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vasodilatory actions of testosterone (ie, regulation of the
autonomic vascular nervous system) and the restoration of
normal vascular function . Testosterone may help to
preserve sexual function via protection against tissue
damage from aging and diabetes. Furthermore, testosterone
exerts a facilitating action on phosphodiesterase type
5 (PDE5) inhibition, thus keeping plasma PDE5 levels
within the normal range Testosterone may also
have role in sexual desire.
Overall, data suggest that TTH has positive effects on
male sexual function in hypogonadal subjects ; the role
of TTH in men who are not clearly hypogonadal is uncertain.
Randomized controlled trials (RCTs) have shown that TTH
improves sexual arousal, interest, and drive . In two
large RCTs, TTH only improved erectile function in
hypogonadal men with ED .
2. LUTS
LUTS have represented a relative contraindication for TT
because of the assumed belief that testosterone may
exacerbate symptoms by increasing prostatic growth
. A recent systematic review analyzed data from
patients with mild LUTS who were randomized to TTH or
no treatment in 14 trials (n = 2029) The findings showed
no significant difference in International Prostate Symptom
Score (IPSS) change from baseline over average follow-up of
34.4 mo. Moreover, observational studies have found that
long-term TTH may decrease the IPSS with only a marginal
increase in prostate volume No data are available on
TTH in men with severe LUTS (IPSS >19).
3. Prostate cancer
Historically, TTH in the presence of previous or current PCa
was contraindicated However the relationship be-
tween PCa and TTH is not clear. Recent literature does not
link high intrinsic testosterone levels with PCa and
low testosterone is associated with higher Gleason score
cancers and poor prognosis Recent data from
observational or controlled studies among hypogonadal
men without PCa and treated with TTH found no evidence of
a higher risk of PCa development . The same lack of
higher PCa risk is found in studies among men receiving TTH
after curative treatment for low-risk PCa . The major
criticism is the still short follow-up for these trials, which
limits the possibility of detecting new-onset or recurrent
PCa at a later stage. No trials have evaluated patients treated
for high-risk PCa. Reports on TTH in men on active
surveillance are too scarce to draw meaningful conclusions.
4. Male fertility
TTH reduces endogenous testosterone production via
negative feedback on the hypothalamic-pituitary-gonadal
axis and leads to hypospermatogenesis and even azoosper-
mia In addition, reduction/suppression of intratesticular
testosterone due to TTH leads to an inability of round
spermatids to complete the elongation process, with the
overall result of detachment of round spermatids from the
seminiferous epithelium . The overall rate of spermato-
genesis recovery with TTH will often be satisfactory, but
depends on ethnicity and pretreatment or treatment
parameters. All men recover to pretreatment values within
24 mo Higher rates of recovery may be seen with older
age, shorter treatment duration, short-acting testosterone
preparations, higher sperm concentrations at baseline, faster
suppression of spermatogenesis, and lower blood concen-
trations of luteinizing hormone at baseline Men with
a desire for fatherhood or an unfulfilled wish for children
should either not be treated with testosterone or be
counseled regarding sperm recovery after 6–24 mo.
5. Risks of TTH
There are several risks or considerations to be aware of.
(1) A possible link between TTH and cardiovascular disease
(CVD) is controversial . On the basis of five cohort
studies and two meta-analyses, the US Food and Drug
Administration required testosterone products to carry a
warning about a possible increase in the risk of CVD
. Meanwhile, the European Medicines Agency conclud-
ed that there is no consistent evidence of a higher risk of
CVD with TTH Some studies even indicate that TTH has
a protective effect. Large-scale, long-term RCTs are needed
to definitively define the CVD effects of TTH. (2) As
androgens stimulate erythropoiesis, hemoglobin and he-
matocrit should be measured before and throughout TTH to
avoid overstimulation and the risk of thrombosis. (3)
Mammary carcinoma represents an absolute contraindica-
tion, as androgens are aromatized to estrogens and may
stimulate estrogen receptor–positive cancers.
6. Conclusions
With the increasing interest in men’s health, the EAU has
formulated the following statements:
- Testosterone is a crucial sex hormone linked to the
physiological development of the male gender across all
stages of growth. It leads the integrity and maintains
functioning of several systems and organs (including the
male sexual and reproductive system, erythropoiesis, and
bone, lipid, and glucose metabolism).
- Obesity and poor general health are the main causes of
late-onset male hypogonadism. Losing weight and
improving lifestyle are important advice points for men
with hypogonadism, since these will result in normaliza-
tion of testosterone and reduce associated health risks.
- Testosterone deficiency is linked to a number of signs and
symptoms potentially affecting every man in his com-
plexity and masculinity, and is therefore of close
urological interest. For this reason, the urologist should
attach importance to the need for knowledge, vocational
education, and training in this specific area.
- TTH should be given only to symptomatic men in whom
the deficiency has been confirmed by laboratory tests.
Testosterone levels should be monitored regularly during
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