ObesityNCT01381016

Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

A study testing Estradiol, Gonadotropin-releasing hormone (GnRH) and Progesterone in people with Obesity and Infertility, 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 sole purpose of this study is to evaluate pathophysiology of disease. The disease state that is being evaluated is the obesity-related alterations in reproductive hormones The obesity epidemic in the United States is advancing at an accelerated pace. It is estimated that by 2015, 41% of U.S. Read more about this study

Who is it for?: Ages 18 to 42 years, women onlyHealthy volunteers can take part
Conditions the study is for: Obesity, Infertility
What is being tested?: Estradiol, Gonadotropin-releasing hormone (GnRH) and Progesterone
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Jun 2011to Jan 2013
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 18 to 42 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Age 18-42 at study entry
Regular menstrual cycles every 25-40 days
BMI 18- 25 kg/m2 or ≥30kg/m2
Good general health
Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
Baseline hemoglobin >11 gm/dl.

Who cannot join

Positive screen for Activated Protein C resistance
Any contraindications to exogenous estrogen, including previous thromboembolic events or stroke, history of an estrogen-dependent tumor, active liver disease, undiagnosed abnormal uterine bleeding, hypertriglyceridemia, smoking, hypertension
History of chronic disease affecting hormone production, metabolism or clearance (including diabetes mellitus) or abnormal renal or liver function at screening, such as elevated aspartate or alanine aminotransferases or elevated blood urea nitrogen (BUN) or creatinine
Current use of thiazolidinediones or metformin (known to interact with reproductive hormones)
Use of hormones affecting hypothalamic-pituitary ovarian axis within three months of enrollment
Strenuous exercise (>4 hours per week)
Pregnancy, breast-feeding or current active attempts to conceive

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado, Anschutz Medical Campus
Aurora, Colorado, 80045

Other trials in United States

About this study

The sole purpose of this study is to evaluate pathophysiology of disease. The disease state that is being evaluated is the obesity-related alterations in reproductive hormones

The obesity epidemic in the United States is advancing at an accelerated pace. It is estimated that by 2015, 41% of U.S. adults will be obese as defined by a body mass index (BMI) of greater than 30 kg/m2. The U.S. government's 2010 Dietary Guidelines regard obesity as the single greatest health hazard in this century. Female adult obesity is associated with menstrual cycle irregularities, ovulatory dysfunction and a higher risk of obstetrical complications. This reproductive phenotype of obesity is worsened by further increases in BMI and is not solely due to anovulatory infertility. While the association of adiposity with subfertility is well documented in population studies, the underlying mechanisms remain poorly understood. The main objective of this proposal is to clarify the nature of the obesity-related reproductive endocrine abnormalities and identify potential etiologies amenable to therapy.
Hypothesis: The hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity.

Read the detailed description

Design: paired assessments Pre and Post estrogen administration in obese and normal weight women
AIM 1: To test the pituitary and hypothalamic responsiveness in obesity, we will examine the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) pulsatility during frequent blood sampling.
AIM 2: To test the ovarian responsiveness in obesity, we will examine urinary reproductive hormones (E1c, estrone conjugates, and Pdg, pregnanediol glucuronide) over an entire menstrual cycle.
AIM 3: To test the hypothesis that central adiposity is associated with reproductive hormone alterations in obesity, we will quantitatively assess body composition by dual energy x-ray absorptiometry (DXA).

Conditions: Obesity, Infertility
Being tested: Estradiol, Gonadotropin-releasing hormone (GnRH), Progesterone
Keywords: LH pulsatility, Obesity, Reproduction
Medical subject headings: Obesity, Infertility

What participants receive

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

EstradiolDrug
Also called Climara, transdermal estrogen
Subjects were instructed to apply 0.1 mg/d transdermal estrogen for one month.
Gonadotropin-releasing hormone (GnRH)Drug
Also called Lutrelef or gonadorelin acetate
Pituitary response was assessed to determine how estradiol administration alters pituitary sensitivity to GnRH.
ProgesteroneDrug
Also called Prometrium or medroxyproge sterone acetate
Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.

Study groups in NCT01381016
Study group	Role	What they receive
Group 1 - Normal Weight	Other	Group 1: Normal weight (BMI 18-25 kg/m2) Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary. Receives: Drug: Estradiol; Drug: Gonadotropin-releasing hormone (GnRH); Drug: Progesterone
Group 2 - Obese	Experimental	Group 2: Obese (BMI >30 kg/m2) Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary. Receives: Drug: Estradiol; Drug: Gonadotropin-releasing hormone (GnRH); Drug: Progesterone

What is being measured

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

Luteinizing Hormone Pulse Amplitude
The study is powered on luteinizing hormone pulse amplitude because it is the clinical outcome for which the most data is available. The primary comparison is whether there is a significant reduction in the pulse amplitude in the obese between the pre- and post-treatment periods and whether there is no change in the pulse amplitude in the normal weight patients between the pre and post-treatment periods.
Measured: Baseline
Luteinizing Hormone Pulse Amplitude
Measured: Post estradiol at one month

Timeline

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

Jun 2011Jan 2013

First posted27 Jun 2011 (estimated)
Study startJun 2011
Primary completionJan 2013
Study completionJan 2013

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 (3)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 N/A
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01381016
Sponsor's protocol ID: 11-0293
Status last verified: Apr 2015
First submitted: 22 Jun 2011
Last updated: 20 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
PubMed 17440019
Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-1415. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30.
PubMed 18829008
Roth LW, Allshouse AA, Lesh J, Polotsky AJ, Santoro N. The correlation between self-reported and measured height, weight, and BMI in reproductive age women. Maturitas. 2013 Oct;76(2):185-8. doi: 10.1016/j.maturitas.2013.07.010. Epub 2013 Aug 16.
PubMed 23958434

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 20 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Estrogen Sensitivity and Ovulatory Dysfunction in Obesity
ClinicalTrials.gov ID: NCT01381016
Acronym / sponsor ID: 11-0293
Conditions: Obesity, Infertility
Keywords: LH pulsatility, Obesity, Reproduction
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Study start: Jun 2011
Primary completion: Jan 2013 (actual)
Study completion: Jan 2013 (actual)
First posted: 27 Jun 2011 (estimated)
Results: Posted 18 Feb 2015

Clinical summary

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

The sole purpose of this study is to evaluate pathophysiology of disease. The disease state that is being evaluated is the obesity-related alterations in reproductive hormones

The obesity epidemic in the United States is advancing at an accelerated pace. It is estimated that by 2015, 41% of U.S. adults will be obese as defined by a body mass index (BMI) of greater than 30 kg/m2. The U.S. government's 2010 Dietary Guidelines regard obesity as the single greatest health hazard in this century. Female adult obesity is associated with menstrual cycle irregularities, ovulatory dysfunction and a higher risk of obstetrical complications. This reproductive phenotype of obesity is worsened by further increases in BMI and is not solely due to anovulatory infertility. While the association of adiposity with subfertility is well documented in population studies, the underlying mechanisms remain poorly understood. The main objective of this proposal is to clarify the nature of the obesity-related reproductive endocrine abnormalities and identify potential etiologies amenable to therapy.
Hypothesis: The hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity.

Detailed description

Design: paired assessments Pre and Post estrogen administration in obese and normal weight women
AIM 1: To test the pituitary and hypothalamic responsiveness in obesity, we will examine the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) pulsatility during frequent blood sampling.
AIM 2: To test the ovarian responsiveness in obesity, we will examine urinary reproductive hormones (E1c, estrone conjugates, and Pdg, pregnanediol glucuronide) over an entire menstrual cycle.
AIM 3: To test the hypothesis that central adiposity is associated with reproductive hormone alterations in obesity, we will quantitatively assess body composition by dual energy x-ray absorptiometry (DXA).

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Group 1 - Normal Weight	Other	Drug: Estradiol, Drug: Gonadotropin-releasing hormone (GnRH), Drug: ProgesteroneGroup 1: Normal weight (BMI 18-25 kg/m2) Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.
Group 2 - Obese	Experimental	Drug: Estradiol, Drug: Gonadotropin-releasing hormone (GnRH), Drug: ProgesteroneGroup 2: Obese (BMI >30 kg/m2) Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.

Who may qualify

Ages: 18 to 42 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Age 18-42 at study entry
Regular menstrual cycles every 25-40 days
BMI 18- 25 kg/m2 or ≥30kg/m2
Good general health
Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening

Key exclusion criteria (7 listed)

Positive screen for Activated Protein C resistance
Any contraindications to exogenous estrogen, including previous thromboembolic events or stroke, history of an estrogen-dependent tumor, active liver disease, undiagnosed abnormal uterine bleeding, hypertriglyceridemia, smoking, hypertension
History of chronic disease affecting hormone production, metabolism or clearance (including diabetes mellitus) or abnormal renal or liver function at screening, such as elevated aspartate or alanine aminotransferases or elevated blood urea nitrogen (BUN) or creatinine
Current use of thiazolidinediones or metformin (known to interact with reproductive hormones)
Use of hormones affecting hypothalamic-pituitary ovarian axis within three months of enrollment

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: Climara, transdermal estrogenSubjects were instructed to apply 0.1 mg/d transdermal estrogen for one month.	Drug	Group 1 - Normal Weight, Group 2 - Obese
Gonadotropin-releasing hormone (GnRH)Also: Lutrelef or gonadorelin acetatePituitary response was assessed to determine how estradiol administration alters pituitary sensitivity to GnRH.	Drug	Group 1 - Normal Weight, Group 2 - Obese
ProgesteroneAlso: Prometrium or medroxyproge sterone acetateSubjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.	Drug	Group 1 - Normal Weight, Group 2 - Obese

Primary outcome

Luteinizing Hormone Pulse Amplitude
Time frame: Baseline
The study is powered on luteinizing hormone pulse amplitude because it is the clinical outcome for which the most data is available. The primary comparison is whether there is a significant reduction in the pulse amplitude in the obese between the pre- and post-treatment periods and whether there is no change in the pulse amplitude in the normal weight patients between the pre and post-treatment periods.
Luteinizing Hormone Pulse Amplitude
Time frame: Post estradiol at one month

Results and safety

Results posted to the registry on 18 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	13	10
Experimental	17	11

Primary outcome: Luteinizing Hormone Pulse Amplitude

Time frame: Baseline. Mean (Standard Error). Unit: IU/L

Measure	Group 1 - Normal Weight n = 10	Group 2 - Obese n = 11
Value	2.73 (.46)	1.12 (.19)

Primary outcome: Luteinizing Hormone Pulse Amplitude

Time frame: Post estradiol at one month. Mean (Standard Error). Unit: IU/L

Measure	Control n = 10	Experimental n = 11
Value	2.18 (.4)	1.59 (.29)

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	0 of 11 (0%)	0 of 11 (0%)	Not reported
Experimental	1 of 15 (6.7%)	0 of 15 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17440019Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
Background: PubMed 18829008Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-1415. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30.
Derived from this study: PubMed 23958434Roth LW, Allshouse AA, Lesh J, Polotsky AJ, Santoro N. The correlation between self-reported and measured height, weight, and BMI in reproductive age women. Maturitas. 2013 Oct;76(2):185-8. doi: 10.1016/j.maturitas.2013.07.010. Epub 2013 Aug 16.

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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.

Alex Polotsky, MD 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, Gonadotropin-releasing hormone (GnRH) and Progesterone in people with Obesity and Infertility, 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 6 inclusion and 7 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 20 Apr 2015. 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 18 Feb 2015). 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?

Luteinizing Hormone Pulse Amplitude (time frame: Baseline). 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 NCT01381016, which also lists 3 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 20 Apr 2015.