ObesityPhase 3POWERNCT00687739

Prevention of Obesity in Women Via Estradiol Regulation

A Phase 3 study testing leuprolide acetate, Estradiol Transdermal and progressive resistance exercise training in people with Obesity, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 49 years, women onlyHealthy volunteers can take part
Conditions the study is for: Obesity
What is being tested?: leuprolide acetate, Estradiol Transdermal and progressive resistance exercise training
Type of treatment: Injection or infusion, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 79 participants
Where: 1 siteUnited States
Study dates: May 2008to Jun 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 49 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 20Show fewer

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)
Chronic hepatobiliary disease, defined as liver function tests (AST, ALT, alkaline phosphatase, total bilirubin) greater than 1.5 times the upper limit of normal
Thyroid dysfunction, defined as ultra sensitive TSH less than 0.5 or greater than 5.0 mU/L
Uncontrolled hypertension, defined as resting BP greater than 150/90 mmHg
Cardiovascular disease, including indicators of ischemic heart disease or serious arrhythmias at rest or during the graded exercise test; follow-up diagnostic testing to rule out cardiovascular disease by a cardiologist will be allowed
Orthopedic or other problems that would interfere with participation in the exercise program

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado Denver
Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: Estrogen Deficiency and Mechanisms of Fat Accumulation

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

Read the detailed description

Many factors contribute to the current epidemic of obesity. Although estrogen status is not commonly recognized as a determinant of obesity risk in women, there is strong evidence from large randomized controlled trials that estradiol (E2)-based hormone therapy (HT) reduces weight gain by about 40% in postmenopausal women. Importantly, there is also strong evidence that E2 reduces abdominal fat accumulation, a fundamental component of the Metabolic Syndrome. Some studies suggest risks of HT outweigh the benefits for some women. However, this does not negate the importance of learning the mechanisms by which E2 influences energy balance and fat patterning.

This study uses gonadotropin releasing hormone (GnRH) analog therapy to determine the effects of chronic (5-month) sex hormone suppression on resting energy expenditure (REE), altered hypothalamic-pituitary-adrenal (HPA) axis activity, and fat gain.

It is hypothesized that REE will be reduced in response to chronic sex hormone suppression, promoting fat gain. It is also hypothesized that stress-induced hypothalamic-pituitary-adrenal (HPA)axis activity will be amplified during sex hormone suppression; altered HPA axis activity leading to cortisol excess causes abdominal fat accumulation. Finally, it is hypothesized that E2 add-back therapy will lessen these responses.

Participants will be randomized so that half of the women in each treatment arm will participate in an exercise training program, consisting of progressive resistance exercise to prevent the decline in fat-free mass (FFM) and the increase in fat mass that has been observed in young women in response to GnRH analog therapy.

Conditions: Obesity
Being tested: leuprolide acetate, Estradiol Transdermal, progressive resistance exercise training
Keywords: hormone therapy, obesity, postmenopause, disease /disorder proneness /risk, insulin sensitivity /resistance, metabolic syndrome, women's health
Medical subject headings: Obesity, Disease Susceptibility, Metabolic Syndrome

What participants receive

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

leuprolide acetateDrug
Also called Lupron
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Estradiol TransdermalDrug
Also called Climara
0.075 mg patch per day for 5 months
progressive resistance exercise trainingBehavioural
45 minute exercise sessions 4 times per week for 5 months

Study groups in NCT00687739
Study group	Role	What they receive
1	Placebo comparator	GnRH agonist + placebo Receives: Drug: leuprolide acetate
2	Active comparator	GnRH agonist + placebo + exercise Receives: Drug: leuprolide acetate; Behavioral: progressive resistance exercise training
3	Experimental	GnRH agonist + Estradiol Receives: Drug: leuprolide acetate; Drug: Estradiol Transdermal
4	Experimental	GnRH agonist + Estradiol + exercise Receives: Drug: leuprolide acetate; Drug: Estradiol Transdermal; Behavioral: progressive resistance exercise training

What is being measured

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

Resting Energy Expenditure (REE)
Resting energy expenditure measured by indirect calorimeter at baseline and after 5 months of treatment.
Measured: 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
Measured: Before and after 5 months of treatment

Secondary outcomes (3)

Total Energy Expenditure (TEE)
24-hour energy expenditure measured by indirect calorimetry in a room calorimeter
Measured: Before and after 5 months of treatment
Fat Mass
Total body fat mass measured by DXA
Measured: Before and after 5 months of treatment
Fat-free Mass
Total body fat-free mass measured by DXA
Measured: Before and after 5 months of treatment

Timeline

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

May 2008Jun 2014

First posted2 Jun 2008 (estimated)
Study startMay 2008
Primary completionJun 2014
Study completionJun 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 79 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00687739
Sponsor's protocol ID: 06-0512
Other IDs: R01AG018198
Acronym: POWER
Status last verified: Mar 2025
First submitted: 29 May 2008
Last updated: 1 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 15082697
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.
PubMed 15687338
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.
PubMed 15167310
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.
PubMed 29631362

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Estrogen Deficiency and Mechanisms of Fat Accumulation
ClinicalTrials.gov ID: NCT00687739
Acronym / sponsor ID: POWER / 06-0512
Conditions: Obesity
Keywords: hormone therapy, obesity, postmenopause, disease /disorder proneness /risk, insulin sensitivity /resistance, metabolic syndrome, women's health
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 79 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: National Institute on Aging (NIA)
Study start: May 2008
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 2 Jun 2008 (estimated)
Results: Posted 9 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
1	Placebo comparator	Drug: leuprolide acetateGnRH agonist + placebo
2	Active comparator	Drug: leuprolide acetate, Behavioral: progressive resistance exercise trainingGnRH agonist + placebo + exercise
3	Experimental	Drug: leuprolide acetate, Drug: Estradiol TransdermalGnRH agonist + Estradiol
4	Experimental	Drug: leuprolide acetate, Drug: Estradiol Transdermal, Behavioral: progressive resistance exercise trainingGnRH agonist + Estradiol + exercise

Who may qualify

Ages: 18 to 49 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (20 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
leuprolide acetateAlso: Lupron3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months	Drug	1, 2, 3, 4
Estradiol TransdermalAlso: Climara0.075 mg patch per day for 5 months	Drug	3, 4
progressive resistance exercise training45 minute exercise sessions 4 times per week for 5 months	Behavioural	2, 4

Primary outcome

Resting Energy Expenditure (REE)
Time frame: Before and after 5 months of treatment
Resting energy expenditure measured by indirect calorimeter at baseline and after 5 months of treatment.
Cortisol Response (Area Under the Curve) to CRH Under DEX Suppression
Time frame: Before and after 5 months of treatment
Cortisol response to corticotropin releasing hormone (CRH) during dexamethasone (DEX) suppression; DEX/CRH stimulation test

3 secondary outcomes

Total Energy Expenditure (TEE)
Time frame: Before and after 5 months of treatment
Fat Mass
Time frame: Before and after 5 months of treatment
Fat-free Mass
Time frame: Before and after 5 months of treatment

Results and safety

Results posted to the registry on 9 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GnRH Agonist + Placebo	25	23
GnRH Agonist + Placebo + Exercise	15	12
GnRH Agonist + Estradiol	25	23
GnRH Agonist + Estradiol + Exercise	14	12

Primary outcome: Resting Energy Expenditure (REE)

Time frame: Before and after 5 months of treatment. Mean (95% Confidence Interval). Unit: kcal/d

Measure	GnRHag+PL n = 16	GnRHag+PL+ex n = 8	GnRHag+E2 n = 16	GnRHag+E2+ex n = 8
Value	-37.8 (-88.7 to 13.0)	-87.2 (-185.9 to 11.4)	14.6 (-34.8 to 64.0)	-19.3 (-95.1 to 56.4)

GnRHag+PL vs GnRHag+PL+ex vs GnRHag+E2 vs GnRHag+E2+ex: p <0.05, ANCOVA

Population analysed: Participants who completed 24-h visits in the room calorimeter before and after the intervention. This could not be accomplished in all participants in the trial because of scheduling difficulties and/or lack of availability of the calorimeter. The primary analysis was by drug group only (placebo vs estradiol), collapsed across exercise grouping.

Primary outcome: Cortisol Response (Area Under the Curve) to CRH Under DEX Suppression

Time frame: Before and after 5 months of treatment. Mean (95% Confidence Interval). Unit: ng/mL x min

Measure	GnRHag+PL n = 15	GnRHag+E2 n = 15
Value	189 (-2481 to 2859)	-3115 (-5322 to -907)

GnRHag+PL vs GnRHag+E2: p <0.05, ANCOVA

Population analysed: Women who completed the DEX/CRH stimulation test before and after the intervention. The Outcome Measure evaluation was only conducted in a subgroup of women - those in the Drug intervention arms. This evaluation was not done in the exercise arms.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the time eligibility was established through the completion of the study, over approximately 1 year.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GnRH Agonist + Placebo	0 of 23 (0%)	0 of 23 (0%)	Not reported
GnRH Agonist + Placebo + Exercise	0 of 12 (0%)	0 of 12 (0%)	Not reported
GnRH Agonist + Estradiol	1 of 23 (4.3%)	0 of 23 (0%)	Not reported
GnRH Agonist + Estradiol + Exercise	0 of 12 (0%)	0 of 12 (0%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15082697Anderson 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.
Background: PubMed 15687338Sites 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.
Background: PubMed 15167310Utian 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.
Derived from this study: PubMed 29631362Gavin 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Wendy M Kohrt, PhD principal investigator

University of Colorado, Denver

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 20 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: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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?

Yes. Results are posted in the registry (first posted 9 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resting Energy Expenditure (REE) (time frame: Before and after 5 months of treatment). 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 NCT00687739, which also lists 4 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 1 Apr 2025.