Timing Estrogen After MenoPaUSe

NCT01605071 | Completed Results DMC

• 2 other identifiers: 11-0788R01DK088105
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the current study is to test whether the effect of estrogen on insulin metabolism depends on the timing of treatment relative to when a woman went through menopause. The investigators hypothesize that estrogen will improve insulin sensitivity in early postmenopausal women, but decrease insulin sensitivity in late postmenopausal women.

Conditions

Insulin Resistance

Keywords

menopause; estrogen; insulin sensitivity; estrogen receptors

Outcome Measures

Primary Outcomes (1)

• Insulin-mediated Glucose Disposal Rate (Hyperinsulinemic-euglycemic Clamp)

  Estrogen mediated change in glucose disposal rate and time since menopause * Baseline GDR (no difference between groups) * E2 mediated change (significant difference between groups) randomized order of testing, cross-over design

  after 1wk estradiol or placebo

Secondary Outcomes (4)

• Skeletal Muscle Estrogen Receptor Expression

  after 1wk estradiol or placebo

• Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)

  after 1wk estradiol or placebo

• Adipose Tissue Estrogen Receptor Expression

  Baseline

• Adipose Tissue Estrogen Receptor Expression (ERα:ERβ)

  Baseline

Study Arms (2)

Early Postmenopausal

ACTIVE COMPARATOR

Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy

Drug: Estradiol

Late Postmenopausal

ACTIVE COMPARATOR

Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy

Drug: Estradiol

Interventions

Estradiol DRUG

1 week of transdermal estradiol (0.15mg) 1 week of transdermal placebo

Also known as: Climara

Early Postmenopausal; Late Postmenopausal

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 45-70 yr
• postmenopausal (no menses ≥12 mo or bilateral oophorectomy and FSH \>30 IU/L)
• ≤6yrs or ≥10yrs of menopause (last menses or oophorectomy)
• BMI \<30 kg/m2 and weight stable (±2kg in past 2mo)
• non-smokers
• sedentary to moderately active (\<3 days/wk of structured exercise)
• naïve to estrogen-based hormone therapies (previous use ≤6 months)
• CBC, CMP and TSH values within normal ranges specified by lab

You may not qualify if:

• underwent a partial hysterectomy (i.e., one or both ovaries left intact)
• underwent menopause (natural, chemical, or surgical) prior to age 45yr
• are between \>6yr and \<10yr of menopause (last menses or oophorectomy)
• previously used (\>6 mo) or are currently using any formulation of estrogen-based HT (e.g., oral Premarin, transdermal 17beta-estradiol, selective estrogen receptor modulators)
• have T2DM or are being treated with glucose-lowering/ insulin sensitizing medications
• have uncontrolled hypertension (SBP\>140 and/or DBP\>90 mmHg)
• have hypertriglyceridemia (\>400 mg/dL)
• have contraindications to estrogen therapy (history of venous thromboembolism, heart disease, myocardial infarction, hormone sensitive cancer)
• have contraindications to biopsies (severe anemia, blood clotting disorders)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (8)

• Van Pelt RE, Schwartz RS, Kohrt WM. Insulin secretion and clearance after subacute estradiol administration in postmenopausal women. J Clin Endocrinol Metab. 2008 Feb;93(2):484-90. doi: 10.1210/jc.2007-1657. Epub 2007 Nov 6.

  PMID: 17986638 BACKGROUND

• Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, Cauley JA, Barrett-Connor E; Heart and Estrogen/progestin Replacement Study. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003 Jan 7;138(1):1-9. doi: 10.7326/0003-4819-138-1-200301070-00005.

  PMID: 12513038 BACKGROUND

• Bonds DE, Lasser N, Qi L, Brzyski R, Caan B, Heiss G, Limacher MC, Liu JH, Mason E, Oberman A, O'Sullivan MJ, Phillips LS, Prineas RJ, Tinker L. The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial. Diabetologia. 2006 Mar;49(3):459-68. doi: 10.1007/s00125-005-0096-0. Epub 2006 Jan 27.

  PMID: 16440209 BACKGROUND

• Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV; Women's Health Initiative Investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-1187. doi: 10.1007/s00125-004-1448-x. Epub 2004 Jul 14.

  PMID: 15252707 BACKGROUND

• Pentti K, Tuppurainen MT, Honkanen R, Sandini L, Kroger H, Alhava E, Saarikoski S. Hormone therapy protects from diabetes: the Kuopio osteoporosis risk factor and prevention study. Eur J Endocrinol. 2009 Jun;160(6):979-83. doi: 10.1530/EJE-09-0151. Epub 2009 Mar 25.

  PMID: 19321660 BACKGROUND

• Park YM, Keller AC, Runchey SS, Miller BF, Kohrt WM, Van Pelt RE, Kang C, Jankowski CM, Moreau KL. Acute estradiol treatment reduces skeletal muscle protein breakdown markers in early- but not late-postmenopausal women. Steroids. 2019 Jun;146:43-49. doi: 10.1016/j.steroids.2019.03.008. Epub 2019 Mar 27.

  PMID: 30928279 DERIVED

• Park YM, Pereira RI, Erickson CB, Swibas TA, Cox-York KA, Van Pelt RE. Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor alpha and beta in postmenopausal women. PLoS One. 2017 May 4;12(5):e0176446. doi: 10.1371/journal.pone.0176446. eCollection 2017.

  PMID: 28472101 DERIVED

• Pereira RI, Casey BA, Swibas TA, Erickson CB, Wolfe P, Van Pelt RE. Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action. J Clin Endocrinol Metab. 2015 Dec;100(12):4456-62. doi: 10.1210/jc.2015-3084. Epub 2015 Oct 1.

  PMID: 26425886 DERIVED

Related Links

• IMAGE research group study website

MeSH Terms

Conditions

Insulin Resistance

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Kimberly Cox-York
• Organization: University of Colorado Denver, Anschutz Medical Campus

KIMBERLY.COX-YORK@CUANSCHUTZ.EDU

Study Officials

• Rachael E Van Pelt, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2012
• First Posted: May 24, 2012
• Study Start: September 1, 2011
• Primary Completion: November 1, 2015
• Study Completion: January 1, 2017
• Last Updated: March 1, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)