Hk. Genant et al., LOW-DOSE ESTERIFIED ESTROGEN THERAPY - EFFECTS ON BONE, PLASMA ESTRADIOL CONCENTRATIONS, ENDOMETRIUM, AND LIPID-LEVELS, Archives of internal medicine, 157(22), 1997, pp. 2609-2615
Background: Prospective studies have shown that doses equivalent to co
njugated equine estrogens of 0.625 mg/d or higher are needed to produc
e a significant increase in bone mineral density of the lumbar spine.
Objectives: To determine the effects of unopposed esterified estrogens
on bone mineral density, lipid levels, and endometrial tissue structu
re, and to relate these effects to changes in plasma estradiol levels.
Methods: Four hundred six postmenopausal women were given calcium, 10
00 mg/d, and randomly assigned to receive continuous esterified estrog
ens (0.3, 0.625, or 1.25 mg/d) or placebo for 24 months. Bone mineral
density measurements and endometrial and laboratory assessments were c
onducted every 6 months; plasma estradiol concentrations were measured
after 12, 18, and 24 months. Results: All doses of esterified estroge
ns produced significant increases in bone mineral density of the lumba
r spine compared with baseline and with placebo at 6, 12, 18, and 24 m
onths. Mean plasma estradiol levels increased with esterified estrogen
s dose, and individual subject bone mineral density changes appeared r
elated to plasma estradiol concentrations. Clinically relevant rates o
f endometrial hyperplasia were noted only in the groups receiving 0.62
5 and 1.25 mg of esterified estrogens daily. Lipid changes were dose r
elated and apparent in all groups. Conclusions: Esterified estrogens a
t doses from 0.3 to 1.25 mg/d, administered unopposed by progestin, pr
oduce a continuum of positive changes on bone and lipids. Plasma estra
diol concentrations increased with esterified estrogens dose and were
related to positive bone mineral densities. The 0.3-mg dose resulted i
n positive bone and lipid changes without inducing endometrial hyperpl
asia.