And It's About Time There Was Some Support For Cushing's!
Trial Information
Summary: Effects of luteinizing hormone on androgen secretion in polycystic ovary syndrome. PCOS is a very common disorder, occurring in 5-7% of women of childbearing age. This disorder results in irregular periods, infertility, and excess hair growth. Even though PCOS is very common, the cause is not known. As a result, our present treatments are not always effective. We currently wish to study whether luteinizing hormone (LH) drives over-production of testosterone in women with PCOS, who typically have elevated blood levels of both LH and testosterone.
In normal women, the ovary produces small amounts of testosterone (an androgen, or "male hormone"). This testosterone production is driven by a hormone called LH, which is produced and secreted by the pituitary (the pituitary is a small gland located beneath the brain). In the polycystic ovary syndrome, the ovaries produce too much testosterone. Why this happens is not entirely clear. Recent research suggests that the ovaries over-respond to LH signals by making too much testosterone. Why the ovaries might over-respond to LH is also unknown, but it may involve long-term exposure to high levels of LH (which commonly occurs in patients with PCOS), or exposure to high levels of insulin (elevated insulin levels are also commonly found in patients with PCOS). Our study was designed to see exactly how much testosterone ovaries will produce in response to specific LH doses in normal women and women with PCOS. This will help tell us whether or not ovaries in patients with PCOS really do secrete excess testosterone in response to LH. We also will investigate whether or not using certain medications can reverse this likely abnormality in PCOS.
This study involves two GCRC admissions for those with PCOS. One admission will be performed before and one after treatment with one of four medications for 4-6 weeks. These medications include metformin, rosiglitazone, leuprolide, or flutamide. Each PCOS subject will take only one of these medications. Metformin and rosiglitazone are medicines used to reduce insulin requirements in the treatment of diabetes (and recently PCOS) and are taken orally. Metformin and rosiglitazone both decrease insulin levels. Leuprolide is a medicine used to decrease LH secretion from the pituitary and is given for certain gynecologic disorders such as endometriosis. It is given as an injection every 3 weeks (those in this study will receive 2 such injections). Flutamide is a medicine that blocks the effects of "male hormones" (androgens). It also is sometimes used for PCOS patients in clinical practice.
For each admission, you will report to the General Clinical Research Center (GCRC) at the University of Virginia in the evening. At 8:00 p.m., a catheter will be placed in a forearm vein. This will be used to administer hormone infusions during the study. At 10:00 p.m., you will be given a dose of a medication called ganirelix under the skin. Ganirelix is what is called a GnRH antagonist. This medicine temporarily decreases LH secretion from your pituitary. At midnight, you will take a pill of dexamethasone, which is a medication similar to a hormone (called cortisol) that your body normally makes. Dexamethasone will temporarily keep your adrenal glands from secreting any androgens (or "male hormones").
At 7:00 a.m., a second catheter will be placed in an arm vein. This catheter is for blood sampling. At 8:00 a.m., we will begin to take blood samples for LH, testosterone, and some other hormones. These samples will be drawn every 10 minutes for the following 22 hours. At 10:00 a.m. you will begin to receive 3 different doses of human LH hormone and one dose of saline (or salt water). You will receive one of these infusions every 4 hours (that is, at 10:00 a.m., at 2:00 p.m., at 6:00 p.m., and at 10:00 p.m.). These infusions will be given in random order (except that the highest LH dose will be given last). At 2:00 a.m. (the second night), a single dose of GnRH (which is a normal hormone produced in the brain) will be given. The frequent blood sampling will stop at 6:00 a.m., and you will be discharged from the GCRC that morning after a final blood draw at 8:00 am. In all, you will stay at the GCRC for two nights and the intervening day.
We are also looking for normal control volunteers to take part in this study. They will have only one overnight admission and will not take any medication prior to their admission. For your time in completing the study, you will be compensated $300 if you have PCOS and $225 if you are a normal control.
Patient Inclusion/Exclusion Criteria: To be included in this study as a PCOS subject, you must:
Melissa Gingrich, Ph.D., Research Assistant
University of Virginia School of Medicine Center For Research in Reproduction Box 800391
Health Sciences Center
Charlottesville, VA 22908-0391
Telephone: 804-243-6911
Fax: 804-982-0701
Email: pcos@virginia.edu
