Postmenopausal Women Estrogen and Progesterone Infusion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00455741
Recruitment Status : Unknown
Verified October 2013 by Janet E. Hall, MD, Massachusetts General Hospital.
Recruitment status was:  Active, not recruiting
First Posted : April 4, 2007
Last Update Posted : November 1, 2013
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Postmenopause Aging Drug: Estradiol infusion Drug: Progesterone infusion Not Applicable

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning
Study Start Date : November 2000
Actual Primary Completion Date : February 2007
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
1 Drug: 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.
Drug: 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 Outcome Measures :
  1. LH response to estrogen positive feedback [ Time Frame: 5 days of estrogen/progestone infusion ]

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00455741

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institute on Aging (NIA)
Principal Investigator: Janet E Hall, M.D. Massachusetts General Hospital

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital Identifier: NCT00455741     History of Changes
Other Study ID Numbers: 2000P-002496
R01AG013241 ( U.S. NIH Grant/Contract )
First Posted: April 4, 2007    Key Record Dates
Last Update Posted: November 1, 2013
Last Verified: October 2013

Keywords provided by Janet E. Hall, MD, Massachusetts General Hospital:
hormone replacement

Additional relevant MeSH terms:
Polyestradiol phosphate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female