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Effect of Race on Gonadotropin Responses

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00455962
First received: April 2, 2007
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Premenopause Healthy Drug: Estradiol steroid infusion Drug: Progesterone steroid infusion Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Comparisons will be made between response to estradiol and progesterone infusion in young African-American and Caucasian women.
Masking: No masking
Masking Description:
No masking.
Primary Purpose: Other
Official Title: Effect of Race on Gonadotropin Responses to Short Term Negative and Positive Feedback Effects of Gonadal Steroids

Resource links provided by NLM:


Further study details as provided by Janet E. Hall, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Enrollment: 23
Study Start Date: January 2005
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: African American women 18-35 yo
intervention: estradiol steroid infusion and progesterone steroid infusion
Drug: Estradiol steroid infusion
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
Other Name: E2
Drug: Progesterone steroid infusion
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
Other Name: P
Active Comparator: Caucasian women 18-35 yo
intervention: estradiol steroid infusion intervention: progesterone steroid infusion
Drug: Estradiol steroid infusion
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
Other Name: E2
Drug: Progesterone steroid infusion
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
Other Name: P

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455962

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Investigators
Principal Investigator: Janet E Hall, M.D. Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Janet E. Hall, MD, Clinical Associate in Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00455962     History of Changes
Other Study ID Numbers: 2003P-001397
Sundry Department Fund ( Other Identifier: MGH-REU Department Fund )
R01AG013241 ( U.S. NIH Grant/Contract )
Study First Received: April 2, 2007
Results First Received: March 16, 2017
Last Updated: March 16, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Coded individual level data with all identifiers removed will be available on request to the PI.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janet E. Hall, MD, Massachusetts General Hospital:
estrogen
progesterone
African-American
Caucasian
infusion
gonadotropins
healthy

Additional relevant MeSH terms:
Estradiol
Polyestradiol phosphate
Progesterone
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins

ClinicalTrials.gov processed this record on July 21, 2017