Hypogonadism refers to a deficiency in androgen secretion and / or sperm production. Most androgen-deficient patients are infertile, while most infertile patients have serum testosterone levels within the normal range. Defects of steroid secretion by the Leydig cell may be either primary or secondary. The clinician must be able to distinguish one condition from the other in order to plan appropriate treatment, and the basic scientist focusing on andrology should understand the clinical implications of dysregulation of the reproductive axis.
Patients with androgen undersecrerion are traditionally classified as having either primary testicular dysfunction or a hypothalamic-piruitary disorder; however, combinations of the two may occur during aging, or as in hepatic cirrhosis, type 2 diabetes, and sickle-cell disease, and many other chronic diseases (Table Common Causes of Male Hypogonadism). A decreased-androgen effect mimicking true hypogonadism may be seen in patients with androgen receptor abnormalities, postreceptor signaling abnormalities, and failure to convert testosterone to dihydrotestosterone (dihydrotestosterone) (5α-reductase deficiency). The most useful laboratory tests in the management of a patient with hypogonadism are the measurement of plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations. If these hormone measurements are borderline and the patient has clinical symptoms or signs of hypogonadism, the free or bioavailable testosterone can be measured to diagnose hypogonadism in patients with low free testosterone and elevated sex hormone-binding globulin (sex hormone binding globulin), as in the case of elderly men.
With the basal concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone, a clinician can usually determine the anatomical level of the reproductive disorder. Low concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone are indicative of hypogonadorropic hypogonadism (); pre-pubertal onset is usually indicative of a congenital defect, pituitary or hypothalamic neoplasm, or inflammatory disorder. Prolacrin concentrations should be checked to identify patients with hyperprolactinemia.
Anterior pituitary hormone function should be assessed and a magnetic resonance imaging (MRI) scan performed to exclude hypothalamic-piruitary mass lesions. Elevated follicle-stimulating hormone and luteinizing hormone concentrations in the presence of low testosterone indicate primary pantesticular failure. A karyotype could be performed to exclude Klinefelter’s syndrome (KS). Isolated elevations of follicle-stimulating hormone in the presence of normal luteinizing hormone and testosterone indicate isolated germinal epithelium damage as is commonly seen in azoospermic infertile men. Elevated luteinizing hormone concentrations in the presence of elevated testosterone and estradiol levels suggest androgen resistance; genital skin fibroblast studies or gene analysis will define the abnormality of the androgen receptor.
Table Common Causes of Male Hypogonadism
|Hypothalamic — pituitary disorders (secondary Leydig cell dysfunction)|
|Idiopathic GnRH deficiency, Kallmann’s syndrome, Prader-Willi, Laurence-Moon-Biedl syndromes, multiple hypothalamic deficiency, pituitary hypoplasia|
|Trauma, postsurgical, postirradiation|
|Tumor (adenoma, craniopharyngioma, others)|
|Vascular (pituitary infarction, carotid aneurysm)|
|Infiltrative (sarcoidosis, histiocytosis, tuberculosis, fungal infection, hemochromatosis)|
|Systemic illness, malnutrition, anorexia nervosa, obesity, diabetes mellitus|
|Drugs (drug-induced hyperprolactinemia, sex steroids)|
|Testicular disorders (primary Leydig cell dysfunction)|
|Chromosomal (Klinefelter’s syndrome and variants, XX male gonadal dysgenesis)|
|Defects in androgen biosynthesis|
|Orchitis (mumps, other viral, HIV, leprosy)|
|Toxins (alcohol, opiates, fungicides, insecticides, heavy metals, cotton seed oil)|
|Drugs (cytotoxic drugs, ketoconazole, cimetidine, spironolactone)|
|Systemic illness (uremia, liver failure)|
|End-organ disorder (impaired androgen action)|
|Androgen receptor defects|
|Postreceptor transduction abnormalities|
Hypogonadism may consist of testosterone deficiency, testosterone resistance, or impaired spermatogenesis.
Testosterone deficiency in men encompasses disorders involving the testes (primary), the hypothalamus or pituitary (secondary), or combinations of the two hormonal sites. Impaired spermatogenesis may be seen in association with testosterone deficiency or as an isolated problem. The clinical manifestations of testosterone deficiency depend on the age of onset and the severity of the disorder. The classical symptoms of decreased male phenotype and decreased sexuality may be coupled with decreased muscle and bone mass and increased fat mass. Infertility due to decreased sperm production or function is the result of multiple mechanisms, but these are still not very well understood. Testing for hypogonadism is described in this post.