From the Guidelines
Testosterone replacement therapy (TRT) should be considered in men with clinical symptoms of hypogonadism and consistently low serum testosterone levels, as evidenced by the most recent and highest quality study 1. The workup for TRT should begin with a thorough history and physical examination, focusing on symptoms such as:
- Decreased libido
- Erectile dysfunction
- Fatigue
- Decreased muscle mass
- Increased body fat
- Mood disturbances Laboratory testing should include:
- At least two morning (between 8-10 AM) total testosterone measurements, as levels fluctuate throughout the day and are highest in the morning 1
- Free testosterone measurement if total testosterone is borderline
- Luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and a complete blood count to help determine if hypogonadism is primary (testicular) or secondary (pituitary/hypothalamic) A prostate-specific antigen (PSA) test and digital rectal examination should be performed in men over 40 to assess prostate health before initiating therapy 1. Bone density testing may be warranted in men with severe or long-standing hypogonadism. These comprehensive evaluations are essential because testosterone replacement carries risks including polycythemia, sleep apnea exacerbation, and potential cardiovascular effects, while addressing the underlying cause can sometimes resolve symptoms without the need for long-term hormone therapy 1. The method of testosterone replacement should be individualized for each patient, with transdermal testosterone preparations suggested for most hypogonadal men due to their ability to produce normal serum testosterone concentrations and convenience 1. Testosterone levels should be monitored to determine that normal serum testosterone concentrations are being achieved, with testing 2 to 3 months after treatment initiation and every 6 to 12 months thereafter 1.
From the FDA Drug Label
INDICATIONS AND USAGE Testosterone gel 1.62% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired). Hypogonadotropic hypogonadism (congenital or acquired).
INDICATIONS AND USAGE Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
INDICATIONS AND USAGE Males Testosterone Enanthate Injection, USP is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) – Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy Hypogonadotropic hypogonadism (congenital or acquired) – Gonadotropin or luteinizing hormone‑releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
The indications for testosterone replacement therapy (TRT) workup are:
- Primary hypogonadism (congenital or acquired)
- Hypogonadotropic hypogonadism (congenital or acquired) These conditions include testicular failure due to various causes, idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation 2, 3, 4.
From the Research
Indications for Testosterone Replacement Therapy (TRT) Workup
The indications for TRT workup include:
- Symptomatic hypogonadism in men, characterized by low testosterone levels and symptoms such as decreased libido, erectile dysfunction, and depressed mood 5, 6, 7
- Low energy and fatigue, decreased muscle mass and strength, decreased bone mineral density, and increased body fat, particularly abdominal fat 7
- Men with a serum total testosterone level < 300 ng/dL and symptoms of hypogonadism 7
- Men with hypogonadism who have not responded to other treatments and have a low quality of life due to their symptoms 8, 9
Diagnostic Criteria
The diagnostic criteria for hypogonadism include:
- Low serum testosterone levels, typically defined as a total testosterone level < 300 ng/dL 7
- Symptoms of hypogonadism, such as decreased libido, erectile dysfunction, and depressed mood 5, 6, 7
- Physical examination and medical history to rule out other causes of symptoms 6, 9
Treatment Options
The treatment options for hypogonadism include:
- Testosterone replacement therapy (TRT) using various formulations, such as buccal, nasal, subdermal, transdermal, and intramuscular (IM) 8, 9
- Human chorionic gonadotropin (hCG), selective estrogen receptor modulator (SERM), estrogen antagonist, or aromatase inhibitor to stimulate endogenous testosterone production 8