What the Brain Needs to Signal to Increase LH and FSH
The brain needs pulsatile GnRH (gonadotropin-releasing hormone) secretion from the hypothalamus to increase LH and FSH levels. 1, 2
Understanding the Hypothalamic-Pituitary-Gonadal Axis
In a male patient with low testosterone but normal LH and FSH, the issue is not that the brain needs to increase LH and FSH—these are already at appropriate levels. The problem is that the testes are not responding adequately to the existing gonadotropin signals. However, to directly answer what increases LH and FSH secretion:
The GnRH Pulse Generator
- Pulsatile GnRH secretion from the hypothalamus is the primary driver of LH and FSH release from the pituitary gonadotropic cells 2, 3
- The frequency and amplitude of GnRH pulses determine the pattern of gonadotropin secretion 1, 4
- Slow frequency GnRH pulses favor FSH secretion, while higher frequency pulses favor LH secretion 1
Negative Feedback Mechanisms That Suppress LH and FSH
Understanding what suppresses these hormones clarifies what's needed to increase them:
- Testosterone acts primarily at the hypothalamus to slow GnRH pulse frequency, thereby reducing LH and FSH 5, 4
- Estradiol (from testosterone aromatization) acts at both the hypothalamus and pituitary to suppress gonadotropin secretion 6, 5
- When testosterone levels drop, the hypothalamic GnRH pulse generator increases its firing frequency, leading to elevated LH and FSH 4
Clinical Context: Normal LH/FSH with Low Testosterone
This hormonal pattern suggests the hypothalamic-pituitary axis is functioning normally but the testes are failing to respond appropriately (primary testicular dysfunction with compensatory mechanisms not yet fully activated, or secondary hypogonadism that is subtle). 1, 7
Key Diagnostic Considerations
- Measure FSH levels >7.6 IU/L, which strongly suggest non-obstructive azoospermia or testicular dysfunction 7, 8
- Check LH and calculate free testosterone (accounting for SHBG) to distinguish primary testicular failure from secondary hypogonadism 7, 8
- Exclude reversible causes: thyroid dysfunction, hyperprolactinemia, obesity, and metabolic stress can all disrupt the hypothalamic-pituitary-gonadal axis 7, 8
Critical Pitfall to Avoid
Never prescribe exogenous testosterone if fertility is desired—it will completely suppress GnRH, LH, and FSH through negative feedback, causing azoospermia that can take months to years to recover 7, 8
Treatment to Restore Gonadotropin Secretion
If the goal is to increase LH and FSH (for example, in hypogonadotropic hypogonadism):
- Pulsatile GnRH therapy is the most physiological approach, directly replacing the missing hypothalamic signal 1, 2
- hCG injections mimic LH action and can stimulate testosterone production, with FSH analogues added if needed 7, 2
- Clomiphene or aromatase inhibitors block estrogen negative feedback, allowing increased GnRH pulse frequency and amplitude, though benefits are limited 7, 8
However, in your specific scenario with normal LH/FSH and low testosterone, the brain is already signaling appropriately—the problem lies at the testicular level, not the hypothalamic-pituitary level. 1, 7