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Male late-onset hypogonadism: pathogenesis, diagnosis and treatment

Nature Reviews Urology volume 8, pages 335–344 (2011)Cite this article

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Abstract

Some aging men develop a condition of suppressed serum testosterone levels, which is associated with diffuse sexual, physical and psychological symptoms. Several terms are used for this syndrome, but late-onset hypogonadism (LOH) is preferred. The diagnosis of LOH is often uncertain because symptoms (occurring in 20–40% of men) and low circulating testosterone (found in 20% of men >70 years of age) seldom occur together. The strict diagnostic criteria for LOH include reproducibly low serum testosterone levels and sexual symptoms, including erectile dysfunction and reduced frequency of sexual thoughts and morning erections. Using these diagnostic criteria, only 2% of 40–80-year-old men have LOH. Obesity and impaired general health (including diabetes mellitus, cardiovascular and chronic obstructive pulmonary disease, and frailty) are more common reasons for low testosterone than advanced age per se. It seems logical, therefore, to begin by treating these conditions before testosterone replacement therapy is initiated. Even then, testosterone should only be used if there are no contraindications, such as unstable cardiac disease, serious prostate symptoms and high hemoglobin level. The long-term benefit of testosterone replacement therapy is uncertain, and the experimental nature of the treatment, and its associated risks, must be fully explained to the patient before treatment begins.

Key Points

  • A small proportion of aging men develop late-onset hypogonadism (LOH), which denotes a subnormal (though usually borderline) serum testosterone level, combined with diffuse sexual, physical and psychological symptoms

  • The diagnosis of LOH is challenging, because the associated symptoms, which are seen in ∼20–40% of men, and low testosterone levels, which are found in >20% of men aged >70 years, are seldom observed in the same individual

  • The strict diagnostic criteria include consistently low serum total testosterone levels (<8 nmol/l or 8–11 nmol/l with calculated free testosterone <220 pmol/l) and sexual symptoms, including erectile dysfunction, and decreased morning erections and sexual thoughts

  • LOH is more often associated with obesity and poor health than with aging per se; thus, lifestyle modification, weight reduction and treatment of comorbidities are the first-line treatments

  • Testosterone replacement can be offered to men with LOH unless there are contraindications, such as unstable cardiac disease, prostate symptoms or high hemoglobin level, and even then the effects of long-term treatment are uncertain

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Figure 1: Relationship between age, BMI, and reproductive hormones of 3,220 men aged 40–79 years, from the EMAS study.
Figure 2: Mean baseline testosterone levels of 80 young patients with classic forms of hypogonadism (such as Klinefelter syndrome, congenital hypogonadotropic hypogonadism, or anorchia) in comparison to the levels of testosterone observed in men with LOH.
Figure 3: Algorithm for the diagnosis and treatment of LOH.
Figure 4: Effect of age, BMI and comorbidities on the prevalence of LOH.

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Author information

Authors and Affiliations

  1. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN, London, UK

    Ilpo Huhtaniemi

  2. Department of Clinical Physiopathology, Endocrinology Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    Gianni Forti

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Both authors contributed equally to researching data for the article, discussion of content, writing, and editing the manuscript before submission.

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Correspondence to Ilpo Huhtaniemi.

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Huhtaniemi, I., Forti, G. Male late-onset hypogonadism: pathogenesis, diagnosis and treatment. Nat Rev Urol 8, 335–344 (2011). https://doi.org/10.1038/nrurol.2011.47

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