A Randomized Controlled Trial of Intravaginal Prasterone versus Hyaluronic Acid Gel for Vulvovaginal Atrophy in Postmenopausal Breast Cancer Survivors

International Journal of Obstetrics and Gynecology | Vol. 14, No. 9, September 2026 | pp. 951–962

DOI: 10.46882/2026/IJOG/000560

Original Research Article

Title: A Randomized Controlled Trial of Intravaginal Prasterone versus Hyaluronic Acid Gel for Vulvovaginal Atrophy in Postmenopausal Breast Cancer Survivors

Names of Authors: Chloé Mercier¹, Alessandra Rossi²

Authors’ Affiliations:
¹ Département de Gynécologie-Obstétrique, Hôpital Européen Georges-Pompidou, Paris, France
² Unità de Ginecologia e Ostetricia, Ospedale San Raffaele, Milan, Italy

Abstract:
Managing severe genitourinary symptoms in postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy is restricted by absolute contraindications to systemic or local estrogen creams. This randomized, double-blind active-controlled clinical trial compared the tissue-restoring efficacy and hormonal safety profile of once-daily non-estrogenic intravaginal prasterone (DHEA, 6.5 mg) capsules versus a non-hormonal hyaluronic acid vaginal gel. One hundred and forty breast cancer survivors presenting with moderate-to-severe vaginal dryness and dyspareunia were randomized into two equal groups (n = 70 per group) for a treatment course of 12 weeks. Primary outcomes were updates to the Vaginal Health Index (VHI) score, vaginal pH drops, and serial serum estradiol tracking using high-sensitivity mass spectrometry. At week 12, both groups achieved a significant reduction in subjective dyspareunia scores (p < 0.001). However, the prasterone cohort demonstrated a significantly greater increase in mean VHI scores (21.4 ± 2.2 vs. 16.5 ± 1.8, p < 0.001) and a more pronounced vaginal pH reduction below 4.6 (p = 0.003) compared to the hyaluronic acid group. Crucially, serial blood sampling confirmed that serum estradiol levels remained strictly within safe postmenopausal baseline margins (< 5 pg/mL) in both treatment branches. Daily intravaginal prasterone provides superior local tissue rejuvenation and symptom relief for vulvovaginal atrophy in breast cancer survivors compared to non-hormonal lubricants without causing systemic estrogen reabsorption.

Keywords: Vulvovaginal Atrophy; Prasterone; Breast Cancer Survivors; Hyaluronic Acid; Dyspareunia; Intracrinology.

Manuscript Timeline: Received: June 20, 2026; Revised: August 15, 2026; Accepted: September 05, 2026; Published: September 10, 2026.

Citation: Mercier C, Rossi A. A Randomized Controlled Trial of Intravaginal Prasterone versus Hyaluronic Acid Gel for Vulvovaginal Atrophy in Postmenopausal Breast Cancer Survivors. International Journal of Obstetrics and Gynecology. 2026; 14(9): 951–962.

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