From the Guidelines
The workup for primary hypogonadism should begin with confirming the diagnosis through laboratory testing, including morning total testosterone levels, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) 1. In primary hypogonadism, testosterone will be low while LH and FH will be elevated due to the lack of negative feedback on the pituitary. Additional tests should include:
- Complete blood count
- Comprehensive metabolic panel
- Prolactin level
- Thyroid function tests to rule out other causes Karyotype analysis may be indicated, especially in younger patients, to identify genetic causes such as Klinefelter syndrome. Semen analysis should be performed if fertility is a concern. Bone density testing is recommended as hypogonadism increases the risk of osteoporosis. Imaging studies such as testicular ultrasound may be necessary if testicular abnormalities are detected on physical examination. Once primary hypogonadism is confirmed, testosterone replacement therapy can be initiated in symptomatic patients, with options including intramuscular injections, transdermal patches, gels, or pellets. Patients should be monitored for improvement in symptoms, testosterone levels, hematocrit, PSA, and lipid profile at 3-6 month intervals initially, then annually. Bone density should be reassessed after 1-2 years of therapy. It is also important to note that the initial evaluation for male factor infertility should include a physical exam (PE) performed by an examiner with appropriate training and expertise, a reproductive history, and at least one properly performed semen analysis 1. A full evaluation by an urologist or other specialist in male reproduction should be carried out if the initial screening evaluation demonstrates an abnormal PE, an abnormal male reproductive or sexual history, or an abnormal semen analysis is found. Further evaluation of the male partner should also be considered in couples with unexplained infertility and in couples in whom there is a treated female factor and persistent infertility. The ASRM does not recommend endocrine testing as a primary first line investigation, but rather suggests it in men with abnormal semen parameters, impaired sexual function or clinical findings that suggest a specific endocrinopathy 1.
From the FDA Drug Label
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. The workup for primary hypogonadism is not explicitly stated in the drug label. Key points:
- The label mentions the indications for testosterone replacement therapy, including primary hypogonadism.
- It does not provide information on the diagnostic workup for primary hypogonadism. 2
From the Research
Diagnosis of Primary Hypogonadism
The workup for primary hypogonadism involves a comprehensive health history, evaluation of signs and symptoms, complete physical examination, as well as laboratory and diagnostic testing 3.
- Clinical signs and symptoms of primary hypogonadism include delayed puberty, eunuchoid stature, and underdeveloped secondary sex characteristics 4, 5.
- Laboratory confirmation is based on the measurement of low morning testosterone levels on two different occasions 6.
- Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are used to distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism 4, 5, 6.
- In primary hypogonadism, the production of testosterone in the Leydig's cells of the testes does not function properly, resulting in elevated serum LH concentrations 4, 5.
Laboratory Testing
- Measurement of serum testosterone levels is essential for the diagnosis of primary hypogonadism 6.
- Serum LH and FSH levels are used to confirm the diagnosis and distinguish between primary and secondary hypogonadism 4, 5, 6.
- Other laboratory tests, such as complete blood count, liver function tests, and lipid profile, may be ordered to rule out other underlying conditions 3.
Physical Examination
- A complete physical examination is necessary to evaluate the signs and symptoms of primary hypogonadism, including delayed puberty, eunuchoid stature, and underdeveloped secondary sex characteristics 4, 5.
- The physical examination should also include an assessment of the testes, penis, and prostate gland 3.