Testosterone Therapy in Men With Hypogonadism: An Endocrine Society* Clinical Practice Guideline

Abstract

We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone-binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.

Oral glucose load and mixed meal feeding lowers testosterone levels in healthy eugonadal men

“…Participants achieved reductions in serum testosterone levels by as much as 39% with the glucose load and 56% after a mixed meal; this drop resulted in serum testosterone levels dropping below the normal range in a significant number of participants. Thus, our observations support the recent recommendations by the Endocrine Society guidelines that measurement of testosterone in the evaluation of androgen deficiency should be performed after an overnight fast [1]. As this reduction in serum testosterone concentrations was non-trivial even in healthy non-diabetic men, it is conceivable that this decrement might be of a greater magnitude in men who are obese or have metabolic syndrome.…”

“…The diagnosis of hypogonadism is based on the laboratory finding of consistently low serum testosterone levels in the presence of specific symptoms of androgen deficiency [1]. Hence, precise measurement of testosterone is critical in making an accurate diagnosis.…”

“…As various clinical practice guidelines suggest specific, cutoffs for testosterone levels, care must be taken to avoid factors that transiently lower serum testosterone levels as otherwise these patients might be misclassified as hypogonadal. Use of accurate assays in the measurement of sex steroids is important and has received much emphasis recently [1, 2]. In addition to the assays, several other considerations are also important during the evaluation of androgen deficiency.…”

“…Indeed, a large body of data confirms that serum testosterone secretion has a diurnal rhythm and its concentration varies widely during the day, with peak levels occurring during the morning hours [3, 4]. Based on these observations, clinical practice guidelines for male androgen deficiency have recommended that serum testosterone levels, in a patient presenting for evaluation of hypogonadism, should be assessed in the morning [1]. …”

Serum testosterone, sex hormone‐binding globulin and sex‐specific risk of incident type 2 diabetes in a retrospective primary care cohort

“…However, studies of androgen deprivation therapy, which result in significant hypogonadism, are not an ideal model to compare to the relatively modest reductions in testosterone observed in community-dwelling older men. The 2018 Endocrine Society Clinical Practice Guideline on testosterone therapy in men with hypogonadism no longer recommend screening men with T2DM for low serum testosterone, and advise against using testosterone therapy to improve glycaemic control 36. However, our results do not imply endorsement of testosterone pharmacotherapy to restore circulating testosterone levels above 20 nmol/L in otherwise healthy men.…”