Oral Contraceptives and Triglyceride Transport: Acquired Heparin Resistance as the Mechanism for Impaired Post-Heparin Lipolytic Activity

Paired studies of oral fat tolerance in six women before and during therapy with ethinyl estradiol (50 μg)-medroxyprogesterone acetate (10 mg) failed to demonstrate impairment in triglyceride disposal despite depression of postheparin lipolytic activity (PHLA) during treatment. This decline in PHLA, measured against an artificial triglyceride emulsion, was also seen in experiments utilizing natural triglyceride-rich lipoprotein and artificial phospholipid and monoglyceride substrates. It did not appear to be caused by estrogen per se, a circulating inhibitor of the lipolytic reaction induced by the oral contraceptive, or the depletion during therapy of a plasma activator of lipoprotein lipase. However, an alternative explanation for the decrease in PHLA during therapy was provided by the demonstration of acquired competitive inhibition of the release of triglyceride lipase activity by heparin: ascending doses of heparin administered to three women during therapy produced a progressive increase in levels of PHLA relative to those recorded at comparable doses of heparin before therapy. Parallel studies of partial thromboplastin time in two of the women revealed no inhibition of the anticoagulant properties of heparin during oral contraceptive treatment. Thus oral contraceptives may induce a form of resistance to heparin which leads to an isolated decline in PHLA but no major impairment in plasma triglyceride removal.