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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1322-1036 | Other Identifier | World Health Organization |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Preventative Health Advice | Experimental | Participants will be given preventative health advice and asked to wear an activity & sleep monitor. |
|
| At Risk for Heart Disease | Active Comparator | Medications will be given to each participant in this arm that lowers your heart disease risk. |
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| Overweight Women | Active Comparator | Women who fit in this category will receive medication for lowering insulin resistance and/or a weight loss medication. |
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| Women with Obesity | Active Comparator | Women that are over a BMI of 30 kg/m2 will be offered a GLP-1 antagonist. |
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| Women With Hot Flashes | Active Comparator | Women with Hot flashes will have either hormonal or non-hormonal medication to reduce the number and/or severity of hot flashes. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Metformin will be given to participants who have a elevated HbA1c and also for weightloss. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 2 years |
| Epigenetic aging measurements of "GrimAge" | Epigenetic aging, as assessed by GrimAge. GrimAge assesses lifespan from examining DNA Methylation. | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 2 years |
| TNF-alpha |
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Inclusion Criteria:
Exclusion Criteria:
We are studying the menopausal transition which only happens in women.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Carrie Hsu, BA | Contact | 303-724-5276 | carrie.hsu@cuanschutz.edu | |
| Nalia Naushad | Contact | naila.naushad@cuanschutz.edu |
| Name | Affiliation | Role |
|---|---|---|
| Nanette Santoro, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado-School of Medicine | Recruiting | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1285753 | Background | 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. | |
| 26551272 | Background | 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. |
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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.
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Participants will be placed into treatment interventions based on their health and screening tests.
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| semaglutide | Drug | Overweight women and women with obesity will take Semaglutide for weight-loss |
|
| Anti-hypertensives | Drug | a. 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. |
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| Lipid Lowering Medication | Drug | . 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. |
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| Life style intervention | Behavioral | 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. |
|
| Fezolinetant | Drug | 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 therapy | Drug | Participants will be treated with estrogen and/or progesterone for treatment of hot flashes in women during the study. |
|
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.
| Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 19470968 | Background | 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. |
| 20082925 | Background | 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. |
| 33651741 | Background | 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. |
| 33210602 | Background | 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. |
| 32080740 | Background | 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. |
| 31496122 | Background | 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. |
| 33470142 | Background | 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. |
| 39480425 | Background | 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. |
| 32439010 | Background | 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. |
| 37900422 | Background | 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. |
| 38178979 | Background | 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. |
| 35041662 | Background | 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. |
| 33764994 | Background | 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. |
| 25259787 | Background | Mogul HR, Freeman R, Nguyen K, Frey M, Klein LA, Jozak S, Tanenbaum K. Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance): a randomized trial of normoglycemic women with midlife weight gain. PLoS One. 2014 Sep 26;9(9):e108264. doi: 10.1371/journal.pone.0108264. eCollection 2014. |
| 26789348 | Background | Mogul H, Freeman R, Nguyen K. METFORMIN-SUSTAINED WEIGHT LOSS AND REDUCED ANDROID FAT TISSUE AT 12 MONTHS IN EMPOWIR (ENHANCE THE METABOLIC PROFILE OF WOMEN WITH INSULIN RESISTANCE): A DOUBLE BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL OF NORMOGLYCEMIC WOMEN WITH MIDLIFE WEIGHT GAIN. Endocr Pract. 2016 May;22(5):575-86. doi: 10.4158/EP151087.OR. Epub 2016 Jan 20. |
| 35797481 | Background | "The 2022 Hormone Therapy Position Statement of The North American Menopause Society" Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 Jul 1;29(7):767-794. doi: 10.1097/GME.0000000000002028. |
| 34415665 | Background | Simpson DJ, Chandra T. Epigenetic age prediction. Aging Cell. 2021 Sep;20(9):e13452. doi: 10.1111/acel.13452. Epub 2021 Aug 20. |
| 33706956 | Background | Karlamangla AS, Shieh A, Greendale GA. Hormones and bone loss across the menopause transition. Vitam Horm. 2021;115:401-417. doi: 10.1016/bs.vh.2020.12.016. Epub 2021 Jan 29. |
| 32770384 | Background | Moreau KL, Hildreth KL, Klawitter J, Blatchford P, Kohrt WM. Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress. Geroscience. 2020 Dec;42(6):1699-1714. doi: 10.1007/s11357-020-00236-7. Epub 2020 Aug 8. |
| 18663170 | Background | Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K. Menopause and the metabolic syndrome: the Study of Women's Health Across the Nation. Arch Intern Med. 2008 Jul 28;168(14):1568-75. doi: 10.1001/archinte.168.14.1568. |
| 22990755 | Background | El Khoudary SR, Wildman RP, Matthews K, Thurston RC, Bromberger JT, Sutton-Tyrrell K. Progression rates of carotid intima-media thickness and adventitial diameter during the menopausal transition. Menopause. 2013 Jan;20(1):8-14. doi: 10.1097/gme.0b013e3182611787. |
| 30401549 | Background | Bromberger JT, Epperson CN. Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstet Gynecol Clin North Am. 2018 Dec;45(4):663-678. doi: 10.1016/j.ogc.2018.07.007. Epub 2018 Oct 25. |
| 31568098 | Background | El Khoudary SR, Greendale G, Crawford SL, Avis NE, Brooks MM, Thurston RC, Karvonen-Gutierrez C, Waetjen LE, Matthews K. The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause. 2019 Oct;26(10):1213-1227. doi: 10.1097/GME.0000000000001424. |
| ID | Term |
|---|---|
| D008687 | Metformin |
| C000591245 | semaglutide |
| D000959 | Antihypertensive Agents |
| D057911 | Angiotensin Receptor Antagonists |
| C000608808 | fezolinetant |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045504 | Molecular Mechanisms of Pharmacological Action |
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