Know Cancer

forgot password

Effect of Race on Gonadotropin Responses to Short Term Negative and Positive Feedback Effects of Gonadal Steroids

18 Years
45 Years
Open (Enrolling)
Premenopause, Healthy

Thank you

Trial Information

Effect of Race on Gonadotropin Responses to Short Term Negative and Positive Feedback Effects of Gonadal Steroids

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.

Inclusion Criteria

Premenopausal Women

- Will be non-smokers or smoke less than 10 cigarettes/day

- African-American women aged 18 to 35 years and Caucasian women aged 18 to 45 years

- 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

- With no evidence of androgen excess.

- Subjects must have no known sensitivity to any medications used in the relevant
protocol and be willing to use abstinence or barrier methods of contraception for the
duration of the study.

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Outcome Measure:

LH response to estrogen positive feedback

Outcome Time Frame:

5 days of estradiol and progesterone infusion

Safety Issue:


Principal Investigator

Janet E Hall, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

January 2005

Completion Date:

December 2011

Related Keywords:

  • Premenopause
  • Healthy
  • estrogen
  • progesterone
  • African-American
  • Caucasian
  • infusion
  • gonadotropins
  • healthy



Massachusetts General Hospital Boston, Massachusetts  02114-2617