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The primary care physician (PCP) plays an important role in the diagnosis of male hypogonadism. Diagnosing hypogonadism is important since testosterone is required for normal virilization, sexual function, and bone and muscle mass. Although men with reproductive problems initially will discuss their symptoms with their PCP, the symptoms are often nonspecific. The PCP needs to carefully determine whether hypogonadism is a possibility and, if so, how to accurately make the diagnosis. Once the diagnosis of hypogonadism is confirmed, the PCP must evaluate its etiology.


Normal Physiology

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus in a pulsatile manner approximately every 2 hours and stimulates the pituitary gland to release the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are required for normal spermatogenesis and testosterone production by the testes. There is a negative feedback loop so that when testosterone is decreased, gonadotropins are upregulated. A defect in the hypothalamus, pituitary gland, or testes can result in decreased testosterone production (Fig. 7-1).


The hypothalamic-pituitary-gonadal axis. (A) Normal physiology. GnRH stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion of the pituitary gland, which in turn stimulate testosterone secretion by testes. (B) Secondary hypogonadism. Defect at level of hypothalamus or pituitary gland resulting in decreased FSH and LH secretion. (C) Primary hypogonadism. Defect at level of the testes resulting in increased FSH and LH.

Etiologies of Hypogonadism

When the diagnosis of hypogonadism is made, the etiology must be determined. The first step is to evaluate whether the hypogonadism is due to a hypothalamic/pituitary etiology or testicular etiology. This can be determined by measuring LH and FSH (Fig. 7-1). If LH and FSH levels are low or inappropriately normal with low testosterone, then a disorder of the hypothalamus/pituitary gland is responsible for the hypogonadism. If LH and FSH levels are appropriately elevated in the setting of low testosterone, the disorder resides in the testes.1,2

Primary Hypogonadism

Primary hypogonadism is characterized by a defect at the level of the testes. Laboratory testing reveals low serum testosterone and elevated FSH and LH. Causes of primary hypogonadism can be genetic or acquired. One of the most common genetic etiologies of hypogonadism is Klinefelter syndrome, which occurs in 1 in 1000 live births and has a spectrum of severity depending on the degree of mosaicism. The men with chromosomal mosaicism (47,XXY/46,XY) may present later in life. A karyotype is recommended for all patients with primary hypogonadism of unknown etiology, as patients with Klinefelter syndrome may require screening for breast cancer and autoimmune disease. Acquired causes of primary hypogonadism include testicular trauma, testicular torsion, chemotherapy, radiation therapy, viral infections such as human immunodeficiency virus (HIV) ...

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