Endothelial dysfunction, insulin resistance and inflammation in congenital hypogonadism, and the effect of testosterone replacement.
Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56 ± 2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.
Department of Endocrinology and Metabolism, Gulhane School of Medicine, 06018 Etlik Ankara, TURKEY.
Alper
A
Sonmez
Cem
C
Haymana
Aydogan
A
Aydogdu
Serkan
S
Tapan
Yalcin
Y
Basaran
Coskun
C
Meric
Kamil
K
Baskoy
Mustafa
M
Dinc
Mahmut
M
Yazici
Abdullah
A
Taslipinar
Cem
C
Barcin
Mahmut Ilker
MI
Yilmaz
Erol
E
Bolu
Omer
O
Azal
D000328:Adult; D001786:Blood Glucose; D015992:Body Mass Index; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000151:congenital / Q000188:drug therapy / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D012307:Risk Factors; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D013739:Testosterone