One of the most frequent questions here is whether someone should start TRT.

While this is
often subjective, I wanted to create a reference post as a starting point for anyone wondering
about the basics of whether to start treatment. Rather than solely depending on the wisdom of
Reddit, I have created a summary of professional recommendations on starting TRT.

This post is going to heavily borrow from Investigation, treatment and monitoring of late-onset
hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations (2009), with some
updates. In the publication, five professional societies agreed on guidelines on when TRT is
indicated for patients. The post also incorporates information from a 2015 meeting of
experienced clinicians who provided input from their professional practices. I have attempted
to shorten this and pull out the important points for patients; for full info, see the linked
documents.

I am not a doctor and this does not constitute medical advice. Note that these are general
recommendations and not firm requirements. Talk to a doctor about your symptoms and lab
results. If your doctor is not familiar with the limitations of reference ranges, I highly
recommend the following article by a leader in the field: Testosterone reference ranges and
diagnosis of testosterone deficiency

Testosterone replacement therapy (TRT or TTh) typically requires both symptoms and
corroborating lab tests. There are no differences in the below for men of different ages.

Symptoms
 Low libido (most common), erectile dysfunction, decreased muscle mass and strength,
increased body fat, decreased bone mineral density and osteoporosis, decreased
vitality, and depressed mood are associated with low testosterone.
 Low libido or erectile dysfunction alone, combined with low serum testosterone, are
enough to try TRT.

Basic Labs (see section below on testing)

 Blood sample should be taken between 7am and 11am.
o Most physicians want two separate tests to confirm hypogonadism.
o Men over 45 may not require a morning sample, as diurnal variation in
testosterone declines between 40 and 50.
 Total testosterone:
o above 350 ng/dl (12 nmol/l): Generally does not indicate a benefit from TRT
o below 230 ng/dl (8 nmol/l): Generally indicates a benefit from TRT
o between 230 ng/dl (8 nmol/l) and 350 ng/dl (12 nmol/l): Repeat test and add
SHBG and/or free testosterone. SHBG can be used to calculate free testosterone
via the Vermeulen equation.
 Free testosterone
o < 65 pg/ml (225 pmol/l) generally indicates a benefit from TRT
 o <15 pg/mL (0.0520 nmol/L) if test method is via immunoassay
 If results are still inconclusive at this point, a short trial of approximately 3 months may
be justified to see if symptoms improve.

Advanced/Additional Criteria

If symptoms exist, other tests may indicate a problem associated with testosterone.

 A test for luteinizing hormone (LH) indicates primary or secondary hypogonadism.

o Increased levels of LH (above 10 IU/L) may indicate testosterone deficiency, even
in the presence of normal total or free T levels. The presence of elevated LH
indicates there is inadequate T-mediated negative feedback at the level of the
hypothalamus and pituitary, which is a sign that the body needs higher T levels.
 A prolactin test is indicated when total testosterone is less than 150 ng/dl (5.2 nmol/l)
OR if secondary hypogonadism is suspected. High prolactin may be indicative of
pituitary problems.
 If genetic testing has been done, androgen receptor CAG repeats > 24 (10-15% of men)
reduce androgen receptor sensitivity and may indicate TRT.
 Testicular volume <10 mL
 DHT < 300 pmol/L

Treatment guidelines
 The goal should be improvement in symptoms, not a specific serum testosterone level.
If no improvements are seen in 3-6 months for libido and sexual function, muscle
function, or improved body fat, treatment should be discontinued and further root
cause investigation is necessary.
 TRT is contraindicated in men with prostate or breast cancer (or at high risk for them),
hematocrit >52%, untreated sleep apnea, or untreated congestive heart failure.
 Monitor for prostate disease (PSA test and digital rectal exam) and hematocrit at 3-6
months, 12 months, then every year thereafter. Hematocrit should remain below 55%.

Notes on testing methods

 The most accurate method of testing total testosterone is liquid chromatography with
tandem mass spectrometry (LC-MS/MS). Other testing methods can distinguish
between normal and hypogonadal men, but are especially unreliable under 250 ng/dl (8
nmol/l) and should be used as an indicator only.
 The only reliable method of testing free testosterone is equilibrium dialysis. Otherwise,
free testosterone can reliably be calculated from total testosterone and SHBG, if the
total testosterone assay is accurate (see above).
 Estradiol exists in low levels in men, and LC-MS/MS testing (sometimes known as
sensitive estradiol) is recommended. Immunoassays are not reliable.