DISCUSSION

As life expectancy has increased in the last century,

so has the prevalence of hypogonadism, which has

important negative sequelae on the health of men.

The prevalence of hypogonadism is within the 12%

to 37% range in population based studies.

1,7

Accord-

ing to data from the Centers for Disease Control,

74% of men visit a physician ofﬁce annually.

Ex-

trapolating data from the United States Census and

the reported prevalence of hypogonadism, approxi-

mately 14 million men 45 years old or older who visit

a primary care physician ofﬁce may have androgen

deﬁciency.

Many of these men are interested in

maintaining fertility. As a result, balancing the

medical and fertility concerns of hypogonadal pa-

tients is a growing challenge for physicians.

Currently, the armamentarium for the medical

treatment of male hypogonadism includes clomi-

phene citrate, anastrozole and exogenous T with the

former 2 uses being off label. Clomiphene citrate, a

selective estrogen receptor modulator, is effective for

increasing serum T and safe in hypogonadal pa-

tients on long-term therapy.

Anastrazole, a potent

aromatase inhibitor, increases serum T and bio-

available T, while decreasing E production.

While

these 2 treatment options preserve the hypothalamic-

pituitary-gonadal axis and spermatogenesis, minimal

improvements in hypogonadal symptoms and lean

body mass have been observed.

9,10

Exogenous T induced decrements in semen pa-

rameters are well documented. Administering exog-

enous T in eugonadal men caused negative feedback

in the hypothalamic-pituitary-gonadal axis and re-

sulted in azoospermia or severe oligospermia (less

than 5 million per ml) in 70% after 18 months of

therapy.

Notably, TRT cessation only partially re-

stored fertility in up to 85% of these men. Further-

more, TRT induced infertility is a growing phenom-

enon in the setting of continued abuse of anabolic

steroids.

High dose HCG (3,000 IU every other

day) has been used to successfully reverse exoge-

nous T induced spermatogenic impairment, while

low dose HCG has maintained intratesticular T lev-

els during TRT, suggesting that it could also pre-

serve semen parameters in men on TRT.

6,13

Our data demonstrate that concomitant adminis-

tration of low dose HCG in men on TRT preserves

spermatogenesis. Not surprisingly, in our series pre-

treatment semen parameters were below the 50th

percentile using 2010 WHO semen parameter crite-

ria, given that our cohort comprised hypogonadal

men.

None of the men in the cohort became azoo-

spermic during treatment and no signiﬁcant de-

crease in semen parameters was noted compared to

pretreatment data at any point during followup. The

protective effect of low dose HCG appears to be

independent of the T formulation since no differ-

ences in semen parameters were found between the

transdermal and injectable groups.

Our study is limited by several factors, including

its retrospective nature, followup duration, small

sample size and a lack of a control arm. A larger

sample size might have enabled us to better com-

pare the observed effect among the different T for-

mulations. Furthermore, pregnancy information was

incomplete in the cohort, in part because not all

patients actively pursued pregnancy during the

study period. Men were not queried regarding the

timeline for achieving pregnancy and female fertil-

ity factors were not assessed for each couple. Fur-

ther followup of our cohort will provide additional

data on the pregnancy outcome associated with con-

comitant low dose HCG therapy in the setting of

TRT.

To our knowledge this is the ﬁrst report of fer-

tility preservation in the setting of TRT with co-

administration of low dose HCG. A future prospec-

tive study with longer followup, larger sample size

and a proper control group is needed to validate

the observed beneﬁt of HCG and pregnancy out-

comes.

Table 2.

Mean pre-TRT and post-TRT semen analysis

Mean

Pre-TRT

Mean Post-TRT (days)

0–60 60–120 120–180 180–360

Greater Than

360

Semen vol (million)

2.9

2.7

1.8

2.7

2.5

p Value

0.84

0.04

0.86

0.56

0.39

Density (million/ml)

35.2

22.9

20.7

32.9

35.6

30.2

p Value

0.13

0.15

0.77

0.98

0.61

% Motility

46.7

42.2

49.5

54.2

p Value

0.68

0.51

0.93

0.08

2.3

2.7

2.4

2.5

2.3

p Value

0.9

0.05

0.62

0.1

0.96

TMS (million)

84.6

63.4

37.7

77.7

87.3

73.6

p Value

0.44

0.11

0.77

0.94

0.71

Table 3.

Semen analysis in 7 patients with transdermal and 19

with injectable TRT

TRT

Mean

SD Sperm

Count/Million

Mean

SD %

Motility

Mean

SD FP

Total

Motile

Before:

Transdermal

35.5

28.3

43.6

42.2

10.2

2.3

0.1

Injectable

33.7

49.8

51.3

2.4

0.3

p Value

0.08

0.6

0.93

0.14

After:

Transdermal

30.8

20.7

2.7

0.6

Injectable

30.6

26.8

46.7

51.3

2.4

0.3

p Value

0.99

0.64

0.68

0.22

HUMAN CHORIONIC GONADOTROPIN PRESERVES SPERMATOGENESIS

649