From the Guidelines
Elevated FSH levels are typically indicative of primary testicular failure, characterized by impaired sperm production, which can be due to various conditions such as non-obstructive azoospermia, where FSH levels are usually greater than 7.6 IU/L, as noted in the 2024 AUA/ASRM guideline 1. When considering the potential causes of high FSH, it's essential to differentiate between obstructive and non-obstructive azoospermia. Key factors to consider include:
- Testicular size and whether they are fully descended into the scrotum
- Presence of bilaterally dilated and/or indurated epididymides
- Absence of the vas deferens
- Semen analysis results, including volume, pH, and presence of sperm Some critical conditions associated with high FSH levels include:
- Non-obstructive azoospermia, where testes are atrophic, and FSH levels exceed 7.6 IU/L
- Klinefelter syndrome, a genetic disorder characterized by extra X-chromosomes, leading to impaired spermatogenesis
- Y-chromosome microdeletions, found in approximately 5% of severely oligospermic males, as reported in a meta-analysis assessing the frequency of these microdeletions in North America and Europe 1. In clinical practice, it is crucial to recommend 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, as karyotype abnormalities are the most common known genetic abnormalities causing male infertility 1.
From the Research
Reasons for High FSH Levels
- High FSH levels can be associated with low response in infertility treatment, as well as reproductive ageing 2
- Physiological conditions such as puberty, hereditary dizygotic twinning, after use of oral contraceptives, and during lactation can also lead to elevated FSH levels 2
- Pathological conditions like unilateral ovariectomy, recovery from hypothalamic amenorrhea, and excessive smoking can cause significant increases in FSH 2
- In men, an elevated FSH level is indicative of abnormal spermatogenesis and may indicate primary testicular failure 3
- FSH levels >4.5 IU/L have been associated with abnormal semen analysis in terms of morphology and sperm concentration 3
Factors Influencing FSH Levels
- Intra-, inter-, and between different assays variation can affect FSH concentrations 2
- Hourly, cycle day dependent, intercycle, and lifetime variation can also impact FSH levels 2
- Autoimmune antibodies have been found to be more prevalent in women with high FSH levels, suggesting an autoimmune basis for premature ovarian failure 4
Health Implications of High FSH Levels
- Primary ovarian insufficiency, characterized by declining ovarian function and reduced fecundity, can lead to vasomotor symptoms, urogenital atrophy, osteoporosis, and increased mortality 5, 6
- Hormone replacement therapy is recommended to alleviate symptoms and mitigate long-term health risks in women with primary ovarian insufficiency 5, 6