My LH and FSH are normal but my testosterone is low; what should I do next to evaluate and manage this?

Evaluation and Management of Low Testosterone with Normal LH and FSH

Immediate Diagnostic Priority

Your hormone pattern—low testosterone with normal LH and FSH—indicates secondary (hypogonadotropic) hypogonadism, not primary testicular failure, and requires immediate evaluation to identify the underlying cause before any treatment is initiated. 1, 2

This pattern is distinctly different from primary testicular failure, where you would see elevated LH and FSH with low testosterone. 1 Your normal gonadotropins suggest the problem originates in the hypothalamus or pituitary gland, which is failing to appropriately increase LH and FSH secretion in response to low testosterone. 2, 3

Essential Diagnostic Workup

You must undergo the following tests immediately to determine the cause:

Mandatory Hormonal Testing

• Measure serum prolactin levels to screen for hyperprolactinemia, which commonly causes secondary hypogonadism by suppressing gonadotropin secretion. 1, 4 If prolactin is elevated on initial testing, repeat the measurement to confirm it is not spurious. 1

• Obtain morning total testosterone (between 8-10 AM) on at least two separate occasions to confirm the diagnosis, as testosterone levels fluctuate and single measurements can be misleading. 1

• Calculate free testosterone using equilibrium dialysis method along with sex hormone-binding globulin (SHBG) levels, as total testosterone alone may be misleading, particularly if SHBG is abnormal. 1

• Check thyroid function (TSH and free T4) because thyroid disorders commonly disrupt the hypothalamic-pituitary-gonadal axis and can cause secondary hypogonadism. 1

Critical Imaging and Additional Testing

• If prolactin is persistently elevated, you require referral to an endocrinologist and likely need pituitary MRI to evaluate for prolactinoma or other pituitary tumors. 1

• If your total testosterone is <150 ng/dL with low or low-normal LH, obtain pituitary MRI regardless of prolactin levels, as non-secreting pituitary adenomas may be present. 1

• Measure serum iron saturation to exclude hemochromatosis, which can infiltrate the pituitary and cause secondary hypogonadism. 1, 3

Fertility Assessment (If Relevant)

• If you desire fertility now or in the future, undergo testicular examination to assess testicular size and consistency, and measure FSH to evaluate your baseline reproductive health status before starting any treatment. 1

• Never start exogenous testosterone therapy if fertility is a concern, as it will completely suppress LH and FSH through negative feedback, causing azoospermia that can take months to years to recover. 1, 5, 6

Common Reversible Causes to Evaluate

Before concluding this is permanent secondary hypogonadism, systematically exclude these reversible causes:

• Medications: Chronic opioid use, corticosteroids, and anabolic steroids all suppress the hypothalamic-pituitary axis. 1

• Metabolic factors: Obesity (BMI >25), poorly controlled diabetes, and metabolic syndrome impair gonadotropin secretion. 1 Weight loss and metabolic optimization can normalize testosterone levels in functional hypogonadism. 1

• Systemic diseases: Hemochromatosis, sarcoidosis, and histiocytosis X can infiltrate the pituitary. 2, 3

• Nutritional status: Severe caloric restriction, excessive exercise, and eating disorders suppress gonadotropin secretion. 2, 3

• Sleep disorders: Obstructive sleep apnea is associated with hypogonadotropic hypogonadism. 1

Treatment Algorithm Based on Findings

If Reversible Cause Identified

• Address the underlying condition first (optimize thyroid function, discontinue offending medications, treat hyperprolactinemia, achieve weight loss if obese). 1

• Recheck testosterone, LH, and FSH after 3-6 months of addressing reversible factors to determine if hypogonadism has resolved. 1

If Fertility is Desired

• Refer to reproductive endocrinologist for treatment with human chorionic gonadotropin (hCG) injections, which stimulate testicular testosterone production and preserve spermatogenesis. 1, 5, 2

• FSH injections may be added after testosterone normalizes on hCG if sperm counts remain low. 1, 5

• Pulsatile GnRH therapy is an alternative option if GnRH deficiency is confirmed and pituitary function is intact. 2, 4

If Fertility is Not a Concern

• Testosterone replacement therapy is appropriate once secondary causes are excluded and fertility is not desired. 1, 6, 4

• Transdermal testosterone preparations (gel or patch) are preferred as they produce stable physiological testosterone levels, though injectable testosterone is a cost-effective alternative. 1, 6

• Monitor testosterone levels 2-3 months after initiating therapy to ensure adequate replacement, and periodically thereafter. 1, 6

Critical Pitfalls to Avoid

• Do not assume this is "age-related hypogonadism" without thorough evaluation, as secondary hypogonadism always requires investigation for underlying pathology. 1, 6

• Do not start testosterone replacement before measuring prolactin and obtaining pituitary imaging if indicated, as this could mask a pituitary tumor. 1

• Do not use testosterone replacement if you have any interest in preserving fertility, as recovery of spermatogenesis after testosterone-induced azoospermia is unpredictable and can take years. 1, 5, 6

• Do not rely on a single testosterone measurement, as levels fluctuate significantly and diagnosis requires confirmation on at least two separate morning samples. 1