Effects of metformin and leuprolide acetate on insulin resistance and testosterone levels in nondiabetic postmenopausal women: a randomized, placebo-controlled trial.
OBJECTIVE
To determine whether insulin sensitizers lower androgen levels and whether androgen suppression improves insulin resistance in nondiabetic postmenopausal women.


METHODS
Randomized, double-blind, placebo-controlled study.


METHODS
Clinical and Translational Research Center of a university hospital.


METHODS
Thirty-five postmenopausal women aged 50-79 years with insulin resistance and higher T levels.


METHODS
Subjects were randomized to metformin plus leuprolide acetate (LA) placebo, LA plus metformin placebo, or LA placebo plus metformin placebo in a 1:1:1 fashion during a 12-week period.


METHODS
Insulin sensitivity (M) assessed by euglycemic-hyperinsulinemic clamp and free T by equilibrium dialysis.


RESULTS
In those randomized to metformin, free T decreased by 19% compared with placebo, along with an expected improvement in M. Total T also decreased significantly, whereas sex hormone-binding globulin (SHBG) did not change. In those randomized to LA, the percent change in M was not different from placebo, despite a 48% relative decrease in free T levels.


CONCLUSIONS
These data are the first to establish a causal link between insulin resistance and T in postmenopausal women. They confirm that treatment of insulin resistance decreases T production in this population and demonstrate that pharmacologic lowering of T does not affect insulin resistance.
Division of Endocrinology, Diabetes, and Metabolism, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Shrita M
SM
Patel
Nayyar
N
Iqbal
Shailja
S
Kaul
Sarah J
SJ
Ratcliffe
Michael R
MR
Rickels
Muredach P
MP
Reilly
Theresa
T
Scattergood
Arpita
A
Basu
Carissa
C
Fuller
Anne R
AR
Cappola
D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D016729:Leuprolide / Q000494:pharmacology*; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
D005300:Fertility Agents, Female; D007004:Hypoglycemic Agents; D010919:Placebos; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin; D016729:Leuprolide