One cannot forget that clomiphene citrate has been linked to
thromboembolic catastrophic events in males and females
including stroke and pulmonary embolism (0.1-1%) as per FDA
labeling.
5
Thus,
“
wait and see
”
approach for 3 months with
assessment of LH, FSH, testosterone, and testicular volume may
be the prudent initial approach.
4
Regardless of its limitations,
authors should be applauded for their work as they bring an
important issue that full history and physical examination and
correction of underlying endocrinologic issues is mandatory in
all men undergoing vasectomy reversal.
Darius A. Paduch, M.D., Ph.D.,
James Buchanan Brady
Urological Health Center, Weill Cornell Medical College,
New York, NY
References
1.
Corona G, Rastrelli G, Forti G, et al. Update in testosterone therapy
for men.
J Sex Med
. 2011;8:639-654; quiz 655
.
2.
Giagulli VA, Triggiani V, Corona G, et al. Evidence-based medicine
update on testosterone replacement therapy (TRT) in male hypogonad-
ism: focus on new formulations.
Curr Pharm Des
. 2011;17:1500-1511
.
3.
Hsieh TC, Pastuszak AW, Hwang K, et al. Concomitant intramuscular
human chorionic gonadotropin preserves spermatogenesis in men un-
dergoing testosterone replacement therapy.
J Urol
. 2013;189:647-650
.
4.
Politou M, Gialeraki A, Merkouri E, et al. Central retinal vein oc-
clusion secondary to clomiphene treatment in a male carrier of factor
V Leiden.
Genet Test Mol Biomarkers
. 2009;13:155-157
.
5. FDA labeling for clomiphene citrate. U.S. Food and Drug Admin-
istration.
016131s026lbl.pdf
. Accessed September 30, 2014.
UROLOGY
84: 1340
e
1341, 2014.
Ó
2014 Elsevier Inc.
REPLY
Lost in the aftermath of the exponential growth of testosterone
supplementation therapy (TST) are numerous downstream ef-
fects dealt with by the male fertility specialist. One previously
unappreciated effect of TST is how the suppression of sper-
matogenesis creates a dilemma for the vasectomy reversal sur-
geon, potentially affecting the method of reconstruction, and
thus, the outcomes. In the present article, preoperative testicular
salvage therapy was used to optimize spermatogenesis before
reversal. The proposed protocol for salvage therapy after
discontinuation of TST routinely recommended included a
combination of clomiphene citrate (25 mg daily) with human
chorionic gonadotropin (3000 units subcutaneously every other
day) for a period of 3 months before reassessment. In this study,
because some patients elected to only use clomiphene, the
population ultimately studied included men who received
clomiphene with or without human chorionic gonadotropin.
One of the primary criticisms cited in the editorial comment
dealt with supposed
“
catastrophic events
”
resulting from the use of
clomiphene citrate. However, in spite of decades of use, the only
example stated was a case report detailing a single patient with
factor V Leiden
e
carrier status presenting with 1 week of unilat-
eral blurry vision after clomiphene therapy. The patient
’
s visual
acuity was 20/60 on presentation, and after he was diagnosed with
central retinal vein occlusion and treated with clopidogrel, his
vision returned to normal.
1
Notwithstanding case reports of
thrombotic complications, the true incidence of such events is
unknown and likely exceedingly small. Indeed, recent literature
attests to the safety of clomiphene citrate in hypogonadal men.
2
Despite varying degrees of suppression of gonadotropins with
TST that depend on many factors, most patients develop sup-
pression of spermatogenesis ranging from oligospermia to azoo-
spermia.
3
Although two-thirds of men re-establish
“
normal
”
sperm concentrations of
>
20 million/mL within 6 months after
discontinuation of TST, 10% require between 1 and 2 years to
reach this result.
3
Although the preoperative hormone assessment
provides initial guidance, gonadotropin levels unfortunately do
not always correlate with spermatogenesis while on TST.
4
Although our study does not de
fi
nitively prove that salvage
therapy provides bene
fi
t for vasectomy reversal outcomes because
of its study design, it does provide a proof of concept. The pro-
posed alternative to salvage therapy of abrupt withdrawal of TST
and
“
wait and see
”
has a myriad of drawbacks. First, it is impos-
sible to know how long it will take for spermatogenesis to return,
especially given the inability to assess progress via semen analysis.
More importantly, abrupt withdrawal of TST is a cruel punish-
ment leading to very severe hypogonadal symptoms. Because
most patients on TST will become profoundly hypogonadal with
serum levels
<
100 ng/dL after cessation of TST, the side effects
could mirror those observed with androgen deprivation therapy
for metastatic prostate cancer including severe sexual symptoms,
extreme fatigability, and mood disorders. Finally, and more
practically speaking, patients and their partners desiring vasec-
tomy reversal for conception may not tolerate a prolonged
waiting period of unknown length before surgery. The authors
’
proposed algorithm provides a safe option to facilitate the pre-
operative recovery of spermatogenesis.
Robert M. Coward, M.D.,
Department of Urology, University
of North Carolina School of Medicine, Chapel Hill, NC
Douglas A. Mata, M.D.,
Scott Department of Urology, Baylor
College of Medicine, Houston, TX; Department of
Biochemistry and Cell Biology, Wiess School of Natural
Sciences, Rice University, Houston, TX
Ryan P. Smith, M.D.,
Department of Urology, School of
Medicine, University of Virginia, Charlottesville, VA
Jason R. Kovac, M.D., Ph.D., and
Larry I. Lipshultz, M.D.,
Scott Department of Urology, Baylor
College of Medicine, Houston, TX
References
1.
Politou M, Gialeraki A, Merkouri E, et al. Central retinal vein oc-
clusion secondary to clomiphene treatment in a male carrier of factor
V Leiden.
Genet Test Mol Biomarkers
. 2009;13:155-157
.
2.
Moskovic DJ, Katz DJ, Akhavan A, et al. Clomiphene citrate is safe
and effective for long-term management of hypogonadism.
BJU Int
.
2012;110:1524-1528
.
3.
Liu PY, Swerdloff RS, Christenson PD, et al; Hormonal Male
Contraception Summit Group. Rate, extent, and modi
fi
ers of sper-
matogenic recovery after hormonal male contraception: an integrated
analysis.
Lancet
. 2006;367:1412-1420
.
4.
Amory JK, Anawalt BD, Bremner WJ, Matsumoto AM. Daily testos-
terone and gonadotropin levels are similar in azoospermic and non-
azoospermicnormal men administered weeklytestosterone:implications
for male contraceptive development.
J Androl
. 2001;22:1053-1060
.
UROLOGY
84: 1341, 2014.
Ó
2014 Elsevier Inc.
UROLOGY 84 (6), 2014
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