Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism.
BACKGROUND
Excessive testosterone in males or estrogens in females could explain their differences in coronary heart disease event rates. As a contraceptive testosterone is likely to be used at large scale the role of testosterone in increasing the risks of coronary heart disease needs investigation.


OBJECTIVE
To look at the role of testosterone in development of insulin resistance and other cardiovascular risk factors.


METHODS
Prospective, before-after study on ten male subjects with idiopathic hypogonadotrophic hypogonadism pre- and post-testosterone replacement therapy; outcome measures: anthropometry, lipoprotein profile and M value (whole body glucose disposal rates on standard hyperinsulinemic euglycemic clamp; at insulin infusion rate: 40 mU x (m-2)).


RESULTS
Pre-treatment serum testosterone was 0.43 (0.515) ng x mL(-1), LH was 1.29 (0.08) IU x L(-1), and FSH was 1.54 (0.08) IU x L(-1). None had glucose intolerance. After replacement testosterone levels increased to 9.4 ng x mL(-1) (p=0.0005); weight increase of 5.0 kg (p=0.140), body mass index increase of 1.2 kg x m(-2) (p=0.28), and the change in waist to hip ratio (p=0.31) were not statistically significant. M-value (mg x kg x min(-1)) did not change after testosterone therapy (5.86 [0.72] vs 5.29 [0.82], p=0.62). Insulin levels (mU x L(-1)) achieved during the clamps were 89.5 (14.2) before and 146 (32.2) after androgen therapy (p=0.127). There was no change in glucose area under curve (mg x min x dL(-1)) (14406 [502.2] vs 12557 [826.5], p=0.312). On testosterone replacement therapy total and LDL cholesterol levels (mg x dL(-1)) declined (122.5 [13.4] vs 91.6 [5.0], p=0.04; 65.9 [9.9] vs 39.4 [7.3], p=0.05); Ratio of total cholesterol to HDL ratio also decreased significantly (p=0.05). Changes of serum triglycerides (p=0.25) and HDL cholesterol (p=0.19) did not attain statistical significance.


CONCLUSIONS
Insulin sensitivity does not decrease on testosterone replacement therapy of male subjects with idiopathic hypogonadotrophic hypogonadism. Testosterone replacement was associated with decrease in other cardiovascular risk factors.
Tripathy
D
D
Department of Endocrinology, All India Institute of Medical Sciences, New Delhi.
Shah
P
P
Lakshmy
R
R
Reddy
K S
KS
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001824:Body Constitution; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D007333:Insulin Resistance; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone