Insulin ResistanceTEMPUSNCT01605071
Timing Estrogen After MenoPaUSe
A study testing Estradiol in people with Insulin Resistance, run by University of Colorado, Denver at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- Estradiol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Jan 2017
- Phase
- Interventional
- 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 45 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Time Past Menopause, Duration of Estrogen Deficiency, and Insulin Action
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.
Read the detailed description
Large clinical trials have shown a reduced incidence of type 2 diabetes in postmenopausal women randomized to estrogen-based hormone therapy compared to placebo. Moreover, studies suggest development of diabetes is reduced in postmenopausal women who used hormone therapy for a part of the postmenopausal period compared to women who never used hormone therapy. Consistent with this, our preliminary data suggest that the timing of estrogen treatment relative to the menopause may be an important determinant of whether there are favorable effects on insulin action. Our observations suggest that estrogen improves insulin sensitivity in early postmenopausal women, but may decrease insulin sensitivity in those more than 10 years past menopause. More and more studies suggest estrogens have divergent effects on cardiovascular risk when initiated close to the onset of menopause rather than distant from the menopause; we hypothesize this is also true for diabetes risk. The goal of this study is to determine whether the effects of estrogen on insulin metabolism are different in women who are early postmenopausal compared to late postmenopausal. To meet our goal, we propose to measure insulin sensitivity in women who are within 6 years of the onset of menopause or more than 10 years beyond the menopause and who have not used hormone therapy previously. All women will be studied on two separate occasions, one day with and one day without short-term (1 week) treatment with transdermal estradiol. We expect that estradiol will increase insulin sensitivity in early postmenopausal women and decrease insulin sensitivity in late postmenopausal women. We also expect that estrogen receptors in fat and muscle may change with increasing time after menopause. Thus, we will collect fat and muscle biopsies to compare changes in estrogen receptors between early and late postmenopausal women and in response to 1 week of estradiol treatment. We believe these studies will provide evidence for a benefit of estradiol on insulin sensitivity when administered early, but not late, after menopause; likely contributing to delayed onset of type 2 diabetes in postmenopausal women.
- Conditions
- Insulin Resistance
- Being tested
- Estradiol
- Keywords
- menopause, estrogen, insulin sensitivity, estrogen receptors
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called Climara
1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
| Study group | Role | What they receive |
|---|---|---|
| Early Postmenopausal | Active comparator | Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy Receives: Drug: Estradiol |
| Late Postmenopausal | Active comparator | Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: after 1wk estradiol or placebo
Secondary outcomes (4)
Skeletal Muscle Estrogen Receptor Expression
Estrogen receptors (ERα and ERβ) differences in time since menopause and estrogen treatment
randomized order of testing, cross-over design
Measured: after 1wk estradiol or placebo
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
Estrogen receptors (ERα and ERβ) differences in time since menopause and estrogen treatment
randomized order of testing, cross-over design
Measured: after 1wk estradiol or placebo
Adipose Tissue Estrogen Receptor Expression
Adipose tissue estrogen receptor expression associated with age and menopause
Abdominal and femoral subcutaneous adipose tissue ERα and ERβ expression
Measured: Baseline
Adipose Tissue Estrogen Receptor Expression (ERα:ERβ)
Adipose tissue estrogen receptor expression associated with age and menopause
Abdominal and femoral subcutaneous adipose tissue ratio of ERα:ERβ expression
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study startSep 2011
- Primary completionNov 2015
- Study completionJan 2017
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 (8)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachael E Van Pelt, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605071
- Sponsor's protocol ID
- 11-0788
- Other IDs
- R01DK088105
- Acronym
- TEMPUS
- Status last verified
- Feb 2021
- First submitted
- 22 May 2012
- Last updated
- 1 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 17986638Kanaya 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.
PubMed 12513038Bonds 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.
PubMed 16440209Margolis 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.
PubMed 15252707Pentti 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.
PubMed 19321660Park 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.
PubMed 30928279Park 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.
PubMed 28472101Pereira 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.
PubMed 26425886
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Time Past Menopause, Duration of Estrogen Deficiency, and Insulin Action
- ClinicalTrials.gov ID
- NCT01605071
- Acronym / sponsor ID
- TEMPUS / 11-0788
- Conditions
- Insulin Resistance
- Keywords
- menopause, estrogen, insulin sensitivity, estrogen receptors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Sep 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 24 May 2012 (estimated)
- Results
- Posted 1 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Large clinical trials have shown a reduced incidence of type 2 diabetes in postmenopausal women randomized to estrogen-based hormone therapy compared to placebo. Moreover, studies suggest development of diabetes is reduced in postmenopausal women who used hormone therapy for a part of the postmenopausal period compared to women who never used hormone therapy. Consistent with this, our preliminary data suggest that the timing of estrogen treatment relative to the menopause may be an important determinant of whether there are favorable effects on insulin action. Our observations suggest that estrogen improves insulin sensitivity in early postmenopausal women, but may decrease insulin sensitivity in those more than 10 years past menopause. More and more studies suggest estrogens have divergent effects on cardiovascular risk when initiated close to the onset of menopause rather than distant from the menopause; we hypothesize this is also true for diabetes risk. The goal of this study is to determine whether the effects of estrogen on insulin metabolism are different in women who are early postmenopausal compared to late postmenopausal. To meet our goal, we propose to measure insulin sensitivity in women who are within 6 years of the onset of menopause or more than 10 years beyond the menopause and who have not used hormone therapy previously. All women will be studied on two separate occasions, one day with and one day without short-term (1 week) treatment with transdermal estradiol. We expect that estradiol will increase insulin sensitivity in early postmenopausal women and decrease insulin sensitivity in late postmenopausal women. We also expect that estrogen receptors in fat and muscle may change with increasing time after menopause. Thus, we will collect fat and muscle biopsies to compare changes in estrogen receptors between early and late postmenopausal women and in response to 1 week of estradiol treatment. We believe these studies will provide evidence for a benefit of estradiol on insulin sensitivity when administered early, but not late, after menopause; likely contributing to delayed onset of type 2 diabetes in postmenopausal women.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Postmenopausal | Active comparator | Drug: EstradiolPostmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy |
| Late Postmenopausal | Active comparator | Drug: EstradiolPostmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy |
Who may qualify
- Ages
- 45 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| EstradiolAlso: Climara1 week of transdermal estradiol (0.15mg) 1 week of transdermal placebo | Drug | Early Postmenopausal, Late Postmenopausal |
Primary outcome
Insulin-mediated Glucose Disposal Rate (Hyperinsulinemic-euglycemic Clamp)
Time frame: after 1wk estradiol or placebo
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
4 secondary outcomes
Skeletal Muscle Estrogen Receptor Expression
Time frame: after 1wk estradiol or placebo
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
Time frame: after 1wk estradiol or placebo
Adipose Tissue Estrogen Receptor Expression
Time frame: Baseline
Adipose Tissue Estrogen Receptor Expression (ERα:ERβ)
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17986638Van 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.
- Background: PubMed 12513038Kanaya 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.
- Background: PubMed 16440209Bonds 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.
- Background: PubMed 15252707Margolis 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.
- Background: PubMed 19321660Pentti 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.
- Derived from this study: PubMed 30928279Park 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.
- Derived from this study: PubMed 28472101Park 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.
- Derived from this study: PubMed 26425886Pereira 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.
- IMAGE research group study websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Rachael E Van Pelt, 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?
A study testing Estradiol in people with Insulin Resistance, run by University of Colorado, Denver at 1 site in United States.
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 8 inclusion and 9 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 Mar 2021. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Mar 2021). 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?
Insulin-mediated Glucose Disposal Rate (Hyperinsulinemic-euglycemic Clamp) (time frame: after 1wk estradiol or placebo). 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 NCT01605071, which also lists 8 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 Mar 2021.