Testosterone therapies have been increasingly used in ag-
ing men, as well as in men of reproductive age. Compared to
the 1970s, men are fathering children at an older age. Com-
bined with the maturation of the Baby Boomer population,
it is anticipated that there may be a signi
cant increase in
hypogonadal, aging men desiring to father children. The
treatment of hypogonadism requires symptomatology, as
well as low serum T levels, generally regarded to be around
300 ng/dL. With the recent introduction of several newer
commercial T preparations and an increased public awareness
of androgen de
ciency syndromes, use of hormone replace-
ment therapies has been increasing. During the past 5 years
there has been an increase in T prescriptions by 170%
However, men desiring to maintain their reproductive poten-
tial may not be fully aware of the risks of exogenous T
Many T users/abusers and clinicians are unaware of the
fact that the use of exogenous T has been shown to suppress
the hypothalamic-pituitary-gonadal axis and result in
infertility. Physicians need to educate their patients about
the potentially deleterious effects exogenous T can have on
spermatogenesis and on fertility. The use of IM T has been in-
vestigated as a male contraceptive agent
T inhibits GnRH and gonadotropin secretion. Exogenous
administration of synthetic T results in negative feedback
on the hypothalamic-pituitary axis, inhibiting GnRH, and,
thus, inhibition of the secretion of FSH and LH. Suppression
of gonadotropins results in a decrease in intratesticular T
(ITT) levels and overall T production. Normally, ITT concen-
trations are roughly 50
100 times serum levels. Exogenous
T therapies can suppress ITT production to such a degree
that spermatogenesis can be dramatically compromised at
ITT concentrations to less than 20 ng/mL
. Intratesticular
T is an absolute prerequisite for normal spermatogenesis.
Complete inhibition of ITT can result in azoospermia
(10, 11)
In men using anabolic steroids, despite normal-to-high
serum androgen concentrations, ITT concentrations neces-
sary to maintain spermatogenesis may be lacking. Many
male users of anabolic steroids develop hypogonadotropic
hypogonadism with subsequent testicular atrophy. Anabolic
steroid use commonly results in oligozoospermia or azoosper-
mia along with abnormalities of sperm motility and morphol-
(12, 13)
Recovery of Spermatogenesis after Exogenous T
Rates of success in recovering spermatogenesis after use of
exogenous T are generally quite favorable. The
rst strategy
that should be used for the hypogonadal male interested in fa-
thering children is the cessation of use of exogenous T. A
study by the World Health Organization Task Force evaluated
271 men who received 200 mg of T enanthate weekly
. Af-
ter 6 months, 157 (65%) of the men were azoospermic. The
mean time to azoospermia was 120 days. After 6 months of
treatment, the patients entered the recovery phase. Although
84% of men were able to achieve a sperm density
20 mil-
lion/mL after a median of 3.7 months, only 46% of patients
were able to achieve their baseline sperm density.
evaluated the recovery of spermatogenesis after
exogenous T administration in 26 men with a recent history of
anabolic steroid use. In this relatively small study, all men
who discontinued exogenous T usage were treated with hCG
3,000 units IM every other day for a minimum of 3 months.
Of the two men who remained azoospermic, one had insuf
cient follow-up and the other was suspected of continued
anabolic steroid use. Men who were using IM T at the time
of presentation recovered spermatogenesis in an average of
3.1 months. However, men receiving transdermal T supple-
mentation at the time of presentation took an average of
7.4 months. Mills
concluded that impairment of fertility
after T replacement therapy suppression is reversible and
that the rate of sperm may be related to the delivery system.
The published literature represents the best available
evidence regarding the recovery of spermatogenesis after T
supplementation. However, the preponderance of the litera-
ture re
ects results with the use of T therapy as a male contra-
ceptive agent. This situation may very well not be re
ective of
the hypogonadal male seen in clinical practice. The caveat is
that the consistency of spermatogenesis recovery in clinical
practice may not be as predictable as seen in contraceptive
T as a Male Contraceptive
Pharmaceutical companies have tried to develop hormonal
male contraceptives with the intent of causing a withdrawal
ofthe gonadotropin supporttothe testis withresultant suppres-
sion of spermatogenesis and ITT
studied alone, as well as in combination with progestagens
. Testosterone used as a contraceptive agent is a good model
to determine the effect and time to recovery with cessation of T
treatment. These trials have not examined the use of agents to
promote recovery of natural T or spermatogenesis.
A study by Wang et al.
found that oligozoospermia
induced by exogenous T was associated with normally func-
tioning spermatozoa. Data were analyzed from eight subjects
whose sperm concentrations were between 1.3 and 10
mL at the suppression phase. Testosterone enanthate (200 mg)
was administered IM weekly during the suppression and T
treatment (ef
cacy) phases (total 15 months). Sperm function
tests were performed during the pretreatment, during sup-
pression (usually after 6
10 weeks of treatment, when sperm
concentration was anticipated to decrease to
10 million/
mL), and during recovery phases. Investigators found that
the sperm concentration was reduced, but sperm motility, mo-
tility characteristics, and morphology were not affected by T
enanthate treatment. The residual spermatozoa in the ejacu-
late exhibited normal hyperactivation, could acrosome react,
and maintained the capacity to penetrate and fuse with the
oocyte. The investigators concluded that suppression of sper-
matogenesis to moderate oligozoospermia (
10 million/mL)
with exogenous T was not associated with impaired sperm
VOL. 99 NO. 3 / MARCH 1, 2013
Fertility and Sterility®