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Changes in Plasma Lipoprotein and Apolipoprotein Composition in Relation to Oral Versus Percutaneous Administration of Estrogen Alone or in Cyclic Association with Utrogestan in Menopausal Women

Lipid Research Unit, Laval University Hospital Sainte-Foy, Quebec, Canada G1V 4G2
Molecular Endocrinology Unit, Laval University Hospital Sainte-Foy, Quebec, Canada G1V 4G2
Department of Gynecology, Laval University Hospital Sainte-Foy, Quebec, Canada G1V 4G2
Department of Reproductive Endocrinology Hôpital Necker Paris, France

Address correspondence and requests for reprints to: Sital Moorjani, Ph.D., Centre Hospitalier de l’Université Laval (S-102), 2705 Boulevard Laurier, Sainte-Foy, Québec, Canada G1V 4G2.

Sixty-three postmenopausal women were assigned to four treatment groups and received either Premarin or percutaneous 17β-estradiol (Oestrogel) alone or in combination with micronized progesterone (Utrogentan). The oral administration of estrogen alone to hysterectomized women resulted in: 1) a significant increase in triglyceride levels in plasma and all major lipoprotein fractions, 2) a significant increase in very low density lipoprotein cholesterol, 3) a significant decrease in low density lipoprotein (LDL) cholesterol but not LDL apo B concentration, 4) a significant increase in all the lipid components of high density lipoprotein (HDL) as well as apo AI, 5) and a significant increase in HDL₂ cholesterol. In contrast, percutaneous administration of estrogen to hysterectomized women only increased HDL₂ cholesterol and the triglyceride and cholesterol content of the whole HDL fraction. These results suggest that the route of estrogen administration is important in determining effects on lipoprotein metabolism.

The same two estrogens were given to women with natural menopause, along with utrogestan, a micronized progesterone. The simultaneous administration of Utrogestan reversed the HDL cholesterol elevating effect of percutaneous estrogen alone, but it had no effect on other plasma lipoproteins. On the other hand, utrogestan in combination with oral estrogen had several potential beneficial effects on plasma lipoproteins. This combination did not negate the effects of oral estrogen alone on HDL, rather it further increased the concentrations of HDL cholesterol and apo AI. It also did not negate the LDL cholesterol lowering effect of oral estrogen alone. Furthermore, utrogestan lowered the magnitude of hypertriglyceridemia induced by oral estrogen alone. These results suggest that Utrogestan has lower potency of androgenic action and has desirable effects when given in cyclic combination with estrogen.

Received July 26, 1990.

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