Professor Mathis Grossmann Professor , department of medicine , Austin Health , University of Melbourne ; head of clinical andrology and consultant endocrinologist , endocrine unit , Austin Health , Heidelberg , Victoria .

First published online on 2 August 2024

INTRODUCTION

THIS is part one of a two-part

series . Part one provides a practical approach to the clinical and biochemical assessment of the man presenting with a clinical suspicion of hypogonadism , that is , clinical features consistent with androgen deficiency and a lowered serum testosterone . This will provide guidance to first , recognise pitfalls in the evaluation of androgen deficiency , second , to distinguish organic from functional hypogonadism and third , to decide when , and when not , to consider testosterone treatment . Management of infertility is beyond the scope of this article and will not be discussed . Part two will cover the management of low testosterone , including in men who do not have organic hypogonadism , and discuss alternative strategies to testosterone treatment .

BACKGROUND

GPs commonly see men presenting with non-specific clinical features

consistent with androgen deficiency and a lowered serum testosterone . There are two priorities . The first is to recognise men who have organic hypogonadism ( due to medical disease of the testes or of the hypothalamus / pituitary gland ); these men may have serious underlying disease ( for example , a pituitary tumour ) that needs appropriate management . Moreover ( unless fertility is desired ), these men derive marked clinical benefits from testosterone replacement .

The second priority is to recognise that in many older men , especially if they have overweight or obesity and other comorbidities , a low serum testosterone is often a marker of poor health . These men benefit from a holistic management approach . This emphasises lifestyle measures , with a focus on achieving a healthy body weight , including , where appropriate , weight loss medications and bariatric surgery . Thorough care of comorbidities ( for example , optimising diabetes

control , and identification and treatment of obstructive sleep apnoea and depression ) is also very important . If successful , this management approach improves general health . Concomitantly , non-specific androgen deficiency-like symptoms often improve , and serum testosterone may normalise .

AETIOLOGY AND PATHOGENESIS

MALE hypogonadism is a clinical syndrome

, comprising symptoms and signs of androgen deficiency , and infertility . The diagnosis requires consistent clinical features and is confirmed by documenting a low serum testosterone on at least two occasions . Hypogonadism can be classified in three ways : first , into primary ( elevated gonadotropins ) and secondary ( low to low-normal gonadotropins ); second , into organic and functional causes ; and third , into congenital and acquired causes ( see box 1 ). 1 There is no role for measuring serum

testosterone unless there is clinical suspicion of androgen deficiency .

Organic hypogonadism

Organic , or classical , hypogonadism

is caused by conditions affecting the male hypothalamic-pituitary-testicular ( HPT ) axis ( see figure 2 ), and can be congenital ( for example , Kallmann syndrome , see figure 3 ) or acquired ( such as a pituitary tumour ) and is either primary ( elevated gonadotropins ) or secondary ( low or low-normal gonadotropins ).

The most common cause of organic hypogonadism is Klinefelter syndrome , with an estimated birth prevalence in Australian men of 1:450 , although there is evidence that about 50 % of men with Klinefelter syndrome remain undiagnosed . 2 This is , in part , because men with Klinefelter syndrome may have subtle clinical features . However , on physical examination they almost always have very small ( less than 4mL ) testes . Because testicular