Wake Forest University

American Home Products Corporation

Other

Scott A Washburn

Steven Jay Adelman

Thomas B Clarkson

J Koudy Williams

J Mark Cline

Michael R Adams

Janice D Wagner

Thomas C Register

Michael S Dey

Carol Ann Shively

The present invention relates to a method of using 17&agr;-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17&agr;-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17&agr;-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p<0.05) and ovariectomized females (p<0.08). 17&agr;-dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p<0.05) and lowered fasting insulin concentrations (p<0.05) without changing fasting plasma glucose concentrations in males. 17&agr;-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17&agr;-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17&agr;-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

Effects of 17 &agr;-dihydroequilenin on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals

The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17.alpha.-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17.alpha.-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p&lt;0.05) and ovariectomized females (p&lt;0.08). 17.alpha.-dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p&lt;0.05) and lowered fasting insulin concentrations (p&lt;0.05) without changing fasting plasma glucose concentrations in males. 17.alpha.-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17.alpha.-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17.alpha.-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

Effects of 17.alpha.-dihydroequilenin on plasma lipid and lipoprotein,

The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17.alpha.-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17.alpha.-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p&lt;0.05) and ovariectomized females (p&lt;0.08). 17.alpha.-dihydroequilenin treatment increased plasma apolipoprotein A-l concentrations (p&lt;0.05) and lowered fasting insulin concentrations (p&lt;0.05) without changing fasting plasma glucose concentrations in males. 17.alpha.-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17.alpha.-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17.alpha.-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

A method of using a steroidal compound, 17.alpha.-dihydroequilenin, to prevent and treat neurodegeneration and cognitive dysfunction in estrogen deficient females and to reduce the risk of Alzheimer's related dementia and other senile dementia related conditions in both males and females. The method comprises administering 17.alpha.-dihydroequilenin in a therapeutically effective amount to a mammal in need of increased cognitive function or to a mammal susceptible to estrogen deficiency-related neurodegeneration or to senile dementia of the Alzheimer's type.

Method of preventing neurodegeneration and cognitive dysfunction using

This invention provides a method of lowering cholesterol and blood lipid levels, preventing hypercholesterolemia, hyperlipidemia, cardiovascular disease, atherosclerosis, and peripheral vascular disease comprising administering an effective amount of 17.alpha.-dihydroequilenin or a mammalian metabolic conjugate thereof to a mammal in need thereof.

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Winston-Salem, NC, United States of America

Scott A Washburn