From the Guidelines
Elevated FSH, LH, and estradiol in men typically indicate primary hypogonadism, where the testes fail to produce adequate testosterone despite normal or increased stimulation from the pituitary gland. The most common causes of primary hypogonadism include Klinefelter syndrome (XXY chromosomal abnormality), testicular trauma or injury, orchitis (testicular inflammation often from mumps), cryptorchidism (undescended testes), radiation or chemotherapy exposure, and aging (andropause) 1. Other causes of elevated FSH, LH, and estradiol in men may include:
- Certain medications like spironolactone, ketoconazole, and some antipsychotics
- Liver disease which impairs testosterone metabolism
- Obesity which increases aromatase activity converting testosterone to estradiol
- Rare genetic disorders affecting testosterone synthesis
- Alcohol abuse which can damage testicular tissue Diagnosis typically involves confirming these hormone abnormalities with blood tests, physical examination, and possibly testicular ultrasound, karyotyping, or MRI imaging 1. Treatment depends on the underlying cause but may include testosterone replacement therapy, weight loss for obesity-related cases, or medication adjustments. Men with these hormonal abnormalities may experience symptoms like decreased libido, erectile dysfunction, infertility, gynecomastia, and reduced muscle mass 1. It is essential to consider 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. In patients with obesity, treatment with testosterone-replacement therapy should be considered when the morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and the hypogonadism workup has been completed to rule out an etiology of hypogonadism unrelated to obesity 1. The method of testosterone replacement should be individualized for each patient, with transdermal testosterone preparations suggested for most hypogonadal men because they usually produce normal serum testosterone concentrations, and patients typically find them the most convenient 1. Testosterone levels should be tested 2 to 3 months after treatment initiation, and/or after any dose change, to determine that normal serum testosterone concentrations are being achieved 1. Providers should consider obtaining morning serum total testosterone measurements in male patients who complain of fatigue, weight loss, loss of libido or erectile dysfunction, or depressive symptoms or who have evidence of reduced bone mineral density 1. Once the diagnosis of hypogonadism is established, further testing by measuring luteinizing hormone and follicular stimulating hormone should be considered to determine whether it is primary source (testicular failure) or central source (hypothalamic or pituitary dysfunction) 1.
From the Research
Causes of Elevated FSH, LH, and Estradiol Levels in Males
- Elevated FSH levels can be indicative of abnormal spermatogenesis and may indicate primary testicular failure 2
- FSH levels >4.5 IU/L are associated with abnormal semen analysis in terms of morphology and sperm concentration 2
- Peripheral estradiol levels directly reflect the inhibitory tone exerted by estrogens on gonadotropin release and are a major determinant of peripheral testosterone, LH, and FSH levels 3
- Thyroid hormone deficiency can affect gonadal function, with primary hypothyroidism associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone replacement therapy 4
- Hyperthyroidism can lead to elevated concentrations of testosterone and SHBG, as well as estradiol elevations and gynecomastia in men 4
- Gonadotroph pituitary adenomas can cause hypersecretion of testosterone, although this is a rare occurrence 5
Relationship Between Hormone Levels
- Levels of testosterone, LH, and FSH are inversely related to peripheral estradiol levels 3
- Elevated FSH and LH levels can be associated with low testosterone levels 6, 2
- Estradiol levels can affect gonadotropin release, with high levels inhibiting LH and FSH secretion 3