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Long-term effects of transdermal estradiol with and without medroxyprogesterone acetate
S C Pang1, G A Greendale, M I Cedars
1Department of Obstetrics and Gynecology, University of California, Los Angeles (UCLA) Medical Center.
Objective:
To study the long-term biological and metabolical effects of estradiol (E2) administered by transdermal therapeutic systems with and without the addition of medroxyprogesterone acetate (MPA).
Design:
Open, randomized, comparative trial.
Setting:
The reproductive endocrine unit of a tertiary care university-affiliated hospital.
Patients:
Fifty-seven postmenopausal women were given E2 transdermally, whereas 28 were randomized to take MPA by mouth. Fifteen premenopausal women were studied for comparison.
Interventions:
Estradiol, 0.1 mg, was administered by a transdermal therapeutic system for 24.5 of 28 days and was cycled for 96 weeks. Medroxyprogesterone acetate, 10 mg, was given for days 13 to 25 of each 28-day cycle (E+P group), whereas the remainder received E2 only.
Main Outcome Measures:
Serum E2, estrone (E1), luteinizing hormone, follicle-stimulating hormone, low-density, high-density, very low-density, and total cholesterol, triglycerides, blood pressure, renin substrate, plasma renin activity, and serum aldosterone levels were measured in all subjects at baseline and in the postmenopausal women every 24 weeks until the end of study.
Results:
Mean +/- SE levels of E2 rose significantly from baseline at 24 weeks to 426 and 355 pmol/L for the E only and E+P groups, respectively. Smaller increases of estrone (E1) were observed to 263 and 244 pmol/L for the same respective groups. As expected, baseline levels of both gonadotropins were elevated, fell significantly with E2 administration, but remained increased in comparison with values observed in younger women. Decreases of total and low-density lipoprotein (LDL) cholesterol were observed in both groups that reached statistical significance at 48 weeks or later with the exception of LDL cholesterol in the E only group. No significant change of high-density lipoprotein or very low-density lipoprotein cholesterol or triglycerides was observed. There were reductions of mean systolic and diastolic blood pressures in both groups that reached significance at 72 weeks. Mean baseline plasma renin substrate, plasma renin activity, and serum aldosterone levels were within the ranges observed in younger, healthy women and did not change significantly with E2 administration in either group.
Conclusion:
These data support the long-term efficacy and safety of this form of replacement therapy, particularly in combination with MPA, in women with a uterus.