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.
Biological uses
§ 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
Not
sure
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.
Discussion
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
Treatment Plan
Treat with injectable testosterone to improve hypogonadism
symptoms (eg, low libido, mood, and energy), and prescribe a PDE5 inhibitor.
Follow-up
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.
