Hypogonadism in males

Author: Dr Gavin Esson, Foundation trainee, NHS Lothian, Edinburgh, Scotland. DermNet NZ Editor-in-chief: Adjunct Assoc. Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. December 2018.


What is hypogonadism?

Hypogonadism describes the inadequate function of the gonads with impaired production of germ cells and sex hormones. 

What is hypogonadism in males?

Hypogonadism in males refers to diminished testicular function — a reduction in sperm production and in testosterone.

  • Primary hypogonadism is due to disease affecting both testes.
  • Secondary hypogonadism is due to disease of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism).

What causes hypogonadism in males?

Hypogonadism is due to disruption to any section of the hypothalamic–pituitary–gonadal axis pathway (figure 1).

    • The hypothalamus produces gonadotropin-releasing hormone (GnRH).
    • GnRH acts on the pituitary gland, which produces follicle-stimulating hormone (FSH) and luteinising hormone (LH).
    • FSH stimulates spermatogenesis in the testes and LH results in the production of testosterone.
Figure 1. The hypothalamic–pituitary–gonadal axis pathway 

Who gets hypogonadism?

Both primary and secondary hypogonadism in males may be congenital or acquired.

Congenital primary hypogonadism

  • Chromosomal abnormalities; the most common is Klinefelter syndrome (XXY karyotype)
  • Cryptorchidism
  • Myotonic dystrophy (hypogonadism manifests in adulthood)
  • Varicocoele
  • Disorders of androgen synthesis (rare)

Acquired primary hypogonadism

Congenital secondary hypogonadism

  • Isolated gonadotropin deficiency due to genetic mutation, such as Kallmann syndrome, Prader-Willi syndrome and others

Acquired secondary hypogonadism

  • Damage to the pituitary/hypothalamus:
    • Intracranial space-occupying lesion (eg, tumour, cyst)
    • Infiltrative disease (eg, sarcoidosis, haemochromatosis)
    • Infection (eg, meningitis)
    • Pituitary apoplexy (bleeding into pituitary gland)
    • Trauma.
  • Suppression of gonadotrophins:
    • Chronic disease (eg, diabetes, anorexia, obesity, renal disease)
    • Critical illness
    • Chronic opiate, glucocorticoid or anabolic steroid use
    • Hyperprolactinaemia.

What are the clinical features of hypogonadism in males? 

The clinical features of hypogonadism depend on the age at presentation.  

Testosterone deficiency at birth

Hypogonadism at birth may be recognised by ambiguous genitalia (external genitals which are neither clearly male nor clearly female).

Testosterone deficiency pre-puberty

Hypogonadism pre-puberty may be diagnosed by the failure to undergo or complete puberty. The boy may have a young appearance, lack of pubic hair, small genitalia and testes, his voice may fail to break, and he may have difficulty in gaining muscle.

Testosterone deficiency after completion of puberty

After completion of puberty, the features of hypogonadism include decreased libido, erectile dysfunction, osteoporosis, depression, gynaecomastia, shrinking of the testes, and infertility. After some years of testosterone deficiency, decreased muscle mass and body hair may be evident.

What skin changes may be due to hypogonadism in males?

Androgens are responsible for sebaceous gland growth and differentiation, hair growth, and epidermal barrier homeostasis [1]. 

Androgen deficiency results in:

  • Dry, thin and wrinkled skin
  • Lack of hair growth on the breast, axilla, face and genitals
  • Lack of genital pigmentation
  • Gynaecomastia
  • Reduced incidence of acne [2,3].

How is hypogonadism in males diagnosed?

The diagnosis of hypogonadism is based on observing typical clinical features in a man with low serum testosterone. The patient should be referred to a specialist.

Initial investigations should include measuring LH, FSH, and serum testosterone (usually taken in the morning, and repeated at least twice). If testosterone is low:

  • Elevated LH and FSH suggest primary hypogonadism
  • Low LH and FSH suggest secondary hypogonadism.

Further investigations should be directed at identifying the underlying cause.

What is the treatment and outcome for hypogonadism in males?

Effective testosterone replacement in men with hypogonadism has been showed to maintain secondary sexual characteristics, increase libido, muscle strength, fat-free mass, and bone density [4].

Adverse effects of testosterone replacement include

  • Acne
  • Prostate enlargement
  • Stimulation of the growth of breast cancer or prostate cancer
  • Sleep apnoea
  • Heart failure
  • Erythrocytosis.

What are the contraindications to testosterone therapy?

Testosterone should not be started in individuals with breast cancer, prostate cancer or an increased risk of prostate cancer, haematocrit above 50%, untreated obstructive sleep apnoea, severe lower urinary tract symptoms, or uncontrolled heart failure [4].

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Related information

 

References

  1. Zouboulis CC, Degitz K. Androgen action on human skin – from basic research to clinical significance. Experimental Dermatology. 2004, 13:5–10. PubMed.
  2. Kohn FM, Ring J, Schill WB. Dermatological aspects of male hypogonadism. Der Hautarzt. 2000, 51(4):223–30
  3. Snyder PJ, Matsumoto AM, Martin KA. Clinical features and diagnosis of male hypogonadism. UpToDate. HTML: https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-male-hypogonadism. [Accessed September 2017].
  4. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology and Metabolism. 2010, 95 (6):2536–2559. PubMed.

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