The Effects of Aging and Estrogen on the Brain

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:
NCT00386022
First received: October 6, 2006
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to study the effects of aging and estrogen on the brain. Specifically, this study will look how the hypothalamus signals the pituitary gland to secrete reproductive hormones and how that changes with aging.


Condition Intervention Phase
Healthy
Drug: GnRH
Drug: NAL-GLU GnRH antagonist
Drug: Estrogen patch (Climara)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Pituitary Contribution to the Decline in Gonadotropin Secretion With Age

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • pituitary response after GnRH stimulation; LH, FSH and FAS, the peak amplitude, and area under the curve for each GnRH dose per study group [ Time Frame: after each 28-hour admission ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2002
Estimated Study Completion Date: January 2018
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Postmenopausal women 45-55 years old
Drug: GnRH
GnRH doses of 25, 75, 250 and 750 ng/kg will be given IV every 4 hr in random order, with the exception that the highest dose will always be administered last
Drug: NAL-GLU GnRH antagonist
a single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg
Drug: Estrogen patch (Climara)
transdermal estrogen patches (Climara 0.05mg/day, changing the patch every 86 hr)
Experimental: 2
Postmenopausal women 70-80 years old
Drug: GnRH
GnRH doses of 25, 75, 250 and 750 ng/kg will be given IV every 4 hr in random order, with the exception that the highest dose will always be administered last
Drug: NAL-GLU GnRH antagonist
a single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg
Drug: Estrogen patch (Climara)
transdermal estrogen patches (Climara 0.05mg/day, changing the patch every 86 hr)

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • 45-55 or 70-80 years old
  • History of natural menopause defined by the absence of menses for at least 12 months (or history of surgical menopause defined as bilateral oophorectomy) and a FSH level >26 IU/L
  • 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, factor V, and CBC
  • Normal BUN and Creatinine (< 2 times the upper limit of normal)
  • BMI ≤ 30
  • Non-smokers or smoke less than 10 cigarettes/day

Exclusion Criteria:

  • Absolute contraindications to the use of physiologic replacement doses of estrogen, including a negative screening mammogram within the past 24 months
  • History of coronary artery disease
  • On medications thought to act centrally on the GnRH pulse generator
  • Past history of hypersensitivity or allergy to narcotics, vancomycin, muscle relaxants, aspirin, and/or anaphylactic reaction(s) to other drugs
  • Prior history of breast cancer and/or blood clots
  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: NCT00386022

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:
Publications:
Gill S, Sharpless JL, Bo-Abbas Y, Hall JE. Hypothalamic effects of gonadal steroid replacement in postmenopausal women: Quantity of GnRH. Proc The Endocrine Society 82nd Annual Meeting 395:P3-1636, 2000.
Hall JE, Sluss PM, Eriksson K, Sharpless JL, Wide L. Less basic isoforms of endogenous luteinizing hormone (LH) in postmenopausal women result in prolonged plasma disappearance. Proc The Endocrine Society 81st Annual Meeting 292: P2-54, 1999.

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: NCT00386022     History of Changes
Other Study ID Numbers: 2000-P-002498, R01AG013241
Study First Received: October 6, 2006
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Gonadotropin-releasing hormone
Estrogens
postmenopausal women
Pituitary hormones

Additional relevant MeSH terms:
Estrogens
LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hormone Antagonists

ClinicalTrials.gov processed this record on August 28, 2014