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

Vaginal Estradiol Versus Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms, Dysbiosis and Markers of Latency Reversal in Menopausal Women Living With HIV

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Vaginitis; Vaginal Atrophy; Genitourinary Symptoms; Menopause Related Conditions; Perimenopause; HIV (Human Immunodeficiency Virus); Menopausal Complaints
• Intervention / Treatment: Drug: Vaginal estradiol tablets; Other: Vaginal moisturizer

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kerry J Murphy, MD; Phone Number: 718-839-7885; Email: kerry.murphy@einsteinmed.edu
• Study Contact Backup: Name: Marla J Keller, MD; Phone Number: 718-430-3240; Email: marla.keller@einsteinmed.edu

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
      • Contact: Kerry J Murphy, MD; Phone Number: 718-839-7885; Email: kerry.murphy@einsteinmed.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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
• Known severe liver disease including cirrhosis or active Hepatitis B
• Known allergic reaction to Vagifem (estradiol vaginal tablet) or Replens

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaginal Estradiol, Participants Living With HIV; 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; 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.; Other Names: Vagifem
Active Comparator: Vaginal Estradiol, Participants without HIV; 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; 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.; Other Names: Vagifem
Active Comparator: Vaginal Moisturizer, Participants Living with HIV; Participants living with HIV randomized to this group will use vaginal moisturizer for the duration of the study (16 weeks)	Other: Vaginal moisturizer; 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.; Other Names: Replens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the symptoms of the genitourinary syndrome of menopause as defined by change in the composite vaginal symptom index (VSI)	Using a survey administered at each visit, participant symptoms will be assessed over the course of the study. It is anticipated that both the vaginal estradiol and the vaginal moisturizer will lead to improvement in the symptoms of the genitourinary syndrome of menopause.	From Baseline to 16 weeks

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: Yale University; Zymo Research
• Investigators: Principal Investigator: Kerry J Murphy, MD, Albert Einstein College of Medicine

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Menopause; Aging; HIV Infection; Dysbiosis; Vaginal dryness; Atrophic vaginitis; Vaginal microbiome; Genitourinary syndrome of menopause (GSM); Premature aging; Pain with sex; Symptoms of menopause; Symptoms of perimenopause
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; Vaginal Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; HIV Infections; Acquired Immunodeficiency Syndrome; Dysbiosis; Vaginitis; Atrophic Vaginitis; Aging, Premature; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estradiol; Replens
• Other Study ID Numbers: 2026-17642

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of the main study findings, external investigators may contact the Principal Investigator Dr. Kerry Murphy for de-identified datasets.
• IPD Sharing Time Frame: Within 12 months after publication
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No