BPH/LUTS, ED, and hypogonadism
There is not total agreement on the threshold of testosterone value below which a man would be considered hypogonadal. (Currently there are no standards as to when to treat women.) Testosterone can be measured as "free" (that is, bioavailable and unbound) or more commonly, "total" (including the percentage which is chemically bound and unavailable). In the United States, male total testosterone levels below 300 ng/dL from a morning serum sample are generally considered low. Identification of inadequate testosterone in an aging male by symptoms alone can be difficult.
§ Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia.
§ Regulates acute HPA (Hypothalamic–pituitary–adrenal axis) response under dominance challenge
§ Regulator of cognitive and physical energy
§ Maintenance of muscle trophism
§ Testosterone regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans
§ High androgen levels are associated with menstrual cycle irregularities in both clinical populations and healthy women. See libido.
Is it appropriate to treat this patient with a PDE5 inhibitor for BPH/LUTS and ED and testosterone therapy for hypogonadism?
Yes; there is little clinical evidence to suggest that testosterone therapy will exacerbate voiding symptoms in patients with BPH
No; testosterone therapy may exacerbate voiding symptoms in patients with BPH
There is little clinical evidence to suggest that testosterone therapy will exacerbate voiding symptoms in BPH. Testosterone therapy should be initiated in BPH patients after careful consideration and with close monitoring, because the prostate is androgen-dependent and testosterone therapy had been thought to exacerbate LUTS. Recent studies investigating the effects of normalizing testosterone levels in older men suggest that reestablishing eugonadal testosterone levels may positively affect AUA-SI score. This warrants further study in sufficiently powered, randomized, placebo-controlled trials.
Preclinical studies suggest that testosterone protects the prostate from metabolic syndrome–induced prostatic hypoxia, fibrosis, and inflammation, which can play a role in the development or progression of BPH/LUTS. This is interesting because it has been suggested that BPH/LUTS, ED, and hypogonadism may be linked by metabolic syndrome.
For this patient, who has concomitant BPH/LUTS, ED, and hypogonadism, it is appropriate to treat with testosterone therapy to improve the hypogonadism symptoms and with a PDE5 inhibitor to improve the comorbid BPH/LUTS and ED.
The physician should explain to the patient prior to initiating testosterone therapy that testosterone therapy requires meticulous surveillance, including regular DREs and serum PSA testing:
a) Assess testosterone, hematocrit, and PSA levels at 3 and 6 months and then annually after initiation of testosterone therapy
b) In men 40 years of age or older with baseline PSA higher than 0.6 ng/mL, perform DRE and check PSA level before initiating treatment, at 3 and 6 months, and then in accordance with guidelines for prostate cancer screening
i. Refer for urologic consultation in event of the following:
• Increase in serum PSA > 1.4 ng/mL in any 12-month period of testosterone treatment
• PSA velocity of > 0.4 ng/mL/year using the PSA level after 6 months of testosterone administration as the reference (only applicable if PSA data are available for a period exceeding 2 years)
• Prostatic abnormality detected by DRE
• AUA-SI score/International Prostate Symptom Score > 19
ii. Evaluate formulation-specific AEs at each visit
Treat with injectable testosterone to improve hypogonadism symptoms (eg, low libido, mood, and energy), and prescribe a PDE5 inhibitor.
Serum evaluation at 2 weeks shows that the patient's testosterone level is in the eugonadal range (total testosterone, 310 ng/dL). His erectile function (SHIM score, 21 [mild]) and LUTS (AUA-SI score, 7 [mild]) have also improved. The patient is looking forward to enjoying his upcoming trip because of his renewed energy. The physician reminds the patient that it is absolutely necessary for him to continue follow-up monitoring, including PSA and hematocrit levels. The patient agrees to return at 3 and 6 months, about a month before his trip and just after he returns.