Oral estrogen replacement therapy in postmenopausal women selectively raises levels and production rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate.

To characterize the apolipoprotein (apo) subfraction specificity of the increase in high density lipoprotein (HDL) levels that is induced by oral estrogen and to explore the metabolic mechanisms thereof, six healthy, postmenopausal women were studied during each of two 5-week periods of a low-fat diet with and without ethinyl estradiol 0.05 mg/d. With estrogen, HDL cholesterol levels increased 36% (mean+/-SD, 47+/-15 versus 63+/-18 mg/dL, basal versus estrogen periods, respectively; P=.004), plasma levels of apo A-I increased by 27% (147+/-24 versus 186+/-34 mg/dL; P=.003), and apo A-II levels increased 17% (39+/-5 versus 46+/-4 mg/dL; P=.0003). Apo A-I mass in particles that contained apo A-I but no apo A-II (ie, Lp A-I) increased 66% (43+/-13 versus 71+/-17 mg/dL; P=.002) while the sum of apo A-I and apo A-II mass in particles with both apo A-I and apo A-II (ie, Lp A-I/A-II) showed only a nonsignificant 14% increase (144+/-23 versus 163+/-29 mg/dL; P=.12). In radioiodinated-protein turnover studies the production rate (PR) of each species changed in proportion to the change in its plasma concentration: Lp A-I PR increased 76% (4.7+/-1.8 versus 8.2+/-2.5 mg x kg(-1) x day(-1); P=.001) while Lp A-I/A-II PR showed only a nonsignificant increase of 22% (14.1+/-1.8 versus 17.2+/-5.4 mg x kg(-1) x day(-1); P=.2). Hepatic lipase (HL) activity in postheparin plasma decreased 66% with estrogen (10.4+/-4.3 versus 3.5+/-0.8 micromol x mL(-1) x h(-1); P=.005) while lipoprotein lipase activity was unchanged (7.1+/-1.6 versus 7.6+/-1.6 micromol x mL(-1) x h(-1); P>.2). Despite the large decrease in HL activity, the fractional catabolic rate of Lp A-I did not decrease (0.241+/-0.048 versus 0.258+/-0.066 pool/d; P=.2), nor was that of Lp A-I/A-II lessened (0.221+/-0.030 versus 0.233+/-0.053 pool/d; P>.2). Thus, oral estrogen replacement therapy has a novel and potentially antiatherogenic effect: a large and selective increase in Lp A-I levels. The metabolic mechanism of the estrogen-induced increase in Lp A-I concentration appears to be the increase in its PR. Although the ability of estrogen to suppress HL activity has been confirmed, surprisingly this decrease was not accompanied by any decrease in the fractional catabolic rate of Lp A-I or Lp A-I/A-II. This suggests that HL may not play a major role in regulating HDL protein catabolism during suppression of HL by estrogen.