Transdermal Testosterone Gel for Female Sexual Interest and Arousal Disorder in Peri- and Post Menopause

Official title

Transdermal Testosterone Gel for Female Sexual Interest and Arousal Disorder in Peri- and Post Menopause - A Randomized, Double-blind, Placebo-controlled Trial for Improving Sexual Interest and Desire

Overview

Hypoactive sexual desire disorder (HSDD) is described as the most common form of female sexual dysfunction, particularly affecting peri- and postmenopausal women and is associated with significant distress and reduced quality of life. The TESTA-MIND study will evaluate the efficacy and safety of a standardized compounded transdermal testosterone gel in a randomized, double-blind, placebo-controlled design to address the lack of FDA-approved options and limited high-quality evidence for treating decreased libido in women.

Detailed description

Hypoactive sexual desire disorder (HSDD) is the most prevalent form of female sexual dysfunction, particularly affecting peri- and postmenopausal women. Epidemiological studies estimate that between 8-14% of postmenopausal women experience clinically significant reductions in sexual desire that cause distress or interpersonal difficulty, significantly impacting quality of life and intimate relationships. In 2013, with the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of HSDD was merged with female sexual arousal disorder under the category of Female Sexual Interest/Arousal Disorder (FSIAD). Despite this reclassification, clinical and pharmacological trials continue to use HSDD criteria, given their clearer operationalization and applicability in interventional studies.

Testosterone has long been recognized as a key modulator of female sexual desire and arousal. Observational studies show that circulating androgen levels decrease substantially with age and after menopause. Clinical trials of transdermal testosterone have demonstrated improvements in sexual function, specifically increased frequency of satisfying sexual events, enhanced desire, and reduced distress compared with placebo (7-9). Nevertheless, most clinical studies have utilized pharmaceutical-grade formulations not currently available in the United States, leading many clinicians to rely on compounded testosterone creams.

Currently, no FDA-approved testosterone therapy exists for women, and off-label use varies widely in formulation and administration. Transdermal preparations may provide a physiologic, steady release, and offer practical advantages over patches or systemic therapy, but robust randomized data remain scarce.

Evidence regarding compounded testosterone is limited and highlights concerns about variability in formulation, dosing accuracy, and absorption. Professional societies caution against the routine use of compounded hormones, citing the lack of FDA oversight, inconsistent bioavailability, and absence of long-term safety data. While compounded testosterone may represent a pragmatic solution in the absence of FDA-approved formulations, its use requires rigorous evaluation under standardized trial conditions to establish both efficacy and safety.

The TESTA-MIND study is designed to address this evidence gap by investigating the efficacy and safety of a standardized compounded testosterone gel in peri- and postmenopausal women with decreased libido. By conducting a randomized, double-blind, placebo-controlled trial, the investigators aim to provide high-quality data on the therapeutic role of testosterone in this underserved population, while addressing the clinical uncertainty and professional society concerns that currently limit its widespread adoption.

Interventions

• Other Transdermal testosterone gel
  The compounded testosterone gel will be administered using a metered-dose delivery system calibrated to dispense 0.25 mL per actuation, corresponding to an estimated systemic exposure of approximately 300 µg of testosterone per day, within the physiologic range for females.
• Other Transdermal placebo gel
  A testosterone-free compounded gel will be delivered via a metered-dose pump calibrated to dispense 0.25 mL per actuation. The placebo gel will use an identical metered-dose delivery system, packaging, and administration instructions.

Primary outcome measures

• The Female Sexual Function Index score [Time frame: On recruitment, and at 4,8, and 12 weeks of treatment]

Secondary outcome measures (2)

• Patient global impression of improvement [Time frame: On recruitment, and at 4,8, and 12 weeks of treatment]
• Side effects of the treatment [Time frame: On recruitment, and at 4,8, and 12 weeks of treatment]

Eligibility criteria

Inclusion criteria

• Women 40-65 years; peri- or postmenopausal - with one of the following:

• Staging by STRAW+10: stage (-2) or above
• amenorrhea ≥12 mo
• Follicle stimulating hormone in menopausal range
• FSIAD diagnosis according to the DSM-5: (3/5 of the following symptoms)

• reduced or no interest in sex
• few or no thoughts about sex
• decreased sexual arousal or pleasure during sexual activity
• reduced or no arousal in response to visual, written, or verbal cues
• infrequent or no initiation of sexual activity within a relationship
• reduced or no sensations in the genitals

They must also have:

• symptoms lasting 6 months or more
• significant distress about their symptoms
• symptoms that are not more accurately explained by a nonsexual mental health disorder, domestic abuse, medication, substance abuse, or another medical condition

• In a stable relationship or sexually active opportunity (as defined by participant)
• If on systemic estrogen ± progestin or local vaginal estrogen: stable dose ≥8 weeks before randomization and agrees to remain stable
• Able to consent and comply with study procedures

Exclusion criteria

• Current or recent (≤8 weeks) androgen therapy, dehydroepiandrosterone (DHEA), or anabolic steroids
• Total T above premenopausal upper physiologic range at baseline (>55 ng/dL)
• History of hormone-dependent malignancy, untreated endometrial hyperplasia, or active gynecologic malignancy
• Active severe psychiatric disorder (e.g., untreated major depression), substance use disorder, or relationship violence that precludes attribution of effect
• Uncontrolled thyroid disease, significant liver disease, increased liver enzymes, or high cardiovascular risk judged unsafe by the primary care provider
• Pregnancy, attempting conception, or breastfeeding
• Dermatologic conditions preventing transdermal use; known hypersensitivity to the gel components

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Texas — Houston

Publications

• Compounded Bioidentical Menopausal Hormone Therapy: ACOG Clinical Consensus No. 6. Obstet Gynecol. 2023 Nov 1;142(5):1266-1273. doi: 10.1097/AOG.0000000000005395. PMID 37856860
• Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Ro PMID 15082697
• Buster JE, Kingsberg SA, Aguirre O, Brown C, Breaux JG, Buch A, Rodenberg CA, Wekselman K, Casson P. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol. 2005 May;105(5 Pt 1):944-52. doi: 10.1097/01.AOG.0000158103.27672.0d. PMID 15863529
• Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005 Jul;90(7):3847-53. doi: 10.1210/jc.2005-0212. Epub 2005 Apr 12. PMID 15827095
• Meston CM, Freihart BK, Handy AB, Kilimnik CD, Rosen RC. Scoring and Interpretation of the FSFI: What can be Learned From 20 Years of use? J Sex Med. 2020 Jan;17(1):17-25. doi: 10.1016/j.jsxm.2019.10.007. Epub 2019 Nov 15. PMID 31735616
• Glynne S, Kamal A, Kamel AM, Reisel D, Newson L. Effect of transdermal testosterone therapy on mood and cognitive symptoms in peri- and postmenopausal women: a pilot study. Arch Womens Ment Health. 2025 Jun;28(3):541-550. doi: 10.1007/s00737-024-01513-6. Epub 2024 Sep 16. PMID 39283522
• Neijenhuijs KI, Hooghiemstra N, Holtmaat K, Aaronson NK, Groenvold M, Holzner B, Terwee CB, Cuijpers P, Verdonck-de Leeuw IM. The Female Sexual Function Index (FSFI)-A Systematic Review of Measurement Properties. J Sex Med. 2019 May;16(5):640-660. doi: 10.1016/j.jsxm.2019.03.001. Epub 2019 Apr 5. PMID 30956110

Identifiers

NCT: NCT07408440 · HSC-MS-26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗