The effect on cartilage of different forms of application of postmenopausal estrogen therapy: comparison of oral and transdermal therapy

The effect on urine C-telopeptides of type II collagen (uCTX-II) of oral and transdermal estradiol treatment was compared using samples from two randomized, double-blind, placebo-controlled trials. A total of 171 healthy, Danish postmenopausal women, 45–65 years of age completed the 2-year study periods. The uCTX-II marker assessed cartilage degradation, and this response was compared with the effect on urine C-telopeptides of type I collagen (uCTX-I), considered a specific marker of bone resorption. Doses in the oral estradiol treatment groups (continuous combined therapy) were 1 mg 17-β-estradiol + 1 mg drosperinone or 1 mg 17-β-estradiol + 2 mg drosperinone or 1 mg 17-β-estradiol + 3 mg drosperinone or placebo. Doses in the transdermal estradiol treatment groups (continuous combined therapy) were 45 μg 17-β-estradiol + 30 levonorgestrel or 45 μg 17-β-estradiol + 40 μg levonorgestrel or placebo. The effect of oral and transdermal estradiol therapy on cartilage degradation was reflected as a decrease of 19–30% in uCTX-II (P = 0.02 and P = 0.003 vs. placebo) after 1 year of treatment. uCTX-I decreased 70% (P< 0.0001 vs. placebo) reflecting a pronounced effect on bone resorption that was consistent with a 2-year increase in spine and hip BMD of 7–8% and 4–6%, respectively. The results indicate that different regimens of postmenopausal HRT both have an effect on cartilage and bone thus protecting against osteoporosis and osteoarthritis (OA). However, long-term clinical trials are needed to further investigate this issue.