What are the implications of low Follicle-Stimulating Hormone (FSH) in a male?

From the Guidelines

Low FSH in males is typically associated with hypogonadotropic hypogonadism, a condition where the brain doesn't send proper signals to stimulate testosterone and sperm production, often requiring hormone replacement therapy or gonadotropin therapy for fertility purposes. This condition can be caused by various factors, including pituitary tumors, genetic conditions like Kallmann syndrome, excessive exercise, malnutrition, or certain medications 1. Symptoms of low FSH in males may include reduced libido, erectile dysfunction, fatigue, decreased muscle mass, and infertility.

When evaluating a male with low FSH, it's essential to consider the underlying cause and potential impact on fertility. According to the AUA/ASRM guideline (2024), obstructive azoospermia is suspected if the physical examination reveals testes of normal size, fully descended into the scrotum, and bilaterally dilated and/or indurated epididymides with or without absence of the vas deferens, often with FSH levels less than approximately 7.6 IU/L 1. In contrast, non-obstructive azoospermia is more likely the cause when the testes are atrophic, especially in the presence of FSH greater than 7.6 IU/L.

Key points to consider in the diagnosis and management of low FSH in males include:

• Blood tests measuring FSH, LH, and testosterone levels to confirm the diagnosis
• Brain imaging to check the pituitary gland for potential tumors or other abnormalities
• Hormone replacement therapy, such as testosterone replacement, for men not concerned with fertility
• Gonadotropin therapy, including human chorionic gonadotropin (hCG) and FSH injections, for those wanting to father children
• Karyotype testing for males with primary infertility and azoospermia or sperm concentration <5 million sperm/mL when accompanied by elevated FSH, testicular atrophy, or a diagnosis of impaired sperm production 1.

Treatment should be supervised by an endocrinologist or urologist specializing in male reproductive health, taking into account the individual's specific needs and fertility goals.

From the Research

Implications of Low Follicle-Stimulating Hormone (FSH) in Males

• Low FSH levels in males can be indicative of hypogonadotropic hypogonadism, a condition characterized by a dysfunction in the hypothalamus and/or the pituitary gland, leading to low or inappropriately normal gonadotropin levels along with low total testosterone levels 2.
• In men with hypogonadotropic hypogonadism, low FSH levels can be associated with impaired spermatogenesis, which can be responsive to hormonal therapy such as gonadotropin therapy or GnRH supplementary/replacement therapy 2.
• Testosterone replacement therapy can suppress FSH levels, and the combination of FSH and hCG has been shown to be associated with better outcomes than single compounds in promoting testicular growth, spermatogenesis, and pregnancy rates 2.
• Low FSH levels can also be seen in men with primary hypogonadism, where an elevated FSH level is indicative of abnormal spermatogenesis and may indicate primary testicular failure 3.
• A study found that FSH levels >4.5 IU/L were associated with abnormal semen analysis in terms of morphology and sperm concentration, suggesting that the 'normal' range for FSH may need to be reconsidered 3.
• The diagnosis of male hypogonadism is based on clinical signs and symptoms plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions, and serum luteinizing hormone and FSH levels can distinguish between primary and secondary hypogonadism 4.
• The Endocrine Society of Australia recommends that hormonal assessment of male hypogonadism is based on measurement of circulating testosterone, luteinising hormone (LH), and FSH concentrations, and that testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age 5.

Associated Conditions and Treatments

• Hypogonadotropic hypogonadism can be treated with gonadotropin therapy, which can promote puberty and support spermatogenesis onset and preservation in patients with either hypothalamic or pituitary conditions 2.
• Testosterone replacement therapy can have many potential benefits, including improved sexual function, an enhanced sense of well-being, increased lean body mass, decreased body fat, and increased bone density, but it also carries potential risks, including the possibility of stimulating the growth of an occult prostate cancer 4.
• The balance between benefits and risks of androgen replacement therapy is not always clear, especially in men with mild hypogonadism or andropause, and further research is needed to clarify the role of testosterone in these settings 4, 5.