Sex Hormones and Orthostatic Tolerance - Full Text View

Purpose

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	Intervention	Phase
Orthostatic Intolerance	Drug: Ganirelix acetate Drug: 17β-Oestradiol Drug: Progesterone	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Sex Hormones and Orthostatic Tolerance

Resource links provided by NLM:

MedlinePlus related topics: Hormones

Drug Information available for: Estradiol Progesterone Estradiol cypionate Estradiol valerate Estradiol acetate Estradiol hemihydrate Ganirelix Ganirelix acetate

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

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.
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.
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.


Enrollment:	109
Study Start Date:	February 2006
Study Completion Date:	May 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


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

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: NCT01153581

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


Responsible Party:	Yale University
ClinicalTrials.gov Identifier:	NCT01153581 History of Changes
Other Study ID Numbers:	0512000875a 2R01HL071159-04 ( US NIH Grant/Contract Award Number )
Study First Received:	June 28, 2010
Results First Received:	July 8, 2014
Last Updated:	December 1, 2016
Individual Participant Data
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 Estradiol 3-benzoate	Estradiol 17 beta-cypionate Estradiol valerate Ganirelix Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Estrogens Contraceptive Agents Reproductive Control Agents Contraceptive Agents, Female Hormone Antagonists Progestins

ClinicalTrials.gov processed this record on June 23, 2017