A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).
OBJECTIVE
It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established.


METHODS
A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months.


RESULTS
Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe.


CONCLUSIONS
Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.
Department of Internal Medicine, Izzet Baysal Medical School, Abant Izzet Baysal University, TR14280-Golkoy, Bolu, Turkey. mustafa.kanat@gmail.com
M
M
Kanat
E
E
Serin
A
A
Tunckale
O
O
Yildiz
S
S
Sahin
M
M
Bolayirli
H
H
Arinc
A
A
Dirican
Y
Y
Karagoz
Y
Y
Altuntas
H
H
Celebi
A
A
Oguz
D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D000069059:Atorvastatin; D000069438:Ezetimibe; D006854:Hydrocortisone