Male Hormonal Health: Testosterone in Context

Testosterone has become one of the most marketed hormones in the world. Clinics advertise treatment for fatigue, low libido, weight gain and lack of motivation, supplements promise to boost levels naturally, and prescriptions have risen in many countries, often in men who have never had a properly confirmed diagnosis. At the same time, men with genuine testosterone deficiency sometimes go unrecognised. A clear understanding of testosterone physiology, diagnosis and the evidence for treatment helps practitioners navigate between overtreatment and neglect.

How testosterone is regulated

Testosterone is produced mainly by Leydig cells in the testes under the control of luteinising hormone from the pituitary, which in turn responds to gonadotrophin releasing hormone from the hypothalamus. Follicle stimulating hormone, together with high local testosterone concentrations in the testes, drives sperm production. Testosterone feeds back to suppress the hypothalamus and pituitary.

In the blood, most testosterone is bound to sex hormone binding globulin and albumin, and a small fraction is free. Sex hormone binding globulin is lowered by obesity and insulin resistance and raised by ageing, liver disease and hyperthyroidism, which affects the interpretation of total testosterone. Testosterone follows a daily rhythm, highest in the morning, and falls after meals, especially glucose rich ones.

Diagnosis

Endocrine Society guidance recommends diagnosing testosterone deficiency only in men with symptoms and signs consistent with deficiency and unequivocally and consistently low serum testosterone.

• Symptoms more specific to deficiency include reduced libido, reduced spontaneous erections, loss of body hair, small or shrinking testes, hot flushes and low bone density or low trauma fractures. Less specific symptoms include fatigue, low mood, poor concentration and reduced physical performance.
• Testing should be done in the morning, ideally fasting, and repeated on a separate occasion. A harmonised lower limit of around 9.2 nmol/L (264 ng/dL) for total testosterone in healthy young men has been proposed, while some European guidance uses 12 nmol/L. Free testosterone, calculated or measured, helps when sex hormone binding globulin is abnormal or total testosterone is borderline.
• Avoid testing during acute illness, which temporarily lowers testosterone.
• If low, luteinising and follicle stimulating hormones distinguish primary testicular failure from secondary, pituitary or hypothalamic causes. Prolactin, iron studies and further assessment may be needed for secondary causes.

Causes

Functional causes are the most common in middle aged men. Obesity lowers testosterone through reduced sex hormone binding globulin, increased conversion of testosterone to oestradiol in fat tissue and suppression of the hypothalamus. Weight loss raises testosterone, sometimes substantially. Treating sleep apnoea, reducing opioids where possible and improving glucose control can also restore levels.

Ageing and testosterone

Testosterone declines gradually with age, by around one percent a year from middle age on average, but much of the decline observed in population studies is explained by increasing weight and illness. Healthy older men often maintain levels within the normal range. The term andropause, implying an inevitable male equivalent of menopause, is misleading.

What treatment does and does not do

In the Testosterone Trials, older men with low testosterone and symptoms received testosterone gel or placebo for a year. Testosterone modestly improved sexual function, mood and depressive symptoms, corrected mild anaemia and increased bone density, but did not improve vitality or walking distance meaningfully and did not improve cognition. The TRAVERSE trial, in middle aged and older men with low testosterone and cardiovascular risk, found that testosterone was not associated with an increase in major adverse cardiovascular events compared with placebo, but was associated with higher rates of atrial fibrillation, acute kidney injury and pulmonary embolism.

Risks and monitoring

• Fertility: exogenous testosterone suppresses luteinising and follicle stimulating hormones and therefore sperm production, often profoundly. It should not be used in men wishing to conceive.
• Erythrocytosis: a rise in haematocrit, which requires monitoring and dose adjustment.
• Prostate: monitoring according to guidelines; testosterone is contraindicated in some prostate conditions.
• Sleep apnoea: may worsen in some men.
• Cardiovascular and thromboembolic events: considered as above.
• Dependence and suppression: stopping after long term use may leave a period of low testosterone while natural production recovers.

Non medical use of anabolic steroids for muscle building is a separate but related problem, causing infertility, cardiovascular harm, mood effects and prolonged hypogonadism after stopping.

Testosterone boosters

Many supplements marketed to boost testosterone contain ingredients such as tribulus, fenugreek, D aspartic acid, ashwagandha, zinc and vitamin D. A review of popular products found that few ingredients had evidence of raising testosterone, and some products contained doses above tolerable upper limits for certain nutrients. Correcting a genuine zinc or vitamin D deficiency may help; in men without deficiency, benefits are unproven.

A functional approach

1. Take a careful history, including libido, erections, fertility plans, sleep, snoring, alcohol, opioids, anabolic steroid use, weight change and chronic illness.
2. Ensure testing is done correctly: morning, repeated, not during illness.
3. Identify and treat functional causes: weight loss, sleep apnoea treatment, glucose control, medicine review, alcohol reduction, adequate energy intake in athletes.
4. Refer for medical assessment when deficiency is confirmed, particularly with signs of pituitary or testicular disease.
5. Discuss fertility before any testosterone treatment.
6. Support lifestyle factors that benefit hormonal and metabolic health: resistance exercise, sleep, diet quality and stress management.

An illustrative case

A 46 year old man with obesity, type 2 diabetes and fatigue has a total testosterone of 8.1 nmol/L on a single afternoon test and is considering buying testosterone online. He is also hoping to have a second child with his partner. He snores loudly.

His doctor repeats the test in the morning: 9.8 nmol/L, with a low sex hormone binding globulin and normal calculated free testosterone. Luteinising hormone is normal. A sleep study confirms moderate sleep apnoea. The practitioner explains that testosterone treatment would likely suppress his fertility. His plan focuses on sleep apnoea treatment, weight loss with dietary change and resistance exercise, and improved glucose control. After 9 months and a 10 percent weight loss, his testosterone has risen well into the normal range, his energy has improved and his partner has conceived.

Testosterone in context

Testosterone is best understood as a marker of overall male health as much as a hormone to be replaced. In many men, low levels reflect obesity, poor sleep, chronic illness or medicines, and improve when those are addressed. Genuine deficiency deserves diagnosis and treatment; everything else deserves careful assessment before a prescription.