A DOSE-RESPONSE RELATIONSHIP BETWEEN SEX HORMONE-INDUCED CHANGE IN HEPATIC TRIGLYCERIDE LIPASE AND HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL IN POSTMENOPAUSAL WOMEN

In previous studies, we have demonstrated a temporal relationship between the postheparin hepatic triglyceride lipase (HTGL) response to sex steroids and the high-density lipoprotein (HDL) cholesterol response. To determine if this relationship is dose-dependent, we compared the effect of three graduated doses of orally administered estradiol and norgestrel in two groups of six postmenopausal women. With estradiol administration, postheparin HTGL activity decreased from 91 ± 46 to 50 ± 29 nmol/min/mL, baseline to high dose (P < .05); HDL cholesterol increased from 54 ± 6 to 64 ± 10 mg/dL (P < .05); HDL2 cholesterol increased from 16 ± 4 to 23 ± 7 mg/dL (P < .05); and HDL3 cholesterol concentration did not change. With norgestrel administration, HTGL activity increased from 79 ± 19 to 109 ± 24 nmol/min/mL (P < .05); HDL cholesterol decreased from 64 ± 17 to 43 ± 7 mg/dL (P < .05); HDL2 cholesterol decreased from 21 ± 17 to 6 ± 5 mg/dL (P < .05); and HDL3 cholesterol concentration decreased from 43 ± 8 to 38 ± 8 mg/dL (P < .05). The HTGL activity response was inversely correlated with estrogen dose (rs = -.733, P = .0001) and directly correlated with progestin dose (rs = .895, P = .0001). The HDL cholesterol response was directly correlated with estrogen dose (HDL: rs = .741, P = .001; HDL2: rs = .586, P = 0.003) and inversely correlated with progestin dose (HDL: rs = -.933, P = .0001; HDL2: rs = -.866, P = .0001; HDL3: rs = -.576, P = .003). The HDL cholesterol response was inversely correlated with the HTGL response for both sex steroids. This demonstration of a dose-response relationship between orally administered sex steroids and the HTGL and HDL responses adds strong support to the hypothesis that the sex steroid-induced change in HTGL activity may cause the observed change in HDL cholesterol concentration. © 1991.