Administration of Increasing Doses of Gonadotropin Releasing Hormone in Men with Spinal Cord Injury to Investigate Dysfunction of the Hypothalamic-Pituitary-Gonadal Axis

Spinal Cord, 2018 · DOI: 10.1038/s41393-017-0002-x · Published: March 1, 2018

Simple Explanation

This study investigates the hypothalamic-pituitary-gonadal axis in men with spinal cord injury (SCI) by administering different doses of gonadotropin-releasing hormone (GnRH). The goal was to determine if lower doses of GnRH could better identify dysfunction in this hormonal system compared to the standard dose. The study compared the gonadotropin responses (LH and FSH) to varying GnRH doses in hypogonadal (HG) and eugonadal (EG) men with SCI and able-bodied (AB) men. This comparison aimed to uncover subtle central dysregulation in individuals with SCI. The findings suggest a potential hypothalamic-pituitary dysfunction in persons with SCI due to a heightened pituitary sensitivity to GnRH, regardless of gonadal status. This indicates that the standard method of provocative testing may not be sensitive enough to detect subtle abnormalities.

Study Duration

Not specified

Participants

SCI men [16 hypogonadal & 14 eugonadal] and able-bodied (AB) men (27 HG & 11 EG)

Evidence Level

Prospective

Key Findings

1
Lower doses of GnRH did not improve the ability to identify clinical dysfunction of the hypothalamic-pituitary-gonadal axis.
2
The SCI-HG group showed a greater integrated FSH response to GnRH 100 μg compared to the AB groups, suggesting hypothalamic GnRH may be globally depressed in persons with SCI.
3
The SCI-EG group had a greater integrated LH response to GnRH 50 μg than the AB-HG group, reinforcing the possibility of central dysregulation in SCI patients.

Research Summary

This study aimed to determine the optimal GnRH dose to identify hypothalamic-pituitary-gonadal axis dysfunction in men with SCI by comparing gonadotropin responses to different GnRH doses (10, 50, 100 μg) in SCI and able-bodied men with varying gonadal status. The results indicated that lower GnRH doses did not improve the detection of clinical dysfunction. However, SCI groups showed higher gonadotropin responses, suggesting a heightened pituitary sensitivity and potential central dysregulation in SCI. The findings support the concept of central hypothalamic-pituitary axis dysfunction in SCI, regardless of gonadal status, which may influence testosterone levels, body composition, metabolic changes, and spermatogenesis.

Practical Implications

Routine Testosterone Screening

Regular screening of serum testosterone concentration in persons with SCI is recommended to identify and treat potential testosterone deficiencies.

Further Research on Central Dysregulation

Further research is needed to elucidate the mechanisms behind the observed central dysregulation of the hypothalamic-pituitary-gonadal axis in SCI patients.

Personalized Hormone Replacement Therapy

Consideration should be given to initiating personalized hormone replacement therapy in SCI patients with low testosterone levels and no contraindications.

Study Limitations

1
Relatively small number of participants in each sample group.
2
Nutritional status, alcohol consumption and/or opioid usage were not specifically evaluated.
3
Study group comprised of community dwelling individuals who may have had chronic medical conditions requiring outpatient management.

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