Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Effect of Aging on Estrogen Positive Feedback on LH
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Young postmenopausal women
Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women.
干预措施: Estradiol infusion (Drug)
Young postmenopausal women
Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women.
干预措施: Progesterone infusion (Drug)
Older postmenopausal women
Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women..
干预措施: Estradiol infusion (Drug)
Older postmenopausal women
Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women..
干预措施: Progesterone infusion (Drug)
结局指标
主要结局
Effect of Aging on Estrogen Positive Feedback on LH
时间窗: Onset of surge (average of 61 hr from beginnning of infusion until the end of the study (120 hr)
LH area under the curve in response to estrogen positive feedback. Area under the curve was calculated from blood samples drawn every 4 hours from the onset of positive feedback until the end of the study (120 min). The onset of positive feedback is defined as the time when LH first exceeds mean + 2SD of the previous three time points and shows a sustained rise.
Effect of Aging on Estrogen Negative Feedback on LH
时间窗: Baseline at 0 time before infusion, nadir occurred between 8 and 60 hr (mean 24 hr)
Difference between baseline LH (average of 3 samples drawn 15 min apart) and nadir LH based on a 3-point moving average of blood samples drawn every 4 hours over 120 hr, expressed as a percent of baseline (% baseline).
次要结局
- 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Negative Feedback(0 vs 24 hr)
- 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Negative Feedback(Baseline vs 24 hr after the onset of steroid infusion)
- 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Positive Feedback(24 vs 72 hr)
- 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Positive Feedback(24 hr vs 72 hr)
研究者
Janet E. Hall, MD
Associate Physician
Massachusetts General Hospital