Hypothalamic Suppression Decreases Bone Strength Before and After Puberty in a Rat Model

Abstract

The incidence of menstrual irregularities, both primary and secondary amenorrhea, has been reported to be as high as 60%, with the highest incidence in younger athletes, suggesting possible adverse effects on bone development. It was hypothesized that in a rat model, suppressed hypothalamic activity via a gonadotropin-releasing hormone antagonist (GnRH-a) before onset of puberty would result in a relatively larger bone strength deficit compared with suppression after puberty. Hypothalamic suppression was achieved by providing GnRH injections. Animals received injections for 25 days either before puberty (pre group) (age 23-46 days) or after puberty (post group) (age 65-90 days). Body weights and uterine weights were measured. Serum estradiol was assayed. Mechanical strength of the right femora and histomorphometry of the left femur were measured. Suppression of the hypothalamic-pituitary-gonadal axis was confirmed by significant atrophy of uterine tissue and suppressed estradiol levels. The peak moment was significantly lower in the pre and post GnRH-a groups compared with control. The percentage difference of the average peak moment and stiffness values from the respective age-matched control groups yielded a greater percentage difference in the pre group. The cortical area was less in the GnRH-a-treated groups, but no significant difference between the relative deficits between pre and post groups were found. Hypothalamic-pituitary-gonadal axis suppression before puberty resulted in a significantly larger deficit in mechanical strength compared with postpubertal animals. The time before puberty may represent a time when skeletal strength is more compromised. Women experience both primary and secondary amenorrhea; however, the treatment may need to be different for each condition.