Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia.
OBJECTIVE
To determine the prevalence and risk factors of hypogonadotropic hypogonadism in transfusion-dependent patients with thalassemia.


METHODS
The authors examined 29 patients with thalassemia major aged 15 years or older. Luteinizing hormone-releasing hormone tests were performed and beta-thalassemia mutations were analyzed by direct sequencing.


RESULTS
The prevalence of hypogonadotropic hypogonadism was 72%. Failure of puberty was observed in 5 of 11 (45%) boys and 7 of 18 (39%) girls. Arrested puberty was noted in two boys (18%) and five girls (28%). Ten girls (56%) did not menstruate, two (11%) had regular menstrual cycles, one (6%) had irregular menstrual cycles, and five (28%) developed secondary amenorrhea. Twenty-one and eight patients had the beta 0/beta 0 and beta 0/beta+ hematologic phenotypes, respectively. beta 0-thalassemia mutation alleles involved IVS II-654 (C-T), codons 41/42 (-TCTT), codons 27/28 (+C), and codons 17 (A-T). beta+-thalassemia mutations alleles were -28 (A-G) and HbE (codons 26(GAG-AAG)). Hematologic phenotype (odds ratio, 28.50; P = 0.002) was the only risk factor identified in the logistic regression analysis.


CONCLUSIONS
In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patient's iron-overload status.
Chern
Jimmy P S
JP
Department of Internal Medicine, Tao-Yuan General Hospital, Taiwan.
Lin
Kai-Hsin
KH
Tsai
Wen-Yu
WY
Wang
Shih-Chung
SC
Lu
Meng-Yao
MY
Lin
Dong-Tsamn
DT
Lin
Kuo-Sin
KS
Lo
Su Heuy
SH
D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion; D005260:Female; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications* / Q000235:genetics
D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone