What is the diagnosis for a 16-year-old male with hypogonadotropic hypogonadism, as evidenced by low Follicle-Stimulating Hormone (FSH) levels?

From the Guidelines

A 16-year-old male with low FSH should be evaluated for potential hypogonadotropic hypogonadism and treated with human chorionic gonadotropin (hCG) to restore testosterone production and spermatogenesis, as exogenous testosterone therapy can inhibit intratesticular testosterone production and suppress spermatogenesis. The initial workup should include measuring other pituitary hormones (LH, testosterone, prolactin), complete physical examination focusing on pubertal development (Tanner staging), and assessment for delayed puberty signs 1. Some key points to consider in the management of this patient include:

• The degree of response to hCG treatment correlates with the size of the testis prior to treatment 1
• Initial treatment is with hCG injections (500-2500 IU, 2-3 times weekly) followed by FSH injections, when indicated, after testosterone levels are normalized on hCG 1
• Exogenous testosterone administration provides negative feedback to the hypothalamus and pituitary gland, which can result in inhibition of gonadotropin secretion and decrease or cease spermatogenesis altogether, resulting in oligospermia or azoospermia 1
• Recovery of sperm to the ejaculate occurs in most azoospermic males after cessation of testosterone therapy, but the time course of recovery may be prolonged and can be months or rarely years 1. Given the potential negative effects of exogenous testosterone therapy on spermatogenesis, it is essential to avoid this treatment in males pursuing or planning to pursue family building in the near future 1.

From the FDA Drug Label

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. Delayed puberty – Testosterone Enanthate Injection, USP may be used to stimulate puberty in carefully selected males with clearly delayed puberty

The patient is a 16-year-old male with low FSH, which may indicate hypogonadotropic hypogonadism.

• Testosterone enanthate may be used to stimulate puberty in carefully selected males with clearly delayed puberty.
• However, the patient's condition should be evaluated to determine the underlying cause of the low FSH levels.
• Androgen replacement therapy may be necessary to induce development of secondary sexual characteristics.
• The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration 2.

From the Research

Low FSH in a 16-year-old Male

• A 16-year-old male with low FSH levels may be experiencing hypogonadotropic hypogonadism, a condition characterized by low or inappropriately normal gonadotropin levels along with low total testosterone levels 3.
• This condition can be caused by a dysfunction in the hypothalamus and/or the pituitary gland and can be congenital or acquired 3.
• The diagnosis of hypogonadism is based on clinical signs and symptoms plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions 4.
• Serum luteinizing hormone and follicle-stimulating hormone levels distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism 4.

Treatment Options

• Gonadotropin therapy, including human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH), can be effective in promoting puberty and supporting spermatogenesis onset and preservation in patients with hypogonadotropic hypogonadism 3.
• The combination of FSH and hCG has been shown to be associated with better outcomes than single compounds, with similar results obtained with different FSH preparations in male individuals 3.
• Testosterone replacement therapy is also an option, but it may increase the risk of infertility 5.
• Human chorionic gonadotropin (hCG) treatment has been shown to be a viable option for the management of secondary hypogonadism and male infertility, as it triggers testosterone and sperm production without the side effects on fertility seen in testosterone replacement therapy 5.

Specific Considerations

• In cases of isolated FSH deficiency, recombinant human FSH (rhFSH) replacement has been shown to be effective in promoting testicular growth and spermatogenesis 6.
• The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways is complex, and different replacement regimens (e.g., hCG/rFSH vs. testosterone) can have distinct effects on serum steroid hormone profiles 7.
• The choice of treatment should be individualized based on the patient's specific needs and circumstances, taking into account factors such as fertility potential and long-term health and quality of life 7.