Prevention of Obesity in Women Via Estradiol Regulation

NCT00687739 | Completed Phase 3 Results DMC

• 2 other identifiers: 06-0512R01AG018198
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate potential mechanisms by which estradiol deficiency accelerates fat gain and abdominal fat accumulation in women.

Conditions

Obesity

Keywords

hormone therapy; obesity; postmenopause; disease /disorder proneness /risk; insulin sensitivity /resistance; metabolic syndrome; women's health

Outcome Measures

Primary Outcomes (2)

• Resting Energy Expenditure (REE)

  Resting energy expenditure measured by indirect calorimeter at baseline and after 5 months of treatment.

  Before and after 5 months of treatment

• Cortisol Response (Area Under the Curve) to CRH Under DEX Suppression

  Cortisol response to corticotropin releasing hormone (CRH) during dexamethasone (DEX) suppression; DEX/CRH stimulation test

  Before and after 5 months of treatment

Secondary Outcomes (3)

• Total Energy Expenditure (TEE)

  Before and after 5 months of treatment

• Fat Mass

  Before and after 5 months of treatment

• Fat-free Mass

  Before and after 5 months of treatment

Study Arms (4)

1

PLACEBO COMPARATOR

GnRH agonist + placebo

Drug: leuprolide acetate

2

ACTIVE COMPARATOR

GnRH agonist + placebo + exercise

Drug: leuprolide acetate; Behavioral: progressive resistance exercise training

3

EXPERIMENTAL

GnRH agonist + Estradiol

Drug: leuprolide acetate; Drug: Estradiol Transdermal

4

EXPERIMENTAL

GnRH agonist + Estradiol + exercise

Drug: leuprolide acetate; Drug: Estradiol Transdermal; Behavioral: progressive resistance exercise training

Interventions

leuprolide acetate DRUG

3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months

Also known as: Lupron

1; 2; 3; 4

Estradiol Transdermal DRUG

0.075 mg patch per day for 5 months

Also known as: Climara

3; 4

progressive resistance exercise training BEHAVIORAL

45 minute exercise sessions 4 times per week for 5 months

2; 4

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy premenopausal women, aged 18 to 49 years
• Regular menses (no missed cycles in previous year; cycle length 25-35 days)
• Positive luteinizing hormone test or a mid-luteal serum progesterone greater than 3 ng/mL
• Nonsmokers
• Willing to receive all study interventions
• Physically able and willing to be randomized to participate in a supervised resistance exercise training program

You may not qualify if:

• Already performing high-intensity resistance exercise training more than 1 day per week
• On diabetes medications
• Use of hormonal contraception in the past 3 months
• On oral or inhaled glucocorticoids
• Positive pregnancy test
• Intention to become pregnant or start hormonal contraceptive therapy during the period of study
• Lactation
• Hypersensitivity to extrinsic peptide hormones, mannitol, Gonadotropin-releasing hormone (GnRH), leuprolide acetate, benzyl alcohol (the vehicle for injection of leuprolide acetate), or transdermal patch
• Score greater than 16 on the Center for Epidemiologic Studies Depression Scale and Beck Depression Inventory-II score greater than 18, or clinician recommendation to exclude
• Severe osteopenia or osteoporosis (proximal femur or lumbar spine t scores \< -2.0)
• BMI greater than 40 kg/m2, weight change of more than ± 2 kg in last 6 months, or weight-reduced by more than 5 kg from maximal body weight
• Abnormal vaginal bleeding
• History of breast cancer or other estrogen-dependent neoplasms
• History of venous thromboembolic events
• Moderate or severe renal impairment (creatinine clearance \<50 mL/min by Cockcroft-Gault)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (4)

• Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.

  PMID: 15082697 BACKGROUND

• Sites CK, L'Hommedieu GD, Toth MJ, Brochu M, Cooper BC, Fairhurst PA. The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2005 May;90(5):2701-7. doi: 10.1210/jc.2004-1479. Epub 2005 Feb 1.

  PMID: 15687338 BACKGROUND

• Utian WH, Gass ML, Pickar JH. Body mass index does not influence response to treatment, nor does body weight change with lower doses of conjugated estrogens and medroxyprogesterone acetate in early postmenopausal women. Menopause. 2004 May-Jun;11(3):306-14. doi: 10.1097/01.gme.0000117062.54779.bd.

  PMID: 15167310 BACKGROUND

• Gavin KM, Shea KL, Gibbons E, Wolfe P, Schwartz RS, Wierman ME, Kohrt WM. Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone. Am J Physiol Endocrinol Metab. 2018 Aug 1;315(2):E316-E325. doi: 10.1152/ajpendo.00221.2017. Epub 2018 Apr 6.

  PMID: 29631362 DERIVED

MeSH Terms

Conditions

Obesity; Disease Susceptibility; Metabolic Syndrome

Interventions

Leuprolide; Estradiol

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Limitations and Caveats

This was a mechanistically driven study to isolate the effects of estradiol on bioenergetics and HPA axis activity. It was not a therapeutic clinical trial.

Results Point of Contact

• Title: Wendy M Kohrt, PhD
• Organization: University of Colorado Anschutz Medical Campus

wendy.kohrt@ucdenver.edu

3037241913

Study Officials

• Wendy M Kohrt, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: June 2, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 1, 2025
• Results First Posted: December 9, 2019

Record last verified: 2025-03

Locations

US (1)