Effect of Race on Gonadotropin Responses

NCT00455962 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 2003P-001397Sundry Department FundR01AG013241
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Premenopause; Healthy

Keywords

estrogen; progesterone; African-American; Caucasian; infusion; gonadotropins; healthy

Outcome Measures

Primary Outcomes (1)

• 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.

  5 days of estradiol and progesterone infusion

Study Arms (2)

African American women 18-35 yo

ACTIVE COMPARATOR

intervention: estradiol steroid infusion and progesterone steroid infusion

Drug: Estradiol steroid infusion; Drug: Progesterone steroid infusion

Caucasian women 18-35 yo

ACTIVE COMPARATOR

intervention: estradiol steroid infusion intervention: progesterone steroid infusion

Drug: Estradiol steroid infusion; Drug: Progesterone steroid infusion

Interventions

Estradiol steroid infusion DRUG

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

Also known as: E2

African American women 18-35 yo; Caucasian women 18-35 yo

Progesterone steroid infusion DRUG

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

Also known as: P

African American women 18-35 yo; Caucasian women 18-35 yo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 22049179 RESULT

Results Point of Contact

• Title: Janet E. Hall, MD
• Organization: Massachusetts General Hospital

jehall@partners.org

617-877-1112

Study Officials

• Janet E Hall, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate in Medicine

Model Details: Comparisons will be made between response to estradiol and progesterone infusion in young African-American and Caucasian women.

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 4, 2007
• Study Start: January 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 27, 2017
• Results First Posted: April 27, 2017

Record last verified: 2017-06

Locations

US (1)