Reversible Male Hypogonadotropic Hypogonadism Due to Energy Deficit

Henry K. Wong; Rudolf Hoermann; Mathis Grossmann

Disclosures

Clin Endocrinol. 2019;91(1):3-9. 

In This Article

Abstract and Introduction

Abstract

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Design: We reviewed the literature, including two unpublished cases.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

Introduction

Caloric restriction, especially if combined with excessive energy expenditure, can result in a total body energy deficit with detrimental effects on multiple endocrine axes, in particular the reproductive axis.[1] Underlying the impetus to achieve a negative energy balance are body image disorders that have historically been recognized largely in women. The combination of disordered eating/low energy availability, amenorrhoea, and reduced bone mineral density, has been officially recognized as the "female athletic triad" in 1992.[2]

Recently, there has been a gradual shift of attention towards men and with it, the ever-increasing need to pursue a fit muscular physique. Calorie restriction and overtraining can be seen in young men exposed to significant societal pressure to attain what is perceived to be the "ideal" male body image. Muscle dysmorphia, characterized by a pathological preoccupation with muscularity, has been recognized in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) as a subtype of the body dysmorphic disorder and overlaps with eating disorders/anorexia.[3] The recognition that whole body energy deficits, commonly in the context of inadequate caloric intake combined with excessive exercise can lead to a number of serious adverse health outcomes, including significant endocrine complications in both men and women, has prompted the International Olympic Committee (IOC) to define this condition as "relative energy deficit in sport" (RED-S) in 2014, identifying low energy availability as the key aetiological factor.[4] Although exercise-associated hypogonadism in men has been reported since the 1980s,[5] RED-S remains underrecognized and overlooked in clinical practice in men. Endocrine consequences of energy deficit in men have not been systematically reviewed before.

To identify clinical features and endocrine phenotypes associated with energy deficit in men and to assess the response to weight regain, we summarize the existing literature. We also discuss the underlying pathophysiology.

The material discussed in this review is based on PubMed database searches using the search terms "testosterone," "androgen," "hypogonadism," "anorexia," "weight loss," "energy deficit," "exercise" and "men" from inception to December 2018.

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