Patient information

What is hypogonadism?

Hypogonadism is a deficiency in normal circulating levels of sex hormones – in men this is primarily testosterone.

Hypogonadism in men is a serious medical issue, either as a primary condition or as a secondary development due to ageing or illness. However it may be readily treated with testosterone replacement therapy.¹

Signs and symptoms of low testosterone include:²

Delayed puberty and sexual differentiation
Reduced muscle mass and strength
Decreased bone density/osteoporosis/fractures
Erectile dysfunction, potency decline and reduced libido
Sleep disturbance
Low mood and depression
Fatigue/ lack of energy

Hypogonadism may be either congenital (occurring at or before birth) or acquired. Congenital hypogonadism can be due to abnormalities with the foetal chromosomes eg as in a disorder known as Klinefelter’s syndrome. In both cases, hypogonadism may result from either testicular or brain (pituitary/hypothalamic) disorders. Males can be affected at any age and present with clinical features which differ according to the timing of disease onset in relation to puberty.¹

Primary

When the hormone deficiency is the result of testicular disorders, the condition is described as primary hypogonadism.¹

Secondary

When the hormone deficiency is the result of brain (pituitary/hypothalamic) disorders, the condition is described as secondary hypogonadism.¹

Conditions where low testosterone levels are common include:¹

Diseases affecting the pituitary gland
Type 2 diabetes
Chronic obstructive lung disease
Renal failure
HIV-associated weight loss
Drugs – glucocorticoids, ketoconazole
Chronic pain/opiate use
Osteoporosis, especially in a young man
Infertility

Testosterone deficiency syndrome (TDS) / Late onset hypogonadism (LOH)

When signs and symptoms occur together with low testosterone, hypogonadism is increasingly being called testosterone deficiency syndrome (TDS).³

Deficiency of serum testosterone in ageing men is also known as late onset hypogonadism (LOH). The rate of age-related decline in serum testosterone levels varies in different individuals and is affected by chronic disease and medications.¹
Between 6% and 12% of men aged 40-79 years are estimated to have TDS i.e. low testosterone with signs/symptoms.²

Do I have hypogonadism?

You may have longstanding hypogonadism if you matured later than other boys at school and have less obvious masculine features, together with some of the following signs and symptoms:¹

Decreased sexual desire and activity
Decreased energy
Irritability, depressed mood, decreased mental function
Decreased sleep quality
Decreased lean body mass
Decreased muscle mass and strength
Decreased hair (reduced shaving)
Increased abdominal fat
Infertility

Older men may also suffer from some or all of the above signs and symptoms. Although men may not associate their problems with low testosterone, this could in fact be the root cause.

When should I consult my doctor?

Patients with several of the symptoms of hypogonadism ( e.g. low sex drive, sexual difficulty, low mood, depression, reduced intellectual or physical stamina, less shaving), should consult their GP for advice. An early morning (7-11am) blood sample for testosterone is the best test.⁴ A reason to delay seeking advice for a short period is during the recovery phase of an illness, influenza, chest infection, operation, marital tiff, anxiety or periods of stress at work, where time is required for recuperation. For example, sexual function, a part of normal life, the quality of which is affected by any significant medical condition, will usually gradually recover as the condition recovers or the pressures resolve.

How is male hypogonadism diagnosed?

The diagnosis of male hypogonadism is based on a history of several of the symptoms described ( e.g. low sex drive, sexual difficulty, low mood, depression, reduced intellectual or physical stamina, less shaving), medical examination for typical features (increasing obesity, loss of body hair or muscle, softer or small testes, breast development or tenderness) and to exclude other illnesses (high blood pressure, diabetes etc), but, most important, blood tests to confirm a reduced level of testosterone.¹ The blood sample must be obtained in the morning (7-11am),⁴ when testosterone levels are usually highest, as the levels fall after midday due to normal biological fluctuation. If the testosterone level is low, the test should be repeated a week or two later and some other tests made to confirm the diagnosis. A diagnosis should not be made during an acute or subacute illness. Symptoms of hypogonadism or a low testosterone level may be directly or indirectly caused by some medicines, e.g. glucocorticoids, ketoconazole and opioids. Low levels of testosterone are often associated with type 2 diabetes, kidney disease, chronic obstructive lung disease, HIV and some other chronic conditions.¹

How is male hypogonadism treated?

Both primary and secondary male hypogonadism, including TDS in ageing men, can be treated by testosterone replacement therapy (TRT). But it is first important to be certain of the diagnosis and to exclude other causes, for example a growth of the pituitary gland (within the brain), which may need surgical removal or medical treatment. The symptoms of hypogonadism may also be induced by some drugs, and changing medicines can alleviate the problem. TRT is aimed at inducing and maintaining secondary sex characteristics and at improving patients’ sexual function, sense of well-being, and bone mineral density.¹

In men with secondary hypogonadism who are planning a family,¹ pituitary hormone injections can be given for a period of time to encourage natural fertility. This will first normalise testosterone levels in the body. When the family is complete treatment is switched to TRT, for life.

TRT can be administered in the following forms:

Testosterone capsules – administered orally but need to be taken two times a day with food, and can result in peaks and troughs of serum testosterone.
Testosterone patches – for use on skin. These can be placed on the back, abdomen, upper arm or thigh. The patches need to be changed on a daily basis. The commonest side effect is skin irritation at the site of application.
Testosterone implants – these are cylindrical pellets that are placed under the skin of the abdomen or buttock. They are typically given every six months or so, requiring a minor surgical procedure under local anaesthesia.
Intramuscular injections – testosterone esters are administered as a deep intra-muscular injection usually every two to three weeks. These injections may produce peaks and troughs of testosterone, require clinic visits for administration, and may be painful. A longer acting injection, typically given every 12 weeks is also available.
Testosterone gel – a thin layer of gel is applied daily to the skin. Testosterone is absorbed through the skin, maintaining normal blood levels over 24 hours. Application site reactions are the main side effects with gels. One potential problem is transfer of gel from person to person if direct skin contact occurs.⁵
Buccal system – A twice-daily tablet is placed above the incisor teeth and rests in the top gum (on the buccal mucosa). Testosterone is slowly released into the blood stream. Side effects are usually local, including gum irritation, inflammation and a bitter taste.

If one type of testosterone supplement is inconvenient or creates a side effect such as mood swings or skin irritation, or is not strong enough, then patients are able to switch until they find a preparation that suits them.

What tests are needed during testosterone replacement therapy (TRT)?

Before TRT is commenced it is important to check the man’s general condition and exclude other treatable causes of testosterone deficiency. Urinary function, prostate health, liver function and the function of the pituitary and hypothalamus in the brain and blood count are typically assessed. TRT must not be given to men with prostate or breast cancer. There are precautions for use in men with sleep breathing problems (sleep apnoea), and a number of other conditions which the doctor will assess if TRT is being considered.¹ Once TRT is started similar checks are carried out at three months and then annually. A bone density scan for osteoporosis is carried out every 1-2 years.¹ If testosterone deficiency syndrome/late-onset hypogonadism is suspected but blood testosterone levels are “borderline”, a trial of TRT can be considered in men for whom alternative causes of the symptoms have been excluded.⁴

What difference will treatment with testosterone make?

A man who needs testosterone replacement therapy (TRT) may soon realise that he has found the correct treatment. TRT normally results in improvements in mood, well-being, sexual function and body composition. Where osteoporosis (bone thinning) is present, bone density increases and the risk of fracture rate may be reduced.^1,4 Indeed diagnosis and treatment can save marriages and jobs.⁶ Furthermore, in men with hypogonadism and type 2 diabetes, early evidence shows a benefit on glycaemic control, insulin resistance and other cardiovascular risk factors.⁶ If the prostate specific antigen (PSA) level rises, early prostate cancer may be detected, prompting appropriate treatment.

What about prostate safety?

There appears to be no strong evidence that testosterone replacement therapy (TRT) directly causes prostate cancer.⁷ However, both prostate and breast cancer are hormone-dependent and may be stimulated to grow during testosterone treatment.¹ Consequently, prostate (and breast) cancer must be excluded before TRT is started.

Further information and references

If you think you may be suffering from hypogonadism /testosterone deficiency syndrome, please consult your doctor. Further information may be obtained from the following websites and references below:

References

Bhasin S, Cunningham GR, Hayes FJ et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006; 91: 1995-2010
Araujo AB, O’Donnell, AB, Brambilla DJ et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts male aging study. J Clin Endocrinol Metab 2004; 89: 5920-5926
Morales A, Schulman CC, Tostain J et al. Testosterone Deficiency Syndrome (TDS) Needs to be Named Appropriately – The Importance of Accurate Terminology. Eur Urol 2006; 50: 407-409
Nieschlag E, Swerdloff R, Behre HM et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM and EAU recommendations. Int J Androl 2005; 28: 125-127
American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocrine Practice 2002; 8: 439-456
Jones TH. Hypogonadism in men with type 2 diabetes. Pract Diab Int 2007; 24[5]: 269-77
Morgentaler A. Testosterone and prostate cancer: An historical perspective on a modern myth. Eur Urol 2006; 50: 935-939