Words of Wisdom
Re: Gonadal Steroids and Body Composition, Strength,
and Sexual Function in Men
Finkelstein JS, Lee H, Burnett-Bowie SA, et al.
N Engl J Med 2013;369:1011–22
Experts’ summary:
The investigators studied and reported on 400 healthy men
aged 20–50 yr who were given monthly injections of goserelin
acetate for 16 wk to suppress endogenous testosterone. Men
were randomly assigned to a placebo gel or one of four doses
of transdermal testosterone gel (1.25, 2.5, 5, or 10 g/d). An
additional 200 men received anastrazole, an aromatase inhi-
bitor, to block the conversion of testosterone to estradiol, in
addition to placebo or testosterone gel. The investigators
examined the changes in percentages of body fat and lean
mass as primary outcomes. The men were also assessed for
subcutaneous and intra-abdominal fat, muscle area and
strength, and sexual function. The findings were clear: Muscle
size and strength were androgen-dose dependent, body fat
was estrogen dependent, and sexual function (libido and
erectile strength) was both androgen dependent and estrogen
Experts’ comments:
The Endocrine Society’s guidelines define
male hypogonadism
as a ‘‘clinical syndrome’’ in which the diagnosis is based on
symptoms or signs and unequivocally low serum testosterone
. The symptoms of hypogonadism vary widely and
include sexual symptoms (eg, decreased erectile function and
decreased libido), decreased mood, decreased muscle mass
and increased fat mass, and decreased bone density. Although
self-reported questionnaires such as the Androgen Deficiency
in the Aging Male questionnaire
and the Aging Males’
Symptoms scale
have attempted to capture the spectrum
of this disease, their specificity remains poor. Because of the
controversy in diagnosis, practitioners uniformly treat men
with a low testosterone level and any one or several symp-
toms of hypogonadism. Consequently, prescriptions for tes-
tosterone products have increased by
170% in the previous
In this study, one of the striking findings is that different
symptoms of hypogonadism can develop at different
gonadal steroid levels. For example, visceral fat increases
even at testosterone levels between 300 and 400 ng/dl.
However, muscle strength and size are unaffected until
testosterone levels are
200 ng/dl. Therefore, the target
levels of testosterone supplementation in a man who is
concerned about weight gain and increase in abdominal
girth could be different from the target in a man who is
concerned about loss of muscle strength and size.
Research thus far has focused almost exclusively on how
estrogen affects women and how testosterone affects men.
This study highlights the important role of estrogen in the
regulation of body fat and sexual function in men. Losing
estrogen did not affect lean mass, muscle size, or leg
strength any more than did testosterone deprivation. The
most adverse effects of estrogen deficiency were on sexual
desire, with men in this group reporting dramatic declines
in arousal and erectile function. Additionally, the increase in
intra-abdominal fat seen in men with decreased estrogen
(due to aromatase inhibition) could increase the risk of
cardiovascular disease, diabetes, and metabolic syndrome if
long-term estrogen deficiency exists.
Some of the limitations of the study include a younger
participant profile and a short follow-up. In summary, this
study provides insight into the different roles of testoster-
one and estradiol in the body composition, strength, and
sexual function of men. The available evidence of long-term
risks and outcomes of testosterone replacement therapy is
still very limited, and much less has been studied about the
effect of estrogen on the same end points. Carefully
designed placebo-controlled trials of testosterone admin-
istration to assess the risks and benefits of both sex
hormones are required.
Conflicts of interest:
Larry I. Lipshultz has been a clinical trials participant,
a consultant, and a speaker for Auxilium and Endo. Ranjith Ramasamy has
nothing to disclose.
Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in
men with androgen de±ciency syndromes: an Endocrine Society
clinical practice guideline. J Clin Endocrinol Metab 2010;95:
EUROPEAN UROLOGY 65 (2014) 843–848
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
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