How Testosterone Cypionate Affects LH

Luteinising hormone is released by the anterior pituitary in response to pulsatile GnRH from the hypothalamus, and it drives Leydig cell testosterone production in the testis. Exogenous testosterone shuts this down:

1. Negative feedback at the hypothalamus: Circulating testosterone and its aromatised product oestradiol both suppress GnRH pulse frequency and amplitude. Oestradiol is the more potent suppressor of the two at the hypothalamic level, which is one reason that adding an aromatase inhibitor does not preserve LH.

2. Direct pituitary suppression: Androgens reduce pituitary responsiveness to whatever GnRH signal remains.

3. Intratesticular testosterone collapses: LH suppression removes the drive for Leydig cell steroidogenesis. Intratesticular testosterone concentrations, which are 50 to 100 times higher than serum in an intact axis, fall by an order of magnitude. Spermatogenesis depends on that intratesticular concentration, not on serum testosterone, which is why a man with excellent serum testosterone on TRT can be azoospermic.

4. This happens at replacement doses: Suppression is not confined to supraphysiological use. Schulte-Beerbühl and Nieschlag (1980, PMID 7353699) measured LH and FSH after injection of both testosterone enanthate and testosterone cypionate, and suppression of gonadotrophins is a defining property of both.

Cypionate versus enanthate: identical. The Endocrine Society's 2018 guideline (PMID 29562364) doses them the same way and counsels the same fertility implications for both.

Any replacement dose (100-200 mg/week):

• LH falls to undetectable, typically below 0.1 IU/L, within 2 to 4 weeks
• FSH follows the same course
• Testicular volume decreases measurably over 3 to 6 months

Supraphysiological doses: no different in kind. LH is already at the floor at replacement doses and cannot fall further.

Spermatogenesis:

• Sperm counts fall over 6 to 12 weeks
• Azoospermia is common but not universal
• Recovery after stopping typically takes 6 to 12 months, and is slower with longer duration of use and older age

With hCG added:

• hCG is an LH analogue and acts directly at the LH receptor. It does not raise measured LH, and on many assays it does not cross-react. Serum LH stays suppressed while the testis is being stimulated regardless.
• This is why LH is not a useful marker of whether an hCG protocol is working. Intratesticular function is better assessed through testicular volume, semen analysis and, indirectly, through testosterone response.

Reversibility: LH recovery after stopping testosterone typically takes 3 to 6 months, sometimes longer.

Baseline before starting is essential, and it is diagnostic rather than monitoring:

• LH and FSH before the first injection distinguish primary hypogonadism (high LH, testicular failure) from secondary hypogonadism (low or normal LH, pituitary or hypothalamic cause). Once exogenous testosterone is started, that distinction can no longer be made without a lengthy washout.
• A semen analysis before starting is worth considering for any man who may want children later. It is inexpensive and cannot be reconstructed retrospectively.

On protocol:

• Routine LH monitoring on established TRT has little value. It will be undetectable and will stay undetectable.
• The exception is fertility management, where LH and FSH are checked alongside semen analysis during a restart protocol.

During a restart or PCT:

• Check LH, FSH and total testosterone at 4 to 6 weeks after stopping, then every 6 to 8 weeks.
• Semen analysis at 3 months and 6 months if fertility is the goal.
• Recovery is slow, and a single suppressed reading at 6 weeks is not a failure.

If fertility matters, plan before starting, not after:

• Sperm cryopreservation before starting TRT is the only fully reliable option and is inexpensive relative to the alternatives.
• Concurrent hCG at 250 to 500 IU two or three times weekly maintains intratesticular testosterone and preserves spermatogenesis in many men, and is far easier than restoring it later.
• Enclomiphene and clomiphene raise endogenous LH by blocking hypothalamic oestrogen receptors, and are alternatives to testosterone for men with secondary hypogonadism who want to preserve fertility.

Testicular atrophy:

• Expected. Reversible in most men, though not always fully.
• hCG maintains testicular volume as well as spermatogenesis.

Do not interpret a suppressed LH on hCG as failure: hCG acts at the LH receptor directly and does not raise measured LH. Testicular volume and semen analysis are the meaningful endpoints.

Do not switch esters to preserve fertility: cypionate and enanthate suppress the axis identically.

Further reading: hCG, fertility and TRT