Overview

This trial is active, not recruiting.

Conditions postmenopause, aging
Treatments estradiol infusion, progesterone infusion
Sponsor Massachusetts General Hospital
Collaborator National Institute on Aging (NIA)
Start date November 2000
End date February 2007
Trial size 40 participants
Trial identifier NCT00455741, 2000P-002496, R01AG013241

Summary

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 stop this system when the blood has sufficient estrogen levels. This is called estrogen feedback. This study will determine which areas of the brain are affected by estrogen feedback by administering estrogen and progesterone, both natural hormones.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Arm
(Other)
estradiol infusion
Graded 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.
progesterone infusion
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 of the 5-day study.

Primary Outcomes

Measure
LH response to estrogen positive feedback
time frame: 5 days of estrogen/progestone infusion

Eligibility Criteria

Female participants from 45 years up to 80 years old.

Two groups of postmenopausal women, young (age 45-55) and old (age 70-80) who meet the following criteria: - History of natural menopause defined by the absence of menses for at least 12 months (or history of surgical menopause defined as bilateral oophorectomy) - On no hormonal medication or herbal supplements and/or over the counter menopause therapy for a minimum of 2 months prior to study - 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 - No absolute contraindications to the use of physiologic replacement doses of estrogen and/or progesterone and no history of coronary artery disease - On no medications thought to act centrally on the GnRH pulse generator. 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. - No prior history of breast cancer or blood clots - Non-smokers or smokes less than 10 cigarettes/day - No prior history of allergic reaction to any dyes used with x-rays or scans and/ or any other contraindications to PET scans - Will not have metal implants, pacemakers, aneurysm clips, implanted hearing aids and/or any other contraindications to MRI scan

Additional Information

Official title Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning
Principal investigator Janet E Hall, M.D.
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2013.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.