How to Test for a Male’s Hormone Needs

By Jim Paoletti, BS Pharmacy, FAARFM, FIACP, Director of Education at Power2Practice

Male testosterone production usually begins to decline around the mid-40s. The decline in production by the testes can be more precipitous with excessive weight, stress, lack of exercise, lack of quality sleep, and medications including statins, opioids, oxycodone, spironolactone, cimetidine, SSRIs, beta blockers, benzodiazepines, sulfonylurea, antipsychotics, ketoconazole, corticosteroids, antihistamines, and chemotherapy agents.

Any time a patient’s testosterone level is low for his age, the potential causes for low production should be thoroughly evaluated and addressed in an attempt to naturally raise endogenous testosterone production.

When we see men with hormone imbalance symptoms, we must test for more than just testosterone.

Initial testing should include:

  • Testosterone, either total and free, or at least the free active testosterone
  • SHBG if only total testosterone is measured and not the free testosterone
  • Estradiol, and estrone if patient is significantly over weight or already administering testosterone replacement therapy
  • Progesterone
  • Cortisol, 4 times in a day in saliva
  • PSA
  • Hematocrit
  • Fasting Insulin and Fasting Glucose
  • If symptoms of low thyroid function: TT4, fT4 direct, fT3 direct, TSH, TPO, 25-OH-Vitamin D and ferritin
  • If family risk or other factors warrant then cardio-metabolic risk factors should be looked at.

While testosterone replacement therapy is always an option, the solution to the problem of low testosterone may not be a simple case of restoring testosterone levels with exogenous administration.

For example…

High cortisol levels: 

  • decrease testosterone production
  • interfere with testosterone function at its receptor
  • increase conversion of testosterone to estrogen in fat tissue

High estrogen levels:

  • suppress testosterone receptors in target tissues
  • increase SHBG which binds testosterone 3 times more tightly than estradiol
  • decrease LH (luteinizing hormone) which in turn acts to decrease testicular production of testosterone

Testosterone replacement therapy when high cortisol is present may not be of sufficient benefit unless problems affecting the cortisol production are addressed. Similar interaction issues exist with low thyroid function, high insulin or blood sugar, and high estrogen levels.

Progesterone competes with testosterone for 5-α-reductase, and the metabolite from progesterone competes with testosterone and DHT (Dihydrotestosterone) for androgen receptors. Therefore, it is used in some patients as a mild antiandrogen for BPH or hair loss. It may also help with sleep and support cortisol production in patients with low cortisol levels. 

If PSA is high, testosterone replacement therapy should be postponed until a through prostate exam is completed. A PSA velocity (increase over time) is monitored.

SHBG binds both testosterone and estrogen. If a testosterone level is tested in blood, it is a most often measurement of whole testosterone, which is both the bound and unbound testosterone. If SHBG globulin is high, the total testosterone may look normal, but the free or active testosterone could be low and causing symptoms.

Measuring testosterone in saliva reflects the free testosterone and therefore can eliminate the need to measure SHBG.

For patients administering a testosterone replacement product…

Topical testosterone:

  • Testing should be done in saliva or capillary blood spot testing, as venous serum and urinary testing are not valid for topical administration of hormones.


  • Capillary blood spot testing should be used because saliva is not valid.
  • Both estradiol and estrone levels should be measured in follow-up testing, as some men store estrogen more as estrone than estradiol.

Any testing for a patient on testosterone replacement therapy should be done at mid-dosing interval.

For example, if the patient is receiving weekly testosterone injections, measurement should be done 3-4 days after the last injection.


Jim Paoletti, BS Pharmacy, FAARFM, FIACP, is a Clinical Consultant with over 30 years’ experience creating and using bio-identical hormone therapies in both retail pharmacy and clinical practice.

Jim is a Diplomat in Functional Medicine in addition to being a former faculty member for the Fellowship of Functional Medicine.

At Power2Practice, Jim applies his wealth of knowledge and experience by hosting live webinars and creating useful content, such as blogs, podcasts and clinical support tools.


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