Exercise-Hypogonadal Male Condition

Discussion in 'Men's Health Forum' started by Michael Scally MD, May 5, 2017.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History

    Context - A subset of men following completion of puberty subsequently experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise and/or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men.

    Objective - To investigate the neuroendocrine mechanisms, genetics and natural history underlying FHH.

    Design - Retrospective study in an academic medical center.

    Participants - Healthy post-pubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of bodyweight). Healthy age-matched men served as controls.

    Interventions - Clinical assessment, biochemical/neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency.

    Main outcome measures - Reproductive hormone levels, endogenous GnRH-induced luteinizing hormone (LH) pulse patterns and rare genetic variants.

    Results - Ten men with FHH were compared to 18 age-matched controls. Patients had significantly lower BMI, testosterone, LH and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty while one FHH subject showed a completely apulsatile LH secretion. Following decreased exercise and weight gain, five FHH men normalized serum T levels and symptoms resolved. Rare missense variants in NSMF (n=1) and CHD7 (n=1) were identified in two FHH men.

    Conclusions - FHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.

    Dwyer AA, Chavan NR, Lewkowitz-Shpuntoff H, et al. Functional hypogonadotropic hypogonadism in men: Underlying neuroendocrine mechanisms and natural history. 2019. Functional hypogonadotropic hypogonadism in men: Underlying neuroendocrine mechanisms and natural history
     
    Millard Baker likes this.
  2. Old

    Old Member

    Given what happens to bones of endurance athletes this isn't surprising. Isn't the negative effect of endurance exercise due to the rise of cortisol which has a catabolic effect on bones, joint, etc. ?

    And doesn't cortisol reduce testosterone and anabolism? Studies about taking cortisol/prednisone and the effects on testosterone seem to be all over the map. Here is one with report 33% reduction Testosterone levels during systemic and inhaled corticosteroid therapy. - PubMed - NCBI and another one with greater reduction Reduction of Serum Testosterone Levels During Chronic Glucocorticoid Therapy | Annals of Internal Medicine | American College of Physicians


    As for 'improved performance of 18.6%', is that not what cortisol would do? Elsewhere posted in the forum is info that too much exercise raises cardiovascular risks (another effect of prolonged elevated cortisol). So much for aerobicmania ...

    Here is a general study on exercise and cortisol alterations for difference exercise intensities Exercise and circulating cortisol levels: the intensity threshold effect. - PubMed - NCBI
    Note: "once corrections for plasma volume reduction occurred and circadian factors were examined, low intensity exercise [40% VO2max] actually resulted in a reduction in circulating cortisol levels"​
     
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Wong HK, Hoermann R, Grossmann M. Reversible male hypogonadotropic hypogonadism due to energy deficit. Clinical Endocrinology 2019;0. https://doi.org/10.1111/cen.13973

    Context - Calorie restriction and overtraining are increasingly seen in young men who suffer from increasing societal pressure to attain a perceived ideal male body image. The resulting energy deficit can lead to multiple endocrine consequences, including suppression of the male gonadal axis.

    Design - We reviewed the literature, including two unpublished cases.

    Results - We identified 23 cases, aged median (range) 20 years (16‐33), with a body mass index of 15.9 kg/m2 (12.5‐20.5). Total testosterone was 3.0 nmol/L (0.6‐21.3), and luteinizing hormone (LH) 1.2 mIU/L (<0.2‐7.5), with 91% of cases demonstrating hypogonadotropic hypogonadism.

    Associated findings included evidence of growth hormone resistance (increased growth hormone in 57% and low insulin like growth factor‐1 in 71%), hypercortisolaemia (50%), and a nonthyroidal illness picture (67%).

    In cases with longitudinal measurements following weight regain, serum testosterone (n=14) increased from median [interquartile range] 3.2 nmol/L [1.9‐5.1] to 14.3 nmol/L [9.3‐21.2] (p<0.001), and LH (n=8) from 1.2 IU/L [0.8‐1.8] to 3.5 IU/L [3.3‐4.3] (p=0.008).

    Conclusions - Hypogonadotropic hypogonadism can occur in the context of energy deprivation in young otherwise healthy men and may be underrecognized. The evidence suggests that gonadal axis suppression and associated hormonal abnormalities represent an adaptive response to increased physiological stress and total body energy deficit.

    The pathophysiology likely involves hypothalamic suppression due to dysregulation of leptin, ghrelin and proinflammatory cytokines. The gonadal axis suppression is functional, because it can be reversible with weight gain. Treatment should focus on reversing the existing energy deficit to achieve a healthy body weight, including psychiatric input where required.
     
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Zekarias K, Shrestha RT. Role of Relative Malnutrition in Exercise Hypogonadal Male Condition. Medicine and science in sports and exercise 2019;51:234-6. Role of Relative Malnutrition in Exercise Hypogonadal Male... : Medicine & Science in Sports & Exercise

    OBJECTIVE: Exercise hypogonadal male condition is a well-recognized condition in women but much less understood in men. The aim of this case report is to highlight exercise-induced hypogonadotropic hypogonadism in a male who recovered with lifestyle modifications.

    METHODS: We report a case of an adolescent male who developed hypogonadotropic hypogonadism secondary to excessive exercise and malnutrition that was followed up for a year without exogenous testosterone supplementation. Informed consent was obtained from the patient for his information to be used in a manuscript submitted to a journal.

    RESULTS: An 18-yr-old adolescent male presented to the clinic with symptoms of fatigue and low endurance, low libido, and lack of morning erections. At the time of his presentation, he was running about 60 miles per week for school cross-country team in addition to cross training with kickboxing. Physical examination was remarkable for low body mass index of 19 kg.m but was otherwise normal. Biochemical workup confirmed hypogonadotropic hypogonadism and a mild pancytopenia. Other pituitary laboratory values and MRI of the brain were unremarkable. Bone marrow biopsy performed for anemia showed features consistent with malnutrition. With a working diagnosis of exercise hypogonadal male condition, he was advised to reduce the frequency and intensity of his exercise and increase calorie intake. Cell counts and testosterone levels normalized, and his symptoms resolved without any further interventions.

    CONCLUSION: Significant reversible hypogonadism can develop after intensive and prolonged exercise. One of the mechanisms of hypogonadism in endurance athletes performing intensive exercise could be relative malnutrition. Further studies to evaluate the role of nutrition and body mass index in male endurance athletes presenting with hypogonadism are needed to identify the underlying mechanism of this condition.
     
    Millard Baker likes this.
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History

    Context - After completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men.

    Objective - To investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH.

    Design - Retrospective study in an academic medical center.

    Participants - Healthy postpubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of body weight). Healthy age-matched men served as controls.

    Interventions - Clinical assessment, biochemical and neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency.

    Main Outcome Measures - Reproductive hormone levels, endogenous GnRH-induced LH pulse patterns, and rare genetic variants.

    Results - Ten men with FHH were compared with 18 age-matched controls.

    Patients had significantly lower body mass index, testosterone, LH, and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH, and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty, and one FHH subject showed a completely apulsatile LH secretion.

    After decreased exercise and weight gain, five men with men had normalized serum testosterone levels, and symptoms resolved. Rare missense variants in NSMF (n = 1) and CHD7 (n = 1) were identified in two men with FHH.

    Conclusions - FHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.

    Dwyer AA, Chavan NR, Lewkowitz-Shpuntoff H, et al. Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History. The Journal of Clinical Endocrinology & Metabolism 2019;104:3403-14. Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History
     
    Millard Baker likes this.