Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners.

Exercise-induced hypogonadotropic hypogonadism is well recognized among female endurance athletes but is less commonly observed in male endurance athletes. We have reported a well-characterized case of severe acquired hypogonadotropic hypogonadism in a male distance runner with osteopenia, stress fracture, and sexual dysfunction. Using this case as an index, we hypothesized that the presence of 1 or more specific risk factors would prospectively identify male endurance athletes with exercise-induced hypogonadotropic hypogonadism. These include a history of stress fracture, sexual dysfunction, or the initiation of endurance exercise before age 18 years. We studied 28 male endurance runners younger than 50 years who ran more than 40 miles per week. Of these runners, 15 had 1 or more of the above risk factors (group 1), and the remaining 13 had none of the putative risk factors (group 2). A group of 10 sedentary control subjects was also studied (group 3). There was no difference between groups 1 and 2 in weekly training mileage. Group 1 was younger than group 2 (32 +/- 10 years versus 39 +/- 6 years, P < .05) and had a lower body mass index (22.4 +/- 1.9 kg per m2 versus 23.9 +/- 2.2 kg per m2, P < .05). By bioelectric impedance, preliminary data showed that group 1 had a reduced body fat content (group 1, 14.5% +/- 2.8%; group 2, 16.9% +/- 2.0%; and group 3, 17.5% +/- 4.1%; P < .05). Fasting morning concentrations of free testosterone (group 1, 45.3 +/- 26.4 pmol/l; group 2, 88.8 +/- 24.3 pmol/l; and group 3, 69.1 +/- 21.5 pmol/l) and luteinizing hormone (group 1, 1.7 +/- 0.7 IU per liter; group 2, 2.0 +/- 1.1 IU per liter; and group 3, 1.9 +/- 0.6 IU per liter) did not differ among the groups (P > .05). One subject with primary hypogonadism was identified in group 1. The presence of the aforementioned risk factors does not predict the occurrence of exercise-induced hypogonadotropic hypogonadism among male endurance runners in this pilot study. A larger sample size or more discriminating risk factors (or both) may be necessary to identify this uncommon but potentially debilitating condition.

Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate.

OBJECTIVE: To assess the efficacy of estrogen antagonist therapy on the function of the hypothalamic-pituitary-testicular axis in a young male runner with significant morbidity attributable to idiopathic hypogonadotropic hypogonadism. DESIGN: An uncontrolled case study. SETTING: The outpatient endocrinology clinic of a university tertiary referral center. PATIENT(S): A 29-year-old male who has run 50 to 90 miles per week since 15 years of age and who presented with a pelvic stress fracture, markedly decreased bone mineral density, and symptomatic hypogonadotropic hypogonadism. INTERVENTION(S): Clomiphene citrate (CC) at doses up to 50 mg two times per day over a 5-month period. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, and T before and after CC therapy, as well as clinical indicators of gonadal function. RESULT(S): Barely detectable levels of LH and FSH associated with hypogonadal levels of T were restored to the normal range with CC therapy. The patient experienced improved erectile function, increased testicular size and sexual hair growth, and an improved sense of well being. CONCLUSION(S): Exercise-induced hypogonadotropic hypogonadism exists as a clinical entity among male endurance athletes, and CC may provide a safe and effective treatment option for males with debilitating hypogonadism related to endurance exercise.

Leukotriene C4-stimulated contractions in bullfrog lung are affected by cold acclimation and calcium antagonists.

Leukotriene C4 (LTC4) contracts isolated bullfrog lung. This study examined effects of cold-acclimation and the involvement of extracellular and intracellular Ca++ on the contractile response to LTC4. The response to LTC4 was greater in lungs from warm-acclimated (22 degrees C) frogs compared with cold-acclimated (5 degrees C) frogs at incubation temperatures of both 22 degrees C and 5 degrees C. LTC4, LTC5, and N-methyl LTC4 were equally effective in stimulating lung contraction at concentrations from 1-100 nM. Nicardipine (3 microM) partially antagonized the response to LTC4, but verapamil, nifedipine, or nitrendipine at the same concentration was ineffective. Ethylene glycol tetraacetic acid (EGTA, 0.3 mM) prevented the response to 30 nM LTC4, but the response was restored when the lung was retested in EGTA-free medium containing Ca++, suggesting that extracellular Ca++ was involved in the response. Caffeine (10 mM) or thapsigargin (1 mM) inhibited the responses to LTC4, suggesting a role for intracellular Ca++ in the contraction.