Sex Hormones and Orthostatic Tolerance

Study Description

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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 Design

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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

Arms and Interventions

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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

Outcome Measures

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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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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)

Investigators

Principal Investigator:	Nina Stachenfeld, PhD	Yale University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Yale University
ClinicalTrials.gov Identifier:	NCT01153581 History of Changes
Other Study ID Numbers:	0512000875a; 2R01HL071159-04 ( U.S. NIH Grant/Contract )
First Posted:	June 30, 2010
Results First Posted:	January 30, 2017
Last Update Posted:	January 30, 2017
Last Verified:	December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
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; Hormones; Estradiol; Polyestradiol phosphate; Progesterone; Ganirelix	Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Estradiol valerate; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Estrogens; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Hormone Antagonists