Postmenopausal Women Estrogen and Progesterone Infusion

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00455741
First received: April 2, 2007
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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 Intervention
Postmenopause
Aging
Drug: Estradiol infusion
Drug: Progesterone infusion

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • LH response to estrogen positive feedback [ Time Frame: 5 days of estrogen/progestone infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: November 2000
Estimated Study Completion Date: January 2018
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455741

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Janet E Hall, M.D. Massachusetts General Hospital
  More Information

Additional Information:
No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00455741     History of Changes
Other Study ID Numbers: 2000P-002496, R01AG013241
Study First Received: April 2, 2007
Last Updated: October 31, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
menopause
estrogen
progesterone
hormone replacement
aging
PET

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

ClinicalTrials.gov processed this record on August 28, 2014