Exo-Clinical Trials of Nutritional Supplements for Sexual Dysfunction: Precedents, Principles, and Protocols.

INTRODUCTION: Care-seeking for sexual dysfunction is limited by embarrassment, efficacy/safety concerns, and cost. Nutritional supplements (NSs) are low-cost but unproven.

AIM: To provide hypotheses on whether effective NS combinations for sexual dysfunction can be created following known pharmacology principles and tested with sufficient rigor in Internet-based "exo-clinical" trials (XCTs).

METHODS: PubMed and Google searches were conducted to review the feasibility of XCTs of NS combinations for sexual dysfunction. Findings were synthesized into recommendations for XCTs to treat the most common sexual problems.

MAIN OUTCOME MEASURE: The hierarchy of references used for making recommendations was controlled clinical trials over uncontrolled trials. The frequency of sexual dysfunction was determined in population-representative national surveys.

RESULTS: XCTs of cognitive behavioral therapy show conclusive efficacy for anxiety and depression. 5 small XCTs showed efficacy for female sexual dysfunction and erectile dysfunction (ED), and 2 XCTs of NS for other medical problems substantiated feasibility. To test the feasibility of XCTs for the most common forms of sexual dysfunction-ED, hypoactive sexual desire disorder (HSDD), and sexual performance anxiety-protocol outlines were generated for frugal XCTs; the total estimated subject time burden is ≤1 hour.

CONCLUSION: An XCT is a cost-effective method of evaluating new treatments, including sexual dysfunction and common mental disorders, if compliance is maintained by regular outreach while minimizing the time burden on subjects and handling consent and privacy issues appropriately. NS combinations might expand the opportunities for relief of sexual dysfunction if formulated with pharmacologically active doses of NS with already supported efficacy and safety. The feasibility of XCTs of NS combinations for sexual dysfunction might be tested most productively in men with ED, in women with HSDD, and in men and women with sexual performance anxiety. Pyke RE. Exo-Clinical Trials of Nutritional Supplements for Sexual Dysfunction: Precedents, Principles, and Protocols. Sex Med Rev 2018;XX:XX-XX.