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Approach to older males with low testosterone

Approach to older males with low testosterone
Literature review current through: May 2024.
This topic last updated: Nov 28, 2023.

INTRODUCTION — As males age, their serum concentrations of testosterone decrease. This decline is gradual and of a modest degree, but because many of the changes of aging are similar to those of hypogonadism due to known disease, the decline in testosterone has been postulated to be a cause of these changes of aging. Recent studies show that raising the testosterone levels of older males with low testosterone has some benefits, but no study yet has enrolled enough males and treated and observed them for long enough to determine the risk of this treatment.

The decline in testicular function with aging, its possible consequences, and the results of increasing testosterone levels in older males are reviewed here. Testosterone treatment of male hypogonadism due to known disease is discussed separately. (See "Testosterone treatment of male hypogonadism".)

AGE-RELATED ENDOCRINE CHANGES — Both cross-sectional and longitudinal studies demonstrate a decline in serum testosterone concentration, an increase in sex hormone-binding globulin concentration (SHBG), and a decrease in free testosterone with age.

Serum total testosterone — Several cross-sectional studies show a decline of serum total testosterone concentration with increasing age [1,2]. In one, the European Male Aging Study (EMAS), of 3220 males ages 40 to 79 years, the serum total testosterone concentration fell 0.4 percent per year [1]. In a second study, a gradual decline in testosterone concentration was seen after age 35 years, with a more marked decline after age 80 years [2].

In a study using serum samples from four population-based studies (EMAS, Framingham Heart Study, Osteoporotic Fractures in Men [MrOS], Male Sibling Study of Osteoporosis) of males from ages 19 to 79 that were assayed and standardized against gold-standard measurements performed at the Centers for Disease Control and Prevention (CDC), age-specific harmonized reference ranges were generated. This study demonstrated that the lowest 2.5th percentile values decreased considerably with age, but the 50th percentile value decreased much less and the 97.5th values not at all [3]. For example, the 2.5th percentile model estimate for all males and nonobese males 19 to 39 years was 229 ng/dL and 264 ng/dL, respectively, and that for all males 70 to 79 years was 119 ng/dL, whereas the values for the 50th percentile were 507 and 446 ng/dL and for the 97.5th percentile were 902 and 902 ng/dL, respectively.

Longitudinal studies also show a decrease in testosterone with increasing age, and in three of them, the decrease was greater than that in cross-sectional studies [4-6]. In 890 males participating in the Baltimore Longitudinal Study of Aging, serum testosterone decreased at a fairly constant rate, independent of other clinical variables [6]. In the Massachusetts Male Aging Study, longitudinal assessment also showed a decrease in total testosterone with increasing age but a greater decrease in free testosterone [4,5].

Another feature of testosterone with increasing age is a loss of circadian rhythmicity. Whereas young males exhibit a prominent increase in the morning, peaking at approximately 8 AM, older males show a very dampened increase (figure 1) [7].

Serum sex hormone-binding globulin — SHBG concentrations increase gradually as a function of age, as shown in the EMAS [1]. The clinical implication, because SHBG binds testosterone with high affinity, is that with increasing age, less of the total testosterone is free (ie, biologically active). SHBG, however, is lower at all ages in obese males than in nonobese males [1].

Serum free testosterone — The serum free testosterone concentration decreases with increasing age to a greater degree than the total testosterone; the values in 75 to 79-year-old males were approximately 30 percent less than those in 40 to 44-year-old males [1].

Effects of obesity and comorbid conditions — The total testosterone levels in obese males are lower than those in males of normal weight of the same age, partly due to a lower level of SHBG in obesity, but partly due to hypogonadotropic hypogonadism, since their free testosterone levels are also lower those of nonobese males and their luteinizing hormone (LH) levels are not higher (figure 2) [1]. Total and free testosterone levels are lower in males who have one or more comorbid conditions than in males of the same age who have none and their LH levels are not higher, suggesting that they also have hypogonadotropic hypogonadism [1].

Change in gonadotropins — As males age, serum gonadotropin concentrations increase, follicle-stimulating hormone (FSH) more than LH, but the rise is not so great as one would expect from the fall in testosterone, suggesting that the fall in testosterone with aging is due to both secondary and primary hypogonadism.

In the EMAS, the fall in testosterone with age was associated with an increase in LH, suggesting a degree of primary hypogonadism [1], but the fall in testosterone with obesity alone (without aging) was not, suggesting that the effect of obesity was mediated by hypogonadotropic hypogonadism.

Effects on spermatogenesis — Sperm production does not appear to change dramatically with increasing age. Testicular size, which reflects primarily the volume occupied by the seminiferous tubules, was somewhat smaller (mean volume 20.6 mL) in 114 older males than in 42 young males (29.7 mL) [8]. Ejaculated sperm density in 20 fathers ages 24 to 37 years old was slightly lower than that in 22 grandfathers ages 60 to 88 years old, but percent motility was greater in the younger group, resulting in a similar total number of motile sperm in the two groups [9].

In 1174 males recruited for studies of erectile function, the oldest quartile, who were aged 56 to 80 years, had similar semen characteristics to the youngest quartile, aged 45 to 47.8 years [10].

ARE THERE CONSEQUENCES OF AGE-RELATED FALL IN TESTOSTERONE? — No clinical consequences of the decline in serum testosterone with age are known with certainty, but several parallels between the effects of aging and those of hypogonadism due to pituitary or testicular disease suggest that the decline in serum testosterone might be a cause of several effects of aging. The parallels include a decline in libido and sexual activity, decreased muscle mass and strength, depressed mood, decreased bone mineral density (BMD), and anemia. (See "Clinical features and diagnosis of male hypogonadism".)

Hypogonadism is actually uncommon in older males. In a report from the European Male Aging Study (EMAS), 2,966 males aged 40 to 79 were evaluated to determine if males with a low serum testosterone concentration for no apparent reason other than age develop the typical signs and symptoms of male hypogonadism due to known pituitary or testicular disease [11]. The combination of low serum testosterone (<317 ng/dL [11 nmol/L]) and three sexual symptoms, was seen in only 2.1 percent of males (n = 63). More severe hypogonadism (serum testosterone concentration <230 ng/dL [8 nmol/L]) was seen in 27 of the 63 (0.9 percent) hypogonadal males.

The hypogonadal males tended to be older and more obese, and in proportion to their testosterone deficiency they had significantly lower:

Hemoglobin

Heel bone mineral density

Muscle mass

Poorer general health

Severe hypogonadism was also associated with insulin resistance and the metabolic syndrome. The associations were stronger when the serum testosterone concentration was <230 ng/dL (8 nmol/L) than when it was in the 230 to 317 ng/dL range (8 to 11 nmol/L). These data support the concept of a low testosterone syndrome in middle-aged and older males, but only in a small percentage.

EVALUATION FOR POSSIBLE HYPOGONADISM

Who should be tested? — We do not routinely measure serum testosterone in older males. However, older males who have symptoms (eg, decreased libido, depressive mood), physical findings (eg, decreased body hair), or laboratory findings (eg, anemia, low bone mineral density [BMD]) of low testosterone should be evaluated in the same way as younger symptomatic males. (See "Clinical features and diagnosis of male hypogonadism".)

Biochemical testing

The initial test should be a serum testosterone measurement early in the morning, fasting. If the result is low, the test should be repeated at least once, preferably twice.

Testosterone should be measured in a laboratory that performs the assay by liquid chromatography and tandem mass spectroscopy and that participates in the Center for Disease Control and Prevention (CDC)'s accuracy-based testosterone Hormone Standardization (HoSt) program or uses an immunoassay that participates in the HoSt program. In a study using sera from four population studies and a harmonized testosterone assay, the lower limit (2.5th percentile) for nonobese males 19 to 39 years was 264 ng/dL [3].

If the testosterone results are consistently low, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) should be measured to determine if the hypogonadism is primary or secondary. (See "Clinical features and diagnosis of male hypogonadism", section on 'LH and FSH'.)

If secondary, other pituitary hormonal deficiencies should be evaluated. (See "Clinical features and diagnosis of male hypogonadism", section on 'Pituitary function testing'.)

If the hypogonadism is secondary and of moderate severity (eg, <200 ng/dL) and/or associated with other hormonal deficiencies, magnetic resonance imaging (MRI) of the sella area should be ordered.

TESTOSTERONE THERAPY

Testosterone currently overprescribed for males without hypogonadism — There has been a dramatic increase in inappropriate use of testosterone therapy in healthy, middle-aged and older males [12]. This rise is likely due, at least in part, to direct-to-consumer advertising encouraging use of testosterone products for nonspecific symptoms, such as decreased energy and sexual interest. However, treatment is only appropriate for those with well documented hypogonadism as described in the following section.

Potential candidates for therapy — Whether or not older males who have low testosterone for no discernable reason other than age will benefit from testosterone treatment is controversial. In contrast, there is general agreement that older males who have unequivocally low testosterone due to known hypothalamic-pituitary or testicular disease should be treated with testosterone as younger males. In 2015, the US Food and Drug Administration (FDA) directed manufacturers of testosterone products to state in their labels that these products are approved only for males with low testosterone due to known causes [13].

However, other expert groups argue that there may be a role for testosterone therapy in selected patients. Our approach is similar to the Endocrine Society Clinical Practice Guidelines for testosterone therapy in adult males with testosterone deficiency, which were updated in 2018 [14].

We suggest offering testosterone on an individualized basis to older males who have symptoms and conditions suggestive of testosterone deficiency and who have consistently and unequivocally low serum testosterone levels after explicit discussion of the potential risks and benefits.

In contrast, we suggest against routinely prescribing testosterone to older males with low testosterone levels in the absence of symptoms and conditions of androgen deficiency (or symptoms without unequivocally low testosterone levels).

As with hypogonadism due to known disease, testosterone treatment should not be initiated until further evaluation if the patient has a prostate nodule, a prostate-specific antigen (PSA) >4 ng/mL or >3 ng/mL in males at increased risk of prostate cancer (eg, African American males or those who have a first-degree relative with diagnosed prostate cancer), or a hematocrit >48 percent.

The same testosterone preparations available for younger males can be used for older males. (See "Testosterone treatment of male hypogonadism".)

Efficacy — Data from five randomized, placebo-controlled trials including over 500 older males [15-21] during the 1990s showed some beneficial effects of testosterone treatment in older males, but the results were not consistent, possibly because of enrolling males who were not clearly hypogonadal, not increasing the serum testosterone to normal, insufficient duration of treatment, and/or not choosing clinically important outcomes. A committee of the Institute of Medicine (now the National Academy of Medicine) reviewed these and other trials and concluded that there was insufficient evidence to conclude that testosterone treatment of older males has any well-established benefit. The committee recommended that a coordinated set of randomized, placebo-controlled clinical trials should be performed to determine if testosterone does have any benefit [22]. The Testosterone Trials (TTrials) were designed to implement this recommendation.

The Testosterone Trials

Design — The multicenter TTrials were a coordinated set of seven placebo-controlled clinical trials to test the one-year efficacy of testosterone on sexual function, physical function, vitality, cognitive function, anemia, bone density, and cardiovascular risk factors in older males with symptoms of hypogonadism and consistently low testosterone [23].

Males over age 65 years (n = 788) with low serum testosterone (<275 ng/dL [9.54 nmol/L] early in the morning on two occasions) and symptoms and objective evidence of sexual dysfunction, physical dysfunction, and/or reduced vitality were assigned to receive testosterone or placebo gel with balancing by minimization for one year and participated in one or more of three main trials (the sexual function [n = 470], physical function [n = 390], and vitality [n = 474] trials). They could also participate in any of the other trials for which they qualified.

Outcomes — Over 51,000 males were screened to enroll the 790 males who met inclusion criteria (only 1.5 percent of those screened). The median pretreatment testosterone concentration was 232 ng/dL. After one year of testosterone gel therapy, average serum testosterone concentrations increased into the mid-normal range (approximately 500 ng/dL) for males ages 19 to 40 years. The following results were reported:

Sexual functionTestosterone therapy was associated with a moderate improvement in sexual function, including sexual activity (figure 3), sexual desire (libido), and, to a lesser extent, erectile function [24]. The effect on sexual activity and sexual desire was likely of clinical significance because the effect sizes were 0.45 and 0.44, respectively, and participants who were treated with testosterone were significantly more likely than those treated with placebo to respond on a Patient Global Assessment of Change question that their sexual desire was better during treatment than before. The magnitude of rise in serum testosterone and estradiol concentrations was associated with the magnitude of improvement in sexual desire and sexual activity, but not erectile function.

Physical function – There was no significant difference between the testosterone- versus placebo-treated groups in walking distance on a six-minute walk test in the 390 males who were enrolled in the physical function trial, but testosterone did improve walking distance when all 788 males were included [23].

Vitality – (as assessed by Functional Assessment of Chronic Illness Therapy-Fatigue Scale in the vitality trial) did not differ in testosterone- versus placebo-treated males enrolled in the vitality trial (but testosterone improved vitality [energy] slightly when subjects from all three main trials were included) [23]. However, males receiving testosterone reported better mood and lower severity of depressive symptoms when compared with placebo.

Cognitive function – A subgroup of 493 males in the TTrials met criteria for age-associated memory impairment (AAMI), based on subjective memory complaints and objective memory performance lower than younger males [25]. After 6 and 12 months, there were no differences in changes from baseline in testosterone- and placebo-treated males in test scores for memory and other cognitive functions (delayed paragraph recall, visual memory, executive function, or spatial ability), but testosterone improved executive function when all subjects from all three main trials were included.

Anemia – Among the 788 males enrolled in all three trials, 126 were anemic (hemoglobin ≤12.7 g/dL) at baseline, 64 associated with a known cause, such as iron deficiency, and 62 with unexplained anemia [26]. After 12 months of testosterone treatment, more males with unexplained anemia in the testosterone group had increases in hemoglobin of 1 g/dL or more (54 versus 15 percent in the placebo group) and normal hemoglobin values (58 versus 22 percent in the placebo group) (figure 4). Similar results occurred in males who had anemias of known cause (figure 5). This effect of testosterone replacement is consistent with the known stimulatory effect of testosterone on erythropoiesis. Another trial also suggested benefit for anemia [27].

Bone density – A subgroup of 211 males underwent assessment of volumetric bone mineral density (vBMD) and bone strength by quantitative computed tomography (QCT) scanning at baseline and 12 months [28]. After 12 months, testosterone significantly increased mean lumbar spine trabecular vBMD (7.5 versus 0.8 percent), as well as lumbar peripheral and hip trabecular and peripheral vBMD (figure 6), and mean estimated strength of spine trabecular bone (11 versus 2.4 percent), as well as lumbar peripheral and hip trabecular and peripheral bone (figure 7).

Adverse events

Coronary artery plaque – In a substudy of 170 males, one year of testosterone therapy was associated with a greater increase than placebo in noncalcified coronary artery plaque volume, as measured by coronary computed tomographic angiography (CCTA) [29]. There was also a significantly greater increase in total plaque volume in the testosterone group but no change in the coronary calcification score in either group. Of note, 50 percent of the study subjects had severe atherosclerosis at baseline on CCTA. Major limitations of the study were the use of CCTA (a surrogate outcome for atherosclerosis) and the small size and short duration of the trial.

Erythrocytosis – More males in the testosterone group experienced erythrocytosis (hemoglobin ≥17.5 g/dL) (7 versus 0) [23]. The incidence of major adverse cardiovascular events and other adverse events was otherwise similar with testosterone and placebo.

Prostate outcomes – In the same set of trials, testosterone therapy that increased serum testosterone concentrations from moderately low (approximately 230 ng/dL [7.97 nmol/L]) into the midnormal range (approximately 500 ng/dL [17.3 nmol/L]) increased serum PSA concentrations to a small degree [30]. Only 2.5 percent of males experienced an increase above baseline of ≥3.4 ng/mL, A confirmed PSA >4.0 ng/mL occurred in 1.9 percent of males on testosterone and 0.3 percent on placebo.

Four prostate cancers were diagnosed during the 12 months of treatment and the 6 months of follow-up; three in the testosterone arm (two of which were high-grade prostate cancer) and one in the placebo arm.

The TTrials, in short, demonstrated that testosterone treatment of symptomatic older males with unequivocally low testosterone levels is efficacious in improving sexual function, walking, mood, depressive symptoms, anemia, and bone density, all to modest degrees. Testosterone treatment, however, did not improve vitality or cognitive function and was associated with an increase in noncalcified coronary artery plaque volume. Although testosterone treatment was not associated with increased risks of clinical cardiac events or prostate cancer, a much larger and longer trial would be needed to assess these risks with greater certainty.

Monitoring treatment

Serum total testosteroneIf testosterone treatment is prescribed, we recommend monitoring the serum testosterone level during treatment. The author of this topic suggests using a target value in older males that is in the low-normal range for young males (eg, 300 to 400 ng/dL [10.4 to 13.9 nm]) to lower the risk of testosterone-dependent diseases.

PSA – PSA should be repeated three to six months after initiation of testosterone treatment to determine if it has increased more than 1.4 ng/mL above baseline or to >4 ng/mL. If the increase is reproducible, the patient should be referred for urologic evaluation.

Hematocrit – Hematocrit should be measured three to six months after initiation of treatment and at least once a year thereafter because testosterone stimulates erythropoiesis. A high value can occur because of an excessive dose of testosterone or unmasking of a secondary cause.

Potential adverse effects — There are reasons to think that testosterone treatment of older males with low testosterone might exacerbate certain diseases. For example, the prostate gland is testosterone dependent, so it is reasonable to wonder if raising the serum testosterone concentration will increase the risk of prostate cancer or benign prostatic hyperplasia. Erythropoiesis is also testosterone dependent, so raising the testosterone level, especially to supraphysiologic levels, can cause erythrocytosis. Some epidemiologic studies have shown a larger number of cardiovascular events in males treated with testosterone, but others have not. (See "Testosterone treatment of male hypogonadism", section on 'Venous thromboembolism' and "Testosterone treatment of male hypogonadism", section on 'Cardiovascular risks'.)

Prostate cancer Prostate cancer is partly testosterone dependent [31]. This dependency is illustrated by the current practice of treating males who have metastatic and locally advanced prostate cancer by lowering their serum testosterone concentrations with drugs that decrease testosterone synthesis and/or its action [32]. (See "Initial systemic therapy for advanced, recurrent, and metastatic noncastrate (castration-sensitive) prostate cancer".)

In the few clinical trials of testosterone in older males, few cases of prostate cancer occurred [15,17,18,23], but these trials, involving at most 788 males, had too little statistical power to state that testosterone treatment does not increase the risk of prostate cancer. It has been estimated that a trial would require 6000 males randomized to receive testosterone or placebo for five years each to determine if testosterone increases the incidence of prostate cancer by 30 percent [22].

In a 2010 meta-analysis of 51 randomized trials of testosterone therapy in males designed to look at the primary endpoints of mortality, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis, testosterone treatment was not associated with increased incidence of prostate cancer, need for prostate biopsy, or other prostate outcomes when compared with the placebo/nonintervention group [33]. Results were the same when analyzed by subject age (less than or greater than age 65 years). However, as the study authors emphasize, the number of subjects studied and the quality of the observations were not adequate to say that testosterone does not result in worse prostate outcomes. (See "Testosterone treatment of male hypogonadism".)

Benign prostatic hyperplasia The testosterone dependency of benign prostatic hyperplasia has been known for over 100 years and is the basis for one current medical treatment: use of the 5-alpha-reductase inhibitors, finasteride and dutasteride, to block the conversion of testosterone to dihydrotestosterone, its active metabolite within the prostate [34]. In the meta-analysis noted above, testosterone therapy had no adverse effect on lower urinary tract symptoms or other prostate outcomes [33]. In the TTrials of 788 males treated for one year, the number of males whose International Prostate Symptom Score increased above 19 (moderately severe) was similar in the testosterone and placebo groups (testosterone 27, placebo 26) [23]. The number of males observed and duration of the observations are not sufficient to say that testosterone does not worsen lower urinary tract symptoms. (See "Medical treatment of benign prostatic hyperplasia".)

Sleep apnea Data from a small number of males with hypogonadism suggest that even physiologic replacement of testosterone increases sleep apnea [35-37], a condition to which older males are already prone. In contrast, in one meta-analysis [38], the frequency of sleep apnea did not differ between testosterone- and placebo-treated males.

Erythrocytosis Testosterone treatment of older males, especially with long-acting testosterone esters in doses that have been commonly employed, causes erythrocytosis. In one retrospective trial of 45 males whose average age was 71.8 years and who had relatively low serum bioavailable testosterone concentrations, treatment with 200 mg of testosterone ester (enanthate or cypionate) caused an increase in hematocrit to >52 percent in 11 of them (24 percent) [39].

In the trial described above in which males were randomized to receive testosterone enanthate 200 mg/two weeks alone or with finasteride, 14 of 46 males developed an elevated hemoglobin [18].

Even in the TTrials, in which testosterone and hemoglobin levels were monitored at least every three months, the dose of testosterone adjusted accordingly, and the incidence of erythrocytosis was relatively low, the seven males who developed erythrocytosis were all in the testosterone group.

The potential significance of this adverse effect is that in the Framingham Heart Study, males who were in the highest quintile (46 to 70 percent) with regard to hematocrit had greater overall mortality and cardiovascular mortality than those in the middle two quintiles [40].

Lipids Both oral and intramuscular administration of high doses of testosterone have been shown to decrease high-density lipoprotein (HDL) cholesterol concentrations in young hypogonadal males and in males receiving gonadotropin-releasing hormone (GnRH) antagonists, respectively [41,42]. In a meta-analysis of 10 studies of intramuscular testosterone esters and plasma lipids in hypogonadal males, a small, dose-dependent decrease was seen in total cholesterol, low-density lipoprotein (LDL) cholesterol, and HDL [43]. In the TTrials, testosterone was associated in small decreases in both LDL and HDL cholesterol [44].

Cardiovascular Data on the risk of cardiovascular complications with testosterone therapy have been conflicting, with some epidemiologic studies suggesting no increase in cardiovascular events in older males, while others suggest a possible increase in cardiovascular events in some males who take testosterone. Although this issue remains unclear, the FDA issued a safety announcement on March 3, 2015, stating that it was requiring manufacturers of testosterone products to change its labeling of these products to include a warning of possible increased risk of heart attacks and strokes associated with testosterone use [13]. This issue is discussed in detail separately. (See "Testosterone treatment of male hypogonadism", section on 'Cardiovascular risks'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Testosterone therapy in men" and "Society guideline links: Male infertility or hypogonadism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Androgen replacement in men (The Basics)" and "Patient education: Low testosterone in men (The Basics)")

SUMMARY AND RECOMMENDATIONS

Age-related changes serum testosterone – Serum total testosterone concentrations fall slightly with increasing age, and free testosterone concentrations fall more, although still modestly. (See 'Serum total testosterone' above.)

Who should be tested? Older males who have symptoms, physical findings, or other findings suggestive of hypogonadism should be evaluated for low testosterone, just as younger males. (See 'Who should be tested?' above.)

Initial evaluation should be measurement of the serum testosterone in the early morning, fasting, by liquid chromatography-tandem mass spectroscopy in a laboratory that participates in the Centers for Disease Control and Prevention (CDC)'s testosterone Hormone Standardization (HoSt) program. If the result is low for young males (eg, less than 229 ng/dL), the measurement should be performed twice more. (See 'Biochemical testing' above.)

If the testosterone is unequivocally and reproducibly low, we suggest measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine if the hypogonadism is primary or secondary. If secondary, we suggest assessment of other pituitary hormones. If the patient has multiple pituitary hormonal deficiencies and/or if the testosterone is less than 200 ng/dL, we suggest MRI of the sella. (See 'Biochemical testing' above.)

Candidates for testosterone therapy For older males with unequivocally low serum testosterone levels and symptoms and conditions suggestive of hypogonadism, we suggest testosterone therapy (Grade 2C). A detailed discussion of the risks and benefits of testosterone therapy is essential in this population. (See 'Potential candidates for therapy' above.)

We do not prescribe testosterone to older males with low testosterone levels in the absence of symptoms and conditions of androgen deficiency (or symptoms without unequivocally low testosterone levels). (See 'Potential candidates for therapy' above.)

If a digital rectal examination shows a prostate nodule or the prostate-specific antigen (PSA) is >4 ng/mL or >3 ng/mL in males at increased risk of prostate cancer (eg, African American males or those who have a first-degree relative with diagnosed prostate cancer), the patient should be referred for urologic evaluation before prescribing testosterone. (See 'Potential adverse effects' above.)

Monitoring therapy Monitoring includes measurement of serum total testosterone, hematocrit, and PSA as described above. (See 'Monitoring treatment' above.)

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Topic 7457 Version 30.0

References

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