The Effects of Aging and Estrogen on the Pituitary

NCT00386022 | Unknown Phase 2 Results DMC

• 2 other identifiers: 2000-P-002498R01AG013241
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Gonadotropin-releasing hormone; Estrogens; postmenopausal women; Pituitary hormones

Outcome Measures

Primary Outcomes (2)

• Pituitary Response to GnRH

  Baseline LH and FSH responses to each of 4 GnRH doses - peak to nadir amplitude expressed as percent (%) change from nadir

  Peak hormone level within 2 hours post GnRH doses

• Effect of Estrogen on Pituitary Response to GnRH

  LH and FSH responses to each of 4 GnRH doses, expressed as change in amplitude \[amp\] from peak to nadir between plus estrogen and baseline conditions

  Peak hormone level within 2 hours post GnRH doses

Study Arms (2)

Young postmenopausal women

EXPERIMENTAL

intervention: graded doses of GnRH following NAL-GLU GnRH antagonist administration with or without transdermal estrogen patch

Drug: GnRH; Drug: NAL-GLU GnRH antagonist; Drug: Estrogen patch

Older postmenopausal women

EXPERIMENTAL

intervention: graded doses of GnRH following NAL-GLU GnRH antagonist administration with or without transdermal estrogen patch

Drug: GnRH; Drug: NAL-GLU GnRH antagonist; Drug: Estrogen patch

Interventions

GnRH DRUG

GnRH doses of 25, 75, 250 and 750 ng/kg will be given IV every 4 hr at baseline and after transdermal estradiol

Also known as: gonadotropin-releasing hormone, Factryl

Older postmenopausal women; Young postmenopausal women

NAL-GLU GnRH antagonist DRUG

A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg before and after transdermal estradiol

Also known as: GnRH antagonist

Older postmenopausal women; Young postmenopausal women

Estrogen patch DRUG

transdermal estrogen patches 0.05mg/day, changing the patch every 86 hr in second part of sequential study

Also known as: Climara, Estraderm

Older postmenopausal women; Young postmenopausal women

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 thyroid stimulating hormone, prolactin, factor V Leiden, and complete blood count - Normal blood urea nitrogen and creatinine (\< 2 times the upper limit of normal)
• basal metabolic index ≤ 30
• Non-smokers or smoke less than 10 cigarettes/day

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Shaw ND, Histed SN, Srouji SS, Yang J, Lee H, Hall JE. Estrogen negative feedback on gonadotropin secretion: evidence for a direct pituitary effect in women. J Clin Endocrinol Metab. 2010 Apr;95(4):1955-61. doi: 10.1210/jc.2009-2108. Epub 2010 Feb 4.

  PMID: 20133465 RESULT

• Shaw ND, Srouji SS, Histed SN, McCurnin KE, Hall JE. Aging attenuates the pituitary response to gonadotropin-releasing hormone. J Clin Endocrinol Metab. 2009 Sep;94(9):3259-64. doi: 10.1210/jc.2009-0526. Epub 2009 Jun 23.

  PMID: 19549740 RESULT

MeSH Terms

Interventions

Gonadotropin-Releasing Hormone; LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; Estradiol

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Limitations and Caveats

No significant limitations were present in this study and the subsequent analysis.

Results Point of Contact

• Title: Dr. Janet E. Hall
• Organization: Massachusetts General Hospital

hall.janet@mgh.harvard.edu

617-877-1112

Study Officials

• Janet E Hall, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Model Details: The study will is considered sequential as participants were studied at baseline and after one month of low-dose estrogen. Randomization refers to randomization of the order of doses of GnRH between participants.

Study Record Dates

• First Submitted: October 6, 2006
• First Posted: October 11, 2006
• Study Start: January 1, 2002
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2018
• Last Updated: April 13, 2017
• Results First Posted: April 13, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)