How Testosterone Enanthate Affects LH

Exogenous testosterone and its metabolites suppress luteinising hormone (LH) through negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis:

1. Hypothalamic suppression: Elevated circulating testosterone and estradiol (aromatised from testosterone) feed back to the hypothalamus, reducing the pulsatile secretion of gonadotropin-releasing hormone (GnRH). GnRH pulses are the upstream driver of LH production; without them, pituitary LH secretion falls.

2. Pituitary suppression: Testosterone, estradiol, and DHT all act directly on pituitary gonadotroph cells to suppress LH gene expression and secretion. Both the frequency and amplitude of LH pulses are reduced.

3. Dose-dependent but near-complete suppression: Even at replacement doses intended to mimic physiological testosterone levels, exogenous testosterone provides a constant non-pulsatile androgen signal that disrupts the normal feedback rhythm. The pituitary responds by dramatically reducing LH output. LH typically drops to below 1.0 IU/L within 2-4 weeks of starting TRT and to below 0.5 IU/L at supraphysiological doses.

4. Downstream consequence: testicular shutdown: LH is the signal that drives Leydig cells in the testes to produce intratesticular testosterone (ITT). ITT is essential for spermatogenesis: it is maintained at concentrations 50-100x higher than serum testosterone within the testis. When LH is suppressed and ITT collapses, sperm production ceases within 6-12 weeks.

5. Estradiol contribution: Estradiol, produced by aromatisation of testosterone, provides potent negative feedback at the hypothalamus and pituitary. This is why aromatase inhibitors can sometimes modestly raise LH in men, though this is not a reliable fertility preservation strategy.

TRT doses (100-200 mg/week):

• LH drops to below 1.0 IU/L within 2-4 weeks of starting treatment
• Values of 0.1-0.5 IU/L are typical at steady state
• Many laboratories report LH as "less than 0.2 IU/L" or even as undetectable at these suppressed levels
• FSH is suppressed simultaneously (see related FSH interaction)

Supraphysiological doses (300-600+ mg/week):

• LH drops to undetectable within 1-2 weeks
• FSH is similarly undetectable
• The more rapid and complete suppression at higher doses means faster onset of azoospermia

Duration of suppression:

• LH remains fully suppressed for the entire duration of exogenous testosterone use. There is no escape from suppression while on TRT, regardless of dose or duration.

Recovery after cessation:

• LH begins recovering within 4-6 weeks of discontinuing testosterone in most men
• Full LH recovery to normal baseline (above 1.5 IU/L) typically takes 3-6 months for short-term users (less than 1-2 years of TRT)
• Long-term users (5-10+ years) may require 12-24 months or longer for complete HPG axis recovery
• In a small percentage of long-term users, LH recovery is incomplete, representing persistent hypogonadotropic hypogonadism
• Recovery to normal LH does not immediately restore sperm production; spermatogenesis lags by an additional 2-3 months after LH normalises

LH testing while on TRT is not clinically useful:

• LH will be suppressed at every test while exogenous testosterone is being administered. A suppressed LH on TRT is not a diagnostic finding; it is an expected pharmacological effect.
• Do not order LH tests to "monitor TRT efficacy." They add no clinical information during active treatment.

LH is important at two time points:

1. Baseline (before starting TRT): LH at baseline distinguishes primary hypogonadism (high LH with low testosterone, indicating testicular failure) from secondary hypogonadism (low LH with low testosterone, indicating hypothalamic or pituitary dysfunction). This classification changes management and should be documented before TRT is started.

2. After cessation (HPTA recovery monitoring): For men coming off TRT (either by choice, for fertility, or as part of PCT after a cycle), LH is the key marker of HPG axis recovery. Recommended testing timeline: 12 weeks after last injection, and again at 24 weeks. Testing earlier than 12 weeks is premature for long-acting esters like enanthate (half-life 4.5 days; 5 half-lives is approximately 22 days before drug is effectively cleared).

For PCT monitoring:

• Check LH at 12 weeks post-cessation
• If LH is recovering (above 2 IU/L), continue monitoring
• If LH remains undetectable at 12 weeks, consider evaluation for persistent hypogonadotropic hypogonadism
• Semen analysis is the functional endpoint for fertility recovery and should be ordered at 6 months post-cessation

If fertility preservation is needed while on TRT:

• Add human chorionic gonadotropin (HCG) to the TRT protocol. HCG is an LH analogue that directly stimulates testicular Leydig cells, bypassing the suppressed pituitary.
• Standard HCG dose for fertility maintenance: 500-1000 IU every other day or 3 times per week subcutaneously
• HCG maintains intratesticular testosterone and, with it, spermatogenesis, despite suppressed endogenous LH
• HCG should be started before testicular atrophy becomes advanced for best results
• Some men add FSH (recombinant FSH or HMG) if HCG alone is insufficient for sperm production

If coming off TRT to restore fertility:

• Stop testosterone and begin HCG 500-1000 IU every other day for 6-8 weeks to stimulate Leydig cell recovery while endogenous LH recovers
• Some protocols add clomiphene citrate (Clomid) 25-50 mg/day or enclomiphene after the HCG phase to stimulate pituitary LH production directly
• Allow 6-12 months after stopping TRT before concluding fertility is impaired; recovery is slow and variable

Testicular atrophy on TRT:

• Long-term LH suppression leads to testicular atrophy (reduction in testicular volume) because the testes are receiving no LH stimulation
• HCG prevents or reverses testicular atrophy by maintaining Leydig cell function
• Atrophy is reversible in most cases after HCG therapy or cessation of TRT, though recovery may be incomplete after very long-term use

Post-cycle therapy (PCT) after a steroid cycle:

• Clomiphene 25-50 mg/day or tamoxifen 20 mg/day stimulate the pituitary to produce LH by blocking estrogen receptor feedback
• HCG is often used during the early PCT phase (before SERMs) to restore testicular responsiveness before asking the pituitary to produce LH
• The goal of PCT is to accelerate LH recovery and normalise endogenous testosterone production; it does not fully prevent the recovery lag but shortens it