PremenopausePhase 1/2NCT00455962
Effect of Race on Gonadotropin Responses
A Phase 1/2 study testing Estradiol steroid infusion and Progesterone steroid infusion in people with Premenopause and Healthy, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to attempt to determine why estrogen levels are increased in African-American women as compared to Caucasian women by evaluating estrogen feedback on the brain. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premenopause, Healthy
- What is being tested?
- Estradiol steroid infusion and Progesterone steroid infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Dec 2011
- Phase
- Phase 1/2
- 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 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- African-American women aged 18 to 35 years and Caucasian women aged 18 to 36 years. Subjects will be asked to volunteer information on ethnicity (self classification). Only African-American and Caucasian subjects will be included in this aim to address the specific hypotheses.
- BMI <30
- In good general health with normal TSH, prolactin and hemoglobin
- Normal BUN and Creatinine (< 2 times the upper limit of normal)
- On no medications for > 2 months before the study
- Regular menstrual cycles every 25 to 35 days and ovulation documented by a luteal phase progesterone > 3 ng/ml
- Willing to use abstinence or barrier methods of contraception for the duration of the study.
Who cannot join
- postmenopausal
- smoking >9 cigarettes per day
- evidence of androgen excess.
- sensitivity to any medications used in the relevant protocol
- race other than African-American or Caucasian
- Hispanic ethnicity
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Effect of Race on Gonadotropin Responses to Short Term Negative and Positive Feedback Effects of Gonadal Steroids
The purpose of this study is to attempt to determine why estrogen levels are increased in African-American women as compared to Caucasian women by evaluating estrogen feedback on the brain. African-American women have increased bone mineral density, higher rates of twins, greater incidence of fibroids, and increased incidence of breast cancer below 40 years of age as compared to Caucasian women. These traits or illnesses are all believed to be estrogen-dependent. In fact, previous research has demonstrated increased estrogen levels in African-American women as compared to Caucasian women. However, the reason for these differences in estrogen levels has not been studied in humans. One possibility is that estrogen feedback on the brain differs between African-American and Caucasian women. Two small glands in the brain (hypothalamus and pituitary) respond to estrogen. The hypothalamus secretes GnRH (Gonadotropin-Releasing Hormone) that signals the pituitary to secrete the reproductive hormones, LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone). These hormones act on the ovaries and signal the ovaries to produce estrogen and progesterone. Estrogen in the bloodstream then acts on the brain to stop this system when the blood has enough estrogen levels. This is called estrogen feedback. This study will determine whether there are differences in estrogen feedback between African-American and Caucasian women.
Read the detailed description
Several independent lines of evidence have suggested that reproductive endocrine dynamics may differ between African-American (AAW) and Caucasian (CW) women. There is an increased incidence of dizygotic twinning in African-American women and a further increase in the incidence reported in African women compared to Caucasian, Hispanic and Asian populations. While the etiology of dizygotic twinning is not well understood, an increase in its incidence may imply an alteration in the integrated control of the reproductive axis which usually favors development of a single ovulatory follicle. It is widely appreciated that the incidence of leiomyomas is increased in African-American women. Growth factors are likely to play a role in their control, but there is also ample evidence that leiomyomas are responsive to gonadal steroids, decreasing in size following the menopause and in response to hypoestrogenism caused by gonadotropin downregulation. African-American women under 40 years of age have a higher risk of breast cancer than women of all other ethnicities in that age group, again raising the question of whether there are also differences in reproductive hormone dynamics. Finally, bone density is increased in African-American women. In a cross-sectional study of 54 African-American and 39 Caucasian women between the ages of 20 and 90, Perry et al found that the increase in bone density in AAW was associated with increased serum levels of both estradiol and testosterone. Woods et al also described increased levels of estradiol, estrone and androstenedione levels in AAW compared with control women on a controlled low-fat, high-fiber diet. In contrast, a recent longitudinal cohort study has suggested that AAW have lower levels of estradiol with increasing age and BMI in comparison with CW. We have compared reproductive hormone levels in AAW and CW < 35 years old with a history of regular ovulatory cycles. Our preliminary data indicate that in comparison to age and BMI matched CW, estradiol levels are consistently elevated across the cycle in AAW in the absence of changes in LH, FSH, progesterone, inhibin A or inhibin B. These relationships suggest both altered negative and forward feedback interrelationships between FSH and LH and estradiol in the setting of normal inhibin levels. In the current protocol we will seek to understand the mechanisms underlying these feedback differences, which have never been addressed in these populations.
A graded infusion of estradiol and progesterone can be used to assess differences in negative and positive feedback of gonadal steroids on LH and FSH. We have hypothesized that differences exist in feedback regulation of the hypothalamus and pituitary as a function of African-American or Caucasian race in reproductive aged women.
- Conditions
- Premenopause, Healthy
- Being tested
- Estradiol steroid infusion, Progesterone steroid infusion
- Keywords
- estrogen, progesterone, African-American, Caucasian, infusion, gonadotropins, healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol steroid infusionDrug
Also called E2
Estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr
Progesterone steroid infusionDrug
Also called P
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr
| Study group | Role | What they receive |
|---|---|---|
| African American women 18-35 yo | Active comparator | intervention: estradiol steroid infusion and progesterone steroid infusion Receives: Drug: Estradiol steroid infusion; Drug: Progesterone steroid infusion |
| Caucasian women 18-35 yo | Active comparator | intervention: estradiol steroid infusion intervention: progesterone steroid infusion Receives: Drug: Estradiol steroid infusion; Drug: Progesterone steroid infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
LH Peak in Response to Estrogen Positive Feedback
Estradiol levels are consistently higher in African-American vs Caucasian women across the menstrual cycle. This study was designed to determine if African-American women are more sensitive to estrogen positive feedback to generate the preovulatory LH surge using a controlled estrogen infusion paradigm.
Measured: 5 days of estradiol and progesterone infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2007 (estimated)
- Study startJan 2005
- Primary completionDec 2011
- Study completionDec 2011
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 (1)Papers the sponsor has linked to this study.
- Other trials for PremenopauseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 1/2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Comparisons will be made between response to estradiol and progesterone infusion in young African-American and Caucasian women.
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Janet E. Hall, MD, Massachusetts General Hospital
- Investigators
- Janet E Hall, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00455962
- Sponsor's protocol ID
- 2003P-001397
- Other IDs
- Sundry Department Fund, R01AG013241
- Status last verified
- Jun 2017
- First submitted
- 2 Apr 2007
- Last updated
- 27 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Coded individual level data with all identifiers removed will be available on request to the PI.
Publications
Shaw ND, Klingman KM, Srouji SS, Histed SN, Hall JE. Gonadotropin responses to estrogen-positive and -negative feedback are identical in African-American and Caucasian women. J Clin Endocrinol Metab. 2012 Jan;97(1):E106-9. doi: 10.1210/jc.2011-2102. Epub 2011 Nov 2.
PubMed 22049179
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Race on Gonadotropin Responses to Short Term Negative and Positive Feedback Effects of Gonadal Steroids
- ClinicalTrials.gov ID
- NCT00455962
- Acronym / sponsor ID
- 2003P-001397
- Conditions
- Premenopause, Healthy
- Keywords
- estrogen, progesterone, African-American, Caucasian, infusion, gonadotropins, healthy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Aging (NIA)
- Study start
- Jan 2005
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 4 Apr 2007 (estimated)
- Results
- Posted 27 Apr 2017
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 attempt to determine why estrogen levels are increased in African-American women as compared to Caucasian women by evaluating estrogen feedback on the brain. African-American women have increased bone mineral density, higher rates of twins, greater incidence of fibroids, and increased incidence of breast cancer below 40 years of age as compared to Caucasian women. These traits or illnesses are all believed to be estrogen-dependent. In fact, previous research has demonstrated increased estrogen levels in African-American women as compared to Caucasian women. However, the reason for these differences in estrogen levels has not been studied in humans. One possibility is that estrogen feedback on the brain differs between African-American and Caucasian women. Two small glands in the brain (hypothalamus and pituitary) respond to estrogen. The hypothalamus secretes GnRH (Gonadotropin-Releasing Hormone) that signals the pituitary to secrete the reproductive hormones, LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone). These hormones act on the ovaries and signal the ovaries to produce estrogen and progesterone. Estrogen in the bloodstream then acts on the brain to stop this system when the blood has enough estrogen levels. This is called estrogen feedback. This study will determine whether there are differences in estrogen feedback between African-American and Caucasian women.
Detailed description
Several independent lines of evidence have suggested that reproductive endocrine dynamics may differ between African-American (AAW) and Caucasian (CW) women. There is an increased incidence of dizygotic twinning in African-American women and a further increase in the incidence reported in African women compared to Caucasian, Hispanic and Asian populations. While the etiology of dizygotic twinning is not well understood, an increase in its incidence may imply an alteration in the integrated control of the reproductive axis which usually favors development of a single ovulatory follicle. It is widely appreciated that the incidence of leiomyomas is increased in African-American women. Growth factors are likely to play a role in their control, but there is also ample evidence that leiomyomas are responsive to gonadal steroids, decreasing in size following the menopause and in response to hypoestrogenism caused by gonadotropin downregulation. African-American women under 40 years of age have a higher risk of breast cancer than women of all other ethnicities in that age group, again raising the question of whether there are also differences in reproductive hormone dynamics. Finally, bone density is increased in African-American women. In a cross-sectional study of 54 African-American and 39 Caucasian women between the ages of 20 and 90, Perry et al found that the increase in bone density in AAW was associated with increased serum levels of both estradiol and testosterone. Woods et al also described increased levels of estradiol, estrone and androstenedione levels in AAW compared with control women on a controlled low-fat, high-fiber diet. In contrast, a recent longitudinal cohort study has suggested that AAW have lower levels of estradiol with increasing age and BMI in comparison with CW. We have compared reproductive hormone levels in AAW and CW < 35 years old with a history of regular ovulatory cycles. Our preliminary data indicate that in comparison to age and BMI matched CW, estradiol levels are consistently elevated across the cycle in AAW in the absence of changes in LH, FSH, progesterone, inhibin A or inhibin B. These relationships suggest both altered negative and forward feedback interrelationships between FSH and LH and estradiol in the setting of normal inhibin levels. In the current protocol we will seek to understand the mechanisms underlying these feedback differences, which have never been addressed in these populations.
A graded infusion of estradiol and progesterone can be used to assess differences in negative and positive feedback of gonadal steroids on LH and FSH. We have hypothesized that differences exist in feedback regulation of the hypothalamus and pituitary as a function of African-American or Caucasian race in reproductive aged women.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Comparisons will be made between response to estradiol and progesterone infusion in young African-American and Caucasian women.
| Arm | Type | Receives |
|---|---|---|
| African American women 18-35 yo | Active comparator | Drug: Estradiol steroid infusion, Drug: Progesterone steroid infusionintervention: estradiol steroid infusion and progesterone steroid infusion |
| Caucasian women 18-35 yo | Active comparator | Drug: Estradiol steroid infusion, Drug: Progesterone steroid infusionintervention: estradiol steroid infusion intervention: progesterone steroid infusion |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- African-American women aged 18 to 35 years and Caucasian women aged 18 to 36 years. Subjects will be asked to volunteer information on ethnicity (self classification). Only African-American and Caucasian subjects will be included in this aim to address the specific hypotheses.
- BMI <30
- In good general health with normal TSH, prolactin and hemoglobin
- Normal BUN and Creatinine (< 2 times the upper limit of normal)
- On no medications for > 2 months before the study
Key exclusion criteria (6 listed)
- postmenopausal
- smoking >9 cigarettes per day
- evidence of androgen excess.
- sensitivity to any medications used in the relevant protocol
- race other than African-American or Caucasian
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 |
|---|---|---|
| Estradiol steroid infusionAlso: E2Estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr | Drug | African American women 18-35 yo, Caucasian women 18-35 yo |
| Progesterone steroid infusionAlso: PProgesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr | Drug | African American women 18-35 yo, Caucasian women 18-35 yo |
Primary outcome
LH Peak in Response to Estrogen Positive Feedback
Time frame: 5 days of estradiol and progesterone infusion
Estradiol levels are consistently higher in African-American vs Caucasian women across the menstrual cycle. This study was designed to determine if African-American women are more sensitive to estrogen positive feedback to generate the preovulatory LH surge using a controlled estrogen infusion paradigm.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22049179Shaw ND, Klingman KM, Srouji SS, Histed SN, Hall JE. Gonadotropin responses to estrogen-positive and -negative feedback are identical in African-American and Caucasian women. J Clin Endocrinol Metab. 2012 Jan;97(1):E106-9. doi: 10.1210/jc.2011-2102. Epub 2011 Nov 2.
- Individual participant dataSharing planned: Undecided. Coded individual level data with all identifiers removed will be available on request to the PI.
Related trials for Premenopause
Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruitingPhase 4
Migraine Menopause Study
Migraine, Menopausal
RecruitingObservational study
The Immunobiological Mechanisms of Depression in Perimenopause
Perimenopause, Major Depressive Episode (MDE)
Recruiting
Hemodynamics After Resistance Training
Perimenopause
Active, not recruiting
Relaxation Techniques and Pilates for Menopause Symptoms
Women Over 40 Years of Age in the Perimenopausal or Menopausal Stage, Presenting With Associated Symptoms
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.
Janet E Hall, M.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Estradiol steroid infusion and Progesterone steroid infusion in people with Premenopause and Healthy, run by Massachusetts General Hospital 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 7 inclusion and 6 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 27 Jul 2017. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 27 Apr 2017). 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?
LH Peak in Response to Estrogen Positive Feedback (time frame: 5 days of estradiol and progesterone infusion). 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 NCT00455962, which also lists 1 linked publication.
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 27 Jul 2017.