Biologic effects of 17 alpha-dihydroequilin sulfate.
OBJECTIVE
To determine the independent biologic effects of 17 alpha-dihydroequilin sulfate.


METHODS
Prospective randomized study.


METHODS
University of Southern California Medical Center.


METHODS
Twenty-one postmenopausal women, mean age 50 +/- 2 (+/-SEM) years, and mean body mass index 27 +/- 2.


METHODS
Women were randomized to receive daily oral doses of either 1.25 mg of estrone sulfate (E1S), 0.2 mg of 17 alpha-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90 days of treatment.


RESULTS
After 30 and 90 days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7% +/- 6.0% and 61.3% +/- 13.0%, whereas 17 alpha-dihydroequilin sulfate reduced SHBG levels, 20.8% +/- 68% and 12.4% +/- 7.5%, respectively. Nevertheless, the combination of E1S and 17 alpha-dihydroequilin sulfate significantly increased SHBG levels, 103% +/- 27.9% and 98.2% +/- 19.1%, compared with baseline at 30 and 90 days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90 days of treatment, CBG levels significantly increased 30.9% +/- 5.5% with E1S, decreased by 7.2% +/- 5.0% with 17 alpha-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5% +/- 2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90 days compared with baseline, 96.5% +/- 39% and 91.5% +/- 22.6%, and with the combination increased 66.4% +/- 13.3% and 79.2% +/- 24.4%, respectively. Fewer changes were evident with 17 alpha-dihydroequilin sulfate alone, decreasing 4.4% +/- 22% and 2.6% +/- 21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone.


CONCLUSIONS
17 alpha-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption.
Wilcox
J G
JG
University of Southern California School of Medicine, Los Angeles, USA.
Stanczyk
F Z
FZ
Morris
R S
RS
Gentzschein
E
E
Lobo
R A
RA
D002118:Calcium / Q000652:urine; D008076:Cholesterol, HDL / Q000097:blood; D003094:Collagen / Q000652:urine; D003404:Creatinine / Q000652:urine; D004857:Equilin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004970:Estrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D014156:Transcortin / Q000378:metabolism
D008076:Cholesterol, HDL; D012738:Sex Hormone-Binding Globulin; D004857:Equilin; D004970:Estrone; C014482:dihydroequilin; D005640:Follicle Stimulating Hormone; D003094:Collagen; D014156:Transcortin; D003404:Creatinine; C017296:estrone sulfate; D002118:Calcium