Sex Hormones and Orthostatic Tolerance

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.

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.

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

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

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.

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.

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.

Inclusion Criteria: Healthy, English-speaking non-smoking women age 18- 34 with regular menses Exclusion Criteria: Gynecologic: current or past estrogen-dependent neoplasia, unexplained vaginal bleeding, history of uterine fibroids, current pregnancy, known or suspected breast or uterine cancer, partial or complete hysterectomy Cardiac: myocardial infarction, ventricle tachycardia or fibrillation, angina, valvular disease, congestive heart failure, orthopnea, paroxysmal nocturnal dyspnea, current arrhythmias, prosthetic valves Pulmonary: current cigarette smokers, or pipe or cigar smokers, chronic obstructive pulmonary disease, adult asthma, dyspnea on exertion, current bronchitis, pneumonia, or tuberculosis, lung carcinoma, pulmonary embolus, recent Vascular: claudication or history of peripheral vascular disease, abdominal or thoracic aortic aneurysm, or repair of same, cerebral aneurysm, vascular malformations, hypertension, systolic or diastolic, or strong family history of hypertension Gastrointestinal: GI malignancy, hepatitis, current, splenomegaly from any cause, Cholecystitis, current diverticulosis or diverticulitis, inflammatory bowel disease, ulcerative colitis, Crohn's Disease, previous gastrointestinal surgery Infectious Disease: any intercurrent infection Hematologic/Oncologic: receiving chemotherapy or radiation therapy, any metastatic malignancy, anemia (hematocrit < 35), thrombocytopenia or thrombocytosis, neutropenia, hematologic malignancy, bleeding dyscrasia Neurologic: history of cerebral vascular accident with any neurologic sequels, uncontrolled seizures (e.g. more than 1 seizure/year), transient ischemic attacks, dementia, neurologic conditions producing dyscoordination, peripheral neuropathy, or myopathy, severe migraine headaches Endocrine: diabetes mellitus, any untreated endocrinopathy Renal: chronic renal disease, any history of renal disease or impairment, current urinary tract infection Musculoskeletal: inflammatory arthritis history (e.g., rheumatoid, psoriatic, Reiters), any history of pathologic fractures, including vertebral compression fractures Pharmacologic: any illegal drug use, alcohol use greater than an average of 4 oz/day over 30 days, coumadin or heparin use, current systemic antifungal use

Our data are stored in locked files, and our spreadsheets and raw data are available should they be requested