Sex Hormones and Orthostatic Tolerance

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: NCT01153581
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : January 30, 2017
Last Update Posted : December 13, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Yale University

Brief Summary:
This study is designed to determine the causes of "orthostatic intolerance" which occurs more commonly in women than in men. Orthostatic tolerance is the ability to remain standing up right for long periods of time, or to avoid dizziness when moving to standing from a seated or lying position.

Condition or disease Intervention/treatment Phase
Orthostatic Intolerance Drug: Ganirelix acetate Drug: 17β-Oestradiol Drug: Progesterone Phase 2

Detailed Description:
In this study we are interested in determining the impact of female reproductive hormones (estrogen and progesterone) on orthostatic tolerance (described above) so we administer these hormones to participants. We also test participants' orthostatic tolerance in our laboratory and use this information to place subjects into groups.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Sex Hormones and Orthostatic Tolerance
Study Start Date : February 2006
Actual Primary Completion Date : December 2012
Actual Study Completion Date : May 2013

Arm Intervention/treatment
Experimental: Ganirelix acetate
Subjects were given 250 μg in 0.5ml normal saline for 16 days. (Organon, Roseland, NJ, USA)
Drug: Ganirelix acetate
Ganirelix acetate: .25 ml/day by subcutaneous injection
Other Name: Antagon

Experimental: 17β-Oestradiol, E2
The same women added 17β-Oestradiol, E2; 0.2 mg day−1 patch (Vivelle; CIBA Pharmaceuticals, Summit, NJ) for days 4-16.
Drug: 17β-Oestradiol
17 beta estradiol: 0.2 mg/day (patches)
Other Names:
  • 17 beta estradiol
  • estradiol

Experimental: Progesterone
The same women added progesterone (P4, 200 mg day−1 Prometrium, oral, Solvay Pharmaceuticals, Marietta, GA, USA) on days 13-16.
Drug: Progesterone
progesterone, 200 mg day−1 oral
Other Names:
  • P4
  • Prometrium

Primary Outcome Measures :
  1. Orthostatic Tolerance [ Time Frame: 2 months ]
    We used a measure called cumulative stress index to determine orthostatic tolerance, which is the amount of time at a level of negative pressure each subject can maintain before feeling as if she is going to pass out. This is calculated by multiplying the pressure in mm Hg by the time in min.

  2. Baroreceptor Function [ Time Frame: 2 months ]

    This is a measure of how the body responds to changes in pressure induced by changes in position such as sitting, lying standing. The pressure changes are induced by gravity. The measurement described below to assess baroreceptor function is units of change in forearm vascular resistance for a given change in lower body negative pressure. This allows us to determine how good the body is at sending signals to the periphery to respond to postural changes.

    Baroreflex sensitivity is defined as the change in interbeat interval (IBI) in milliseconds per unit change in BP. For example, when the BP rises by 10 mmHg and IBI increases by 100 ms, BRS would be 100/10 = 10 ms/mmHg.

  3. Skin Microvascular Responses [ Time Frame: 2 months ]
    Changes in blood flow in the small vessel in the skin are measured in response to sequential heat and drug stimulation. It is measured in volts, and then corrected for a maximum level and expressed as "% max." This is measured with a Laser Doppler probes, which measures volts.

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Ages Eligible for Study:   18 Years to 34 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy, English-speaking non-smoking women age 18- 34 with regular menses

Exclusion Criteria:

  • Gynecologic:

    1. current or past estrogen-dependent neoplasia,
    2. unexplained vaginal bleeding,
    3. history of uterine fibroids,
    4. current pregnancy,
    5. known or suspected breast or uterine cancer,
    6. partial or complete hysterectomy
  • Cardiac:

    1. myocardial infarction, ventricle tachycardia or fibrillation,
    2. angina,
    3. valvular disease,
    4. congestive heart failure, orthopnea, paroxysmal nocturnal dyspnea,
    5. current arrhythmias,
    6. prosthetic valves
  • Pulmonary:

    1. current cigarette smokers, or pipe or cigar smokers,
    2. chronic obstructive pulmonary disease,
    3. adult asthma,
    4. dyspnea on exertion,
    5. current bronchitis, pneumonia, or tuberculosis,
    6. lung carcinoma,
    7. pulmonary embolus, recent
  • Vascular:

    1. claudication or history of peripheral vascular disease,
    2. abdominal or thoracic aortic aneurysm, or repair of same,
    3. cerebral aneurysm, vascular malformations,
    4. hypertension, systolic or diastolic, or strong family history of hypertension
  • Gastrointestinal:

    1. GI malignancy,
    2. hepatitis, current,
    3. splenomegaly from any cause,
    4. Cholecystitis,
    5. current diverticulosis or diverticulitis, inflammatory bowel disease, ulcerative colitis, Crohn's Disease,
    6. previous gastrointestinal surgery
  • Infectious Disease: any intercurrent infection
  • Hematologic/Oncologic:

    1. receiving chemotherapy or radiation therapy,
    2. any metastatic malignancy,
    3. anemia (hematocrit < 35),
    4. thrombocytopenia or thrombocytosis,
    5. neutropenia,
    6. hematologic malignancy,
    7. bleeding dyscrasia
  • Neurologic:

    1. history of cerebral vascular accident with any neurologic sequels,
    2. uncontrolled seizures (e.g. more than 1 seizure/year),
    3. transient ischemic attacks,
    4. dementia,
    5. neurologic conditions producing dyscoordination, peripheral neuropathy, or myopathy,
    6. severe migraine headaches
  • Endocrine:

    1. diabetes mellitus,
    2. any untreated endocrinopathy
  • Renal:

    1. chronic renal disease,
    2. any history of renal disease or impairment,
    3. current urinary tract infection
  • Musculoskeletal:

    1. inflammatory arthritis history (e.g., rheumatoid, psoriatic, Reiters),
    2. any history of pathologic fractures, including vertebral compression fractures
  • Pharmacologic:

    1. any illegal drug use,
    2. alcohol use greater than an average of 4 oz/day over 30 days,
    3. coumadin or heparin use,
    4. current systemic antifungal use

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): NCT01153581

United States, Connecticut
John B. Pierce Laboratory
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Nina Stachenfeld, PhD Yale University

Responsible Party: Yale University Identifier: NCT01153581     History of Changes
Other Study ID Numbers: 0512000875a
2R01HL071159-04 ( U.S. NIH Grant/Contract )
First Posted: June 30, 2010    Key Record Dates
Results First Posted: January 30, 2017
Last Update Posted: December 13, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Our data are stored in locked files, and our spreadsheets and raw data are available should they be requested

Additional relevant MeSH terms:
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
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
Hormone Antagonists