Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial.
BACKGROUND
Increasingly strong links are being recognized between diabetes, insulin resistance and liver fat accumulation [e.g. nonalcoholic fatty liver disease (NAFLD)]. Recent data indicating that hormone replacement therapy (HRT) may lessen diabetes risk is intriguing but explanatory mechanisms are unclear.


OBJECTIVE
Post hoc investigation of the possibility that HRT may favourably influence liver enzyme levels commonly elevated in patients with diabetes. We examined liver function test data from a 6-month trial of a low-dose continuous combined HRT (1 mg 17beta oestradiol and 0.5 mg norethisterone acetate).


METHODS
Double-blind, randomized placebo-controlled.


METHODS
Fifty women with type 2 diabetes.


METHODS
Liver enzyme levels (AST, ALT, gamma-glutamylytransferase [GGT], and alkaline phosphatase [ALP]).


RESULTS
Forty-five women completed the study with 19/22 in the active group demonstrating compliance as measured by sex hormone changes. Relative to placebo recipients (n = 23), women randomized and compliant to HRT demonstrated significant reductions in ALT [-14 (-23 to -6) U/l, P = 0.002], AST [-9.2 (-14 to -5) U/l, P < 0.001] and ALP [-60.8 (-80 to -42) U/l, P < 0.001]. Circulating concentrations in GGT were also significantly reduced (P = 0.035). All changes were significant using an intention-to-treat analysis.


CONCLUSIONS
HRT containing low-dose oestradiol and norethisterone reduces serum concentrations of liver function enzymes, potentially due to a lowering of liver fat accumulation. Better understanding of mechanisms by which this HRT improves liver function tests could help the design of new therapies to treat individuals with NAFLD.
McKenzie
Joyce
J
Department of Medicine, Glasgow Royal Infirmary University NHS Trust, Glasgow, Scotland, UK.
Fisher
B Miles
BM
Jaap
Alan J
AJ
Stanley
Adrian
A
Paterson
Kenneth
K
Sattar
Naveed
N
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D004311:Double-Blind Method; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000201:enzymology*; D008111:Liver Function Tests; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D009640:Norethindrone / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000097:blood
D004958:Estradiol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D009640:Norethindrone