Testicular responses to hCG stimulation at varying doses in men with spinal cord injury.

STUDY DESIGN: Prospective. OBJECTIVES: To test whether provocative stimulation of the testes identifies men with chronic spinal cord injury (SCI), a population in which serum testosterone concentrations are often depressed, possibly due to gonadal dysfunction. To accomplish this objective, conventional and lower than the conventional doses of human chorionic gonadotropin (hCG) were administered. METHODS: Thirty men with chronic SCI (duration of injury >1 year; 18 and 65 years old; 16 eugonadal (>12.1 nmol l-1) and 14 hypogonadal (⩽12.1 nmol l-1)) or able-bodied (AB) men (11 eugonadal and 27 hypogonadal) were recruited for the study. Stimulation tests were performed to quantify testicular responses to the intramuscular administration of hCG at three dose concentrations (ithat is, 400, 2000 and 4000 IU). The hCG was administered on two consecutive days, and blood was collected for serum testosterone in the early morning prior to each of the two injections; subjects returned on day 3 for a final blood sample collection. RESULTS: The average gonadal response in the SCI and AB groups to each dose of hCG was not significantly different in the hypogonadal or eugonadal subjects, with the mean serum testosterone concentrations in all groups demonstrating an adequate response. CONCLUSIONS: This work confirmed the absence of primary testicular dysfunction without additional benefit demonstrated of provocative stimulation of the testes with lower than conventional doses of hCG. Our findings support prior work that suggested a secondary testicular dysfunction that occurs in a majority of those with SCI and depressed serum testosterone concentrations.

Bone loss at the distal femur and proximal tibia in persons with spinal cord injury: imaging approaches, risk of fracture, and potential treatment options.

Persons with spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have severe bone loss below the level of lesion associated with increased risk of long-bone fractures. The pattern of bone loss in individuals with SCI differs from other forms of secondary osteoporosis because the skeleton above the level of lesion remains unaffected, while marked bone loss occurs in the regions of neurological impairment. Striking demineralization of the trabecular epiphyses of the distal femur (supracondylar) and proximal tibia occurs, with the knee region being highly vulnerable to fracture because many accidents occur while sitting in a wheelchair, making the knee region the first point of contact to any applied force. To quantify bone mineral density (BMD) at the knee, dual energy x-ray absorptiometry (DXA) and/or computed tomography (CT) bone densitometry are routinely employed in the clinical and research settings. A detailed review of imaging methods to acquire and quantify BMD at the distal femur and proximal tibia has not been performed to date but, if available, would serve as a reference for clinicians and researchers. This article will discuss the risk of fracture at the knee in persons with SCI, imaging methods to acquire and quantify BMD at the distal femur and proximal tibia, and treatment options available for prophylaxis against or reversal of osteoporosis in individuals with SCI.

Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

STUDY DESIGN: Prospective study. OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). METHODS: Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 µg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. RESULTS: The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (P<0.05). The SCI-responder group had a greater LH area under the curve to GnRH stimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. CONCLUSIONS: The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury.

Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p < 0.0005), trunk (24.1 ± 4.1 vs. 25.8 ± 3.8 kg; p < 0.005), leg (14.5 ± 2.7 vs. 15.8 ±2.6 kg; p = 0.005), and arm (7.6 ± 2.3 vs. 8.0 ± 2.2 kg; p < 0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p < 0.01) and percent predicted basal energy expenditure (73 ± 9 vs. 79 ± 10%; p < 0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.