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|
Organization (Year) |
Testing Requirement |
Diagnostic Threshold and Notes |
|
Endocrine Society (2018) |
Fasting total testosterone measured on 2 separate mornings, both
unequivocally low, plus consistent symptoms or signs |
Lower limit 264 ng/dL (CDC-standardized assays). Measure free
testosterone if SHBG may be altered (obesity, diabetes) or total testosterone
is borderline |
|
American Urological Association (2018) |
Total testosterone measured on 2 separate early mornings, both low
(Strong Recommendation, Grade A) |
Consistently <300 ng/dL. Ideally the same lab and method for both
samples |
|
Society for Endocrinology and Association for Clinical Biochemistry and
Laboratory Medicine, UK (2024) |
Total testosterone measured on 2 consecutive fasting mornings, both low |
Action threshold <8 nmol/L (~230 ng/dL). 8–12 nmol/L is a gray zone
that needs careful clinical correlation |
|
References: 1: Sargis RM, Davis AM.
Evaluation and Treatment of Male Hypogonadism. JAMA. 2018;319(13):1375–1376.
doi:10.1001/jama.2018.3182 2: Bhasin S, Brito JP,
Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu
FC, Yialamas MA. Testosterone Therapy in Men With Hypogonadism: An Endocrine
Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 May
1;103(5):1715-1744. doi: 10.1210/jc.2018-00229. PMID: 29562364. 3: Mulhall JP, Trost LW,
Brannigan RE, Kurtz EG, Redmon JB, Chiles KA, Lightner DJ, Miner MM, Murad
MH, Nelson CJ, Platz EA,
Ramanathan LV, Lewis RW. Evaluation and Management of Testosterone
Deficiency: AUA Guideline. J Urol. 2018 Aug;200(2):423-432. doi:
10.1016/j.juro.2018.03.115. Epub 2018 Mar 28. PMID: 29601923. 4: Zucker IJ, Masterson TA.
Comparison of American Urological Association and Endocrine Society
guidelines on testosterone replacement. Int J Impot Res. 2022
Nov;34(7):626-629. doi: 10.1038/s41443-021-00477-w. Epub 2021 Oct 18. PMID:
34663926. 5: Jayasena CN, de Silva NL,
O'Reilly MW, MacKenzie F, Marrington R, Jones H, Livingston M, Downie P,
Hackett G, Ramachandran S, Tomlinson J, David J, Boot C, Patel M, Tarling J,
Wu F, Quinton R. Standardising the biochemical confirmation of adult male
hypogonadism: A joint position statement by the Society for Endocrinology and
Association of Clinical Biochemistry and Laboratory Medicine. Clin Endocrinol
(Oxf). 2024 Nov;101(5):531-534. doi: 10.1111/cen.14929. Epub 2023 Jul 1.
PMID: 37393195. (UK) 6: Grossmann M, Jayasena CN,
Anawalt BD. Approach to the Patient: The Evaluation and Management of Men ≥50
Years With Low Serum Testosterone Concentration. J Clin Endocrinol Metab.
2023 Aug 18;108(9):e871-e884. doi: 10.1210/clinem/dgad180. PMID: 36995891;
PMCID: PMC10438885. |
||
We are living
in the age of testosterone – for the second or third time. Some are taking it to caricature levels. I
started writing about it on this blog 13 years ago – as a form of cheating in sports and health and wellness hype.
I have written about a study that carefully screened men for
hypogonadism and
demonstrated moderate benefit on sexual functioning and some benefit with mood
and depressive symptoms but no effect on physical functioning or vitality. Since then, testosterone prescribing has
continued unabated and expanded with the growth of telemedicine and advertising
to the target audience. As a psychiatrist working during that time, I saw men
who were clearly taking supraphysiological doses of testosterone for the
anabolic effects. I did not have to
speculate about that use when I saw men with obvious muscular hypertrophy who
told me they were taking testosterone because they liked the interpersonal
effects when people noticed they had muscle.
The major
guidelines for testosterone replacement therapy are produced in the above
table. The indication for replacement is hypogonadism by clinical evaluation
and laboratory determination. The
laboratory guidelines vary slightly between organizations but they are
generally consistent. The current
guideline in UpToDate uses a determination of two morning determinations of
testosterone and a diagnosis of hypogonadism that considers the many causes of
primary and secondary hyopgonadism. The
indications for therapy are more concrete than many medications that are
purportedly overprescribed. Cultural
factors are more prominent than ever with the current administration mandating
testosterone screening (2) for active and reserve military to optimize human
performance and address Operator Syndrome. Interestingly the Operator Syndrome is
a collection of physical and psychological injuries – some of which may have
been pre-existing conditions. The
endocrine aspect of this syndrome is secondary hypogonadism from blast
injuries. There is a significant
differential diagnosis of both secondary and primary hypogonadism that include
functional etiologies like acute and chronic illnesses, malnutrition, other
endocrinopathies, various drugs, infections, and various toxins. The value of including this as a feature of a
non-specific syndrome seems questionable to me.
The best approach to this problem is a comprehensive assessment by an
endocrinologist – not a testosterone level.
What about
the mass screening aspects? The pie
diagram is from the EMAS study (4) of 3,369 men ages 40-79. The interesting finding is that only 2% of
that population has symptomatic hypogonadism that would be treated with
testosterone. 5% had low testosterone
that normalized on repeat. 10% had
persistently low testosterone but no symptoms of hypogonadism. 83% had normal
testosterone on the first test.
After the DOD
release, Hennigar, et al did a retrospective study of pre-existing health data
on military personnel with a focus on testosterone (5). The analysis was based on a sample of 479 men
with an average age 29.9 years. Weighted
mean morning total testosterone, sex hormone–binding globulin, and free
testosterone concentrations were determined.
Using 2 cutoff levels of <300 ng/dL and < 264 ng/dL – weighted
prevalences of the sample were calculated for < 30 yrs old and ≥ 30 yrs
old. A separate non-obese group was
estimated using the 264 ng/dL cutoff. Extrapolating those prevalence figures to the
active-duty US Army personnel gives a range of 57,788 to 100,691 service men. Using the EMAS study estimate for symptomatic
hypogonadism that number is 7,862.
The authors
of this study qualify their results by saying that this is only one morning
fasting testosterone level. 30% of the low levels are expected to normalize on
repeat, but that would still leave about 20% of this sample in the low range.
The sample was not screened for specific symptoms of low testosterone or
moderate to severe head injury that has been associated with blast injuries and
post-traumatic hypopituitarism (7).
Obesity and body composition contributes and they note the normal weight
cohort has a lower prevalence of low testosterone. The stress of some military conditions can
also suppress testosterone. Army Ranger
training can reversibly suppress testosterone levels by 50% (8). That is attributed to energy deficit, sleep
restriction, heavy physical work, and psychological stress effects on gonadotropin-releasing
hormone and luteinizing hormone pulsatility.
This is a critical observation that appears to be omitted from both the
formulation of Operator Syndrome and the rationale for screening. Treatment in this case would be removal from
the stressful military conditions rather than testosterone replacement. It would also seem to be a factor in
determining the optimal time and status for diagnosing post-traumatic
hypopituitarism.
All the
factors mentioned so far suggest that testosterone is over prescribed in the US
population. Since the US has no comprehensive pharmacosurveillance indirect
estimates are made using other samples. In 2013 an estimated 2.3M men were
using testosterone. That dropped to
about 1.15M men after an FDA warning about cardiovascular effects (9). From
2018-2022 the number of men being treated increased 27% from 1.22M to
1.66M. The data in that study was from
25 state prescription data monitoring programs (PDMPs). Remaining states were prohibited from sharing
that information and the authors suggest that more populous states need to be
included (10).
The current
population of men between the ages of 40 and 79 is estimated to be about 72
million and they make up 21.5% of the total population. Using the EMAS estimate
for true hypogonadism (low total and free testosterone and 3 sexual symptoms of
2.1% yields a total of 1.53M men with true hypogonadism. That number is lower than the estimate of
1.66M from 25 states (10). In that study the fastest growing
testosterone use groups were 35–44 (+58%) and 45–54 (+35%) – groups that
according to the EMAS study have the lowest prevalence of hypogonadism. This age mismatch combined with missing or
normal baseline testosterone levels, non-specific symptoms (fatigue, low
energy), and low treatment rates in the target population of men ≥ 60 with the
highest rates of hypogonadism suggests overprescribing.
There is
additional indirect evidence available. Every
viewing of streaming channels on the Internet generally produces an advertisement
about the easy availability of testosterone prescriptions by telemedicine. A recent secret shopper study (17, 18)
of online platforms offering testosterone therapy found that none of the
assessments were done by a physician and despite normal total and free
testosterone levels and wanting to father a child - 7 of 8 platforms prescribed
testosterone. The associated commentary
says this highlights a problem and this technique might be used by state
medical boards. An earlier study looked
at the relationship between advertising and prescriptions and noted that each
additional testosterone ad exposure was associated with 14 new tests, 5 new
initiations, and 2 initiations without testing per million men. Unbranded
"low T" ads had a stronger effect than branded ads. Advertising was also specifically associated
with starting testosterone without a prior blood test. (19, 20).
At this point
it goes without saying that testosterone and other anabolic steroids are
considered performance enhancing drugs with other magical properties. There is a fountain of youth myth and some men
claim to take them for anti-aging effects. Excessive use can also occur
associated with body dysmorphia and an anabolic androgenic steroid (AAS) use
disorder (22, 23). There is both
pre-clinical data to support the use disorder diagnosis but it is not directly
recognized in either the DSM or ICD.
Some studies suggest that 30% of casual users will go on to develop
dependence on AAS. It can also be
recognized clinically because of the comorbidity with other substance use
disorders most notably opioid use disorder. In treatment settings, supraphysiological
doses of testosterone can also be an indication.
To summarize,
there is a clear indication for testosterone replacement therapy for
hypogonadism that requires two fasting morning blood tests with specific
cutoffs as noted in the table at the top of this post. In reality, much more is required because of
the causes of primary and secondary hypogonadism that can be both medical (like
TBI) or functional (like the stressors of the military environment). There is no indication for mass screening and
no reason to believe that replacing testosterone in men with or without
hypogonadism will enhance military effectiveness. Testosterone has no anti-aging or vitality
enhancing properties at physiological doses.
At supraphysiological doses, it is an androgenic anabolic steroid and
cause muscle hypertrophy, irritability and aggression, and persistent
hypogonadism when withdrawn. In a study
of quality of life in former AAS users abstinent for 2 years – the nonusing
strength trainers had a quality of life score comparable to young adults with a
previous ischemic stroke (16).
Any man
considering testosterone replacement should adhere to the guidelines from the
endocrine and urological societies. For
those members of the military that may not have a choice – I am hoping that you
have access to a VA endocrinologist to make any treatment decisions. They knew all about it in 1986 when I trained
there and have been refining the guidelines for the past 40 years.
George Dawson,
MD, DFAPA
References:
1: Hennigar SR, Heymsfield SB, Bukhari AS,
Lieberman HR, Berryman CE. Testosterone Screening Thresholds in Active-Duty US
Male Service Members. JAMA. Published online October 15, 2026.
doi:10.1001/jama.2026.19794
2: Health and human performance optimization to
enhance military readiness.
Published
July 15, 2026. Accessed 10/30/2026. PDF
“Effective
immediately, all Active Duty and Reserve Component personnel aged thirty
and older
will be screened for testosterone deficiency as a mandatory element of their
Periodic
Health
Assessment (PHA). Service members under the age of thirty may also request this
screening
during their PHA.
This
enhanced screening protocol directly supports the Department's focus on Human
Performance
Optimization while comprehensively addressing Operator Syndrome. Originally
identified
among Special Forces in 2020 through collaborative research between the
Department
of War (Do
W) and leading academic institutions, Operator Syndrome represents a unique
convergence
of health challenges that require proactive clinical intervention.
Additionally,
applying
lessons learned from treating Operator Syndrome across the Total Force
including
targeted
testosterone therapy directly optimizes Warfighter readiness….”
3: Frueh BC, Madan A, Fowler JC, Stomberg S,
Bradshaw M, Kelly K, Weinstein B, Luttrell M, Danner SG, Beidel DC. “Operator
syndrome”: A unique constellation of medical and behavioral health-care needs
of military special operation forces. The International Journal of Psychiatry
in Medicine. 2020 Jul;55(4):281-95.
4: Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ,
Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS,
Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F,
Huhtaniemi IT; EMAS Group. Identification of late-onset hypogonadism in
middle-aged and elderly men. N Engl J Med. 2010 Jul 8;363(2):123-35. doi:
10.1056/NEJMoa0911101. Epub 2010 Jun 16. PMID: 20554979.
5: Hennigar SR, Heymsfield SB, Bukhari AS,
Lieberman HR, Berryman CE. Testosterone Screening Thresholds in Active-Duty US
Male Service Members. JAMA. 2026 Oct 15:e2619794. doi: 10.1001/jama.2026.19794.
Epub ahead of print. PMID: 42879141; PMCID: PMC13673370.
7: Mubarak,
M., Modgil, V. Routine testosterone screening in military personnel: an
opportunity for evidence-based implementation in men’s health. Nat Rev Urol
(2026). https://doi.org/10.1038/s41585-026-01181-4
8: Friedl KE, Nindl BC, Potter AW.
Stress-associated testosterone suppression: central adaptation or hypogonadism?
J Clin Endocrinol Metab. 2026 Jul 15;111(8):e1951-e1960. doi:
10.1210/clinem/dgag181. PMID: 42044038; PMCID: PMC13368364.
9: Walker RF, Zakai NA, MacLehose RF, et al.
Association of Testosterone Therapy With Risk of Venous Thromboembolism Among
Men With and Without Hypogonadism. JAMA Intern Med. 2020;180(2):190–197.
doi:10.1001/jamainternmed.2019.5135
10: Selinger S, Thallapureddy A. Cross-sectional
analysis of national testosterone prescribing through prescription drug
monitoring programs, 2018-2022. PLoS One. 2024 Aug 28;19(8):e0309160. doi:
10.1371/journal.pone.0309160. PMID: 39196907; PMCID: PMC11355536.
11: Pope HG Jr, Wood RI, Rogol A, Nyberg F,
Bowers L, Bhasin S. Adverse health consequences of performance-enhancing drugs:
an Endocrine Society scientific statement. Endocr Rev. 2014 Jun;35(3):341-75.
doi: 10.1210/er.2013-1058. Epub 2013 Dec 17. PMID: 24423981; PMCID: PMC4026349.
12: Kanayama G, Hudson JI, DeLuca J, Isaacs S,
Baggish A, Weiner R, Bhasin S, Pope HG Jr. Prolonged hypogonadism in males
following withdrawal from anabolic-androgenic steroids: an under-recognized
problem. Addiction. 2015 May;110(5):823-31. doi: 10.1111/add.12850. Epub 2015
Feb 25. PMID: 25598171; PMCID: PMC4398624.
13: Baggish AL, Weiner RB, Kanayama G, Hudson JI,
Lu MT, Hoffmann U, Pope HG Jr. Cardiovascular Toxicity of Illicit
Anabolic-Androgenic Steroid Use. Circulation. 2017 May 23;135(21):1991-2002.
doi: 10.1161/CIRCULATIONAHA.116.026945. PMID: 28533317; PMCID: PMC5614517.
14: Pope HG Jr, Kanayama G. Body Image Disorders
and Anabolic Steroid Withdrawal Hypogonadism in Men. Endocrinol Metab Clin
North Am. 2022 Mar;51(1):205-216. doi: 10.1016/j.ecl.2021.11.007. Epub 2022 Feb
8. PMID: 35216717.
15: Bhasin S, Seidman S, Travison TG, Pencina KM,
Lincoff AM, Nissen SE, Miller MG, Flevaris P, Li X, Wannemuehler KA, Pope HG.
Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response
to Testosterone-Replacement Therapy. J Clin Endocrinol Metab. 2024 Jun 17;109(7):1814-1826.
doi: 10.1210/clinem/dgae026. PMID: 38205962.
16: Pope HG Jr, Kanayama G. Reduced Quality of
Life in Former Androgen Users: An Evolving Public-Health Concern. J Clin
Endocrinol Metab. 2024 Apr 19;109(5):e1400-e1401. doi: 10.1210/clinem/dgad661.
PMID: 37955864.
17: Dubin JM, Jesse E, Fantus RJ, et al.
Guideline-Discordant Care Among Direct-to-Consumer Testosterone Therapy
Platforms. JAMA Intern Med. 2022;182(12):1321–1323.
doi:10.1001/jamainternmed.2022.4928
18: Woloshin S, Gill LL. Direct-to-Consumer
Low-Testosterone Clinics—Where Is the Federation of State Medical Boards? JAMA
Intern Med. 2023;183(4):288–289. doi:10.1001/jamainternmed.2022.7008
19: Kravitz
RL. Direct-to-Consumer Advertising of Androgen Replacement Therapy. JAMA.
2017;317(11):1124–1125. doi:10.1001/jama.2017.1364
20: Layton JB, Kim Y, Alexander GC, Emery SL.
Association Between Direct-to-Consumer Advertising and Testosterone Testing and
Initiation in the United States, 2009-2013. JAMA. 2017;317(11):1159–1166.
doi:10.1001/jama.2016.21041
21: Kanayama G, Brower KJ, Wood RI, Hudson JI,
Pope Jr HG. Anabolic–androgenic steroid dependence: an emerging disorder.
Addiction. 2009 Dec;104(12):1966-78.
22: Kanayama G, Hudson JI, Pope Jr HG. Features
of men with anabolic-androgenic steroid dependence: A comparison with
nondependent AAS users and with AAS nonusers. Drug and alcohol dependence. 2009
Jun 1;102(1-3):130-7.
23: Bhasin S, Storer TW, Berman N, Callegari C,
Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The
effects of supraphysiologic doses of testosterone on muscle size and strength
in normal men. N Engl J Med. 1996 Jul 4;335(1):1-7. doi: 10.1056/NEJM199607043350101.
PMID: 8637535.
Supplementary
1: I was fortunate to train and work with many
excellent endocrinologists at the Milwaukee VAMC and at St. Paul-Ramsey Medical
Center/Regions Hospital. I learned a lot
in the process and ended up seeing many complex endocrine problems in clinical
practice and serving on relevant committees with some of those same
endocrinologists. Based on that experience I do not see any potential
advantages to consider post TBI hypopituitarism as a feature of another
syndrome. I personally saw it diagnosed and treated many times at the Milwaukee
VAMC often associated with panhypopituitarism and recognized and treated
several of those cases in clinical practice.
They were all secondary to TBI or neurosurgery complications.
Supplementary
2: I was equally fortunate to train and work with many vets. One of them described Jungle Warfare School to
me. I will not attempt to recreate the scenarios he told me about - and will only say it clearly puts members of
the military at risk and places them under extreme physiological stress. The
neuroendocrine system has always been an area of research in psychiatry. I was
a research fellow in a program where we tested the HPA axis and adrenal
responsiveness in patients stressed by depression. A thorough characterization of some of these
stressful training programs may be a batter place to start than just measuring
testosterone levels and considering the patient to have hypogonadism.
The political
atmosphere that these recommendations occur in cannot be ignored. They are being made by a Department of War
Secretary who has taken to lecturing experienced military personnel about
fitness for duty and suggesting goals that are long on aggression and short on
strategy. Combined with the DOGE effects
of reducing VAMC staffing and medical care I think it is reasonable to be
concerned about whether members of the military will get adequate assessments
for any abnormal tests rather than just a prescription. Congress should be
watching this as an experiment if the guidelines for testosterone replacement
are not met and if the effects of testosterone are not carefully followed.
