Menopausal HT for Women Living With HIV (HoT) (HoT)

May 20, 2026 updated by: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Menopausal Hormone Therapy for Women Living With HIV (HoT)

Women living with HIV have been shown to experience more frequent and severe hot flashes and night sweats (collectively known as vasomotor symptoms) as compared to women living without HIV. This correlates with disturbed sleep, increased depressive symptoms, increased anxiety, worse mental function, interference with activities of daily living including work, and worse overall quality of life.

Hormone therapy is considered to be the most effective therapy for hot flashes and night sweats and the most appropriate choice to prevent bone loss at the time of menopause for women without HIV. However, the usefulness of hormone therapy has not been specifically studied in women living with HIV.

This trial is being done to see if:

  • There is evidence to support the use of hormone therapy (estradiol with or without progesterone) for the treatment of hot flashes and night sweats in women living with HIV
  • Hormone therapy improves mental function, mood, sleep, quality of life, bone health, heart health, and inflammation in women living with HIV
  • Hormone therapy is safe and tolerable for women living with HIV

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

105

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • 31788 Alabama CRS
        • Principal Investigator:
          • Sonya Heath, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90035
        • Recruiting
        • University of California, Los Angeles CARE Center CRS (601)
        • Principal Investigator:
          • Kara Chew, MD, MS
        • Contact:
      • San Diego, California, United States, 92103
        • Recruiting
        • UCSD Antiviral Research Center CRS (701)
        • Principal Investigator:
          • Timothy Wilkin, MD, MPH
        • Contact:
      • San Francisco, California, United States, 94110
        • Recruiting
        • 801 University of California, San Francisco HIV/AIDS CRS
        • Principal Investigator:
          • Annie Luetkemeyer, MD
        • Contact:
      • Torrance, California, United States, 90502
        • Recruiting
        • Harbor - UCLA Med. Ctr. CRS
        • Contact:
        • Principal Investigator:
          • Eric S. Daar, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital CRS (6101)
        • Principal Investigator:
          • Kristine Erlandson, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • The Ponce de Leon Center CRS (5802)
        • Contact:
        • Principal Investigator:
          • Valeria Cantos, MD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University CRS (2701)
        • Contact:
        • Principal Investigator:
          • Amesika Nyaku, MD, MS
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • 201 Johns Hopkins University CRS
        • Contact:
        • Principal Investigator:
          • Charles Flexner, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hosp. ACTG CRS (107)
        • Contact:
        • Principal Investigator:
          • Jennifer Manne-Goehler, MD
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • 101 Massachusetts General Hospital (MGH) CRS
        • Principal Investigator:
          • Rajesh Gandhi, MD
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • 2101 Washington University Therapeutics (WT) CRS
        • Principal Investigator:
          • Rachel Presti, MD, PhD
        • Contact:
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Recruiting
        • New Jersey Medical School Clinical Research Center CRS (31786)
        • Contact:
        • Principal Investigator:
          • Shobha Swaminathan, MD
    • New York
      • New York, New York, United States, 10010
        • Recruiting
        • Weill Cornell Chelsea CRS (7804)
        • Principal Investigator:
          • Kristin Marks, MD
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia Physicians and Surgeons (P&S) CRS (30329)
        • Principal Investigator:
          • Magdalena Sobieszczyk, MD, MPH
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27516
        • Recruiting
        • 3201 Chapel Hill CRS
        • Principal Investigator:
          • David A. Wohl, MD
        • Contact:
      • Greensboro, North Carolina, United States, 27401
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • Recruiting
        • 2401 Cincinnati CRS
        • Principal Investigator:
          • Carl Fichtenbaum, MD
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case CRS (2501)
        • Contact:
        • Principal Investigator:
          • George Yendewa, MPH, TM, FACP
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University CRS (2301)
        • Contact:
        • Principal Investigator:
          • Carlos Malvestutto, MD, MPH, FIDSA
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • Univ of Pittsburgh
        • Principal Investigator:
          • Sharon Riddler, MD, MPH
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston AIDS Research Team CRS (31473)
        • Contact:
        • Principal Investigator:
          • Roberto Arduino, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

  • Living with HIV
  • Assigned female sex at birth
  • Between the ages of 40 and 60 years
  • In the late menopausal transition (perimenopause) or early postmenopause
  • Experiencing hot flashes and/or night sweats
  • Willing and able to complete a daily diary
  • Does not have medical condition that would contraindicate hormone therapy
  • Not taking medications to treat hot flashes
  • Not taking medications that cannot be combined with hormone therapy
  • Receiving antiretrovirals (HIV medication) for more than 1 year
  • Not pregnant and willing and able to use at least non-hormonal birth control to prevent pregnancy
  • Willing and able to provide informed consent after discussion with the research staff

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A: Hormone Therapy

PARTICIPANTS WITH INTACT UTERUS: Transdermal estradiol gel plus oral micronized progesterone daily for 12 weeks.

PARTICIPANTS WITHOUT A UTERUS: Transdermal estradiol gel daily for 12 weeks.
Drug: Transdermal estradiol gel
All participants: Estradiol gel 0.1%, 0.75 grams (corresponding to estradiol 0.75 mg) applied to the skin of the upper thigh once daily for 12 weeks.
Drug: Micronized Progesterone
Participants with intact uterus: Encapsulated micronized progesterone 100 mg orally once daily for 12 weeks.
Placebo Comparator: Arm B: Hormone Therapy Placebo

PARTICIPANTS WITH INTACT UTERUS: Transdermal placebo gel plus oral encapsulated placebo pill daily for 12 weeks.

PARTICIPANTS WITHOUT A UTERUS: Transdermal placebo gel alone daily for 12 weeks.
Drug: Placebo for estradiol gel
All participants: Placebo for estradiol gel 0.1%, 0.75 grams applied to the skin of the upper thigh once daily for 12 weeks.
Drug: Placebo for micronized progesterone
• Participants with intact uterus: Encapsulated placebo for micronized progesterone 100 mg orally once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in vasomotor symptoms (VMS) frequency
Time Frame: From 5 weeks prior to randomization to Week 12
Change in self-reported mean VMS frequency per day from 5-week observation phase prior to randomization to the one-week period prior to week 12 visit following.
From 5 weeks prior to randomization to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in vasomotor symptom (VMS) severity
Time Frame: From 5 weeks prior to randomization to week 12
Change in self-reported mean severity of VMS from 5-week observation phase prior to randomization to the one-week period prior to week 12 visit following randomization; severity scale is ordinal: none (0), mild (1), moderate (2), severe (3).
From 5 weeks prior to randomization to week 12
Percentage of participants with adverse events associated with hormone therapy
Time Frame: From randomization to week 12
Adverse events (AE) associated with study treatment with severity grade of 3 or higher as per DAIDS Toxicity grading scale.
From randomization to week 12
Percentage of participants with occurrence of abnormal vaginal bleeding
Time Frame: From randomization to week 12
Abnormal vaginal bleeding adverse event defined as any of the following: any report of heavy bleeding, 2 or more episodes of spotting or greater at intervals of < 21 days among participants in late menopausal transition, any occurrence after 6 weeks of hormone treatment among post-menopausal participants.
From randomization to week 12
Percentage of participants with intolerance of hormone therapy
Time Frame: From randomization to week 12
Intolerance of hormone therapy is defined as permanent discontinuation prior to the week 12 visit that was not required per protocol nor recommended due to safety considerations.
From randomization to week 12
Change in weight
Time Frame: From randomization to week 12
Absolute and Percent change in total body weight from randomization visit to week 12 visit.
From randomization to week 12
Change in body mass index (BMI)
Time Frame: From randomization to week 12
Absolute change in BMI from randomization visit to week 12 visit
From randomization to week 12
Change in waist circumference
Time Frame: From randomization to week 12
Absolute change in minimum waist circumference from randomization visit to week 12 visit
From randomization to week 12
Change in waist-to-hip ratio
Time Frame: From randomization to week 12
Change in waist-to-hip circumference ratio between the randomization visit and the week 12 visit
From randomization to week 12
Percentage of participants with female sexual distress
Time Frame: Week 12 visit
Female sexual distress defined as, at the week 12 visit, endorsing frequently or always to question regarding how often distressed or bothered about sex life in the past 4 weeks.
Week 12 visit
Change in sleep
Time Frame: From randomization to week 12
Change in total sleep scores from randomization visit to week 12 visit as measured by the Pittsburgh Sleep Quality Index (PSQI). Total sleep score determined by summing responses from seven assessments, where each assessment is scored from 0 (best) to 3 (worst). The minimum possible total sleep score is 0 (best) and the maximum possible score is 21 (worst). Higher total scores suggest more severe sleep problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes.
From randomization to week 12
Change in insomnia
Time Frame: From randomization to week 12
Change in total insomnia scores from randomization visit to week 12 visit as measured by the Insomnia Severity Index (ISI). Total insomnia score determined by summing responses from seven assessments, each rated on a Likert 5-point scale, where 0 indicates no problems and 4 indicates severe problems. The minimum possible total insomnia score is 0 (best) and the maximum possible score is 28 (worst). Higher total scores suggest more severe insomnia problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes.
From randomization to week 12
Change in quality of life
Time Frame: From randomization to week 12
Change in total health-related quality of life score, from randomization visit to week 12 visit as measured by Menopause specific Quality of life questionnaire (MenQOL). Total health-related quality of life score is determined by averaging responses from four domain-specific scores (vasomotor [3 items], physical [16 items], psychosocial [7 items], sexual functioning [3 items], each ranging from 1 (best) to 8 (worst)). Domain-specific scores represent the average score among the items in a domain. The score for each item, ranging from 1 (best) to 8 (worst), represents the sum of the presence of the symptom (1 for no, 2 for yes) and the severity, rated on a Likert 7-point scale (0, not bothered at all to 6, extremely bothered), The minimum possible quality of life score is 1 (best) and the maximum possible score is 8 (worst). Higher scores suggest more severe quality of life problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes.
From randomization to week 12
Change in neurocognitive test results
Time Frame: From randomization to week 12
Change in neurocognition as measured by the neuropsychological (NP) battery from randomization visit to week 12 visit.
From randomization to week 12
Change in depression symptoms
Time Frame: From randomization to week 12
Change in depression symptoms score from randomization visit to week 12 visit as measured by Patient Health Questionnaire-9 (PHQ-9). Total depression score determined by summing responses from nine assessments, where each assessment is scored from 0 (not at all) to 3 (nearly every day). The minimum possible total sleep score is 0 (best) and the maximum possible score is 27 (worst). Higher total scores suggest more severe depression problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes.
From randomization to week 12
Change in anxiety symptoms
Time Frame: From randomization to week 12
Change in anxiety symptoms score from randomization visit to week 12 as measured by Generalized Anxiety Disorder 7-item (GAD-7). Total anxiety score determined by summing responses from seven Likert assessments, where each assessment is scored from 0 (best) to 3 (worst). The minimum possible total anxiety score is 0 (best) and the maximum possible score is 21 (worst). Higher total scores suggest more severe anxiety problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes.
From randomization to week 12
Change in sexual function
Time Frame: From randomization to week 12
Change in total sexual function score from randomization visit to week 12 visit as measured by the female sexual function index (FSFI). Total sexual function score is determined by summing six domain-specific scores (desire [2 items], arousal [4 items], lubrication [4 items], orgasm [3 items], satisfaction [3 items], and pain [3 items]), ranging from 0 (worst) to 6 (best). Domain-specific scores represent the sum of the scores for each item within a domain (ranging from 0 (worst) to 6 (best)), multiplied by a factor to adjust for relative weighting (0.6 for desire; 0.3 for arousal; 0.3 for lubrication; 0.4 for orgasm; 0.4 for satisfaction; and 0.4 for pain). The minimum possible sexual function score is 2 (worst) and the maximum possible score is 36 (best). Lower scores indicate worse sexual function. Change in total score calculated as Week 12 minus baseline. Positive change indicates better outcomes.
From randomization to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Aging (NIA)
Exeltis
Xiromed LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2026

Primary Completion (Estimated)

September 20, 2027

Study Completion (Estimated)

September 20, 2027

Study Registration Dates

First Submitted

February 19, 2025

First Submitted That Met QC Criteria

February 28, 2025

First Posted (Actual)

March 4, 2025

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG A5424
  • UM1AI068636 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie results in the publication, after deidentification.

IPD Sharing Time Frame

Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) by NIH.

IPD Sharing Access Criteria

  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG).
  • For what types of analyses? To achieve aims in the proposal approved by the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG).
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections Group (ACTG) "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) Data Use Agreement before receiving the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infection

Clinical Trials on Transdermal estradiol gel

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe