HCG Alternatives for TRT: Enclomiphene, Kisspeptin, and What Actually Works

For years, HCG (human chorionic gonadotropin) was the standard addition to testosterone replacement therapy in the UK. It helped maintain testicular volume, sperm production, and fertility while on TRT. But over the last 18-24 months, HCG availability has become inconsistent — some UK compounding pharmacies have stopped stocking it, some TRT clinics have moved away from it entirely, and prescribing has become more sporadic.

If you're on TRT or considering it, you need to know what's actually available now and what the evidence actually supports.

Why HCG Mattered (And Still Does)

Testosterone replacement suppresses your hypothalamic-pituitary-gonadal (HPG) axis. Your LH (luteinizing hormone) drops, and with it, your body's signal to produce testosterone endogenously and maintain sperm production.

HCG mimics LH. It keeps your testes stimulated, maintains testicular size, and preserves fertility. Without it, testicular atrophy is common during TRT.

The problem: HCG supply in the UK has become unreliable. Prices have risen. Some clinics have deprioritized it. If you want to maintain fertility or testicular function on TRT, you now need to understand the alternatives.

The Alternatives: What's Available and What Works

1. Enclomiphene (SERM)

What it is: A selective estrogen receptor modulator — specifically, the active isomer of clomiphene citrate.

How it works: Unlike full clomiphene (which is a 50/50 mixture of two isomers), enclomiphene is the pure active form. It blocks negative feedback at the hypothalamus and pituitary, which increases your body's natural production of LH and FSH.

The evidence: Limited but growing. Enclomiphene has been studied for male fertility and hypogonadism in small trials. It appears to increase LH and FSH while maintaining or increasing testosterone levels. One small randomized controlled trial showed enclomiphene increased testosterone and sperm concentration compared to placebo.

Practical use for TRT: Some UK TRT clinics now offer enclomiphene as an HCG alternative. The typical dose is 12.5-25mg daily. It works slowly — you're looking at 4-8 weeks to see meaningful changes in LH/FSH.

Advantages: Oral (no injections), evidence-based, available through some UK clinics and private prescribers, relatively well-tolerated.

Disadvantages: Slower onset than HCG, less directly stimulating to the testes, requires consistent daily adherence, not as widely studied in combination with TRT.

Real-world notes: Men report maintaining or recovering testicular size on enclomiphene + TRT, though usually not as effectively as enclomiphene + HCG together. It's a reasonable first-line alternative if HCG is unavailable.

2. Kisspeptin (Hypothalamic Peptide)

What it is: A neuropeptide (Kiss1) that stimulates GnRH (gonadotropin-releasing hormone) release from the hypothalamus.

How it works: GnRH signals your pituitary to release LH and FSH. Kisspeptin is a critical upstream regulator of this axis. In men with low LH/FSH, boosting kisspeptin can theoretically restore the signal.

The evidence: This is early-stage research territory. The most notable work comes from Professor Waljit Dhillo's group at Imperial College London (UCL). They've shown that kisspeptin injection increases LH, FSH, and testosterone in men with hypogonadism. However, the research is primarily in controlled settings — hospital studies, not long-term outpatient use.

A 2018 study by Dhillo et al. showed kisspeptin-10 injections increased LH and testosterone in men with secondary hypogonadism. The effect was rapid (within hours) but the practical delivery method (intravenous in research settings) is not yet scaled for outpatient use.

Practical use for TRT: Kisspeptin is not yet available as a standard treatment in UK private practice. Some experimental TRT clinics may offer it, but it's not mainstream. If you do access it, expect it to be as an injection, likely weekly or bi-weekly.

Advantages: Addresses the root cause (hypothalamic stimulation), rapid LH response, research shows it works in hypogonadal men, could theoretically work alongside lower TRT doses.

Disadvantages: Very early stage for practical use, limited long-term safety data in routine outpatient settings, not widely available, likely expensive, unclear optimal dosing schedules for TRT context.

Real-world notes: Kisspeptin is where the research is heading. If you hear about a UK clinic offering it, they're on the cutting edge. But it's not yet the standard alternative to HCG. Likely to become more available in the next 2-3 years as research solidifies.

3. Gonadorelin (GnRH Analogue)

What it is: A synthetic form of GnRH — the hormone your hypothalamus naturally releases to signal LH and FSH production.

How it works: Direct replacement of GnRH. Stimulates the pituitary to release LH and FSH.

The evidence: GnRH analogues have a long history in medicine, primarily used for delayed puberty and some fertility conditions. The key point: they work best when dosed in a pulsatile pattern (mimicking your body's natural GnRH pulses), not continuously.

Continuous GnRH dosing actually suppresses LH/FSH (it's how leuprolide works as a prostate cancer treatment). But pulsatile dosing stimulates it.

Practical use for TRT: Some UK TRT clinics use pulsatile gonadorelin for men who want to maintain fertility or reduce HCG dependence. Typically dosed as a subcutaneous injection 1-3 times daily or via a pump.

Advantages: Direct hypothalamic stimulation, long clinical history, can maintain sperm production alongside TRT, some clinics have protocols established.

Disadvantages: Requires pulsatile dosing (not straightforward), injection-based, short half-life means frequent dosing, less convenient than HCG (which is just weekly), not widely available, expensive.

Real-world notes: Gonadorelin is used by some UK clinics but it's not the default. The practical barrier is the pulsatile dosing requirement — it's more complex than a simple weekly injection. If a clinic offers it, they understand HPG axis physiology well.

4. FSH Injections (Follicle-Stimulating Hormone)

What it is: Recombinant or extracted FSH — the hormone responsible for sperm production.

How it works: Direct stimulation of sperm production in the testes. FSH is the primary signal for spermatogenesis.

The evidence: Extensive. FSH is used clinically for male factor infertility and has decades of safety data. Combined with testosterone, FSH injections can maintain sperm production.

Practical use for TRT: Some TRT clinics offer FSH (usually recombinant FSH like Gonal-F) specifically for men focused on maintaining fertility. Typical dose is 75-150 IU, 2-3 times per week.

Advantages: Direct action on sperm production, long clinical history, well-tolerated, can be combined with any TRT regimen.

Disadvantages: Expensive (often £60-100+ per week), requires injections 2-3x weekly (in addition to TRT injections), primarily fertility-focused (less for testicular health or libido), not all clinics offer it.

Real-world notes: FSH is the most evidence-backed option specifically for fertility. If fertility is your priority, FSH + TRT is a solid protocol. But it's not ideal if you just want to maintain testicular size — it's overkill for that goal.

What the Evidence Actually Says

• HCG: Best option for testicular size and sperm production, but availability is the limiting factor.
• Enclomiphene: Reasonable first-line if HCG is unavailable. Some evidence, widely available, oral, slower onset.
• Kisspeptin: Exciting research but too early for routine use. Revisit in 2-3 years.
• Gonadorelin: Works but complex dosing; used by clinics with HPG expertise.
• FSH: Best for fertility specifically; otherwise overkill.

What Should You Actually Do?

If you're starting TRT in 2026:

1. Ask your clinic upfront: What's their standard protocol for testicular health? Can they offer HCG? If not, what's their alternative?

2. If HCG is available: Most clinics still can access it. It remains the gold standard. Ask about cost and frequency.

3. If HCG isn't available: Enclomiphene is the reasonable first alternative. It's oral, evidence-backed enough, and widely available through private prescribers.

4. If fertility is your priority: Combine TRT with FSH or discuss gonadorelin protocols with clinics that offer them.

5. If you want to explore cutting-edge: Ask whether your clinic has access to kisspeptin trials or experimental protocols. Some do.

The Practical Reality

HCG is still available in the UK — it's not gone. But supply is less guaranteed, costs have risen, and clinics are diversifying their protocols. Enclomiphene represents a practical middle ground: oral, evidence-based enough, and widely available.

The framework is shifting from "HCG is standard" to "HCG is one option among several." Understanding these alternatives means you can have an informed conversation with your clinic and make a choice that fits your priorities — whether that's testicular health, fertility, cost, or convenience.

If your current clinic can't explain their HCG alternative protocol clearly, it's worth shopping around.