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Testosterone deficiency or hypogonadism is associated with an increased risk of heart disease, osteoporosis, loss of muscle mass, cognitive impairment, and problems in the sexual sphere.
Testosterone is the primary male hormone and belongs to the group of androgens—also called steroids or anabolic steroids. This hormone is produced in the testicles and contributes to male sexual characteristics such as facial hair, voice deepening, and muscle mass. It also plays a role in bone maintenance, physical and mental activity, sperm production, sex drive, erections, and more.
All men need testosterone for a healthy life, both physically and psychologically. However, the level of this hormone naturally declines with age, estimated at 2% per year starting around age 30-40. Although testosterone deficiency, also called hypogonadism, primarily affects men over 50, its prevalence ranges from 2% to 5% of men at age 50 and reaches 30% by age 80.
Importantly, hypogonadism is associated with an increased risk of heart disease, osteoporosis, muscle loss, cognitive impairment, and sexual problems. Some studies indicate that low testosterone levels may be linked to higher mortality.
Testosterone is produced mainly in the testes (95%) and adrenal glands (5%) with a circadian rhythm (regulation of sleep and wakefulness states): testosterone concentration is highest between 7 and 11 a.m. and decreases for the rest of the day.
The most common causes of testosterone deficiency syndrome are age, obesity, diabetes, metabolic syndrome, some medications (corticosteroids, morphine derivatives, antiandrogens) and various chronic diseases, especially those of an inflammatory nature.
The three most common symptoms of testosterone deficiency are decreased erotic thoughts, low libido, and a reduction in the number of nocturnal or morning erections. Testosterone deficiency produces symptoms in three different areas: sexual, psychological/cognitive, and somatic.
However, the symptoms of hypogonadism are nonspecific and often overlap with other illnesses. For this reason, screening questionnaires for low testosterone are not commonly used, as they tend to produce false positives in many situations other than decreased testosterone.
Hypogonadism is diagnosed by combining two blood tests that show low testosterone levels along with symptoms of androgen deprivation. Before starting treatment, a complete blood count with PSA levels and a bone mineral density scan are necessary.
Whenever possible, the doctor should try to find the underlying cause of the hormonal decline in order to apply the appropriate treatment. Since a large proportion of hypogonadism cases in adult men are related to obesity and metabolic syndrome (high blood pressure, peripheral insulin resistance, obesity, and elevated cholesterol levels), the factors causing this condition must be addressed. It is essential to establish a treatment plan based on lifestyle modifications, including a healthy and balanced diet (Mediterranean or vegetarian) combined with targeted physical exercise.
Exogenous testosterone supplementation significantly improves results, so it is recommended from the start of treatment. Testosterone supplementation is contraindicated in some situations, such as active prostate or breast cancer, moderate or severe heart failure, sleep apnea-hypopnea syndrome, and severe lower urinary tract symptoms.
At the beginning of treatment, the best testosterone formulation is transdermal (percutaneous), which can be easily discontinued if side effects occur. After a certain period, it is possible to switch to long-term injectable supplementation, which achieves very stable testosterone levels with just one injection every 14 weeks.
Treating hypogonadism leads to improvement in several areas: it increases the lean mass/fat mass ratio, improves strength and libido, and enhances erectile function. The improvement is greater when testosterone levels are lower at the start of treatment.
Treatment complications are rare. The most common complication with transdermal gels is dermatitis caused by the alcoholic excipient in the formula. With testosterone, the most common complications are polycythemia (an increased concentration of red blood cells) and elevated liver transaminases.
The monitoring of patients treated with testosterone supplementation to increase libido, among other objectives, is carried out by means of a quarterly blood test, which must include PSA, testosterone, SHBG, blood count and biochemistry with liver profile along with a determination of bone mineral density at the beginning and during the follow-up.
The symptoms of testosterone deficiency or hypogonadism are nonspecific, and many diseases can cause the same symptoms. In an adult, it can produce alterations at three levels:
It is recommended to use validated questionnaires to collect as much information as possible after diagnosis, in order to have a determination of symptoms at time 0 that allows us to establish a starting point and monitor treatment.
The causes of testosterone deficiency syndrome are numerous and include genetic, neurological, testicular, and endocrine problems. Depending on the age of onset, the clinical presentation can vary considerably, since testosterone is an essential hormone for the proper development of boys during puberty. Therefore, if testosterone levels are low before puberty, the symptoms will include delayed puberty and the absence or reduction of male sexual characteristics. Later, during adulthood, the hormonal deficiency does not cause such obvious alterations, although it is associated with numerous diseases and symptoms of hormone deficiency.
Some of the main causes of hypogonadism are:
In general, hypogonadism is caused by four main reasons:
1.- Central failure or hypogonadotropic hypogonadism . This is a brain pathology that causes the hypothalamus and pituitary gland to not produce gonadotropin (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thus preventing the activation of Leydig cells, responsible for secreting about 90% of testosterone, and Leydig cells, which provide structural and metabolic support to male germ cells during spermatogenesis.
2. Testicular failure or hypergonadotropic hypogonadism : commonly caused by problems in the testicle such as torsion, testicular cancer, trauma, and radiation therapy. Although the hypothalamic-pituitary-gonadal axis attempts to activate testicular production, it is insufficient or absent. Low testosterone and sperm count levels are common, along with very high LH and FSH levels.
3. Testosterone receptor inactivity : Even if testosterone and gonadotropin levels are completely normal, they do not perform their function due to a failure in receptor activity. Typically, blood tests are normal, sometimes even showing high levels of LH, FSH, and testosterone.
4. Increased aromatase activity : This occurs when testosterone production is normal or even high, but insufficient testosterone levels result from increased aromatase activity, which breaks down the testosterone produced. This can lead to high levels of LH and FSH—attempting to compensate for the breakdown—low testosterone, and high estradiol.
Early detection of hypogonadism in children can help prevent delayed puberty. Early diagnosis and treatment in adults offers better protection against osteoporosis and other related conditions.
The presence of hypogonadism symptoms without abnormal lab results is not an indication for treatment, as many diseases can produce very similar symptoms. Therefore, it is not reasonable to treat the condition with normal lab results. Furthermore, testosterone has a positive clinical effect even in individuals with normal testosterone levels, which subsequently decline. Given the inhibition of the hypothalamic-pituitary-gonadal axis caused by testosterone treatment and the short duration of the improvement it provides, its use without a medical indication is strongly discouraged.
It's important to note that the cutoff point for what is considered low testosterone varies depending on the specific symptoms and, possibly, on the stage of life. It is generally accepted that testosterone levels below 8 nmol are low and supplementation is recommended. Between 8 and 12 nmol is a gray area, where some men may have testosterone deficiency syndrome and others may not. Above 12 nmol, hypogonadism is not present. However, some men, especially younger ones, may begin to experience symptoms of testosterone deficiency syndrome with levels below 15 nmol. It is generally accepted that above this level, androgen deficiency is not present.
Therefore, a diagnosis requires the presence of symptoms and two blood tests showing low testosterone levels. These tests should analyze not only testosterone but also other parameters such as SHBG, prolactin, LH, FSH (if fertility is desired), PSA, liver function tests, complete blood count, and bone mineral density.
Based on these values, the existence or absence of hypogonadism is diagnosed, the level where the problem occurs (cerebral or testicular), the cause, and the factors that may be facilitating it.
Testosterone deficiency can be treated with testosterone replacement therapy , which involves administering this hormone via gel or injection to restore testosterone levels to normal.
Since testosterone acts on multiple levels of the body, regular monitoring by an andrologist is necessary to avoid unwanted side effects. For this same reason, treatment usually begins with short-acting formulations such as topical gel , and if no significant problems are observed, it is switched to medium- to long-acting formulations such as testosterone injections , which provide very stable levels and promote adherence to treatment, as only four injections per year are required.
Patient follow-up is conducted at 3, 6, and 12 months after the start of treatment . At each visit, clinical progress is assessed (sexual desire, erection, mood, muscle mass, weight), along with blood tests to rule out major complications (PSA level, complete blood count, biochemistry panel with liver profile, testosterone, SHBG). Furthermore, both at the time of diagnosis and during follow-up, a bone mineral density measurement is recommended.
Medication can help counteract the symptoms , achieving:
Cognitive improvement is usually the fastest sign of symptom improvement. Mood, energy levels, and sex drive tend to respond relatively quickly. Furthermore, studies show that chronic testosterone treatment improves muscle mass by increasing strength, reduces fat mass by limiting overweight and obesity, and improves certain parameters of bone mineral density.
For older men with low testosterone levels , the benefits of testosterone replacement are less clear. In middle-aged men , treatment may require a long period before positive signs begin to appear: results can take between 3 and 12 months to become apparent, depending on the symptom or symptoms being addressed. It is advisable to continue treatment for a minimum of 6–12 months before considering discontinuing it.
Testosterone deficiency syndrome in adults is often associated with metabolic syndrome, including obesity, high blood pressure, diabetes, and high cholesterol. Therefore, it is essential to treat not only the condition itself but also its underlying causes through a healthy diet and exercise.
Several scientific studies demonstrate that testosterone supplementation combined with exercise and diet is a better strategy than using isolated testosterone or prescribing diet and exercise alone, so we recommend the combined strategy.
Side effects are uncommon:
Testosterone treatment impacts fertility , as it induces the cessation of sperm production through negative feedback on the hypothalamic-pituitary-gonadal axis. This cessation of spermatogenesis is usually temporary, although not in all cases. Therefore, it is crucial to determine the desire for offspring in men with low testosterone levels. If they desire children, alternatives exist, such as the use of clomiphene or testosterone treatment followed by reactivation of the hypothalamic-pituitary axis with BCHG at the time of conception.
A link between testosterone supplementation and a potential worsening of prostate problems or even the development of prostate cancer has been commonly misinterpreted. Scientific evidence demonstrates that testosterone replacement does not worsen urinary function in any way, nor is it related to the "awakening" of a prostate tumor.
We treat our patients at the ROC Chamberí clinic and in the HM Hospitals network of centers in Madrid: Sanchinarro, Montepríncipe, Madrid Río, Rivas, Puerta del Sur, Nuevo Belén, Policlínico HM Moraleja and Nuevo Norte.
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We treat our patients at the ROC Chamberí clinic and in the HM Hospitals network of centers in Madrid: Sanchinarro, Montepríncipe, Madrid Río, Rivas, Puerta del Sur, Nuevo Belén, Policlínico HM Moraleja and Nuevo Norte.
Coming soon
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