Postmenopausal Women Estrogen and Progesterone Infusion
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies, Postmenopausal Syndrome |
| Therapuetic Areas: | Endocrinology, Other |
| Healthy: | No |
| Age Range: | 45 - 80 |
| Updated: | 5/20/2018 |
| Start Date: | November 2000 |
| End Date: | August 22, 2015 |
Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning
The purpose of the study is to study the effects of aging, estrogen and progesterone on the
brain. Specifically, we want to look at how the hypothalamus and pituitary (two small glands
in the brain) respond to estrogen. The pituitary gland is controlled by the hypothalamus. 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 modulate this system with
changes in LH and FSH. Early changes associated with low levels of estrogen are inhibitory
(estrogen negative feedback) while higher levels of estrogen (such as those present when a
follicle in the ovary is ready to ovulate) stimulate LH to cause ovulation (positive
feedback). This study will determine: 1) hypothalamic and pituitary levels of glucose uptake
(as a measure of brain metabolic activity) at baseline and in association with estrogen
negative feedback on LH (24 hr) and estrogen positive feedback on LH (72 hr); and 2) the
effect of aging on estrogen feedback on LH, assessing negative feedback (nadir ~ 24 hr) and
positive feedback (peak between 72 and 96 hr).
brain. Specifically, we want to look at how the hypothalamus and pituitary (two small glands
in the brain) respond to estrogen. The pituitary gland is controlled by the hypothalamus. 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 modulate this system with
changes in LH and FSH. Early changes associated with low levels of estrogen are inhibitory
(estrogen negative feedback) while higher levels of estrogen (such as those present when a
follicle in the ovary is ready to ovulate) stimulate LH to cause ovulation (positive
feedback). This study will determine: 1) hypothalamic and pituitary levels of glucose uptake
(as a measure of brain metabolic activity) at baseline and in association with estrogen
negative feedback on LH (24 hr) and estrogen positive feedback on LH (72 hr); and 2) the
effect of aging on estrogen feedback on LH, assessing negative feedback (nadir ~ 24 hr) and
positive feedback (peak between 72 and 96 hr).
The transition to menopause is characterized by a decline in the numbers of functional
ovarian follicles followed by a decrease in levels of inhibin A and B and complex changes in
estradiol, which include an initial increase followed by an inevitable decrease. Therefore,
there are dynamic changes in the hypothalamic-pituitary feedback from the aging ovary, prior
to the ultimate loss of feedback that occurs with the complete cessation of ovarian function.
While there is ample evidence that the loss of ovarian function is a major contributor to the
menopause, there is evidence from animal models that primary age-related neuroendocrine
changes may also contribute to reproductive aging. Specifically, there is evidence for
changes in the hypothalamic and pituitary responses to estrogen negative and positive
feedback. An understanding of the age-related changes in the physiology of the hypothalamic
and pituitary responsiveness to gonadal steroid feedback is critical in determining whether
hypothalamic and pituitary changes per se contribute to the menopause and the impact of the
loss of reproductive function on the brain.
ovarian follicles followed by a decrease in levels of inhibin A and B and complex changes in
estradiol, which include an initial increase followed by an inevitable decrease. Therefore,
there are dynamic changes in the hypothalamic-pituitary feedback from the aging ovary, prior
to the ultimate loss of feedback that occurs with the complete cessation of ovarian function.
While there is ample evidence that the loss of ovarian function is a major contributor to the
menopause, there is evidence from animal models that primary age-related neuroendocrine
changes may also contribute to reproductive aging. Specifically, there is evidence for
changes in the hypothalamic and pituitary responses to estrogen negative and positive
feedback. An understanding of the age-related changes in the physiology of the hypothalamic
and pituitary responsiveness to gonadal steroid feedback is critical in determining whether
hypothalamic and pituitary changes per se contribute to the menopause and the impact of the
loss of reproductive function on the brain.
Inclusion criteria:
postmenopausal women young (age 45-55) or old (age 70-80) History of natural menopause
defined by the absence of menses for at least 12 months (or history of surgical menopause
defined as bilateral oophorectomy) Normal TSH, PRL and CBC, and Factor V activity Normal
BUN and Creatinine (< 2 times the upper limit of normal) BMI between 18 to 30 kg/m2 An
increased FSH measured at the screening visit will be consistent with menopause. If the
initial determination is low, a repeat sample may be drawn.
Exclusion criteria:
Hormonal medication or herbal supplements and/or over the counter menopause therapy in the
2 months prior to study Any absolute contraindications to the use of physiologic
replacement doses of estrogen and/or progesterone History of coronary artery disease
Medications thought to act centrally on the GnRH pulse generator History of breast cancer
or blood clots Smoking more than 10 cigarettes/day Prior history of allergic reaction to
any dyes used with x-rays or scans and/ or any other contraindications to PET scans No
metal implants, pacemakers, aneurysm clips, implanted hearing aids and/or any other
contraindications to MRI scan
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