Effect of rejuvenation hormones

on spermatogenesis
Jared L. Moss, M.D., Lindsey E. Crosnoe, B.S., and Edward D. Kim, M.D.
University of Tennessee Graduate School of Medicine, Knoxville, Tennessee
Objective: To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of
spermatogenesis.
Design: Review of published literature.
Setting: Not applicable.
Patient(s): Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies.
Intervention(s): None.
Main Outcome Measure(s): Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis.
Result(s): Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead
to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG)
therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on
infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine
use of aromatase inhibitors is not recommended based on a lack of long-term data.
Conclusion(s): The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring
children at a later age may be unaware of the side-effect prole of hormones used at rejuvenation centers. Testosterone and
anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with
cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1
(IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to
have signicant negative effects on sperm production, but quality data are lacking. (Fertil
Steril

2013;-:--. 2013 by American Society for Reproductive Medicine.)

Key Words: Hormones, rejuvenation, spermatogenesis
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I
n 1970, fewer than 15% of all men
fathering children were over 35
years of age. Today, that percentage
has risen to almost 25%. Likewise, the
number of men in the 50 to 54 age
group has seen a notable increase in
fatherhood (1). Not only is the male
population aging and reproducing
later, but many men are also searching
for the fountain of youth. A 2009 arti-
cle in the Chicago Tribune by Bruce
Jaspen (2) reported that the sale of
anti-aging products sales in the U.S.
alone has exceeded $50 billion
annually. Many of these products are
hormones that are being prescribed in
antiaging centers known as rejuvena-
tion clinics. Because of the off-label
illicit use of these medications and
the unregulated nature of this industry,
little is known about the effect of these
hormones on male fertility. This article
reviews common antiaging hormones
used in rejuvenation clinics and their
mechanism of effect on spermatogene-
sis (Table 1).
MATERIALS AND METHODS
A PubMed literature search was
conducted for the time period of
19842012, focusing on 45 studies
examining the effect of hormones
used for rejuvenation on semen
analysis, pregnancy outcomes, and
time to recovery of spermatogenesis.
Those publications representing level
1 evidence were marked with the
annotation (LOE 1). Six hormones
were reviewed: exogenous testoster-
one, anabolic steroids, human growth
hormone (HGH), clomiphene citrate
(CC), human chorionic gonadotropin
(hCG), and aromatase inhibitors (AI).
These hormones were selected based
on clinical experience and information
publicly promoted by rejuvenation
centers. There were insufcient
published quality data for a meta-
analysis, so a systematic review was
performed for all hormones. Institu-
tional review board approval was not
necessary for a review paper.
Received January 15, 2013; revised and accepted April 2, 2013.
J.L.M. has nothing to disclose. L.E.C. has nothing to disclose. E.D.K. has nothing to disclose.
Reprint requests: Edward D. Kim, M.D., 1928 Alcoa Highway, Suite 222, Knoxville, Tennessee 37920
(E-mail: ekim@utmck.edu).
Fertility and Sterility Vol. -, No. -, -2013 0015-0282/$36.00
Copyright 2013 American Society for Reproductive Medicine, Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.fertnstert.2013.04.003
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EXOGENOUS TESTOSTERONE
Background
Exogenous testosterone therapy is approved by the US Food
and Drug Administration (FDA) for the treatment of
symptomatic hypogonadism. Exogenous testosterone is one
of the most common therapies used for the purpose of male
rejuvenation. Examples of exogenous testosterone include
topical gels, subcutaneous testosterone pellets, and intramus-
cular injectable testosterone. Over the past 5 years, there has
been an increase in testosterone prescriptions by 170%. This
correlates with the recent introduction of newer commercial
products and an increased public awareness of androgen
deciency syndromes (3). It is estimated that more than
13.8 million men R45 years of age visiting a primary care
doctor in the United States have symptomatic androgen
deciency (4). Importantly, many testosterone users/abusers
and clinicians are unaware that exogenous testosterone
suppresses the hypothalamic-pituitary-gonadal (HPG) axis
and may result in infertility. In a recent survey of U.S.
urologists, Ko et al. (5) observed that approximately 25%
have used exogenous testosterone to treat low testosterone
levels associated with male infertility.
Mechanism of Action
Exogenous testosterone inhibits spermatogenesis by suppress-
ing the HPG axis. Specically, testosterone therapy results in
negative feedback on the HPG axis. It inhibits gonadotropin-
releasing hormone (GnRH), thereby inhibiting the secretion of
follicle-stimulating hormone (FSH) and luteinizing hormone
(LH) (Fig. 1). Suppression of gonadotropins results in a decrease
in intratesticular testosterone levels (ITT) and overall
testosterone production. Normally, ITT concentrations are
approximately 50 to 100 times serum levels. As exogenous
testosterone therapies suppress ITT production, spermatogene-
sis can be dramatically compromised (6). Intratesticular
testosterone is an absolute prerequisite for normal spermato-
genesis, and its inhibition can result in azoospermia (7, 8).
Clinical Evidence
Exogenous testosterone supplementation decreases spermpro-
duction. However, when it was evaluated as a male
contraceptive agent, studies showed that most men have
a return to normal sperm production within 1 year after
discontinuing testosterone supplementation (LOE 1) (Table 2)
(9). For example, a study by the World Health Organization
(WHO) Task Force evaluated 271 men who had received 200
mg of testosterone enanthate weekly (LOE 1) (10). After 6
months, 157 (65%) of the men were azoospermic, and the
mean time to azoospermia was 120 days. After 6 months of
treatment, the patients entered the recovery phase where exog-
enous testosterone was discontinued. Although 84% of men
were able to achieve a sperm density >20 million/mL after
a median of 3.7 months, only 46% of patients were able to
achieve their baseline sperm density.
Gu et al. (11) administered testosterone 500 mg monthly
of undecanoate for 30 months to a group of 855 Chinese men
(LOE 1). Using a primary outcome of pregnancy rate, nine
pregnancies were reported in >1,500 person-years of
exposure in the 24-month efcacy phase (855 men) for
a cumulative contraceptive failure rate of 1.1 per 100 men.
Ninety-ve percent of men achieved azoospermia or severe
oligozoospermia (<1 10
6
sperm/mL), and the median
time to onset of azoospermia or severe oligozoospermia was
108 days. The median time to recovery of spermatogenesis
calculated from the beginning of the recovery phase was
196 days. It should be noted that the contraceptive trials
were in men of Chinese ethnicity and that extrapolation of
ndings to men of non-Chinese ethnicities may not be
reliable. Additionally, the use of testosterone therapy in
a broad population of men may have varying results.
A signicant limitation of the published literature
concerning this topic is a lack of pregnancy outcome data.
The published literature represents the best available evidence
to date regarding the recovery of spermatogenesis after
testosterone supplementation, but it is largely limited to
male contraceptive studies. This situation may not be
TABLE 1
Overview of the effect(s) of rejuvenation hormones on spermatogenesis.
Hormone Mode of action Mechanism of effect on spermatogenesis
Testosterone Negative Suppression of the HPG axis results in decreased ITT concentration,
which decreases spermatogenesis.
Anabolic androgenic steroids (AAS) Negative Suppression of the HPG axis results in decreased ITT concentration,
which decreases spermatogenesis.
Clomiphene citrate (CC) Neutral/positive This SERM increases testicular testosterone production, which may be
benecial for spermatogenesis.
Growth hormone/Insulin-like growth
factor (HGH/IGF-1)
Neutral/positive HGH stimulates IGF-1 formation, which may improve sperm maturation
in a paracrine-autocrine manner.
Aromatase inhibitor (AI) Neutral This cytochrome P450 enzyme blocks the conversion of androgens to
estrogen, consequently increasing serum levels of LH, FSH, and
testosterone and may stimulate spermatogenesis.
Human chorionic gonadotropin (hCG) Neutral/positive This LH analog stimulates Leydig cell production of testosterone, which
can initiate and maintain spermatogenesis in hypogonadotropic
hypogonadal men.
Note: FSH follicle-stimulating hormone; HPG hypothalamic-pituitary-gonadal; ITT intratesticular testosterone levels; LH luteinizing hormone; SERM selective estrogen receptor
modulator.
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reective 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 studies (12). It is important to emphasize that
semenanalysis data do not correlate withpregnancyoutcomes
and that none of the literature assesses time to fecundity.
Recommendations
Exogenous testosterone should be avoided in men desiring
future fertility, given the potential detrimental side effects
and lack of data regarding long-term effects on
spermatogenesis.
ANABOLIC ANDROGENIC STEROIDS
Background
Synthetic anabolic androgenic steroids (AAS) have been
FDA-approved for the treatment of testosterone replace-
ment, renal-insufciency associated anemia, hereditary
angioedema, and weight loss. These cholesterol
derivatives of testosterone are both anabolic and andro-
genic, which help patients to build lean muscle and en-
hance masculinization (13). Popular types of AAS are
oral oxandrolone (Oxandrin), oral methandienone (Diana-
bol), injectable stanozolol (Winstrol-V), injectable nandro-
lone decanoate (Deca-Durabolin), and injectable boldenone
FIGURE 1
p
r
i
n
t
&
w
e
b
4
C
=
F
P
O
Rejuvenation hormones and mechanism of action. Exogenous testosterone and anabolic androgenic steroids (AAS) negatively affect the
hypothalamic-pituitary-gonadal (HPG) axis. Selective estrogen receptor modulators (SERMs) block the negative feedback of estrogen on the
HPG axis. Human chorionic gonadotropin (hCG) stimulates Leydig cells. Aromatase inhibitors prevent the conversion of testosterone to estrogen.
Moss. Rejuvenation hormones and spermatogenesis. Fertil Steril 2013.
TABLE 2
Model-based probability of spermatogenic recovery to various thresholds after discontinuation of exogenous testosterone.
Probability of recovery (%, 96% CI)
Within 6 mo Within 12 mo Within 16 mo Within 24 mo
Individual baseline value 54 (4660) 83 (7589) 95 (8998) 100*
20 million/mL 67 (6172) 90 (8593) 96 (9298) 100*
10 million/mL 79 (7383) 95 (9297) 99 (97100) 100*
3 million/mL 89 (8492) 98 (9599) 100* 100*
Note: Adapted from Liu PY et al. Lancet 2006;367:141220.
* Condence interval could not be obtained from the model.
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undecylenate (Equipoise). Although the practice has been
prevalent, Kanayama et al. (14) showed the use of AAS is
on the decline among high school athletes. More recently,
a new population of aging males has surfaced who are
self-administering AAS as a rejuvenation therapy. The
lifetime prevalence of AAS use in males is estimated to
be between 3.0% to 4.2% (15). There are likely hundreds
of thousands of men in their 30s and 40s who began using
AAS in high school and continue to be currently dependent
on AAS (14).
In 2003, the public became aware of this growing
problem among high prole professional athletes when the
Bay Area Laboratory Co-operative (BALCO) in Burlingame,
California, was implicated in a steroid scandal that resulted
in numerous arrests and tainted many professional careers
(16). A growing trend is the use of these illegal drugs from
rejuvenation clinics for noncompetitive reasons by the
regular Joe (17). For example, a rejuvenation center in
Florida was raided by authorities as part of a network of
online clinics and pharmacies for illegal sales of steroids
and growth hormones (18).
Mechanism of Action
The mechanism by which AAS inhibit spermatogenesis is
believed to be the same as exogenous testosterone (Fig. 1).
These hormonal changes can lead to azoospermia, oligozoo-
spermia, severe testicular atrophy, hypogonadotropic
hypogonadism, and increased teratozoospermia (19).
Clinical Evidence
An understanding of how AAS affect spermatogenesis is
complicated by several factors. Data collection is usually
through uncontrolled, observational studies of AAS users
from gymnasiums or the Internet, which introduces
inherent selection biases. These studies are additionally
complicated by dishonesty in reporting nonuse and lack of
toxicology testing for conrmation of compliance. Many
users also may not be fully disclosing concurrent medications
such as antiestrogens, aromatase inhibitors, and human
chorionic gonadotropin (hCG) (14). It is estimated that AAS
users often take 6005,000 mg of AAS per week (2023).
These doses are supraphysiologic in that they are 50 to 100
times greater than the 4050 mg weekly production of
testosterone by the normal male testes (24). Biological
potency of anabolic agents cannot be accurately compared
based on the weight of the product consumed.
Spermatogenesis usually recovers spontaneously within
4 to 6 months after cessation of AAS, but recovery has been
reported to take up to 3 years or longer (2527). Reasons for
the extended recovery time are not yet known, but are
likely related to the variety of medication combinations and
high doses.
Recommendations
Men desiring future fertility should not use AAS,
given the signicant potential for long-term effects on
spermatogenesis.
HUMAN GROWTH HORMONE/INSULIN-LIKE
GROWTH FACTOR 1
Background
Human growth hormone (HGH) is FDA-approved for the
treatment of the hormonal deciency that causes short
stature in children, adult short-bowel syndrome, adult
growth hormone deciency due to rare pituitary tumors or
the treatment thereof, and muscle-wasting disease associated
with human immunodeciency virus/acquired immunode-
ciency syndrome (HIV/AIDS). With limited success, HGH
has been used off-label to treat men with poor sperm counts
(28). Additionally, HGH has been abused by athletes
looking for a performance advantage as well as patients of
rejuvenation clinics seeking to improve their appearance
and well-being (29). As an example, a rejuvenation clinic
is Los Angeles, California, states on their Web site that
HGH can increase muscle, improve mental acuity, boost
the sex drive, burn fat more quickly, and increase energy
and strength (30). Quality data supporting these claims
efcacy and safety are lacking.
Mechanism of Action
Growth hormone is a protein that is synthesized and secreted
by cells called somatotrophs in the anterior pituitary gland. A
critical concept in understanding growth hormone activity is
that it has two distinct types of effects, direct and indirect.
Direct effects are the result of growth hormone binding its
receptor on target cells. Indirect effects are mediated primarily
by insulin-like growth factor-1 (IGF-1), a hormone that is
secreted from the liver and other tissues in response to growth
hormone. A majority of the effects of HGH are due to IGF-1
acting on its target cells. In the testicle, levels of IGF-1 are
measurably elevated when stimulated by HGH, which
may stimulate maturation of spermatozoa in a paracrine-
autocrine manner (31).
Clinical Evidence
Radicioni et al. (28) examined the use of recombinant HGH in
infertile men with idiopathic oligozoospermia. This uncon-
trolled study was designed to evaluate the short-term efcacy
of recombinant HGH on spermatogenesis in 10 infertile men
with severe oligozoospermia (15 10
6
) and normal or min-
imally elevated gonadotropin levels. All of the men received
injections of 4 IU of recombinant HGH three times per week
for 180 days. The posttreatment semen analysis showed that
ve responders experienced a signicant increase in seminal
parameters, including spermconcentration and motility. They
concluded that HGH may be a reasonable option in men with
idiopathic oligozoospermia who have failed other treatments.
In another uncontrolled trial, Ovesen et al. (31) examined
HGH treatment in 18 subfertile males with oligozoospermia
(<5 10
6
sperm/mL) or asthenozoospermia (percentage
motile sperm <30 and >15 10
6
sperm/mL). The results
showed that seminal IGF-1 levels and sperm motility
increased signicantly in both groups although the sperm
counts did not. There were three pregnancies in the aztheno-
zoospermic group and none in the oligozoospermic group.
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Recommendations
Quality data regarding the effect of HGH on spermatogenesis
when it is used as a rejuvenation medication are completely
lacking. There is no persuasive evidence that HGH, along
with gonadotropin, is efcacious in promoting spermatogen-
esis in males with hypogonadotropic hypogonadism. The
studies examining the HGH treatment in infertile men were
uncontrolled and are unconvincing, but they do suggest
a potential benet for sperm count and motility.
CLOMIPHENE CITRATE
Background
Clomiphene citrate (CC) is a selective estrogen receptor
modulator (SERM) that has been FDA-approved to initiate
ovulation in women (32). Additionally, this SERM is used
off-label continuously in men of reproductive age to treat
hypogonadism and low sperm concentration. Clomiphene
citrate is also used by men taking AAS in a cyclic fashion
as an aid to recovery of natural testosterone production after
AAS or exogenous testosterone cessation. It is usually applied
in short courses in this population to stimulate normal sex
hormone secretion by producing a gonadotropin surge
(33, 34). Web sites such as Steroid.com outline how to use
and obtain CC while cycling steroids. Although CC can be
used in a continuous or cyclic manner, there is no
convincing evidence to date showing that one is superior to
the other.
Mechanism of Action
Selective estrogen receptor modulators competitively bind to
estrogen receptors on the hypothalamus and pituitary gland
(Fig. 1). As a result, the pituitary sees less estrogen and makes
more LH, which increases testosterone production by the
testes. It is not as effective in raising serum testosterone levels
when LH and FSH levels are already elevated, as seen in
primary testis failure. By increasing ITT, the use of CC in
hypogonadal men with poor sperm counts has been theorized
to promote spermatogenesis (12).
Clinical Evidence
Katz et al. (35) from the Memorial Sloan-Kettering Cancer
Center observed that long-term use of CC was safe and
effective in improving serum testosterone levels (LOE 1). In
this moderately sized analysis, 86 men aged 22 to 37 years
with hypogonadism (T levels <300 ng/dL) were evaluated
and treated for a mean duration of 19 months. The treatment
with CC started at 25 mg every other day and was titrated to
50 mg every other day. The target testosterone level was
550 ng/dL. Once the desired testosterone levels were achieved,
the testosterone/gonadotropin levels were measured twice per
year. In response to questions on the Androgen Deciency in
Aging Males (ADAM) questionnaire, the men reported
improvements in every area except for loss of height. There
was signicant improvement in ve of the 10 variables,
including decreased libido, lack of energy, decreased life
enjoyment, feeling sad/grumpy, and decreased sports
performance. Over a long-term follow-up, this study
demonstrated that CC is an effective and safe alternative to
testosterone supplementation therapy in hypogonadal men.
However, it should be emphasized that studies of limited
length have associated osteoporosis with long-term CC use.
A randomized, prospective trial of CC for hypogonadal
men with normal semen parameters is necessary to validate
the recommendation for the use of SERMs for fertility
preservation. This study would need to demonstrate that
semen proles are not adversely affected. Clomiphene citrate
has been commonly used for the empiric treatment of male
infertility; however, the double-blind, placebo-controlled
studies that demonstrate the effects can be variable,
unpredictable, and show no efcacy.
Recommendations
The off-label use of CC to improve serum testosterone levels
appears to be safe and effective for use up to 2 years. This
treatment represents the best alternative to androgenic
medications for men who wish to maintain fertility while
being treated for symptomatic hypogonadism/rejuvenation.
HUMAN CHORIONIC GONADOTROPIN
Background
Human chorionic gonadotropin is FDA-approved as an
injectable prescription drug for the treatment of female
infertility. Human chorionic gonadotropin, a hormone
produced by the human placenta and found in the urine of
pregnant women, can also be derived from recombinant
sources. It is used off-label in several ways. Similar to CC,
hCG is used by AAS abusers to counteract the hypogonado-
tropic hypogonadism experienced after withdrawal of AAS.
Additionally, the FDA has reported that hCG is being
marketed as a rejuvenation drug to produce dramatic weight
loss as part of an oral hCG diet. The FDA states on their Web
site that this use is fraudulent and not FDAapproved. The FDA
is advising consumers to steer clear of hCG weight-loss
products (36).
Mechanism of Action
Follicle-stimulating hormone and LH are made up of an
alpha chain that is identical to the structure of hCG and
thyroid-stimulating hormone (TSH). Accordingly, hCG is
primarily an LH analog that stimulates Leydig cell production
of testosterone (Fig. 1). When given in the exogenous form,
hCG increases ITT concentrations and serum testosterone
levels by stimulating Leydig cells (37).
Clinical Evidence
In a small case series by Depenbusch et al. (38), 13 azoosper-
mic men with hypogonadotropic hypogonadismwere initially
administered hCG and human menopausal gonadotropin
(hMG) to induce spermatogenesis. Human chorionic
gonadotropin was then administered at 5002,500 IU
subcutaneously twice weekly alone for up to 2 years (range:
324 months). After 12 months, the sperm counts decreased
gradually but remained present in all patients, except one
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man who became azoospermic. This study identied that FSH
is essential for maintenance of quantitatively normal
spermatogenesis and that high doses of hCG are not needed
to stimulate and maintain spermatogenesis.
Roth et al. (39) induced experimental gonadotropin
deciency in 37 normal men with gonadotropin-releasing
hormone (GnRH) antagonists and randomized the men to
receive one of four doses of hCG: 0, 15, 60, or 125 IU SC every
other day or 7.5 g daily testosterone gel for 10 days (LOE 1).
Testicular uid was obtained by percutaneous aspiration for
steroid measurements at baseline and after 10 days of
treatment. The ITT concentrations increased in a dose-
dependent manner, with very low-dose hCG administration
from 77 nmol/L to 923 nM in the 0 IU and 125 IU groups,
respectively (P<.001). Moreover, serum hCG was statistically
signicantly correlated with both ITT and serum testosterone
(P<.01). The investigators concluded that doses of hCG that
were far lower than those used clinically (1,0002,000 IU
SC three times weekly) increased ITT concentrations in
a dose-dependent manner in normal men with experimental
gonadotropin deciency.
Recommendations
Low-dose hCG with testosterone supplementation can
maintain production of ITT and spermatogenesis (40). There
are no fecundity data. The substantial cost and need for
frequent hCG injections are signicant barriers to the use of
this combination, especially when alternative therapies are
available (12).
AROMATASE INHIBITORS (ANASTROZOLE
AND LETROZOLE)
Background
Aromatase inhibitors (AIs) are FDA-approved for the treat-
ment of early and late-stage breast cancer. They work by in-
hibiting the enzyme aromatase, which is involved estrogen
synthesis and conversion. Regarding their off-label use in re-
juvenation clinics, AIs are used by men who are on exogenous
testosterone and AAS therapy to prevent the gynecomastia
associated with increased estrogen levels. As a man's serum
testosterone rises, a corresponding increase in the level of se-
rum estrogen occurs from peripheral conversion via aroma-
tase. From a fertility standpoint, AIs have been used to treat
men with idiopathic male infertility, lower serumtestosterone
to estradiol ratios (<10), and hypogonadism related to
obesity.
Mechanism of Action
Aromatase is a cytochrome P450 enzyme concentrated in the
testes, liver, brain, and adipose tissue. It is responsible for the
conversion of testosterone to estradiol (T/E
2
). Estradiol
inhibits gonadotropin secretion and may exert direct effects
on ITT production; AIs function by blocking the conversion
of androgens to estrogens, consequently increasing serum
levels of LH, FSH, and testosterone and resulting in functional
effects similar to antiestrogens. The primary concern
associated with aromatase inhibitors in men is that
long-term estrogen deciency may lead to osteopenia or
osteoporosis and ultimately may have a negative effect on
bone density.
Clinical Evidence
Raman et al. (41) reported on infertile men with T/E
2
ratios
(<10) treated with either testolactone or anastrozole. Men in
both treatment groups showed signicant improvements
in their T/E
2
ratios, sperm concentration, morphology, and
motility. However, in a crossover study, Clark et al. (42)
examined the effect of testolactone on oligozoospermic
infertility. This study enrolled 25 men with idiopathic
oligozoospermia who were administered testolactone
(2 g/day) or placebo for 8 months. The two arms were then
crossed and observed for an additional 8 months. This study
failed to show any spermatogenic benets or improved
fertility.
In the small subset of 25 infertile men receiving anastro-
zole for oligozoospermia, the sperm concentration increased
signicantly from 5.5 to 15.6 million per mL, and the total
motile sperm concentration (TMSC) per ejaculate increased
from 833 to 2,931 million (P<.005). No change was noted
in the azoospermic cohort who were receiving anastrozole,
and no pregnancies were reported for any of the men in the
study, regardless of their semen parameter improvements.
Letrozole, a nonsteroidal third-generation AI, was recently
shown by Saylam et al. (43) to be effective in infertile men
with lowserumT/E
2
ratios <10. Of the 10 men with oligosper-
mia, the mean total motile sperm concentration signicantly
increased from 6.4 2.7 million to 15.7 5.01 million after
treatment. The partners of two of the 10 oligospermic
men (20%) achieved spontaneous pregnancy, and four of
17 azoospermic men (23.5%) were noted to have sperm in
their ejaculate, with a mean total motile sperm concentration
of 1.11 0.69 million.
Recommendations
Aromatase inhibitors have no demonstrated detrimental
effect on spermatogenesis and can be used to help preserve
fertility in hypogonadal men. However, based on the lack of
long-term data, their use cannot be recommended for men
who wish to preserve their fertility.
CONCLUSION
The use of hormones for rejuvenation is increasing with the
aging of the Baby Boomer population. Men desiring children
at a later age may be unaware of the side-effect prole of the
hormones used at rejuvenation centers. Testosterone and AAS
have well-established detrimental effects on spermatogenesis,
although recovery may be possible with cessation.
Clomiphene citrate, HGH/IGF-1, hCG, and AIs do not appear
to have signicant negative effects on sperm production, but
quality data are lacking.
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Fertility and Sterility
1 Effect of rejuvenation hormones on
spermatogenesis
J. L. Moss, L. E. Crosnoe, and E. D. Kim
Knoxville, Tennessee
Testosterone and anabolic androgenic steroids suppre-
ss spermatogenesis. Clomiphene citrate, HGH/IGF-1,
hCG, and aromatase inhibitors offer a protective effect
for spermatogenesis, with either a neutral or positive
overall effect.
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VIEWS AND REVIEWS