Individualized Estrogen Dosing in Women Undergoing Premenopausal Bilateral Oophorectomy

Abstract

Early menopause (prior to age 46 years) due to bilateral oophorectomy results in an abrupt loss of estrogen and other ovarian hormones and an increased risk of cardiovascular disease (CVD). Administration of estrogen partially mitigates this increased CVD risk; however, optimal dosing strategies for lowering CVD risk have not been studied. Current standard care is to use a dose of estrogen higher than that used for vasomotor symptom treatment in women after natural menopause in order to approximate the physiologic estradiol levels in premenopausal women (standard care); however, estradiol levels are not generally measured. An individualized approach that titrates estradiol levels to premenopausal hormone levels (individualized dosing) may be better for CVD risk mitigation in this younger population.The goal of this study was to compare the effect of estradiol dosing strategies (standard care vs. individualized dosing) on subclinical predictors of CVD in women with early menopause due to bilateral oophorectomy.We studied a total of 18 women at baseline and 6 months following surgical and medical intervention: 6 women underwent bilateral oophorectomy and were treated with standard care (age 41±2 years), 7 women underwent bilateral oophorectomy followed by estrogen therapy dosage based on individualized dosing (39±2 years), and 5 women served as time controls (did not undergo bilateral oophorectomy and were studied during the early‐follicular phase of the menstrual cycle at both visits; 34±3 years). At each time point, we assessed parameters of subclinical CVD including resting aortic blood pressure, carotid‐femoral pulse wave velocity, and blood pressure changes during a handgrip test and a cold pressor test.At baseline, serum estradiol levels were similar amongst groups (p>0.05). After 6 months, women who received individualized dosing of estrogen therapy had higher serum estradiol levels (179±23 pg/ml) than women who received standard care (53±25 pg/ml, p=0.01) and women in the control group (78±27 pg/ml, p=0.03). Systolic and diastolic aortic blood pressures did not change between baseline and 6 months, nor did they differ amongst groups at any time point (p>0.05 for all). There were no group or time differences in the change in mean blood pressure during the handgrip exercise or cold pressor test across 6 months (p>0.05 for all).Over a 6‐month follow‐up, despite differences in serum estradiol levels following two different estradiol dosing strategies after bilateral oophorectomy, there were no group differences or detrimental changes in subclinical CVD parameters across time. It is yet to be seen if differences in these parameters will be apparent following a longer duration after bilateral oophorectomy.