Secondary (Hypogonadotropic) Hypogonadism
This patient has secondary (hypogonadotropic) hypogonadism, characterized by low testosterone with inappropriately low/normal FSH and LH, indicating hypothalamic-pituitary axis dysfunction rather than primary testicular failure. 1
Diagnostic Classification
The laboratory values confirm hypogonadotropic hypogonadism:
- Testosterone <0.5 nmol/L (<14 ng/dL) - severely deficient 1
- FSH 3 IU/L and LH 1.6 IU/L - inappropriately low/normal for the degree of testosterone deficiency 1
- Estradiol <30 pmol/L - consistent with severe hypogonadism 1
In primary hypogonadism, FSH and LH would be elevated (>10-15 IU/L) as the pituitary attempts to compensate for testicular failure. 1, 2 The low-normal gonadotropins here indicate the problem originates at the hypothalamic-pituitary level. 1, 3
Essential Additional Workup
Before initiating treatment, you must:
Measure serum prolactin - mandatory in all patients with low testosterone and low/normal LH to screen for prolactinoma or other pituitary tumors 1, 4
Obtain pituitary MRI - required if testosterone <150 ng/dL with low/normal LH, regardless of prolactin level, to exclude non-secreting adenomas 1
Assess other pituitary hormones - evaluate for combined pituitary hormone deficiencies (thyroid, cortisol, growth hormone) 1, 5
Determine etiology - investigate acquired causes including:
Treatment Strategy
If Fertility is NOT Currently Desired:
Testosterone replacement therapy is the treatment of choice to restore virilization, sexual function, bone density, muscle mass, and quality of life. 4, 3, 2
Testosterone enanthate 50-400 mg intramuscularly every 2-4 weeks is the standard initial approach. 6 Most patients require 100-200 mg every 2 weeks; doses above 400 mg/month are rarely needed due to prolonged action. 6
Alternative formulations include:
Monitor testosterone levels 2-3 months after initiation, then periodically, targeting mid-normal range. 4 Assess clinical response including libido, erectile function, energy, mood, and muscle mass. 4
If Fertility IS Desired (Current or Future):
Testosterone monotherapy must NOT be prescribed as it suppresses spermatogenesis and will worsen infertility. 1, 4
Instead, use gonadotropin therapy:
- Human chorionic gonadotropin (hCG) combined with FSH (recombinant FSH, highly purified urinary FSH, or human menopausal gonadotropins) 1, 7
- Administered subcutaneously or intramuscularly 7
- Typical duration: 12-24 months to achieve spermatogenesis 7
- Success rates: ~80% achieve spermatogenesis, ~50% achieve pregnancy 7
Alternative for mild cases: Selective estrogen receptor modulators (SERMs) or aromatase inhibitors may be considered for men with low testosterone who wish to preserve fertility. 1, 4
Critical Pitfalls to Avoid
- Never start testosterone without measuring prolactin first in patients with low/normal LH - you could miss a prolactinoma 1, 4
- Never give testosterone to men desiring fertility - it will suppress their remaining spermatogenesis 1, 4
- Don't assume this is age-related hypogonadism - the severely low testosterone (<14 ng/dL) and very low gonadotropins demand investigation for structural pituitary disease 1
- Monitor for gynecomastia if using gonadotropin therapy, as hCG stimulates aromatase and estradiol production 7
Prognosis Factors
Better outcomes with gonadotropin therapy occur in patients with:
- Post-pubertal onset of hypogonadism 7
- No history of cryptorchidism 7
- Larger baseline testicular volume 7
- Higher baseline inhibin B levels 7
- Repeated treatment cycles 7
Approximately 10% of patients may experience reversal of hypogonadism, though the mechanism remains unclear. 7