British Society for Sexual Medicine (BSSM): Assessment and Management of Testosterone Deficiency in Adult Men (2018 edition)

Classification of conditions associated with low serum tesoterone

1. Primary (hypergonadotropic) TD - testicular failure - raised LH/FSH (Klinefelter syndrome, undescended testes, mumps orchitis, cancer treatment)

2. Secondary (hypogonadotropic) TD - commoner- hypothalamus-pituitary dysfunction - Low LH/FSH (age>50y, prolactinoma, obesity/metabolic syndrome, late-onset hypogonadism)

3. Combined Primary and Secondary TD- variable LH/FSH (glucocorticoids, alcoholism, sickle cell disease, haemochromatosis, thalassaemia)

4. Impaired action/suppression of testosterone
   Side-effects of glucocorticoids, opioids, anticonvulsants, antipsychotics, antiretrovirals, chemotherapy

Diagnosis

Requires BOTH characteristic symptoms and signs of TD AND reduced serum total testosterone (TT) or free testosterone (FT).

Symptoms and Signs

The 3 most common symptoms relate to sexual dysfunction:

• Erectile Dysfunction (ED)

• Loss of early morning erections

• Low sexual desire

Psychological

Mood (e.g. anger, irritability)
Decreased well-being
Impaired cognition (memory, concentration)

Cardiometabolic

Increased body mass index (BMI): obesity and visceral obesity
Metabolic syndrome
Insulin resistance and type 2 diabetes

Physical

Decreased body hair
Gynaecomastia
Decreased muscle mass and strength
Hot flushes/sweats
Sleep disturbances
Fatigue
Osteoporosis/height loss/ low trauma fractures

Sexual

Delayed puberty
Small testes
Infertility
Decreased sexual desire and activity
Decreased frequency of sexual thoughts
Erectile dysfunction (ED)
Delayed ejaculation
Decreased volume of ejaculate
Decreased or absent morning/night-time erections

Who should be screened for TD

1. Adult men with consistent and multiple signs of TD

2. All men presenting with ED, loss of spontaneous erections or low sexual desire

3. All men with type 2 diabetes mellitus, BMI >30 kg/m2 or waist circumference >102 cm (40.2 inches)

4. All men on long-term opiate, antipsychotic or anticonvulsant medication

Assessment

History taking

Validated questionnaires:
Androgen Deficiency in the Ageing Male (ADAM) OR Ageing Males’ Symptoms (AMS) Scale

Physical examination

Given the need to assess TD in context of cardiovascular risk factors and risk of prostate cancer and bone health
and establish a baseline for monitoring Testosterone replacement therapy

1. Measure height, weight, BMI and waist circumference

2. Assess
   body hair (including facial and pubic)
   breast enlargement
   abnormalities of the penis, testicles and scrotum
   prostate via digital rectal examination (DRE)

3. Arrange blood investigations:

   Total Testosterone (TT), Prostate-specific antigen (PSA), HbA1C, Lipids, FBC/Haematocrit

4. Screen for osteoporosis Age>50y
   NICE states to offer treatment if QFracture or FRAX score suggests risk greater than 1%

Measurement of serum testosterone

Early morning (7–11 am)
Fasting
At least 2 occasions, preferably 4 weeks apart.

If first TT <12 nM (equates to low/borderline TT) measure
Repeat TT
LH (and FSH) (to distinguish primary vs secondary TD)
SHBG and Albumin to calculate free Testosterone FT
PRL and TFTs (check for hypothalamus-pituitary dysfunction)

Management of testosterone deficiency

1. Assess cardiovascular risk factors before commencing testosterone therapy and optimize secondary prevention in men with established disease

2. Offer weight-loss and lifestyle advice as appropriate

3. Offer Testosterone replacement therapy (via referral to Endocrinology) if symptomatic of testosterone deficiency AND boderline/confirmed TD

Normal testosterone TT > 12 nM or FT>0.225 nM
Borderline TD TT 8-12 nM and/or FT 0.180-0.225 nM
Confirmed Testosterone deficiency TD TT < 8 nM or FT<0.180 nM
Testosterone replacement therapy aim for symptom improvement and TT 15–30 nmol/L

• Borderline TD or cnfirmed TD associated with high LH/FSH - primary TD
  - refer to endocrinology for further investigation and for trial of Testosterone replacement therapy

• Borderline TD or confirmed TD associated with low LH/FSH or high PRL- Secondary TD
  - refer to endocrinology for further investigation and for trial of Testosterone replacement therapy

• Very low TD (<5.2n M) and low LH/FSH or high PRL
  - suggests pituitary disease as a cause of secondary TD —> refer to endocrinology for pituitary MRI to exclude Pituitary Adenoma

Trial of Testosterone replacement therapy (and lifestyle modification and ideal weight)

• Shared Care arrangement with secondary care specialist input

• Evaluate patients at 3, 6 and 12 months, then every 12 months

• At each review check symptomatic improvement:
  Sexual symptoms (sexual desire, erectile function) improve by 6w
  Metabolic syndrome, obesity, lean muscle mass, lipid improvements may take 6m
  Maximal benefit is often seen beyond 12m
  Failure to benefit by 6m should prompt treatment cessation and clinical re-evaluation

• At each review check
  TT, SHBG, albumin (therapeutic target TT 15–30 nmol/L)
  FBC haematocrit (stop treatment if exceeds 54%)
  PSA
  Any increases >1.4 ng/mL over any 1-year period or a velocity >0.4 ng/mL/year during sequential measurement over >2 years warrants urological evaluation

• Monitor bone mineral density and cardiovascular risk if it was abnormal before starting tesoterone replacement

Contraindications to testosterone replacement therapy

1. Prostate cancer (locally advanced or metastatic)

2. Concerns about possible prostate cancer such as elevated PSA or abnormal/enlarged prostate on DRE

3. Severe LUTS associated wilh BPH

4. An active desire to have children

5. Male breast cancer

6. Haematocrit >54%

7. Severe chronic heart failure (NYHA class 4)

8. Severe untreated sleep apnoea

9. Myocardial infarction or stroke in the past 6m**

10. Thrombophilia**

**The Endocrine Society produced recent guidance on male hypogonaidsm (JAMA 2018) and suggested additional contraindictions of MI, stroke, and thrombophilia

Long-term safety

• There is weak evidence to suggest increased cardiovascular and prostate cancer risks in men receiving testosterone replacement

• Studies to date have been limited in their design, size and duration of treatment (around 1 year)

• Further studies are in progress