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.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label
LH response to estrogen positive feedback
5 days of estradiol and progesterone infusion
Janet E Hall, M.D.
Massachusetts General Hospital
United States: Food and Drug Administration
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