TRT Prescribing Protocols: A Clinical Framework for UK Independent Prescribers
Regulatory and Legal Framework
Controlled Drug Status
- Testosterone (all formulations) is a Class C Controlled Drug under the Misuse of Drugs Act 1971 in the UK.
- Independent prescribers ARE legally able to prescribe testosterone as an independent prescriber (not under supplementary prescribing).
- Prescriptions must comply with all Controlled Drug (CD) prescription requirements:
MHRA-Licensed Products Available in the UK
| Product | Route | Formulation | CD Status |
|---|---|---|---|
| Testogel 16.2mg/g | Transdermal | Gel pump | Yes — C |
| Tostran 2% gel | Transdermal | Gel metered dose | Yes — C |
| Testim 50mg / Androgel | Transdermal | Gel sachets | Yes — C |
| Sustanon 250mg | IM injection | 250mg/ml ampoule | Yes — C |
| Nebido (testosterone undecanoate 1000mg) | IM injection | 4ml ampoule | Yes — C |
| Reandron 1000mg | IM injection | 4ml ampoule | Yes — C |
| Testopatch | Transdermal | Patch | Yes — C |
Diagnostic Criteria
Biochemical Diagnosis of Hypogonadism
Biochemical confirmation requires two morning (07:00–10:00) total testosterone measurements on separate days:
| Total Testosterone | Interpretation |
|---|---|
| <8 nmol/L | Hypogonadism confirmed |
| 8–12 nmol/L | Borderline — calculate free testosterone; consider symptoms |
| >12 nmol/L | Unlikely to benefit from TRT in most guidelines |
- Use SHBG and albumin (fixed at 4.3 g/dL) with total testosterone
- Free T <225 pmol/L is generally considered low
Distinguishing Primary vs Secondary Hypogonadism
| Finding | Interpretation |
|---|---|
| Low T + High LH/FSH | Primary hypogonadism (testicular failure) |
| Low T + Low/Normal LH/FSH | Secondary hypogonadism (pituitary/hypothalamic) |
Pre-Treatment Baseline Investigations
Mandatory
| Investigation | Clinical Rationale |
|---|---|
| Total testosterone (x2 morning) | Diagnostic confirmation |
| LH, FSH | Primary vs secondary classification |
| SHBG + calculated free T | True androgen exposure |
| FBC (haematocrit/Hct) | TRT raises Hct — baseline essential |
| PSA | Prostate cancer screening (mandatory ≥40 years) |
| Prolactin | Exclude prolactinoma |
| Thyroid function (TSH) | Thyroid disease mimics hypogonadism |
| LFTs | Hepatic function at baseline |
| Renal function (eGFR) | Renal clearance |
| Oestradiol (E2) | Baseline aromatisation |
| Blood pressure | Cardiovascular baseline |
Recommended
- HbA1c (metabolic syndrome association)
- Fasting lipids
- DRE (digital rectal examination) if PSA >1.5 ng/mL or age >50
- Semen analysis if fertility is a concern
- Bone density (DEXA) if prolonged low T suspected
- Sleep study / Epworth Sleepiness Scale if OSA suspected
Prescribing Protocols by Formulation
1. Transdermal Gel — First-Line for Many Patients
Testogel 16.2mg/g gel (gel pump):- Starting dose: 40.5mg (2 pumps, 2.5g gel) daily to non-scrotal skin
- Titration sites: shoulders, upper arms, abdomen. Avoid genitalia.
- Allow 5–10 mins to dry; cover with clothing; wash hands
- Do NOT bathe/shower for at least 2 hours post-application
- Monitoring bloods at 3 months: Aim for mid-range total T (15–25 nmol/L), taken 4–8 hours post-application
- Dose range: 20.25mg–81mg daily
- Low T → increase by one pump (8.1mg)
- High T or Hct >50% → reduce by one pump
- High E2 with symptoms → consider AI prescribing (specialist advice; discuss with patient)
2. Long-Acting Injection — Nebido / Reandron
Testosterone undecanoate 1000mg/4ml (Nebido/Reandron):- Loading dose: 1000mg IM at Week 0, then 1000mg at Week 6
- Maintenance: 1000mg every 10–14 weeks adjusted by trough testosterone level
- Trough target: 10–15 nmol/L (measured just before next injection)
- Inject slowly (2 mins minimum) deep into gluteal muscle via Z-track technique
- Pulmonary oil microembolism (POME) risk: Counsel patients to report immediately: cough, dyspnoea, chest pain, dizziness within 30 mins of injection. Patient must be observed for 30 minutes post-injection.
- Trough >18 nmol/L → extend interval by 1–2 weeks
- Trough <8 nmol/L → shorten interval by 1–2 weeks
3. Short-Acting Injection — Sustanon 250
Sustanon 250mg/ml (mixed testosterone esters):- Standard: 250mg IM every 2–4 weeks
- Many patients tolerate better on 125mg every 7–10 days (smooths peaks and troughs)
- Deep IM injection (gluteus or upper outer thigh)
- Monitoring: Trough testosterone just before next injection; target 12–18 nmol/L
Monitoring Schedule
| Visit | Timing | Investigations |
|---|---|---|
| Baseline | Pre-treatment | Full panel as above |
| Visit 1 | 6–12 weeks | Total T (timed), FBC/Hct, PSA, symptoms |
| Visit 2 | 6 months | Total T, SHBG, FBC, PSA, LFTs, BP, symptoms |
| Visit 3 | 12 months | Full metabolic panel + bone density (if applicable) |
| Annual | Ongoing | Total T, FBC, PSA, BP, symptoms, cardiovascular |
Safety Thresholds — When to Act
| Parameter | Threshold | Action |
|---|---|---|
| Haematocrit | ≥52% | Reduce dose or venesection; haematology referral |
| PSA | Rise >1.4 ng/mL in 12 months OR >4 ng/mL absolute | Refer urology; withhold TRT |
| Oestradiol | >200 pmol/L with symptoms | Dose reduction; consider aromatase inhibitor |
| SBP | >160 mmHg | Address hypertension; reassess TRT benefit |
Fertility Considerations
TRT suppresses the hypothalamic-pituitary axis, reducing LH/FSH → reduced spermatogenesis.
For men who wish to preserve fertility:- First-line alternative: Clomiphene citrate (off-label in men) 25–50mg alternate days — stimulates endogenous testosterone without suppressing spermatogenesis
- HCG (human chorionic gonadotropin): 500–2000 IU 2–3x/week SC — maintains testicular function and size alongside TRT
- Refer to fertility/reproductive endocrinology if primary concern is parenthood
Oestradiol Management
Testosterone aromatises to oestradiol. Elevated E2 can cause:
- Gynaecomastia
- Water retention
- Mood disturbances
- Reduced libido
Aromatase inhibitors (off-label in men):
- Anastrozole 0.25–1mg oral twice weekly (specialist advice; not for routine use)
- Only initiate if E2 symptoms AND confirmed elevated E2 (>200–250 pmol/L)
- Do not suppress E2 excessively — oestrogen is important for bone health, lipids, and libido in men
Documentation Requirements
As an independent prescriber, ensure your clinical record documents:
- Two morning testosterone measurements with dates and times
- LH/FSH classification
- Clinical symptom score (e.g., Ageing Males' Symptoms [AMS] scale) at baseline and follow-up
- Exclusion of contraindications
- PSA baseline and ongoing monitoring results
- Haematocrit at baseline and each monitoring visit
- Controlled Drug prescription in accordance with legal requirements
- Fertility counselling documented
- Patient understanding of risks, need for monitoring, and follow-up
Clinical Disclaimer: This guide supports clinical decision-making and does not replace individual clinical judgement. Prescribe in accordance with your scope of practice, indemnity coverage, and the individual patient's clinical circumstances.