Low Testosterone in Men: Symptoms, Diagnosis, and Modern Treatment Methods

What is low testosterone and why is it important?

Testosterone is a key male sex hormone that regulates libido, bone mineral density, muscle mass, fat distribution, and mood. Its levels may decline with age, leading to hypogonadism. A diagnosis is established when total testosterone (TT) is ≤300 ng/dL with symptoms, or when TT is 300-400 ng/dL with objective signs, such as low bone mineral density or elevated HbA1c [1]. Timely diagnosis and treatment are critically important.

Symptoms of testosterone deficiency

Testosterone deficiency manifests with a wide range of non-specific symptoms:

• Decreased libido and sexual dysfunction: Reduced sexual desire and erectile dysfunction [4].
• Mood changes: Fatigue, decreased energy, irritability, difficulty concentrating, symptoms of depression and anxiety.
• Physical changes: Reduced muscle mass, increased fat mass, decreased bone mineral density [1].
• Metabolic disorders: Elevated glycated hemoglobin (HbA1c) levels [1].
• Lower urinary tract symptoms (LUTS): Frequent, urgent, or nighttime urination (nocturia), storage and voiding problems [2, 4, 6]. Importantly, LUTS are not always solely related to the prostate; the bladder plays a significant role, particularly in storage symptoms [4]. The prevalence of LUTS and sexual dysfunction is high in aging men [4].

Diagnosis of low testosterone and comorbid conditions

Comprehensive diagnostics include:

• Blood test for testosterone: Measuring serum total testosterone levels, typically in the morning, to confirm the diagnosis [1].
• Additional laboratory tests: Free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and HbA1c levels [1].
• Assessment of bone mineral density: Densitometry, if indicated [1].
• Diagnosis of LUTS:
  • Anamnesis and physical examination: [5].
  • Urinalysis: [5].
  • PSA measurement: A mandatory test [5].
  • Additional studies (as indicated): Symptom and quality of life questionnaires, voiding diary, post-void residual measurement, urine cytology, urine culture, creatinine measurement, urinary tract ultrasound [5].

Modern approaches to treating testosterone deficiency

Treatment is individualized, taking into account hormone levels, symptoms, and comorbid conditions.

• Clomiphene citrate (CC): This is an effective treatment method for men with low testosterone levels [1]. CC stimulates the pituitary gland to produce gonadotropins, which activate the testes to produce their own testosterone. The starting dose is often 25 mg every other day, with a potential increase to 50 mg every other day if testosterone levels remain low [1]. The goal of therapy is to achieve a total testosterone level of ≥400 ng/dL and an increase of at least 200 ng/dL from baseline [1].
• Testosterone replacement therapy (TRT): Direct administration of testosterone (injections, gels). Testosterone deficiency may contribute to the development of atrial fibrillation (AF), and TRT generally does not increase the frequency of AF. Although some studies suggested such a link, more rigorous analysis revealed the presence of confounding factors. Nevertheless, further clinical studies with AF as a primary endpoint are required for definitive confirmation [3].
• Treatment of lower urinary tract symptoms (LUTS): The approach to managing LUTS is shifting from exclusively prostate-centric to more patient-centered [2].
  • Alpha-blockers: Traditionally used to relax the smooth muscle of the prostate and bladder neck, improving urine flow [4, 6, 8].
  • 5-alpha-reductase inhibitors (5-ARIs): Such as finasteride and dutasteride, reduce prostate size in benign prostatic hyperplasia (BPH) and associated LUTS. They can be used as monotherapy or in combination with alpha-blockers [4, 8].
  • Anticholinergics: Effective for treating overactive bladder symptoms (frequent urination, urinary urgency, nocturia). Despite concerns regarding potential worsening of obstructive symptoms in men with enlarged prostates, studies show that anticholinergic medications can be safe and effective [4, 6].
  • Beta-3 adrenergic agonists: A new class of drugs that have demonstrated significant improvement in urine storage symptoms and good tolerability [2].
  • Phosphodiesterase type 5 (PDE-5) inhibitors: Can also be used to treat LUTS [4].

The importance of a comprehensive approach and follow-up

Successful treatment of testosterone deficiency and comorbid conditions requires a comprehensive approach. This includes medical therapy, lifestyle modifications (a balanced diet, regular physical activity, adequate sleep, and stress management). Regular medical follow-up, monitoring testosterone levels, and assessing treatment efficacy are mandatory to achieve the best results and prevent potential complications. It is important to remember that each case is unique, and only a qualified specialist can develop the most appropriate treatment plan.

Sources

1. Predictive factors of response to clomiphene citrate in the treatment of testosterone-deficient men. PubMed Link
2. Lower urinary tract symptoms: still too much focus on the prostate? PubMed Link
3. Does testosterone replacement therapy increase the risk of atrial fibrillation? Evaluation of current scientific and clinical evidence. PubMed Link
4. Male lower urinary tract symptoms: how do symptoms guide our treatment choice? PubMed Link
5. Clinical guidelines on lower urinary tract symptoms in men. PubMed Link
6. Use of anticholinergic therapy in men. PubMed Link
7. Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates. PubMed Link
8. Current status of 5-alpha-reductase inhibitors in the management of lower urinary tract symptoms and BPH. PubMed Link

Disclaimer: The information provided in this article is for informational purposes only and cannot replace professional medical advice. Always consult a qualified specialist for the diagnosis and treatment of any medical conditions.