In a male patient undergoing infertility evaluation who has low luteinizing hormone, what is the appropriate diagnostic and therapeutic approach?

Approach to Low Luteinizing Hormone in Male Infertility

In a male patient with infertility and decreased LH, immediately measure serum testosterone and prolactin to distinguish hypogonadotropic hypogonadism from other causes, then treat with hCG followed by FSH analogues if fertility is desired—never prescribe testosterone monotherapy as it will worsen infertility. 1

Initial Diagnostic Workup

The combination of low LH in an infertile male indicates potential hypogonadotropic hypogonadism (HH), where deficient LH and FSH secretion prevents Leydig cells from secreting testosterone and disrupts spermatogenesis 1. This requires immediate hormonal characterization:

• Measure serum testosterone (morning, 8-10 AM) to confirm hypogonadism—expect low levels if true HH 1, 2
• Measure serum prolactin to screen for hyperprolactinemia, which can suppress LH secretion 1
• Measure FSH to determine if both gonadotropins are deficient or if this is isolated LH deficiency 1, 3
• Obtain semen analysis to document baseline sperm parameters before treatment 1, 4

If testosterone is low with concomitantly low or low-normal LH/FSH, this confirms secondary (hypogonadotropic) hypogonadism and mandates further evaluation 1, 2.

Determining the Etiology

Once HH is confirmed, identify whether this is hypothalamic versus pituitary dysfunction:

• Measure serum prolactin—if persistently elevated, refer to endocrinology for pituitary imaging to exclude prolactinomas 1
• Check iron saturation to exclude hemochromatosis as a cause of pituitary dysfunction 1
• Order pituitary MRI if testosterone <150 ng/dL with low/low-normal LH, as non-secreting adenomas may be present even without elevated prolactin 1
• Assess for functional causes: chronic opioid use, obesity, metabolic stress, or systemic illness can transiently suppress the hypothalamic-pituitary-gonadal axis 5, 2

Treatment for Fertility Restoration

The cornerstone of fertility treatment in HH is gonadotropin therapy, NOT testosterone replacement 1, 6:

First-Line Treatment Protocol

• Start with hCG injections (typically 1,000-2,500 IU subcutaneously 2-3 times weekly) to stimulate Leydig cells and normalize testosterone production 1, 6, 4
• Monitor testosterone levels after 2-3 months—once normalized, assess semen analysis 6, 4
• Add FSH analogue (recombinant FSH, highly purified urinary FSH, or human menopausal gonadotropin) if sperm counts remain low after testosterone normalization 1, 6

Expected Outcomes

The combination of hCG and FSH for 12-24 months achieves 6:

• Testicular growth in nearly all patients
• Spermatogenesis in approximately 80% of patients
• Pregnancy rates around 50%

Treatment success is higher in men with post-pubertal HH, absence of cryptorchidism history, larger baseline testicular volume, and higher baseline inhibin B levels 6.

Critical Management Pitfalls

Never prescribe testosterone monotherapy to men desiring fertility—it provides negative feedback to the hypothalamus and pituitary, suppressing LH and FSH secretion, which worsens or causes azoospermia that can take months to years to reverse 1, 5.

Common Side Effects to Monitor

• Gynecomastia is the most frequent side effect of hCG therapy due to aromatase stimulation and increased estradiol secretion 6
• Monitor estradiol levels if breast symptoms develop 1

Alternative Fertility Options

If gonadotropin therapy fails or is not feasible:

• Assisted reproductive technology (IVF/ICSI) offers superior pregnancy rates and should be discussed early, particularly considering female partner age 1, 5
• Surgical sperm extraction (TESE, TESA) can be used with ART if sperm production remains inadequate 1

Monitoring and Follow-Up

• Repeat semen analysis every 3-6 months during treatment to assess response 5, 6
• Recheck testosterone, LH, and FSH after initiating hCG to confirm adequate stimulation 1, 6
• Perform genetic testing (karyotype and Y-chromosome microdeletion) if severe oligospermia or azoospermia persists despite treatment, as this guides prognosis 5

Human chorionic gonadotropin alone successfully normalized testosterone, sperm concentration, and semen volume in documented cases of acquired HH, resulting in successful conception 4. The key is early recognition that low LH with infertility represents a treatable endocrine disorder requiring gonadotropin replacement, not testosterone suppression.