Effect of testosterone on hepcidin, ferroportin, ferritin and iron binding capacity in patients with hypogonadotropic hypogonadism and type 2 diabetes.
BACKGROUND
As the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia and the administration of testosterone restores haematocrit to normal, we investigated the potential underlying mechanisms.


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


METHODS
We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. Forty-four men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. Twenty men in testosterone group and 14 men in placebo group completed the study.


RESULTS
Haematocrit levels were lower in men with HH (41·1 ± 3·9% vs 43·8 ± 3·4%, P = 0·001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin or iron, or in the expression of ferroportin or TR in MNC among HH and eugonadal men. Haematocrit increased to 45·3 ± 4·5%, hepcidin decreased by 28 ± 7% and erythropoietin increased by 21 ± 7% after testosterone therapy (P < 0·05). There was no significant change in ferritin concentrations, but transferrin concentration increased while transferrin saturation and iron concentrations decreased (P < 0·05). Ferroportin and TR mRNA expression in MNC increased by 70 ± 13% and 43 ± 10%, respectively (P < 0·01), after testosterone therapy.


CONCLUSIONS
The increase in haematocrit following testosterone therapy is associated with an increase in erythropoietin, the suppression of hepcidin, and an increase in the expression of ferroportin and TR.
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.|Division of Endocrinology, Diabetes and Metabolism, Texas Tech University Health Sciences Center, Odessa, TX, USA.
Sandeep
S
Dhindsa
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Husam
H
Ghanim
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Manav
M
Batra
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Nitesh D
ND
Kuhadiya
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Sanaa
S
Abuaysheh
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Kelly
K
Green
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Antoine
A
Makdissi
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Ajay
A
Chaudhuri
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA. pdandona@KaleidaHealth.org.
Paresh
P
Dandona
D000328:Adult; D000368:Aged; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000097:blood; D005293:Ferritins / Q000097:blood / Q000187:drug effects*; D006400:Hematocrit; D064451:Hepcidins / Q000097:blood / Q000187:drug effects*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000097:blood; D013739:Testosterone / Q000494:pharmacology*; D000098742:Ferroportin
D027682:Cation Transport Proteins; C554270:EPO protein, human; D064451:Hepcidins; D011990:Receptors, Transferrin; D000098742:Ferroportin; D004921:Erythropoietin; D013739:Testosterone; D005293:Ferritins; D007501:Iron