medical TRT is given at
f
xed replacement doses and may not
be a good model to describe pharmacodynamics in the AAS
user. Although some evidence exists describing the recovery
period after exogenous T used as a hormone replacement
(52, 53)
, it is likely that a more complex and global
endocrine disruption exists for the AAS user because of the
stacking and cycling of multiple high-dose synthetic andro-
gens and other ancillary drugs, culminating in a unique phar-
macologic milieu
(48)
. Beyond the systemic consequences of
hypogonadotropic hypogonadism, nonhuman animal studies
suggest direct testicular toxicity results from synthetic
androgen use
(29, 50, 54
–
58)
. However, the signi
f
cance of
these
f
ndings is not well established, and the extent to
which heavy AAS use might contribute to primary gonadal
failure remains unclear and warrants further study.
Adverse Effects and Treatment Recommendations
AAS users commonly report side effects that they consider to
be esthetically unpleasing, such as testicular atrophy,
fl
uid
retention, acne, gynecomastia, and alopecia
(9, 16)
. Sexual
dysfunction was reported by 25% of users, and symptoms of
androgen de
f
ciency, including fatigue and depression, are
common complaints, especially during a post-cycle period.
Polycythemia also is a common adverse event, occurring in
±
40% of patients. Long-term AAS users may have serious un-
derlying hepatic, renal, and cardiovascular disease, with hy-
pertension and dyslipidemia common among chronic users.
ASIH arises from the combination of hyperandrogenism,
resulting from the supraphysiologic supplementation of AAS,
and subsequent hypogonadism. This T de
f
ciency occurs
because typical AAS users alternate between
‘‘
on-cycle
’’
supraphysiologic plasma androgen levels and periods of
androgen de
f
ciency where ancillary drugs such as SERMs,
AIs, and hCG are used in attempts to recover the HPG axis
(7, 9, 17, 19, 25, 32, 48, 59)
. Via suppression of estrogen
and thus its negative feedback, the hypothalamus can
restart the HPG axis (
Fig. 1
).
Diagnostic and treatment recommendations.
Initial testing
typically consists of a hormonal panel (LH, FSH, E
2
, T, free
T, SHBG, and PRL), complete blood cell count, lipid pro
f
le,
prostate-speci
f
c antigen, and a comprehensive metabolic
pro
f
le. Common post-cycle complaints include depressive
mood alterations, fatigue, lethargy, insomnia, and decreased
libido, and any such symptoms should be addressed. Physical
examination should include height, weight, blood pressure,
and body mass index, and common signs consistent with
AAS use, such as acne, gynecomastia, testicular atrophy,
skin striations, and alopecia should be noted if present.
For AAS users seeking treatment and assistance in
permanently discontinuing AAS, certain steps should be
taken. Following establishment of a nonjudgmental, healthy,
and trusting physician-patient relationship, the patient
should be counseled to discontinue all AAS as well as any
self-administered ancillary drugs and supplements. For the
severely symptomatic patients, a 4-week tapered course of
transdermal or injectable TRT may provide immediate symp-
tom improvement. Simultaneous administration of a SERM
(such as clomiphene citrate, 25 mg every other day) will
interact at the hypothalamus causing stimulation of LH and
ultimately increase intratesticular T (
Fig. 1
). For patients
with ASIH-induced gynecomastia, 20 mg tamoxifen daily
will block the breast estrogen receptors and stimulate HPG
axis recovery
(60
–
65)
.
TABLE 1
Commonly reported user-reported side effects and concerns, user strategies for management, and physician recommendations.
Side effect
User strategies for management
What should physicians recommend?
Low endogenous T
SERMs to restart axis
Discontinue AAS
Start recovery protocol with TRT, SERMs, or hCG
Gynecomastia
Tamoxifen
Aromatase inhibitors
Cabergoline and bromocriptine for galactorrhea
Chronic gynecomastia likely unresponsive to medical management
Surgical management is best option for chronic gynecomastia
Acute gynecomastia may be treated with tamoxifen per SERM
recovery protocol
Avoid hCG use if possible. Use of aromatase inhibitors is discouraged
because of possible sexual side effects
Testicular atrophy
hCG injections
Testicular atrophy will resolve discontinuation of AAS and recovery of
HPG axis function
hCG should be reserved for cases unresponsive to
f
rst line SERM
treatment
Sexual dysfunction
PDE5 inhibitors
Herbal aphrodisiacs
Cabergoline
Mesterolone for added androgenic effects
Dapoxetine
PDE5 inhibitors should be
f
rst-line treatment
Herbal aphrodisiacs should be discouraged owing to contamination
concerns
Dapoxetine not yet approved for sexual dysfunction
Hepatic dysfunction
Users of oral AAS concerned with hepatic
function may take herbal supplements such
as milk thistle extract for liver protection
Encourage discontinuation of oral AAS and herbal supplementation
Perform complete metabolic panel to assess liver function
Alopecia
Users often prophylactically take
f
nasteride
to prevent hair loss
Although AAS use may worsen existing alopecia, 5-alpha-reductase
inhibitor use should be discouraged because it may worsen
symptoms of ASIH
Note:
AAS
¼
anabolic-androgenic steroid; ASIH
¼
anabolic-androgenic steroid
–
induced hypogonadism; HPG
¼
hypothalamic-pituitary-gonadal; PDE5
¼
phosphodiesterase-5; SERM
¼
selective
estrogen receptor modulator; TRT
¼
testosterone replacement therapy.
Rahnema. Anabolic steroid
–
induced hypogonadism. Fertil Steril 2014.
1274
VOL. 101 NO. 5 / MAY 2014
ORIGINAL ARTICLE: ANDROLOGY