1. A Comparison of the Effectiveness of Estrogen-Progesterone and Estrogen-Testosterone Combination Therapies in the Prevention of Osteoporosis in Postmenopausal Women There is a large body of research concerning the use of estrogen replacement therapy in the prevention of osteoporosis in postmenopausal women. The addition of either progesterone or testosterone to estrogen replacement therapy has also been examined to a lesser degree. This proposal intends to compare the effectiveness of estrogen-progesterone and estrogen- testosterone combination therapies in the prevention of postmenopausal bone loss that can lead to osteoporosis. Each subject will be given either an estrogen- progesterone combination, estrogen-testosterone combination, estrogen-placebo combination, or placebo only. Serum samples will be taken throughout the trial to measure hormone levels, and bone mineral density scans will be performed periodically to record any change in bone density. The results will be evaluated to compare which combination of hormone therapy is more effective in preventing bone loss, and subsequently, osteoporosis. The use of a second hormone in addition to estrogen could alleviate other problems related to hormone deficiency as well as providing stronger protection against osteoporosis. Stephanie Olajos Biology Department, York College of Pennsylvania Project Summary Introduction Throughout life, bone is constantly remodeling and reshaping itself: osteoclasts dissolve bone mineral and bone matrix and osteoblasts create new bone. In the case of osteoporosis, the activity of the osteoclasts outweighs that of osteoblasts. The result is a loss of bone as that which was destroyed was not recreated. Osteoporosis is a disease characterized by low bone mass and microarchitectural deterioration, both of which lead to increased bone fragility and risk of fracture. The World Health Organization specifies osteoporosis as a bone mineral density of 2.5 standard deviations below the young adult mean. Ten million Americans suffer from osteoporosis (80% of these are women) and eighteen million have osteopenia, or low bone mass, the precursor of osteoporosis. 1.5 million osteoporosis-related fractures occur annually, with the cost to U.S. healthcare between $10-15 million. Hip fractures are commonly associated with osteoporosis. Following such an injury, the one year mortality rate is 24%, while 50% of victims lose physical independence and 25% require long term care. Chronic pain and reduced mobility plague those with osteoporosis, as well as feelings of low self-esteem, depression, and social isolation. Fortunately osteoporosis is both preventable and treatable. Review of Literature Hormone replacement therapy is the cornerstone of both prevention and treatment of bone loss (Miller et al. 2001, Recker et al. 1999) Estrogen has been found to inhibit the bone- destroying activity of osteoclasts (Recker et al. 1999) Progesterone and testosterone have been shown to stimulate the bone building activity of osteoblasts (Wetzel 1999) Estrogen is used most frequently, but the addition of progesterone or testosterone provides better defense against bone loss (Recker et al. 1999, Weinstein, Bewtra, and Gallagher 1990) Hormone replacement therapy has both benefits and risks Healthy bone Osteoporosis Objectives To compare the effectiveness of progesterone and testosterone in preventing bone loss when used in combination with estrogen To evaluate the benefits and risks of combined hormone replacement therapy To determine the long-term effects of hormone replacement therapy Methods A double blind study involving 200 postmenopausal women given a calcium supplement of 1000 mg/day Hormones will be administered in the following forms and doses: Estrogen = 0.3mg tablet of conjugated equine estrogen daily Progesterone = 200 mg tablet of micrnized progesterone daily Testosterone= 150 ug transdermal patch changed weekly Divide the women into one of four treatment groups estrogen + progesterone estrogen + testosterone estrogen + placebo only The study will take place over a duration of three years An initial bone mineral density (BMD) scan should be taken at the beginning of the study, followed by subsequent BMD scans at six month intervals Expected Results Greater increase in BMD in the estrogen + placebo group over the placebo group Greater increase in BMD in the groups receiving progesterone or testosterone as opposed to those receiving estrogen alone The addition of progesterone or testosterone to HRT will have health benefits beyond increased BMD For each individual, the addition of either progesterone or testosterone will be advantageous based on her situation and personal health needs Future Studies The literature points to a need for long-term studies on the effects of hormone replacement therapy. Many studies, such as this, focus on the effectiveness and value of a certain course of HRT. While the importance of finding effective treatments cannot be denied, the potential outcomes of long-term hormone use must also be addressed. Unfortunately, barriers such as funding and patient participation have limited in depth, long-term evaluation. Literature Cited Recker, Robert R., Davies, K. Michael, Dowd, Rachel M., and Heaney, Robert P. The Effect of Low-Dose Continuous Estrogen and Progesterone Therapy with Calcium and Vitamin D on Bone in Elderly Women. 1999. Annals of Internal Medicine. 130:897-904. Weinstein, Louis, Bewtra, Chhanda, and Gallagher, Chris J. Evaluation of a continuous combined low-dose regimen of estrogen- progestin for treatment of the postmenopausal patient. 1990. American Journal of Obstetrics and Gynecology. Vol 162n6 1534- 1542 Wetzel, Wendy. Micronized Progesterone: A New Option for Women’s Health Care. 1999. The Nurse Practitioner v24 i5 p62. The BMD data for all groups will be compared to look for any increases in BMD as well as any significant difference in the values of BMD between treatment groups Acknowledgements Dr. Jeffrey Thompson, Research Mentor Methods Each woman will keep a diary of symptoms for the duration of the study to evaluate any benefits or side effects of individual hormone replacement therapy