Sex Hormones and Orthostatic Tolerance

Yale University

Status and phase: Completed; Phase 2

Conditions: Orthostatic Intolerance

Treatments: Drug: 17β-Oestradiol; Drug: Progesterone; Drug: Ganirelix acetate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01153581

2R01HL071159-04 (U.S. NIH Grant/Contract)

0512000875a

Details and patient eligibility

About

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.

Full 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.

Enrollment: 109 patients

Sex: Female

Ages: 18 to 34 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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109 participants in 3 patient groups

Ganirelix acetate

Experimental group

Description:

Subjects were given 250 μg in 0.5ml normal saline for 16 days. (Organon, Roseland, NJ, USA)

Treatment:

Drug: Ganirelix acetate

17β-Oestradiol, E2

Experimental group

Description:

The same women added 17β-Oestradiol, E2; 0.2 mg day-1 patch (Vivelle; CIBA Pharmaceuticals, Summit, NJ) for days 4-16.

Treatment:

Drug: 17β-Oestradiol

Progesterone

Experimental group

Description:

The same women added progesterone (P4, 200 mg day-1 Prometrium, oral, Solvay Pharmaceuticals, Marietta, GA, USA) on days 13-16.

Treatment:

Drug: Progesterone