About hypogonadism

Hypogonadism is a clinical syndrome
characterised by clinically low testosterone levels.
The condition may be split into two broad categories; primary and secondary hypogonadism.

Testosterone production is regulated by the hypothalamic-pituitary-gonadal axis. The hypothalamus monitors serum testosterone levels and in response to reducing levels, it secretes gonadotropin-releasing hormone to stimulate the pituitary gland which in turn stimulates the testes to secrete the androgen. [1]

In the primary hypogonadism, testosterone production is reduced as a result of partial or complete testicular failure wherein the testes no longer respond to stimulation. In secondary hypogonadism, decreased production is caused by dysfunction in the hypothalamic-pituitary axis.[1]

The cause of hypogonadism can be due to a variety of factors including a genetic predisposition to development, infection, injury, malignancy or comorbidities, which are further outlined below.[2]

Clinical symptoms and indicative symptoms

  • Reduced testes volume
  • Male-factor infertility
  • Decreased body hair
  • Gynecomastia
  • Decrease in lean body mass and muscle strength
  • Metabolic syndrome, insulin resistance, type II diabetes mellitus
  • Decreased bone mineral density (osteoporosis)
  • Mild anaemia

Sexual symptoms

  • Reduced sexual desire and activity
  • Erectile dysfunction
  • Fewer or diminished nocturnal erections

Cognitive symptoms

  • Hot flushes
  • Sleep disturbances and fatigue
  • Depression
  • Anger and irritability


Testosterone plays an integral role in the maintenance of overall health and deficiency leads to the development of a spectrum of clinical symptoms

Recognising the signs and symptoms of clinically relevant testosterone deficiency and hypogonadism is of significant importance. Research indicates that a large portion of men with the condition are undiagnosed and subsequently left untreated. [4]

The EAU guidelines group the major signs and symptoms of hypogonadism into clinical signs and symptoms, sexual symptoms and cognitive symptoms. [4]

Man in his late middle age with arms crossed and looking mildly frustrated


While men experience a natural decline in testosterone as they age, there are a number of factors which increase a patient's risk of developing hypogonadism

They include, but are not limited to: [2] [3]

Trauma or injury

Exposure to environmental toxins

Infection causing damage to the prostate or to the regulatory axis which may be bacterial or viral

Malignancy, either directly from development of cancer in the prostate or from the subsequent treatment which may involve administration of therapeutics or radical prostatectomy


Genetic risk factors such as Klinefelter syndrome and Kallmann syndrome


Hypogonadism is characterised by identification of serum testosterone levels < 300 ng/dL in combination with at least one clinical sign or symptoms.[2] Diagnosis should be made through the following three-pronged approach


History taking and questionnaires

History taking should look to identify the signs and symptoms of hypogonadism listed above. It should also look to identify if the patient has any history of drug abuse including with marijuana, alcohol or anabolic steroids and any other medications they are taking, including opiates.
Systemic illness ongoing acute disease and malnutrition must be assessed and excluded.[4] [5] [10]

Clinicians also frequently use the Androgen Deficiency in Aging Male (ADAM) test to help identify males who are potentially presenting with hypogonadism. [10]


Physical examination

Examination should include height, weight, BMI and waist circumference. [10]

Distribution and degree of body hair should also be assessed, presence of breast enlargement, appearance of penis and testicular size and consistency may also be assessed for abnormalities. The prostate should also be examined. [10]


Laboratory diagnosis

Blood tests should be taken in the early morning to capture the results when serum testosterone levels are naturally highest. This ideally should be done between 7am and 11am.

It is also currently recommended the patient be in a fasting state.[10] This will also allow for hypertension, diabetes and dyslipidemia to be assessed in the same sample. [10]

Based on the results and the clinician’s judgment, hypogonadism can be confirmed, and an appropriate treatment can be selected.[4] [5] [10]

Further tests may then be warranted to determine primary or secondary hypogonadism by measurement of luteinizing hormone.

Treatment guidelines for dosage and titration of Testavan 2% 20mg/g testosterone gel

Treatment options

The standard in the management of testosterone deficiency is the prescription of testosterone replacement therapy (TRT).

These therapies come in a variety of preparations which vary on their route of delivery which provides the opportunity for the clinician to include the hypogonadal individual in the discussion around which option may be best for them.

An important consideration in selecting the right preparation is the consideration of bioavailability which affects the concentration that the treatment can be prepared in and impacts the frequency to which the patient needs to administer the treatment.

Preparations include:

Transdermal gels

Transdermal gels, preparations which are administered via application to the skin, are popular forms of TRT given their ease of use, high bioavailability and non-invasive nature.

Transdermal gels are absorbed directly through the skin into the blood, thereby circumventing liver metabolism. They are simple to apply and are discrete in nature and adverse events are vastly mild-to-moderate and mostly include localised skin irritation and erythema at the application site. [6]

Testosterone transdermal gels have been shown to keep testosterone stable levels. Combining this with their ease of application, this makes them a preferable TRT option over  intramuscular injections which can cause fluctuating serum testosterone levels and are a more invasive option for patients. [8] [9]

Buccal tablets

Buccal or orally administered TRT initially proved difficult to develop as oral preparations were quickly metabolised in the liver before reaching the bloodstream. Some preparations have been developed using an alkylated form of testosterone, however notable adverse events including liver toxicity are frequently reported alongside elevated liver enzymes and other side effects including acne and gynecomastia. [2] [6]

Alternatives are available in the form of buccal mucoadhesive tablets which can be placed on the gum, allowing direct absorption into the blood. While allowing good absorption, these have been shown to cause gum irritation, inflammation and gingivitis [6] [7]

Intramuscular injections

Intramuscular injections come in a number of preparations and afford good bioavailability. A slight drawback with this formulation of TRT is the need to administer through injection which is invasive for the patient and also requires the patient to attend a clinical setting or learn to self-inject, either of which may not be preferred or practical and for some patients, may not be possible. Perhaps one benefit of this therapy is having TRT administered at a much less frequent basis, but requiring the patient to attend a clinic for TRT administration may impact on treatment adherence. Adverse events generally include localised pain and swelling at the injection site.[6]


1. Fraiette et al. Clinics (Sao Paulo). 2013 Feb; 68(Suppl 1): 81–88.
2. Kumar et al. J Adv Pharm Technol Res. 2010 Jul-Sep; 1(3): 297–301.
3. McBride, Carson and Coward. Asian J Androl. 2015 Mar-Apr; 17(2): 177–186.
4. Dohle G et al. EAU Guidelines on Male Hypogonadism 2018.
Available at: http://uroweb.org/guideline/male-hypogonadism/. Accessed date: January 2022.
5. Trinick TR et al. Aging Male 2011;14(1):10–15.

6. Shoskes,Wilson & Spinner. Transl Androl Urol. 2016 Dec; 5(6): 834–843
7. Korbonits M, Slawik M, Cullen D, et al. J Clin Endocrinol Metab 2004;89:2039-43. 10.1210/jc.2003-030319
8. Lakshman & Basaria. Clin Interv Aging. 2009;4:397-412.
9. Ullah, Riche & Koch.Drug Des Devel Ther. 2014; 8: 101–112.
10. Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. The journal of sexual medicine. 2017;14(12):1504-1523.
TRT = testosterone replacement therapy.
*Testosterone unit conversion: 1.0 nmol/L=28.84 ng/dL.

PROMO_1496 Date of Preparation: August 2022