Clinical trial NCT06975111: Focusing on the Menopausal Transition to Improve Mid-Life Women's Health
Official title: Focusing on the Menopausal Transition to Improve Mid-Life Women's Health
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Menopause
Menopause Hot Flashes
Menopause Related Conditions
Cardiovascular
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2025-05-16
Enrollment: 200
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be placed into treatment interventions based on their health and screening tests.
Primary purpose: TREATMENT

Brief 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 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.


Eligibility criteria: Inclusion Criteria:

* aged 45-55
* In the late menopausal transition, defined as 60 days of amenorrhea but less than 365 days of amenorrhea18
* No current use of hormone therapy or hormonal contraception
* 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

Exclusion Criteria:

* 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
* Un- Diagnosed abnormal uterine bleeding
* Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN 2) for participants with a BMI\> 30 kg/m2.

Primary outcomes:
measure: Epigenetic aging measurements of "PhenoAge"
timeFrame: Up to 2 years
measure: Epigenetic aging measurements of "GrimAge"
timeFrame: Up to 2 years
Secondary outcomes:
measure: IL-1
timeFrame: Up to 2 years
measure: TNF-alpha
timeFrame: Up to 2 years
measure: IL-6
timeFrame: Up to 2 years
measure: IL-8
timeFrame: Up to 2 years
measure: Flow-mediated dilation
timeFrame: Up to 2 years
measure: Serum Marker for Ovarian Aging
timeFrame: Up to 2 years
measure: MENQOL survey
timeFrame: Up to 2 years
measure: Eaotoxin levels
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado-School of Medicine
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: "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.
citation: Simpson DJ, Chandra T. Epigenetic age prediction. Aging Cell. 2021 Sep;20(9):e13452. doi: 10.1111/acel.13452. Epub 2021 Aug 20.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.