Association of bone mineral density with vitamin D and estrogen receptor gene polymorphisms during GnRH agonist treatment.
OBJECTIVE
This study examined whether or not a decrease in bone mineral density (BMD) induced by the use of gonadotropin-releasing hormone agonist (GnRHa) during sexual maturation is affected by vitamin D receptor and/or estrogen receptor gene polymorphisms, like the phenomenon observed during the postmenopausal period.


METHODS
In 43 patients who received GnRHa therapy for 6 months to treat uterine myoma or endometriosis at our department and who were confirmed to have pituitary down-regulation, we measured bone density before and after GnRHa treatment using DXA and analyzed the bone metabolism turnover using bone metabolic markers. Polymorphisms were analyzed by RFLP using FokI and TaqI for the vitamin D receptor gene and PvuII and XbaI for the estrogen receptor gene. The then determined gene polymorphism was analyzed in relation to the percentage decreases in BMD following GnRHa treatment.


RESULTS
The patients were divided by f, t into two groups: (f, t) < 2 (Group V-I) and (f, t) > or = 2 (Group V-II). They were also divided by P, x into two groups (P, x) < 3 (Group E-I) and (P, x) > or = 3 (Group E-II). The BMD change was significantly higher in Group V-II than in Group V-I. Group E-II tended to have a higher BMD change than Group E-I, although this difference was not statistically significant.


CONCLUSIONS
Patients who often have f and t polymorphism are more likely to show BMD reduction following GnRHa therapy, like the phenomenon seen during the postmenopausal period, than patients with other gene polymorphisms. Measures to avoid BMD reduction are required when using GnRHa in such patients.
Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan. sekom512@hotmail.com
Masami
M
Seko
Hiroyuki
H
Takeuchi
Katsuyuki
K
Kinoshita
Akifumi
A
Tokita
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000235:genetics*; D016723:Bone Remodeling; D002064:Buserelin / Q000008:administration & dosage; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006239:Haplotypes; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D017274:Nafarelin / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*
D015415:Biomarkers; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide; D002064:Buserelin