The treatment of hypogonadism

in men of reproductive age

Edward D. Kim, M.D.,

Lindsey Crosnoe, B.S.,

Natan Bar-Chama, M.D.,

Mohit Khera, M.D.,

and Larry I. Lipshultz, M.D.

University of Tennessee Graduate School of Medicine, Knoxville, Tennessee;

Mount Sinai Medical Center, New York, New

York; and

Scott Department of Urology, Baylor College of Medicine, Houston, Texas

Objective:

To review the mechanisms of T replacement therapy's inhibition of spermatogenesis and current therapeutic approaches in

reproductive aged men.

Design:

Review of published literature.

Setting:

PubMed search from 1990

–

2012.

Patient(s):

PubMed search from 1990

–

2012.

Intervention(s):

A literature review was performed.

Main Outcome Measure(s):

Semen analysis and pregnancy outcomes, time to recovery of spermatogenesis, serum and intratesticular

T levels.

Result(s):

Exogenous T suppresses intratesticular T production, which is an absolute prerequisite for normal spermatogenesis. Ther-

apies that protect the testis involve hCG therapy or selective estrogen receptor (ER) modulators, but may also include low-dose hCG

with exogenous T. Off-label use of selective ER modulators, such as clomiphene citrate (CC), are effective for maintaining T

production long term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors

is not recommended based on a lack of long-term data.

Conclusion(s):

Exogenous T supplementation decreases sperm production. Studies of hormonal contraception indicate that most men

have a return of normal sperm production within 1 year after discontinuation. Clomiphene citrate is a safe and effective therapy for men

who desire to maintain future potential fertility. Although less frequently used in the general

population, hCG therapy with or without T supplementation represents an alternative treatment.

(Fertil Steril

2013;99:718

–

24.

2013 by American Society for Reproductive Medicine.)

Key Words:

Hypogonadism, selective estrogen receptor modulator, male fertility

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n a recent survey of US urologists,

Ko et al.

(1)

observed that approx-

imately 25% have used exogenous

T to treat low T levels associated with

male infertility. Because of the poten-

tial of T therapies to decrease sper-

matogenesis and of the increasing

number of men receiving hormone re-

placement therapy, this practice pat-

tern is concerning. Although Food

and Drug Administration labeling

for T therapies indicates that treat-

ment

may

result

azoospermia

or impairments of spermatogenesis,

there is a distinct absence of expert

recommendations on the topic of hor-

mone replacement therapy in men of

reproductive age. Regarding the treat-

ment of hypogonadal men of repro-

ductive age, this article will review

[1] the extent of the problem, [2] the

mechanisms by which T therapy

impairs

spermatogenesis,

and

[3]

therapeutic approaches to protect the

testis.

THE EXTENT OF THE

PROBLEM

Symptomatic hypogonadism is a com-

mon problem

(2)

. It is estimated that

more than 6.5 million men in the

United States will have symptomatic

androgen de

ﬁ

ciency by 2025

(3)

Between the ages of 20 and 30 years,

men experience a decline in T and free

T levels by 0.4% and 1.3% per year,

respectively

(4)

. Mulligan et al.

(5)

observed that roughly 39% of men

older than 45 years had low serum T

levels, de

ﬁ

ned as less than 300 ng/dL.

In addition, 20%

–

30% of infertile men

will be found to have low T or increased

LH levels

(6)

Received September 5, 2012; revised October 10, 2012; accepted October 24, 2012; published online

December 7, 2012.

E.D.K. has nothing to disclose. L.C. has nothing to disclose. N.B.-C. has nothing to disclose. M.K. is a con-

sultant for Merck, Slate and MEDA and a speaker for Lilly and Auxilium. L.I.L. is a Board member

of Auxilium Pharmaceuticals; is a consultant with Eli Lilly Pharmaceuticals; has grants/grants

pending from Eli Lilly Pharmaceuticals, Auxilium Pharmaceuticals, Endo Pharmaceuticals, and

ﬁ

zer Pharmaceuticals; and has received payment for lectures from Eli Lilly Pharmaceuticals,

Auxilium Pharmaceuticals, Endo Pharmaceuticals, and P

ﬁ

zer Pharmaceuticals (all outside of

the submitted work).

Reprint requests: Edward D. Kim, M.D., 1928 Alcoa Highway, Suite 222, Knoxville, Tennessee 37920

(E-mail:

ekim@utmck.edu

Fertility and Sterility® Vol. 99, No. 3, March 1, 2013 0015-0282/$36.00

http://dx.doi.org/10.1016/j.fertnstert.2012.10.052

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VOL. 99 NO. 3 / MARCH 1, 2013