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Gradual decline in T level starts in mid-30s, low T affects 20% of men >60 yo;1 dx requires s/sx and ≥2 low levels; eval for other causes of low T before considering testosterone replacement tx (TRT)2 - Consider testing in pts w/ s/sx of hypogonadism, select others;2 don’t screen general population3
- Test early AM total T;2,3 add free T for pts w/ conditions that alter SHBG (eg, obesity, DM, HIV, etc); avoid testing if recent acute illness or certain short-term meds (eg, opioids, glucocorticoids)3
- Use total T <300 ng/dL as cutoff for dx, per AUA;2 per ES <264 ng/dL, but 200-400 ng/dL considered “borderline zone” for retesting;3 ACP states “no clear level” at which to start TRT1
- Confirm initial low total T w/ 2nd test; 30% of men w/ initially low T will have NL level on repeat; if pt has condition that alters SHBG or initial borderline zone level, √ free T on repeat3
- If pt has multiple low total/free T levels, √ LH (+/- FSH); if LH/FSH low/NL, √ prolactin,2,3 iron sat3
- If breast pain/tenderness, gynecomastia, √ estradiol2
- If s/sx of hypopituitarism, abnl sella on imaging √ other pituitary hormones3
- If severe low T (<150 ng/dL), panhypopituitarism, persistent high prolactin, or s/sx of tumor mass effect, √ pituitary MRI3
Footnotes 1 ACP 2020. Qaseem A, et al. Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline from the American College of Physicians. Ann Intern Med. 2020. Jan 21;172(2):126-133. Full-text article
2 AUA 2018. Mulhall JP, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018. Aug;200(2):423-432. PubMed® abstract
S/sx of low T: ↓energy, ↓endurance, ↓beard growth, ↓lean muscle mass, ↓motivation, ↓sex drive; diminished work or physical performance; loss of body hair; obesity; depressive sx, cognitive dysfxn, poor memory or concentration, irritability; erectile dysfxn
Consider checking T levels in absence of s/sx if: unexplained anemia, ↓bone density, DM, exposure to chemo or testicular XRT, HIV, chronic narcotic use, male infertility, pituitary dysfxn, chronic corticosteroid use.
3 ES 2018. Bhasin S, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018. May 1;103(5):1715-1744. Full-text article
Conditions that ↓SHBG:
• obesity
• DM
• use of glucocorticoids, anabolic steroids, some progestins
• nephrotic syndrome
• hypothyroidism
• acromegaly
• SHBG gene polymorphisms
Conditions that ↑SHBG:
• aging
• HIV
• cirrhosis, hepatitis
• hyperthyroidism
• use of some anticonvulsants
• use of estrogens
• SHBG gene polymorphisms
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Dx w/ age-related low T, awaiting tx
Start testosterone replacement tx (TRT) only if multiple ↓levels and s/sx of low T; counsel about risk, benefits, uncertainties; counsel all pts about benefits of lifestyle modifications;1 select IM TRT over gels/creams/patch due to cost2 - Address potentially reversible causes prior to TRT3
- Check DRE, PSA (if >40 yo) & Hct prior to TRT;1,3 don’t start TRT w/o eval if PSA >4 (>3 in high-risk pt) or ↑Hct1,3
- Don’t use TRT if: trying to conceive in near term; breast or prostate CA; palpable prostate nodule/induration; severe untreated OSA; severe LUTS (AUA/IPSS >19); uncontrolled CHF; thrombophilia;3 recent MI/stroke (<6mo per ES, <3-6mo per AUA)
- TRT benefits: Per ACP, consider TRT only for sexual dysfxn, not to ↑energy, vitality, physical fxn or cognition;2 per AUA, TRT may improve sexual fxn, anemia, BMD, lean body mass, depressive sx1
- TRT risks: ↓sperm production/fertility; ↑Hct; acne; detection of subclinical prostate CA or growth of metastatic prostate CA; gynecomastia; male pattern balding; growth of breast CA; OSA; local reactions3
- TRT link to changes in prostate CA, VTE, & CV risk is inconclusive;1,3 continued prostate CA screening is shared decision1,3
- Counsel pt re: costs, transference of gels/creams;1 IM preps preferred to transdermal due to equivalent efficacy, 10x cost difference2
- If pt wishes to preserve fertility, aromatase inhibitors, hCG, SERMs may be used w/ TRT, but evidence is limited1
- Commercial preps preferred to compounded products1
- Don’t use alkylated PO preps due to liver toxicity1,3
Footnotes 1 AUA 2018. Mulhall JP, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018. Aug;200(2):423-432. PubMed® abstract
Only hCG has been approved by the FDA for use in males, specifically to treat males w/ hypogonadotropic hypogonadism. Aromatase inhibitors and SERMs not FDA approved for males.
2 ACP 2020. Qaseem A, et al. Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline from the American College of Physicians. Ann Intern Med. 2020. Jan 21;172(2):126-133. Full-text article
3 ES 2018. Bhasin S, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018. May 1;103(5):1715-1744. Full-text article
Reversible causes of low T:
• androgen synthesis inhibiting meds
• ESRD
• hyperprolactinemia
• opioids, glucocorticoids, anabolic steroids
• EtOH, marijuana abuse
• systemic illness
• eating disorders/nutritional deficiency/excessive exercise
• severe obesity
• sleep disorders
• liver, heart, lung failure
• comorbid illness assoc w/ aging
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Monitor total T levels; target middle of NL ref range, re-eval sx once at target1,3 & d/c testosterone replacement tx (TRT) if sx not improved1,2 - Recheck total T after initiation; timing depends on prep used, per AUA;1 ES recommends recheck after 3-6mo for most preps (can check after 1wk on gels)2
- Adjust dosing to target middle of NL ref range2 (middle tertile of NL, per AUA1)
- After total T level at target, monitor q6-12mo;1 annually, per ACP & ES2,3
- Re-eval sx @ 3-6mo;1 d/c TRT if total T NL but no improvement in sx1,3
Monitor for adverse reactions: - Eval for formulation-specific side effects (eg, rash w/ patch, cough immediately after IM injection) every visit2
- Recheck Hct 3-6mo and 12mo after starting TRT, then q6-12mo1,2
- If Hct >54% & total T high, ↓TRT dose1 (per ES, hold TRT until total T NL, then start ↓TRT dose2)
- If Hct >54% & total T NL/low, √ SHBG & free T: if SHBG low or free T high, ↓TRT dose; if free T NL, refer to heme1 or consider therapeutic phlebotomy2
- If pt elects prostate monitoring: √ PSA, DRE 3-12mo after TRT start; after 1y use standard guidelines, per ES.2 However, AUA1 recommends standard guidelines for all such pts (View prostate CA screening guideline in epocrates)
Footnotes 1 AUA 2018. Mulhall JP, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018. Aug;200(2):423-432. PubMed® abstract
Timing of 1st total T level after TRT initiation:
• transdermal or intranasal: √2-4wk after starting
• short-acting IM or short-acting SQ pellets: √mid-cycle after 3-4 cycles
• long-acting IM: √9wk after starting (mid-cycle between 1st 2 10-wk cycles)
• long-acting SQ pellets: √2-4wk and 10-12wk after implant
2 ES 2018. Bhasin S, et al. Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018. May 1;103(5):1715-1744. Full-text article
3 ACP 2020. Qaseem A, et al. Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline from the American College of Physicians. Ann Intern Med. 2020. Jan 21;172(2):126-133. Full-text article
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