.sxmr.2020.05.001 Witherow-Parkanyi M. Female sexual interest/arousal disorder: history of diagnostic considerations and their implications for clinical practice. Assessing the clinical efficacy of sildenafil for the treatment of female sexual dysfunction. 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.

• Sildenafil works by relaxing blood vessels, increasing blood flow to genital areas.
• Female sexual arousal disorder may potentially be treated with sildenafil.
• Research shows mixed results regarding sildenafil's effectiveness in women.
• Sildenafil is not approved by the FDA specifically for women’s sexual problems.
• Possible risks for women include headaches and low blood pressure.
• Always consult a healthcare provider before trying sildenafil for women.

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.

THE BIG “O” (OVERVIEW)

J Sex Med 2010;7:858–72. Symptoms and associated impact in pre- and postmenopausal women with sexual arousal disorder: a concept elicitation study. Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. doi: 10.1001/jama.300.4.395 Berman JR, Berman LA, Toler SM, Gill J, Haughie S; Sildenafil Study Group.

Addyi (filbanserin)

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond) 2016;12:325–37. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Treatment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the VIOLET Study. Treatment of sildenafil citrate chewable tablets hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the DAISY study. placebo used in patients’ home setting.

The bottom line

doi: 10.1016/s0090-4295(02)01663-1 Mayer M, Stief CG, Truss MC, Uckert S. Phosphodiesterase inhibitors in female sexual dysfunction. Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human clitoris: immunohistochemical and molecular biology study. doi: 10.1016/j.urology.2005.11.055 Park K, Moreland RB, Goldstein I, Atala A, Traish A. Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle.

Jet lag research

Traish AM, Kim NN, Munarriz R, Moreland R, Goldstein I. Biochemical and physiological mechanisms of female genital sexual arousal. Arch Sex Behav 2002;31:393–400. In vitro functional responses of isolated human vaginal tissue to selective phosphodiesterase inhibitors. J Sex Med 2007;4:1604–9. 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).

What side effects can this medicine cause?

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 sildenafil online ireland are the most important and relevant to women with FSAD. 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). 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.

• 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.

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.

• Some women seek sildenafil for increasing genital blood flow and sensation.
• The placebo effect can influence perceived benefits in women using sildenafil.
• Women with cardiovascular risk should avoid sildenafil unless approved by a doctor.
• Topical or alternative therapies might be considered alongside or instead of sildenafil.
• Scientific consensus on sildenafil’s safety for women remains under development.
• Proper dosing and medical oversight are key to minimizing risks.

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

• Sildenafil is a medication primarily used to treat erectile dysfunction in men.
• Women sildenafil is an off-label use aimed at improving female sexual arousal.
• Clinical trials are ongoing to assess efficacy of sildenafil for women.
• Side effects of sildenafil may include headaches, flushing, and nasal congestion.
• Women may experience increased blood flow and libido with sildenafil.
• Proper dosage and medical consultation are essential before use.

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.

What should I do in case of overdose?

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®. 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.

How Viagra Works

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. 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. 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.

How should this medicine be used?

doi: 10.1111/j.1743-6109.2007.00595.x Uckert S, Oelke M, Albrecht K, Breitmeier D, Kuczyk MA, Hedlund P. Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type sildenafil otc 5 (PDE5). J Sex Med 2007;4:602–8. doi: 10.1111/j.1743-6109.2007.00490.x Sexual motivation in couples coping with female sexual interest/arousal disorder: a comparison with control couples. A systematic literature review of health-related quality of life measures for women with hypoactive sexual desire disorder and female sexual interest/arousal disorder.

A Note on Gender and Sex Terminology

Efficacy of flibanserin in women with hypoactive sexual desire disorder: results from the BEGONIA trial. Simon JA, Thorp J, Millheiser L. 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.