Shalender Bhasin, MD. Glenn R Cunningham, MD. Mohit Khera, MD, MBA, MPH

Transcription

1 Shalender Bhasin, MD Program Chair Professor of Medicine Boston University School of Medicine Section Chief Division of Endocrinology, Diabetes & Nutrition Boston, MA Glenn R Cunningham, MD Professor of Medicine, Molecular & Cellular Biology Baylor College of Medicine SLEH-BCM Diabetes Program St. Luke s Episcopal Hospital Houston, TX Mohit Khera, MD, MBA, MPH Assistant Professor of Urology Division of Male Reproductive Medicine & Surgery Scott Department of Urology Baylor College of Medicine Houston, TX We invite you to share your own experiences, comments, and questions with us and your colleagues, and hope you enjoy this novel educational format. The Diagnosis and Management of Men With Androgen Deficiency

2 Recognize androgen deficiency Common clinical disorder, both under- and overdiagnosed, and often suboptimally treated - Consistently low serum testosterone levels - Decreased spermatogenesis Overt signs - Testosterone levels are below 150 ng/dl - Disease affecting the hypothalamus, pituitary, or testes Factors contributing to under-recognition - Nonspecific symptoms may be attributed to other conditions - Patients reluctant to discuss sexual symptoms, physicians reluctant to ask - No consensus on biochemical definition of low testosterone - Unreliability of some testosterone assays Population-level screening not recommended - Case-finding suggested in specific circumstances, such as certain chronic conditions Type 2 diabetes mellitus Metabolic syndrome End-stage renal disease Osteoporosis or low-trauma fracture Treatment with medications affecting testosterone (eg, steroids, opioids) Testosterone replacement therapy (TRT) often beneficial for confirmed androgen deficiency - Restore and maintain normal sexual function - Improve sense of well-being - Improve hemoglobin levels - Improve vertebral bone mineral density - Maintain skeletal muscle mass - Reduce fat mass References Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92: Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95: Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86: Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92: Wu FC, Tajar A, Beynon JM, et al; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:

3 Meet your patient Review referral information, lab results, and pre-visit questionnaire Ask about family and medical history and current symptoms Assess Perform physical exam Recognize symptoms of androgen deficiency Suggestive Signs and Symptoms - Reduced libido - Decreased spontaneous erections - Breast discomfort, gynecomastia - Loss of body hair and reduced need for shaving - Very small or shrinking testes - Height loss, low-trauma fracture, low bone mineral density - Hot flushes, sweats - Infertility - Incomplete sexual development Less-Specific Signs and Symptoms - Decreased energy, motivation, initiative - Depressed mood, dysthymia - Reduced muscle mass and strength - Increased body fat or BMI - Poor concentration and memory - Mild anemia - Diminished strength or work performance Measure testosterone levels at least 2 times - Assess morning total testosterone; if low, repeat for confirmation - Assess free or bioavailable testosterone if Total testosterone levels are ng/dl Binding protein abnormality is suspected > Obesity > Diabetes mellitus > Insulin resistance > Aging > Hepatitis > HIV infection > Thyroid disorders - Exclude acute illnesses or stress, nutritional deficiency, medications, and other possible contributing factors Confirm Diagnosis of androgen deficiency - Consistent signs and symptoms - Unequivocally and consistently low testosterone Order additional tests to determine primary or secondary hypogonadism - Primary - Low testosterone levels, impaired spermatogenesis, elevated follicle-stimulating hormone (FSH), luteinizing hormone (LH) - Secondary - Impaired spermatogenesis and low or inappropriately normal LH and FSH levels Measure prolactin, serum iron, total iron binding capacity and perform MRI (testosterone <150 ng/dl) to exclude hypothalamic or pituitary disease Assess baseline BMD References Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95: Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159:

4 Consider contraindications for TRT Communicate and discuss POtential Benefits Of trt POtential risks Of trt History of prostate or breast cancer Erythrocytosis (hematocrit >50%) Severe lower urinary tract symptoms Palpable prostate nodule or elevated PSA (>4 ng/ml) require additional urologic evaluation Other COntraindiCatiOns Uncontrolled severe heart failure Myocardial infarction, acute coronary event, unstable angina, or coronary revascularization procedure in the previous 6 months Untreated severe obstructive sleep apnea Desire for fertility Improved sexual function and sexual satisfaction Enhanced mood and sense of well-being Increased energy and strength Improved vertebral bone mineral density Enhanced libido, erections, and sexual satisfaction Decreased fat mass/increased lean body mass Increased hemoglobin and hematocrit Acne and oily skin Worsening of male-pattern baldness Suppressed spermatogenesis or infertility Potential increased risk for prostate cancer progression and recurrence Accelerated growth of breast cancer Gynecomastia Sleep apnea Decreased HDL-C References Bhasin S, Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab. 2011;25: Boloña ER, Uraga MV, Haddad RM, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82: Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci. 2005;60: Cunningham GR, Toma SM. Clinical review: Why is androgen replacement in males controversial? J Clin Endocrinol Metab. 2011;96: Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95: Isidori AM, Giannetta E, Gianfrilli D, et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf). 2005;63:

5 Encourage patient buy-in Establish realistic expectations - TRT requires long-term commitment - Match TRT formulation to patient needs - Adherence to treatment and standardized monitoring is essential Identify goals of TRT Improve symptoms and restore physiologic testosterone concentrations ( ng/dl) Minimize side effects Optimize patient safety/convenience Adjust dose to avoid supraphysiologic peaks and hypogonadal valleys Rapid response libido, mood, energy Long-term response body composition, BMD Agree on monitoring plan References Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95: Cunningham GR, Toma SM. Clinical review: Why is androgen replacement in males controversial? J Clin Endocrinol Metab. 2011;96:38-52.

6 Explain the choices PROS AND CONS OF FORMULATIONS/DELIVERY SYSTEMS Formulation* Advantages Potential Disadvantages/ Side Effects 1%-2% testosterone gel Flexible dosing Good skin tolerability Available in sachets, tubes, pumps for easy application Daily administration Risk of transfer to female partner or child via skin contact Application-site reactions 17-alpha methyl testosterone N/A Clinical responses variable Risk of liver toxicity Buccal, bioadhesive tablet Restores normal testosterone levels in most treated patients Twice-daily administration Inability to adjust dose Gum/mouth irritation Unpleasant taste Testosterone enanthate or cypionate Relatively low cost Flexible dosing Treatment every 1-2 weeks Requires intramuscular injection Pain at injection site Associated with peaks and valleys in serum testosterone levels Fluctuations in mood and libido High rate of erythrocytosis especially in the elderly Testosterone pellets Treatment every 3-6 months Subcutaneous insertion Invasive placement/removal for replacement Pain/inflammation at implant site Risk of infection May spontaneously extrude Topical testosterone solution Underarm application, which may limit risk of transfer to others Daily administration Application-site reactions Transdermal testosterone patch Mimics circadian rhythm of testosterone release Simple to administer Daily administration May require 2 patches per day to attain target testosterone range Skin reactions at application site are common *This table identifies formulations currently approved for use in the United States. A longer-acting depot formulation requiring injection every 3 months is available in many countries. Be flexible You and your patient should choose the formulation/delivery system that best suits his needs Monitor, adjust dosage, or switch to other formulations to achieve target testosterone range, accommodate patient needs, and avoid side effects References Cunningham GR, Toma SM. Clinical review: Why is androgen replacement in males controversial? J Clin Endocrinol Metab. 2011;96: Practice Committee of the American Society for Reproductive Medicine; Society for Male Reproduction and Urology. Androgen deficiency in the aging male. Fertil Steril. 2008; 90(suppl 5):S83-S87.

7 Androgen deficiency requires TRT for long periods or for life Establish monitoring plan to meet individual patient needs What to Monitor When to Monitor Testosterone levels* Initial testing within 1-2 months after treatment initiation (at midpoint between injections or 4-10 hours after gel or patch application) Every 6-12 months thereafter Response to TRT (eg, improvements in libido, mood, energy, changes in body composition) Adherence to TRT Adverse events (general and formulation-specific) Hemoglobin, Hematocrit Prostate (DRE and PSA) Bone mineral density (in men with osteoporosis or low-trauma fracture) 3-6 months after TRT initiation Annually thereafter At each visit At each visit Baseline 3-6 months after treatment initiation Annually thereafter Baseline 3-6 months after treatment initiation Thereafter, annual DRE and PSA every 6-12 months or per prostate screening guidelines At baseline Every 1-2 years after TRT initiation *This table identifies formulations currently approved for use in the United States. References Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95: Practice Committee of the American Society for Reproductive Medicine; Society for Male Reproduction and Urology. Androgen deficiency in the aging male. Fertil Steril. 2008;90(suppl 5):S83-S87.

8 Maintain TRT goals long-term Improved sexual function Improved muscle strength and mass Improved bone health Improved well-being Circumstances requiring further investigation Testosterone level <150 ng/dl Interest in fertility Circumstances requiring referral Indications for urologic consult - Abnormal DRE - PSA >1.4 ng/ml within any 12-month period of treatment - PSA velocity >0.4 ng/ml (can be assessed only if there is longitudinal PSA data for more than 2 years) - Severe lower urinary tract symptoms Additional studies underway to assess benefits and risks of long-term TRT References Bebb RA. Testosterone deficiency: practical guidelines for diagnosis and treatment. BC Med J. 2011;53: Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95: Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl. 2003;24: Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95: Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159:

9 [PANEL 1]HEIGHTEN AWARENESS Androgen deficiency is a clinical disorder characterized by consistently low serum testosterone levels, decreased spermatogenesis, and an array of associated signs and symptoms. The disorder usually is recognized when symptoms and signs are overt, testosterone levels are below 150 ng/dl, and there is known disease affecting the hypothalamus, pituitary, or testes. Absent such circumstances, androgen deficiency frequently goes unrecognized, for multiple reasons. Many symptoms of androgen deficiency are nonspecific or easily attributable to other comorbid conditions. Further, patients who have sexual symptoms, such as reduced libido, may find it difficult to discuss them with you, and you may be uncomfortable asking their patients about sexual symptoms. Adding to the confusion is a lack of consensus on how low testosterone should be defined biochemically and the unreliability of some testosterone assays. Population-level screening for androgen deficiency, via measurement of serum testosterone, is not recommended. Case-finding, starting with assessment of testosterone levels, may be appropriate in men with sexual dysfunction or other overt signs and symptoms of testosterone deficiency. Current guidelines suggest case-finding in men with certain chronic conditions that are associated with a higher prevalence of androgen deficiency, such as type 2 diabetes mellitus, metabolic syndrome, end-stage renal disease, osteoporosis, and conditions requiring treatment with steroids or opioids. In men for whom a diagnosis of androgen deficiency is confirmed, intervention with testosterone replacement therapy, or TRT, is often beneficial. When appropriate, TRT can restore and maintain normal sexual function; improve sense of well-being, hemoglobin levels, and vertebral bone mineral density; maintain skeletal muscle mass; and reduce fat mass. Question: Which of the following statements most accurately characterizes androgen deficiency in men? A. It is defined by low testosterone levels alone. B. It is readily diagnosed via recognition of specific symptoms. C. It is a syndrome characterized by signs and symptoms in association with consistently low testosterone levels. Answer: Androgen deficiency is a syndrome characterized by signs and symptoms in association with consistently low testosterone levels. Clinical Pearl: Explore the possibility of androgen deficiency in certain middle-aged and older patients, such as those with type 2 diabetes and symptoms such as low libido and erectile dysfunction. 1

10 [PANEL 2] INITIAL STEPS Patients with suspected androgen deficiency may come to you directly, or may be referred to you by their primary care physician. For each patient, you will want to begin by reviewing referral information and lab work, if available, enquiring about his medical history and current symptoms, and performing a physical exam to assess for signs and symptoms of androgen deficiency. Reduced libido is among the most common symptoms of androgen deficiency in aging men. Other specific signs include erectile dysfunction, loss of early morning erections, breast discomfort or gynecomastia, loss of body hair, and small testes (less than 5 ml). Patients may also have symptoms less specific to androgen deficiency, such as decreased energy, depressed mood, and reduced muscle mass. Crucial to making a diagnosis of androgen deficiency is assessment of testosterone levels. Diagnosis requires determination of symptoms in conjunction with consistently low testosterone levels, based on lab results obtained on at least 2 separate occasions. Current guidelines recommend assessing total testosterone in a blood sample taken in the morning hours (before 10 AM), due to circadian fluctuations in hormone levels. The confirmatory test may also be a morning total testosterone. An assessment of free or bioavailable testosterone may be useful for patients with total testosterone levels that are near the lower limit of normal and who may have alterations in sex-hormone binding globulin, as often seen with conditions such as obesity, diabetes mellitus, insulin resistance, aging, hepatitis, HIV infection, and thyroid disorders. Acute illness, acute stress, nutritional deficiency, and the use of medications such as steroids or opioids must be ruled out as contributing factors. Once low testosterone levels are confirmed, other tests such as those assessing levels of FSH and LH may be needed to pinpoint whether androgen deficiency reflects primary hypogonadism, reflecting defects at the testicular level; or secondary hypogonadism, reflecting defects at the level of the hypothalamus or pituitary. Patients with primary hypogonadism typically have low testosterone levels, impaired spermatogenesis, and elevated LH and FSH levels. Patients with secondary hypogonadism typically have impaired spermatogenesis and low or inappropriately normal LH and FSH levels, and may require additional testing, including prolactin levels and MRI scans, to confirm or exclude the contribution of hypothalamic or pituitary disease. A dual-energy X-ray absorptiometry scan to assess bone mineral density should be obtained prior to treatment of men with documented androgen deficiency. Question: Which one of the following is among the most common symptoms of androgen deficiency in men? A. Gynecomastia B. Reduced muscle mass C. Reduced libido D. Depressed mood Answer: Low libido is one of the most common symptoms of androgen deficiency in aging men. Clinical Pearl: Diagnosis of androgen deficiency requires the presence of consistent signs and symptoms such as low libido, decreased energy or strength, and depressed mood in conjunction with unequivocally low testosterone levels, based on lab results obtained on at least 2 separate occasions. 2

11 [PANEL 3] WEIGHING BENEFITS AND RISKS OF TREATMENT Once a diagnosis of androgen deficiency has been confirmed, TRT can be considered. However, first you should identify any contraindications to treatment. Contraindications include a history of prostate or breast cancer, erythrocytosis, and severe lower urinary tract symptoms. Further urologic evaluation is needed before TRT can be started in patients with a palpable prostate nodule or induration, or a PSA greater than 4 ng/ml (greater than 3 ng/ml in those at high risk of prostate cancer or those younger than age 50 years),. If there are no contraindications, the next important step is a discussion with your patient regarding benefits and risks of TRT. This conversation provides an opportunity to involve your patient as an active and fully informed participant in deciding whether to pursue TRT and in selecting from available treatments. He also should understand that long-term benefits and risks of TRT are not fully understood. Potential benefits of TRT include improvements in sexual function, enhanced mood and sense of well-being, increased energy and strength, and improved vertebral bone mineral density. TRT in androgen-deficient men can enhance libido, erections, and overall sexual satisfaction. TRT has also been shown to decrease fat mass, increase lean mass, and improve muscle strength. Among adverse events, increases in hemoglobin and hematocrit are common and warrant careful monitoring. In epidemiologic studies, high hematocrits are associated with an increased risk of coronary events. Other frequent side effects include acne and oily skin, worsening of male-pattern baldness, and suppressed spermatogenesis men who wish to be fathers in the near future should not receive TRT. In addition, TRT has the potential to increase the risk for prostate cancer progression and recurrence, and can accelerate the growth of breast cancer, though reports of breast cancer in men treated with testosterone are rare. Question: In addition to improvements in sexual function, which of the following is a potential benefit of TRT in aging men with androgen deficiency? A. Reversal of male-pattern baldness B. Improved muscle mass and strength C. Improvement in sleep apnea D. Decreased hemoglobin and hematocrit Answer: Improved muscle mass and strength Clinical Pearl: Ensure that patients with androgen deficiency who are candidates for TRT are fully informed about benefits and risks of TRT, and involve them as active participants in the treatment selection process. 3

12 [PANEL 4] ESTABLISHING TREATMENT GOALS AND EXPECTATIONS Establishing realistic goals of TRT and encouraging patient buy-in to necessary treatment and monitoring are important to treatment success. Patients need to understand that androgen deficiency is, for most men, a chronic condition that requires lifetime treatment and physician supervision. By selecting treatments that meet individual patient needs, and by establishing individualized treatment goals and monitoring plans, you can facilitate patient acceptance and long-term commitment. Primary goals of TRT are to improve symptoms and restore physiologic concentrations of testosterone that is, the mid-normal range for healthy young men. Other goals include minimizing side effects and optimizing safety and convenience. Although usually TRT can yield physiologic concentrations of testosterone within 1-2 months, patients should be aware that dose adjustments may be necessary to optimize therapeutic responses, also, patients need to keep in mind that TRT improves some symptoms more rapidly than others. For example, symptoms such as libido, mood, and energy may improve within 1-3 months. Others symptoms, such as changes in body composition and bone mineral density of the spine, will take longer. A basic plan for monitoring should be established at the time of treatment initiation. Specifics about monitoring plans are discussed in greater detail later in this program. Question: The physician should help patients to have realistic expectations of the effects of TRT. Which of the following is a realistic expectation for TRT? A. Achieving physiologic levels of testerone following TRT initiation usually requires 3-6 months. B. TRT treatment can yield improvements in body composition (lean and fat mass) within 3 months. C. TRT can improve bone density of the spine within 3 months. D. TRT can improve libido within 3 months. Answer: TRT can improve libido within 1-3 months. Improvement in body composition will take longer, as will changes in bone mineral density of the spine, which should not be expected or assessed before 12 months. Clinical Pearl: Primary goals of TRT are to improve symptoms of androgen deficiency by restoring physiologic concentrations of testosterone while optimizing safety and convenience. 4

13 [PANEL 5] SUPPORTING TREATMENT SELECTION Testosterone therapy is available in the United States in a wide array of formulations, all of which can improve symptoms of androgen deficiency. Ideally, TRT in men with androgen deficiency should bring circulating testosterone levels into the normal range, cause few or no adverse effects, and be convenient to use so that patients can manage treatment autonomously. Recent innovations and refinements in formulations and delivery systems have improved the safety and convenience of TRT, and provide many choices to help individualize treatment. For example, intramuscular injections are longlasting up to 2 weeks and are relatively low cost for patients who can learn to self-inject. Several transdermal gel or liquid formulations and a transdermal patch are available for patients averse to injections. Additional formulations are available outside the United States. These include an oral formulation of testosterone, (testosterone undecanoate), a longer-acting depot formulation of testosterone undecanoate requiring injection every 3 months, and a testosterone-in-adhesive matrix patch providing 2 days of transdermal delivery. You should work with your patient to identify the formulation that best suits his needs, being sure to present the full range of choices together with dosing schedules, advantages and disadvantages, costs, and monitoring requirements. Dosing may need modification to achieve target testosterone goals. Question: Which one of the following is an appropriate regimen for testosterone enanthate or cypionate injections? A. Daily B. Once every 1-2 weeks C. Once every 3 weeks D. Once monthly Answer: Testosterone enanthate or cypionate injections are best administered every week or every other week. Clinical Pearl: As TRT gets under way, initial treatment selections and dosing regimens may require adjustment based on patient needs and responses, as well as treatment side effects. 5

14 [PANEL 6] MONITORING TREATMENT Most patients with androgen deficiency require TRT for long periods or for life. To help ensure long-term adherence and maximize efficacy and safety, establishing and implementing a standardized treatment monitoring plan is essential. The optimal time to measure testosterone levels varies with the mode of treatment. For example, for patients receiving intramuscular testosterone formulations, you would measure testosterone levels at the midpoint between injections; for patients using a testosterone gel or patch, the appropriate measurement interval would be 4 to 10 hours after application. As the patient s testosterone levels normalize, clinical responses should be monitored. Responses to be assessed are based on the patient s baseline signs and symptoms and should initially be evaluated between 3 and 6 months. Both testosterone levels and clinical responses may also indicate whether your patient is adhering to treatment. Different organ systems vary in their response to changes in testosterone levels. For example, libido, erectile function, and mood seem to improve with testosterone levels in the low-normal range, whereas changes in muscle mass respond in a dose-dependent manner, and changes in bone mineral density depend on dose and duration of treatment. Be sure to ask your patient about treatment side effects such as skin reactions, injection-site pain, acne, or the development or worsening of sleep apnea at every visit. Safety monitoring should also include measurement of hemoglobin or hematocrit and serum PSA. Once testosterone levels are within the target range, adverse events are under control, and clinical responses are evident, less-frequent monitoring is needed. Testosterone levels and hematocrit or hemoglobin should be assessed annually. PSA testing and DRE should be performed annually in men ages 40 years and older, or as recommended in prostate cancer screening guidelines. In men with osteoporosis or a history of low-trauma fracture, bone mineral density should be assessed every 1-2 years. Question: In patients on TRT, how often should hematocrit be measured? A. Initially at 3-6 months, then annually B. Every 3 months C. Every 6 months D. Every 2 years Answer: Current guidelines recommend that hematocrit be assessed at 3 to 6 months post-initiation of TRT and annually thereafter. Most other assessments that are part of monitoring are performed at similar intervals. Clinical Pearl: Establish a standardized monitoring plan for patients on TRT that includes measurement of testosterone levels, PSA, and hematocrit at periodic intervals. 6

15 [PANEL 7] LOOKING AHEAD: LONG-TERM MANAGMENT Sustaining eugonadal testosterone levels over time in patients with androgen deficiency has multiple benefits. However, over months or years of treatment, situations may arise that require your attention or referral. Patients with secondary hypogonadism who decide that they wish to father children will need to suspend TRT because of its suppressive effects on spermatogenesis; in these men, fertility can often be restored with appropriate gonadotropin therapy. In men with primary hypogonadism, however, the defect in spermatogenesis is not usually treatable and alternate strategies must be explored. Patients who have an abnormal DRE, PSA values exceeding 1.4 ng/ml, or a PSA velocity exceeding 0.4 ng/ml/year should be referred to a urologist, as should patients who develop severe lower urinary tract symptoms. Additional studies are needed, and are under way, to better understand the benefits and risks of long-term TRT in older men with age-related decline in testosterone levels. Question: Under which one of the following circumstances should a patient on TRT be referred to a urologist? A. PSA increase >1.0 ng/ml within any 12-month period of treatment B. PSA velocity >0.2 ng/ml over any 12-month period of treatment C. Severe lower urinary tract symptoms Correct Answer: Referral to a urologist is necessary if the patient develops severe lower urinary tract symptoms. Other reasons for referring to a urologist include an abnormal DRE, a PSA value exceeding 1.4 ng/ml within any 12-month period of TRT, or a PSA velocity exceeding 0.4 ng/ml/year based on data longitudinal data for more than 2 years. Clinical Pearl: TRT is considered appropriate and beneficial for aging men with confirmed androgen deficiency, although research continues to explore its long-term impact. 7