anastrozole. Men in both treatment groups had signi
improvements in their T-to-E
ratios, sperm concentration,
morphology, and motility. In the small subset of 25 infertile
men receiving anastrozole for oligospermia, sperm concen-
tration increased signi
cantly from 5.5
15.6 million/mL,
and the total motile sperm concentration (TMSC) per ejaculate
increased from 833
2,931 million/mL (
.005). No change
was noted in the azoospermic cohort receiving anastrozole,
and no PRs were reported for any of the men in the study re-
gardless of semen parameter improvement.
In men with Klinefelter syndrome, aromatase inhibitors
have been used to treat hypogonadism before microscopic
TESE. Those men who responded to treatment (de
ned as
having a total T of
250 ng/dL) had a higher sperm retrieval
rate than men whose T level after treatment was
250 ng/dL
(77% vs. 55%)
In a recent study by Cakan et al.
, when anastrozole
was added to the treatment of 127 men with idiopathic
oligoasthenospermia who continued to demonstrate low T-
ratios after 3 months of therapy with tamoxifen alone,
increased sperm concentration and motility. Increased PRs
were also noted.
Letrozole, also a nonsteroidal third-generation aromatase
inhibitor, was recently shown by Saylam et al.
to be effec-
tive in infertile men with low serum T-to-E
10. Of the
10 men with oligospermia, the mean TMSC signi
increased from 6.4
2.7 to 15.7
5.01 million/mL after
treatment. Two of the 10 oligospermic men (20%) achieved
spontaneous pregnancy and 4 of 17 azoospermic men
(23.5%) were noted to have sperm in their ejaculate, with
a mean TMSC of 1.11
0.69 million/mL.
Extensive experience with third-generation aromatase
inhibitors in postmenopausal women has not revealed major
side effects related to their usage. Because elevations in liver
enzymes have been described in 7%
17% of patients, caution
should be taken in treating patients who have hepatic disease,
and liver function tests should be monitored. Other adverse
reactions include increases in blood pressure, rash, paresthe-
sias, malaise, aches, peripheral edema, glossitis, anorexia,
nausea/vomiting, and, rarely, alopecia that has spontane-
ously resolved. The prostate-speci
c antigen assessment
may be bene
cial in at-risk populations, as any form of ther-
apy for increasing serum T levels has the potential for increas-
ing prostate-speci
c antigen levels
(34, 35)
. The primary
concern associated with aromatase inhibitors in men is that
long-term E de
ciency may lead to osteopenia or osteoporosis
and ultimately have a negative effect on bone density.
Although most studies published to date describing use of
aromatase inhibitors in men did not appear to be associated
with adverse effects on bone, a recent study
a decrease in spinal bone mineral density after 1 year of anas-
trozole therapy in hypogonadal older men (mean age, 60
years). Long-term potentially detrimental effects of aroma-
tase inhibitors on bone health continue to be a concern and
have limited physician enthusiasm.
In conclusions, exogenous T supplementation decreases
sperm production. However, studies of hormonal contracep-
tion indicate that most men have a return of normal sperm
production within 1 year after discontinuing T supplementa-
tion. If at all possible, exogenous T use should be avoided in
men desiring future fertility given the potential for long-
term effects on spermatogenesis. Clomiphene citrate, an oral
selective ER modulator, is an off-label, but safe and effective
therapy for men who desire to maintain future potential fer-
tility. Although less frequently used in the general population,
hCG therapy with or without T supplementation represents an
alternative treatment. At present, routine use of aromatase in-
hibitors is not recommended based on a lack of long-term
data. Published literature to date is still limited, and this topic
will be a fertile area of interest in upcoming years, especially
regarding data on pregnancy outcomes.
Special thanks to Carolyn Schum for
manuscript review and editing.
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