Vaginal Estradiol vs Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms and the Microbiome in Women Living With HIV

NCT07526948 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 2026-17642
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study about the effects of vaginal estradiol compared to moisturizer on vaginal symptoms of menopause and the microbiome in women with HIV. This research study aims to understand how vaginal products affect the aging of the female genital tract in women living with HIV who are menopausal or perimenopausal and have vaginal or urinary symptoms. There is a comparison group of women who are living without HIV. Participants with HIV and vaginal or urinary menopausal symptoms (e.g., dryness, irritation, soreness, itching, pain with sex, dysuria, urgency, or frequent urinary tract infections) will be asked to apply vaginal estradiol or a vaginal moisturizer (Replens). Participants who have vaginal or urinary menopausal symptoms and do not have HIV will receive vaginal estradiol.

Conditions

Menopausal Complaints; Vaginal Atrophy; Genitourinary Symptoms; HIV (Human Immunodeficiency Virus); Menopause Related Conditions; Vaginitis; Perimenopause

Keywords

Pain with sex; Vaginal dryness; Symptoms of menopause; HIV Infection; Menopause; Vaginal microbiome; Dysbiosis; Aging; Premature aging; Atrophic vaginitis; Genitourinary syndrome of menopause (GSM); Symptoms of perimenopause

Outcome Measures

Primary Outcomes (1)

• Change in the vaginal microbiome (bacteria) as defined by the change in alpha diversity

  Changes in the vaginal microbiome as defined by the change in alpha diversity from baseline to 16 weeks will be assessed. It is hypothesized that this may be a biomarker for improvement in vaginal health.

  From Baseline to 16 weeks

Secondary Outcomes (1)

• Change in the symptoms of the genitourinary syndrome of menopause as defined by change in the composite vaginal symptom index (VSI)

  From Baseline to 16 weeks

Study Arms (3)

Vaginal Estradiol, Participants Living With HIV

EXPERIMENTAL

Participants living with HIV randomized to this arm will use vaginal estradiol tablets for the duration of the study (16 weeks)

Drug: Vaginal estradiol tablets

Vaginal Estradiol, Participants without HIV

ACTIVE COMPARATOR

Participants without HIV enrolled in the study will use vaginal estradiol tablets for the duration of the study (16 weeks). A control group of women without HIV with GSM (n=12) will be treated with vaginal estradiol for 16 weeks but will not be randomized to moisturizer as topical estrogen has already been shown (and is FDA approved) to improve symptoms and the vaginal microbiome in women without HIV infection.

Drug: Vaginal estradiol tablets

Vaginal Moisturizer, Participants Living with HIV

ACTIVE COMPARATOR

Participants living with HIV randomized to this group will use vaginal moisturizer for the duration of the study (16 weeks)

Other: Vaginal moisturizer

Interventions

Vaginal estradiol tablets DRUG

Using a pre-loaded single-use plastic applicator, participants will insert one 10 microgram estradiol tablet intravaginally daily for 2 weeks and then one tablet twice weekly for the remainder of the study for a total of 16 weeks.

Also known as: Vagifem

Vaginal Estradiol, Participants Living With HIV; Vaginal Estradiol, Participants without HIV

Vaginal moisturizer OTHER

Using a pre-loaded single-use plastic applicator, participants will insert one vaginal moisturizer applicator intravaginally twice weekly for the duration of the study for a total of 12 weeks.

Also known as: Replens

Vaginal Moisturizer, Participants Living with HIV

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• female
• at least 40 years old
• menopausal (no menses in 12 months) within 2 years of last menstrual period or perimenopausal in the late menopausal transition, defined as an interval of amenorrhea greater than or equal to 60 days
• have symptoms of the genitourinary syndrome of menopause (GSM) which developed within the prior 2 years. Symptoms of GSM include vaginal symptoms including dryness, soreness, itching, irritation and dyspareunia and/or urinary symptoms including urgency, frequency and recurrent urinary tract infections (UTIs)

You may not qualify if:

• Unexplained or unevaluated abnormal genital bleeding
• Current or suspected pregnancy
• Desired pregnancy
• If less than 55 years old, have had a hysterectomy and have at least one ovary (as menopause cannot be determined in this case by amenorrhea alone)
• Pelvic or vaginal surgery in the prior 60 days
• Used systemic reproductive hormones in the last 2 months
• Used antibiotics in the last 30 days
• Used immunosuppressive medications in the prior 60 days including biologics, chemotherapeutics or post transplant immunosuppressive medications
• Used any vaginal or vulvar preparations in the last month
• Current active vaginal infection diagnosed at study entry
• Any serious disease or condition that may interfere with study compliance
• Current or previous history of breast cancer or estrogen dependent cancer (e.g., ovarian, endometrial)
• Current or previous history of deep vein thrombosis or pulmonary embolism
• Current or previous history of myocardial infarction or stroke
• Known clotting disorder including Protein C, Protein S and antithrombin deficiency, Factor V Leiden or prothrombin mutations

Sponsors & Collaborators

• Yale University: collaborator
• Albert Einstein College of Medicine: lead
• Zymo Research: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Related Publications (7)

• Srinivasan S, Hua X, Wu MC, Proll S, Valint DJ, Reed SD, Guthrie KA, LaCroix AZ, Larson JC, Pepin R, Bhasin S, Raftery D, Fredricks DN, Mitchell CM. Impact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e225032. doi: 10.1001/jamanetworkopen.2022.5032.

  PMID: 35353163 BACKGROUND

• Murphy K, Keller MJ, Anastos K, Sinclair S, Devlin JC, Shi Q, Hoover DR, Starkman B, McGillick J, Mullis C, Minkoff H, Dominguez-Bello MG, Herold BC. Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection. PLoS One. 2019 Apr 26;14(4):e0216049. doi: 10.1371/journal.pone.0216049. eCollection 2019.

  PMID: 31026271 BACKGROUND

• Shen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C, Forney LJ. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016 Apr 22;6:24380. doi: 10.1038/srep24380.

  PMID: 27103314 BACKGROUND

• Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, Koenig D, Gloor GB, Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One. 2011;6(11):e26602. doi: 10.1371/journal.pone.0026602. Epub 2011 Nov 2.

  PMID: 22073175 BACKGROUND

• Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2018 Nov;25(11):1321-1330. doi: 10.1097/GME.0000000000001236.

  PMID: 30358729 BACKGROUND

• Mitchell CM, Reed SD, Diem S, Larson JC, Newton KM, Ensrud KE, LaCroix AZ, Caan B, Guthrie KA. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):681-690. doi: 10.1001/jamainternmed.2018.0116.

  PMID: 29554173 BACKGROUND

• Murphy K, Gromisch M, Connolly J, Wang T, McWalters J, Atrio J, Mahant AM, Gera S, Colanta A, Cajigas A, Kelly L, Estrella H, Gustafson D, Minkoff H, Anastos K, Keller MJ, Herold BC. Impact of vaginal estradiol on the genitourinary syndrome of menopause, vaginal microbiome and mucosal immune mediators in women living with HIV. Clin Infect Dis. 2025 Dec 8:ciaf669. doi: 10.1093/cid/ciaf669. Online ahead of print.

  PMID: 41355723 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Vaginitis; HIV Infections; Dysbiosis; Aging, Premature; Atrophic Vaginitis

Interventions

Estradiol; Replens

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Kerry J Murphy, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kerry J Murphy, MD

CONTACT

718-839-7885; kerry.murphy@einsteinmed.edu

Marla J Keller, MD

CONTACT

718-430-3240; marla.keller@einsteinmed.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The pathologist assigning the vaginal maturation index (VMI) to the samples will be blinded to which group the participant sample is from.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Kerry Murphy

Model Details: Participants living with HIV will be randomly assigned to receive treatment with estradiol vaginal tablets or to vaginal moisturizer (Replens). Participants without HIV will receive treatment with estradiol vaginal tablets.

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2031
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 12 months after publication
• Access Criteria: De-identified electronic datasets of published results will be made available to external investigators in a format in which subsequent statistical analyses can be performed.

Locations

US (1)