pact of T deficiency on the overall health of men was
recently examined in meta-analyses.
2–4
Hypogonad-
ism was found to be linked to cardiovascular mortality,
metabolic syndrome, osteoporosis, frailty, noninsulin
dependent diabetes and depression.
Treatment for hypogonadism typically includes
TRT, which results in satisfactory amelioration of
symptoms and normalization of serum T. However,
treatment with exogenous T decreases serum gonad-
otropins, impairs normal spermatogenesis and sup-
presses intratesticular T. Azoospermia develops in
up to 40% of patients on TRT and, as a result,
treatment of hypogonadal men desiring to reproduce
while on TRT remains a challenge.
5
However, recent
studies indicate that intratesticular T can be main-
tained during TRT with co-administration of low
dose HCG, suggesting that exogenous HCG in the
setting of TRT may also preserve spermatogenesis
in these men.
6
We hypothesized that HCG is protec-
tive and preserves spermatogenesis in patients un-
dergoing TRT.
MATERIALS AND METHODS
After obtaining institutional review board approval, we
retrospectively reviewed the medical records of hypogo-
nadal men who desired fertility preservation during TRT
and presented to a single andrology clinic at Baylor Col-
lege of Medicine between 2006 and 2010. We identified 26
men, who were included in the study. All men were
started on TRT using daily transdermal gels or weekly
intramuscular injections as well as simultaneously on in-
tramuscular HCG (500 IU) every other day. The hypogo-
nadism diagnosis was based on symptoms, including low
libido, erectile dysfunction, low energy, poor concentra-
tion, inadvertent weight gain and sleep disturbances as
well as serum T 300 ng/dl or less.
Baseline T, FT and E were assessed before the start of
TRT, as were baseline semen analyses. Men were followed
after TRT initiation approximately every 2 to 4 months.
The effects of treatment on serum hormone values and
serum parameters were assessed at followup. All serum
hormone evaluations were performed at the Laboratory
for Male Reproductive Research and Testing, Baylor Col-
lege of Medicine on a single Access® 2 assay system.
Data were analyzed using Excel® and SPSS®. The
study was powered to identify a 45% difference in any
semen parameter with an
±
error probability of 20% and a
total sample size of 24 patients required. Statistical com-
parisons between baseline and followup values were per-
formed using the Student t test after evaluating our data
set for parametricity using Q-Q plots and Kolmogorov-
Smirnov goodness of fit testing. Statistical significance
was considered at p
²
0.05.
RESULTS
A total of 31 consecutive hypogonadal men who de-
sired fertility preservation were identified for study
inclusion. In 26 of these men complete data were
available on semen parameters and serum hormone
quantitation before and after TRT. The average
±
SD age of our cohort was 35.9
±
9.5 years. Men were
followed a mean of 6.2
±
4.9 months and up to 18
months (
table 1
). Of the men 19 men were treated
with injectable T formulations, while 7 used trans-
dermal gels. All men received intramuscular HCG
(500 IU) every other day.
In the cohort mean serum hormone levels before
vs during treatment were T 207.2
±
99.2 vs 1,055.5
±
420.9 ng/dl (p
²
0.0001), FT 8.1
±
3.9 vs 20.4
±
13.5
ng/dl (p
³
0.02) and E 2.2
±
1.0 vs 3.7
±
2.6 ng/dl
(p
³
0.11), supporting the efficacy of TRT in these
men. Mean pretreatment semen parameters were
volume 2.9
±
1.4 ml, density 35.2
±
29.6 million per
ml, motility 49.0%
±
10.4%, FP 2.3
±
0.3 and TMS
count 84.6
±
82.4 million.
To ascertain the effects of exogenous TRT and
HCG on semen parameters the men were followed at
2 to 4-months intervals with semen parameters and
hormonal assessment compared to pretreatment pa-
rameters. A statistically significant decrease in se-
men volume was observed at 1 to 2 months of fol-
lowup (p
³
0.04). This small difference was not
observed at any other followup point. Furthermore,
no statistically significant differences were noted in
other semen parameters at any followup time
(
table 2
). No significant differences were observed in
semen parameters between the injectable and trans-
dermal TRT groups (
table 3
). Taken together, these
data indicate that concomitant HCG therapy in the
setting of TRT is effective for preserving semen pa-
rameters.
Table 1.
Patient demographics
No. pts
26
Mean
±
SD age
35.9
±
9.5
Mean
±
SD followup (mos)
6.2
±
4.9
No. TRT formulation:
Transdermal
7*
Injectable
19†
Mean
±
SD pre-TRT hormone levels (ng/dl):
T
207.2
±
99.2
FT
8.1
±
3.9
E
2.2
±
1
Mean
±
SD pre-TRT semen parameters:
Semen vol (ml)
2.9
±
1.4
Sperm density (million/ml)
35.2
±
29
% Sperm motility
49
±
10.4
Forward progression
2.3
±
0.3
TMS (million)
84.6
±
82.4
Mean
±
SD post-TRT hormone levels (ng/dl):
T
1,055.5
±
420.9
FT
20.4
±
13.5
E
3.7
±
2.6
* AndroGel® (5 gm daily) in 2 patients and Testim® (5 gm daily) in 5.
† Testosterone enanthate (200 mg weekly) in 2 patients and testosterone cypi-
onate (200 mg weekly) in 17.
HUMAN CHORIONIC GONADOTROPIN PRESERVES SPERMATOGENESIS
648