Optimizing estradiol serum levels for optimal skeletal and cardiovascular health during transdermal menopausal hormone therapy.

OBJECTIVE

Identify estradiol serum levels associated with vasomotor symptom relief and assess their effects on osteoporosis and cardiovascular prevention using an estradiol hydro-alcoholic gel formulation.

METHODS

Estradiol serum concentrations from two pivotal efficacy and safety trials with transdermal (TdL) estradiol gel were compared to those reported in the KEEPS and ELITE trials regarding skeletal and cardiovascular disease prevention.

RESULTS

A total of 567 patients were included in the intent-to-treat efficacy population. In the first study (n = 216), the daily 2.5 g dose of TdL E2 gel reduced the moderate to severe hot flash frequency from a baseline of 10.5 to 2.0 ± 4.2 (-82%). In the second study (n = 351), a daily 2.5 g dose of TdL E2 gel reduced moderate-to-severe hot flushes from 11.8 to 2.3 ± 3.8, similar to the TdL E2 patch, which decreased them from 10.9 to 1.3 ± 3.2. The serum concentrations of E2 from patients receiving the TdL E2 gel once daily were within the normal range of young premenopausal women in the mid-follicular phase, with a proportional dose‒response effect.

CONCLUSIONS

These results on vasomotor symptoms are consistent with the optimal cardiovascular and skeletal benefits observed in KEEPS (TdL estradiol) and ELITE (oral estradiol), corresponding to serum levels of approximately 60 pg/mL.