Endocrine Abstracts

JOINT883

Background: Hormone therapy (HT) containing estrogen is an effective treatment for the prevention of bone loss in low-estrogenic states. Apart from the inhibiting effect of HT on bone resorption, studies have demonstrated that 17-β-estradiol also increases bone formation in the first 4 weeks of treatment. We hypothesized that this initial increase in bone formation is driven by a rise in serum 17-β-estradiol concentrations, as seen during the menstrual cycle of premenopausal women. Therefore, we investigated whether restoring a monthly cycle in 17-β-estradiol levels is beneficial for bone formation.

Methods: We performed an open-label randomized controlled trial in healthy postmenopausal women aged 45-60 years (without history of hysterectomy). Participants were randomized to transdermal cyclic (4-week cycle consisting of 2 weeks 25 mg/24h, and 2 weeks 50 mg/24h), continuous low-dose (25 mg/24h), or continuous standard-dose 17-β-estradiol (50 mg/24h) for 16 weeks. All participants also received continuous oral micronized progesterone 100 mg once daily. Endpoints of the study were the interaction between treatment and time on serum P1NP concentrations (bone formation) and on serum CTX concentrations (bone resorption). We measured P1NP and CTX every two weeks.

Results: The 48 participants had a mean age of 53.5 (SD 3.3) and had their final menstrual period at 50.5 (SD 3.8) years. P1NP increased in all groups between baseline and week 4, followed by a decrease between week 4 and week 16. The median decrease in P1NP levels (bone formation) was lower in the cyclic (-12.6 μg/l (IQR -20.4 – -0.7), P = 0.03) and low-dose group (-12.0 μg/l (IQR -18.4 – 1.8), P < 0.01) compared to the standard-dose group (-15.2 μg/l (IQR -29.1 – -8.7)). CTX decreased between baseline and week 16 in all groups. The median decrease in CTX values from baseline until week 16 was similar in the cyclic group (-143 ng/l (IQR -221.3 – -71.2), P = 0.45) compared to the standard-dose group (-176.9 ng/l (IQR -218.9 – -123.2)). However, CTX values (bone resorption) remained higher in the low-dose group (-112.2 ng/l (IQR -192.6 – -67.9), P = 0.04) compared to the standard-dose group. After 16 weeks of treatment, the mean changes in P1NP and CTX no longer differed between the groups.

Conclusion: Cyclic 17-β-estradiol administration resulted in higher bone formation over time compared to continuous standard-dose administration, while bone resorption did not differ between the cyclic and continuous standard-dose group. Thus, cyclic estradiol may improve bone health in the short-term.