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MenopausePhase 2/3NCT06975111

Focusing on the Menopausal Transition to Improve Mid-Life Women's Health

A Phase 2/3 study testing Metformin, semaglutide and Anti-hypertensives in people with Menopause and Menopause Hot Flashes, run by University of Colorado, Denver at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

What if midlife women, who are inherently at an increased risk for future cardiometabolic disease due to transitioning into menopause, had access to a suite of evidence-based health interventions? Could these interventions reduce menopause-related inflammation, restore a healthier cardiometabolic profile, reverse… Read more about this study

Who is it for?
Ages 45 to 55 years, women onlyHealthy volunteers can take part
What is being tested?
Metformin, semaglutide and Anti-hypertensives
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
3 sitesUnited States
Study dates
1 Mar 2026to 1 Oct 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 55 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • aged 45-55
  • In the late menopausal transition, defined as 60 days of amenorrhea but less than 365 days of amenorrhea
  • No current use of systemic hormone therapy or hormonal contraception, other than progestin-releasing IUDs or oral, micronized progesterone. Vaginal (non-systemic) estrogen use (FDA-approved products only, used as labelled) is permitted and is NOT an exclusion. Other forms of non-FDA approved hormones will need to be reviewed by the study physicians on-site to determine eligibility. Women choosing to discontinue hormonal contraception and/or systemic hormone therapy may become eligible for the study after a washout period
  • Presence of a uterus and at least one ovary in order to track menstrual patterns
  • Have a smartphone and broadband access adequate to accept telehealth appointments
  • No more than 5% weight loss in the last 3 months

Who cannot join

  • Lack of broadband access (activity and survey data will be collected electronically whenever possible and some visits will be via telehealth)
  • Lack of regular menstrual periods in mid-reproductive life (ages 25-38) when not on hormones or not pregnant.
  • Pregnancy or actively trying to get pregnant
  • Inability to adhere to study protocol schedule
  • Untreated alcoholism
  • Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN 2) for participants with a BMI> 30 kg/m2.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Carrie Hsu, BA contact

303-724-5276

carrie.hsu@cuanschutz.edu

Nalia Naushad contact

naila.naushad@cuanschutz.edu

United States3 sites, 3 recruiting

  • University of Colorado-School of Medicine

    Aurora, Colorado, 80045

    Carrie Hsu, 303-724-5276, carrie.hsu@cuanschutz.edu

    Nanette Santoro, MD

    Recruiting

  • University of North Carolina, School of Medicine

    Chapel Hill, North Carolina, 27599

    Chelsea A Grinnan, RN, 919-908-0010, REI_research@med.unc.edu

    Makayla L Sweeney, BSc, 919-908-0010, REI_research@med.unc.edu

    Recruiting

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

    Brooke Foley, BSN, RN, 804-628-4849, Brooke.Foley@vcuhealth.org

    Michelle Orr, PhD, RN, 804-221-5159, Brooke.Foley@vcuhealth.org

    Recruiting

Other trials in United States

About this study

What if midlife women, who are inherently at an increased risk for future cardiometabolic disease due to transitioning into menopause, had access to a suite of evidence-based health interventions? Could these interventions reduce menopause-related inflammation, restore a healthier cardiometabolic profile, reverse epigenetic aging, and reduce bothersome menopausal symptoms? The ultimate goal of this work is to attenuate future disease and enhance women's quality of life, extend healthspan and increase productivity.

Being tested
Metformin, semaglutide, Anti-hypertensives, Lipid Lowering Medication, Life style intervention

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Metformin will be given to participants who have a elevated HbA1c and also for weightloss.

  • semaglutideDrug

    Overweight women and women with obesity will take Semaglutide for weight-loss

  • Anti-hypertensivesDrug

    Also called The use of angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, or a thiazide diuretic.

    1. Antihypertensives, with the goal of maintaining blood pressure at 130/80 or lower per ACC guidelines19. Per current clinical guidelines and standard of care, hypertension will be treated first with monotherapy using either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, or a thiazide diuretic provided that are no contraindications.

  • Lipid Lowering MedicationDrug

    Also called The use of generic statins

    . First line agents will be generic statin medications (atorvastatin or rosuvastatin)whichever is covered by the participant's health insurance), barring contraindication to their use.

  • Life style interventionBehavioural

    will simply be followed and given preventive advice (maintenance of a normal BMI and physical activity, moderation in salt intake, and no more than 1 alcoholic drink per day). They will be provided with a wearable activity monitor. This advice will be based on guidelines by the American Heart Association and the Menopause Society.

  • FezolinetantDrug

    Women with menopausal symptoms will be treated with hormone therapy (estrogen and progesterone) if appropriate, or with a neurokinin receptor antagonist (Fezolinetant). This can be treatment for women in any arm of the study as well as an arm by its self.

  • Hormonal therapyDrug

    Participants will be treated with estrogen and/or progesterone for treatment of hot flashes in women during the study.

Study groups in NCT06975111
Study groupRoleWhat they receive
Preventative Health AdviceExperimentalParticipants will be given preventative health advice and asked to wear an activity \& sleep monitor.
Receives: Behavioral: Life style intervention; Drug: Fezolinetant; Drug: Hormonal therapy
At Risk for Heart DiseaseActive comparatorMedications will be given to each participant in this arm that lowers your heart disease risk.
Receives: Drug: Metformin; Drug: Anti-hypertensives; Drug: Lipid Lowering Medication; Behavioral: Life style intervention
Overweight WomenActive comparatorWomen who fit in this category will receive medication for lowering insulin resistance and/or a weight loss medication.
Receives: Drug: Metformin; Drug: semaglutide
Women with ObesityActive comparatorWomen that are over a BMI of 30 kg/m2 will be offered a GLP-1 antagonist.
Receives: Drug: semaglutide
Women With Hot FlashesActive comparatorWomen with Hot flashes will have either hormonal or non-hormonal medication to reduce the number and/or severity of hot flashes.
Receives: Drug: Fezolinetant; Drug: Hormonal therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Epigenetic aging measurements of "PhenoAge"

    Change in epigenetic aging, as assessed by PhenoAge. PhenoAge calculates a biological age score based on key biomarkers circulating in the bloodstream. A lower PhenoAge score suggests slower biological aging, while a higher score indicates accelerated aging.

    Measured: Up to 2 years

  2. Epigenetic aging measurements of "GrimAge"

    Epigenetic aging, as assessed by GrimAge. GrimAge assesses lifespan from examining DNA Methylation.

    Measured: Up to 2 years

Secondary outcomes (8)

  1. IL-1

    Inflammatory IL-1 serum levels, examined to determine a person's inflammatory state. Higher levels of IL-1 can indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a woman's health.

    Measured: Up to 2 years

  2. TNF-alpha

    Serum inflammatory marker TNF-alpha. Higher levels of TNF-alpha can indicate more inflammation. TNF-alpha is examined to determine a person's inflammatory state.

    Measured: Up to 2 years

  3. IL-6

    Serum IL-6 levels. IL-6 is examined to determine a person's inflammatory state. Higher levels of IL-6 indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a women's health.

    Measured: Up to 2 years

  4. IL-8

    IL-8 serum levels. IL-8 is examined to determine a person's inflammatory state. Higher levelf of IL-8 indicate more inflammation. Being in an "inflamed state" can have detrimental effects on a women's health.

    Measured: Up to 2 years

  5. Flow-mediated dilation

    Flow-mediated dilation measures the diameter of vascular and endothelial cell function and predicts cardiovascular event risk. The diameter of the target artery is measured by high-resolution external vascular ultrasound in response to an increase in blood flow.

    Measured: Up to 2 years

  6. Serum Marker for Ovarian Aging

    Anti-mullerian hormones (AMH) serum levels will be analyzed. AMH is an indicator of ovarian aging and reflects egg supply. Lower levels of AMH indicate a lower egg supply.

    Measured: Up to 2 years

  7. MENQOL survey

    Menopause-specific Quality of Life (MENQOL) measures quality of life in menopausal women. It is self-administered and consists of a total of 29 items in a Likert-scale format. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month: vasomotor, psychosocial, physical, and sexual. There will be a overall score and we are examining if there is a change in response to treatment.

    Measured: Up to 2 years

  8. Eaotoxin levels

    Eaotoxin is a inflammatory marker that increases when there is an inflammed state in a woman. Serum Eaotoxin will be measured before, during and at the end of the study.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2025
  2. Study start1 Mar 2026
  3. Primary completion31 Oct 2029 (estimated)
  4. Study completion1 Oct 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Participants will be placed into treatment interventions based on their health and screening tests.
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06975111
Sponsor's protocol ID
25-0943
Other IDs
U1111-1322-1036
Status last verified
Nov 2026
First submitted
7 May 2025
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: We will share the information but have not developed the exact plan to share. All information and data will be de-identified prior to sharing. To share the data we will require a proposal detailing the use if IPD.

Publications

  • Brazier JE, Harper R, Jones NM, O'Cathain A, Thomas KJ, Usherwood T, Westlake L. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ. 1992 Jul 18;305(6846):160-4. doi: 10.1136/bmj.305.6846.160.

    PubMed 1285753

  • SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9.

    PubMed 26551272

  • Greendale GA, Huang MH, Wight RG, Seeman T, Luetters C, Avis NE, Johnston J, Karlamangla AS. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology. 2009 May 26;72(21):1850-7. doi: 10.1212/WNL.0b013e3181a71193.

    PubMed 19470968

  • Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, Sutton-Tyrrell K. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol. 2009 Dec 15;54(25):2366-73. doi: 10.1016/j.jacc.2009.10.009.

    PubMed 20082925

  • Samargandy S, Matthews KA, Brooks MM, Barinas-Mitchell E, Magnani JW, Janssen I, Kazlauskaite R, El Khoudary SR. Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: the SWAN heart study. Menopause. 2021 Mar 1;28(6):626-633. doi: 10.1097/GME.0000000000001755.

    PubMed 33651741

  • Tanaka T, Basisty N, Fantoni G, Candia J, Moore AZ, Biancotto A, Schilling B, Bandinelli S, Ferrucci L. Plasma proteomic biomarker signature of age predicts health and life span. Elife. 2020 Nov 19;9:e61073. doi: 10.7554/eLife.61073.

    PubMed 33210602

  • Thurston RC, Carroll JE, Levine M, Chang Y, Crandall C, Manson JE, Pal L, Hou L, Shadyab AH, Horvath S. Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women's Health Initiative (WHI). J Clin Endocrinol Metab. 2020 Apr 1;105(4):1221-7. doi: 10.1210/clinem/dgaa081.

    PubMed 32080740

  • Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, Leipold MD, Lin DTS, Kobor MS, Horvath S. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019 Dec;18(6):e13028. doi: 10.1111/acel.13028. Epub 2019 Sep 8.

    PubMed 31496122

  • Thurston RC, Aslanidou Vlachos HE, Derby CA, Jackson EA, Brooks MM, Matthews KA, Harlow S, Joffe H, El Khoudary SR. Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN. J Am Heart Assoc. 2021 Feb 2;10(3):e017416. doi: 10.1161/JAHA.120.017416. Epub 2021 Jan 20.

    PubMed 33470142

  • Hedderson MM, Liu EF, Lee C, El Khoudary SR, Gold EB, Derby CA, Thurston RC. Vasomotor Symptom Trajectories and Risk of Incident Diabetes. JAMA Netw Open. 2024 Oct 1;7(10):e2443546. doi: 10.1001/jamanetworkopen.2024.43546.

    PubMed 39480425

  • Cho L, Davis M, Elgendy I, Epps K, Lindley KJ, Mehta PK, Michos ED, Minissian M, Pepine C, Vaccarino V, Volgman AS; ACC CVD Womens Committee Members. Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 May 26;75(20):2602-2618. doi: 10.1016/j.jacc.2020.03.060.

    PubMed 32439010

  • Patel D, Ayesha IE, Monson NR, Klair N, Patel U, Saxena A, Hamid P. The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis. Cureus. 2023 Sep 28;15(9):e46108. doi: 10.7759/cureus.46108. eCollection 2023 Sep.

    PubMed 37900422

  • Santoro N, Kuhn K, Pretzel S, Schauer IE, Fought A, D'Alessandro A, Stephenson D, Bradford AP. A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women. PNAS Nexus. 2023 Dec 18;3(1):pgad440. doi: 10.1093/pnasnexus/pgad440. eCollection 2024 Jan.

    PubMed 38178979

  • Legro RS, Hansen KR, Diamond MP, Steiner AZ, Coutifaris C, Cedars MI, Hoeger KM, Usadi R, Johnstone EB, Haisenleder DJ, Wild RA, Barnhart KT, Mersereau J, Trussell JC, Krawetz SA, Kris-Etherton PM, Sarwer DB, Santoro N, Eisenberg E, Huang H, Zhang H; Reproductive Medicine Network. Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial. PLoS Med. 2022 Jan 18;19(1):e1003883. doi: 10.1371/journal.pmed.1003883. eCollection 2022 Jan.

    PubMed 35041662

  • Tannous A, Bradford AP, Kuhn K, Fought A, Schauer I, Santoro N. A randomised trial examining inflammatory signaling in acutely induced hyperinsulinemia and hyperlipidemia in normal weight women-the reprometabolic syndrome. PLoS One. 2021 Mar 25;16(3):e0247638. doi: 10.1371/journal.pone.0247638. eCollection 2021.

    PubMed 33764994

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Metformin, semaglutide and Anti-hypertensives in people with Menopause and Menopause Hot Flashes, run by University of Colorado, Denver at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Carrie Hsu, BA (303-724-5276, carrie.hsu@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Epigenetic aging measurements of "PhenoAge" (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06975111, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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