In an adult male with low serum testosterone and normal LH and FSH, does this indicate secondary (hypogonadotropic) hypogonadism and what should be the next diagnostic and therapeutic steps?

Understanding Normal LH and FSH with Low Testosterone

Yes, LH and FSH are the "brain signals" from your pituitary gland to your testicles, and when they are normal but testosterone is low, this indicates secondary (hypogonadotropic) hypogonadism—meaning the problem is NOT with your brain's signaling, but rather represents a subtle dysfunction where the pituitary's response is inadequate for the degree of testosterone deficiency. 1

What This Hormone Pattern Actually Means

• Secondary hypogonadism is characterized by low testosterone with normal or low LH/FSH levels, which differs fundamentally from primary testicular failure where LH and FSH would be elevated above normal as a compensatory response 1

• The key insight is that "normal" LH/FSH in the context of low testosterone is actually inappropriately normal—meaning your pituitary should be producing higher levels of these hormones to compensate for the low testosterone, but it's not 1, 2

• This pattern indicates impairment of the hypothalamic-pituitary-gonadal axis rather than direct testicular dysfunction 1

Common Reversible Causes to Investigate

Before accepting this as permanent secondary hypogonadism, you must rule out functional causes:

• Obesity is the most common reversible cause, as increased aromatization of testosterone to estradiol in adipose tissue creates estradiol-mediated negative feedback that suppresses pituitary LH secretion 1

• Medications including opiates, GnRH agonists/antagonists, glucocorticoids, estrogens, and progestogens can cause this pattern 1

• Metabolic stress, eating disorders, and endurance exercise can create "functional" hypogonadotropic hypogonadism where gonadotropin levels are in the low-normal range but inadequate for the testosterone levels 2, 3

• Thyroid dysfunction disrupts the hypothalamic-pituitary-gonadal axis and must be evaluated and corrected 4

Essential Diagnostic Steps

Confirm the diagnosis properly:

• Repeat morning testosterone measurements (between 8-10 AM) on at least two separate days to confirm persistent low testosterone 1, 5

• Measure free testosterone by equilibrium dialysis, especially if you are obese, as this provides a more accurate assessment 1

• Check sex hormone-binding globulin (SHBG) levels, as low SHBG can affect total testosterone measurements 1

• Measure prolactin to exclude hyperprolactinemia, which can disrupt gonadotropin secretion 4

• Assess thyroid function (TSH, free T4) as thyroid disorders commonly affect reproductive hormones 4

Critical Treatment Considerations Based on Fertility Goals

The treatment approach differs dramatically depending on whether you want to preserve fertility:

If Fertility is NOT a Concern:

• Testosterone replacement therapy is appropriate and effective for reversing symptoms of androgen deficiency 1, 5
• Lifestyle modifications (weight loss through low-calorie diets and physical activity) can be combined with testosterone therapy to reverse obesity-associated secondary hypogonadism 1

If Fertility IS a Concern or Desired:

• Never use testosterone replacement therapy—it will completely suppress spermatogenesis through negative feedback on the hypothalamus and pituitary, potentially causing azoospermia that takes months to years to recover 1, 4

• Gonadotropin therapy (hCG followed by FSH) is the appropriate treatment, as it can successfully initiate spermatogenesis while maintaining testosterone levels 1, 4

• Combined hCG and FSH therapy provides optimal outcomes, with 75% of men achieving sperm in ejaculate 4

• Alternative options include clomiphene citrate (a selective estrogen receptor modulator), which increased testosterone from 7.6 to 19.3 nmol/L in men with hypogonadotropic hypogonadism, with 67% reporting symptom improvement 6

Why This Matters for Your Prognosis

Secondary hypogonadism has a fundamentally better prognosis than primary testicular failure:

• You can potentially achieve both fertility and normal testosterone levels with appropriate treatment 1

• The pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins, meaning the system is still functional and responsive 7

• In contrast, primary hypogonadism patients can only receive testosterone therapy, which compromises fertility by suppressing the HPG axis 1

Common Pitfall to Avoid

The most critical error is prescribing testosterone replacement to men who may want fertility in the future. Once you start testosterone, it provides negative feedback to the hypothalamus/pituitary, suppressing gonadotropin secretion and potentially causing azoospermia 4, 1. This suppression can persist for months to years after discontinuation, making fertility recovery uncertain and prolonged.