Letter to the Editor NOT referring to a recent journal article
Elevated Serum Estradiol Is Associated with
Higher Libido in Men on Testosterone
Supplementation Therapy
Testosterone has always been considered to be a
male
hormone
, whereas oestrogen has typically been discussed
in the context of being a
female hormone
. Conventionally,
the goal of testosterone supplementation therapy (TST)
in men was to raise serum testosterone levels and lower
oestrogen levels. A recent study by Finkelstein et al.
highlighted an important role for oestrogen in regulation
of sexual function in men on TST
[1]
. In that study, dramatic
declines in libido were observed in conjunction with
decreased levels of serum oestrogen. Although oestrogen is
associated with male sexual behaviour
[2]
, the distinct roles
of testosterone and oestrogen on sexual function in men on
TST are controversial. We thus sought to elucidate the
associations between serum testosterone, estradiol, and
libido in men undergoing TST for symptomatic hypogonad-
ism (total testosterone
<
300 ng/dl and three or more
symptoms on the Androgen Decline in Aging Male [ADAM]
questionnaire).
Men on TST (injections or gels;
n
= 423) presenting to a
large-volume, tertiary referral andrology clinic were asked
to rate the quality of their libido using 5-point Likert scales
(1 = terrible, 5 = excellent) as part of the validated, quanti-
tative ADAM questionnaire
[3]
. Men were categorised
as having low (0.5–5.0 ng/dl) or high (
>
5.0 ng/dl) estradiol
and low (
<
300 ng/dl) or high (
>
300 ng/dl) testosterone.
Serum levels of follicle-stimulating hormone (FSH), luteinis-
ing hormone (LH), serum testosterone, and sex hormone-
binding globulin (SHBG) were collected on the same day that
men completed their ADAM questionnaires. We subsequent-
ly performed univariate (
t
test, chi-square) and multivariate
analyses (ordinal logistic regression) to evaluate factors that
predicted libido.
Men with serum testosterone levels
>
300 ng/dl reported
greater libido than men whose levels were
<
300 ng/dl (3.46
vs 2.92;
p
<
0.01). Men with serum estradiol levels
>
5 ng/dl
reported greater libido than men with estradiol levels
<
5 ng/dl (3.70 vs 3.23;
p
<
0.01). In total, 60.4% of men with
a serum testosterone level
>
300 ng/dl and estradiol level
>
5 ng/dl reported very good or excellent levels of libido
(scored as 4 or 5) compared with 31.3% of men with
testosterone levels
<
300 ng/dl and estradiol levels
<
5 ng/dl
(
p
<
0.01).
Univariate analysis noted associations between libido
and age, and FSH, LH (analysed as continuous variables),
estradiol, and testosterone levels (analysed as categorical
variables, and which remained significant even when
analysed as continuous variables) (
Table 1
). Interestingly,
on multivariate analysis, only estradiol at serum levels
>
5 ng/dl (2.13;
p
= 0.04) was associated with greater libido
(
Table 2
).
While this study highlights the importance of oestrogen
in men on TST, the limitations include a lack of control
group and no score comparisons before and after com-
mencement of TST. Furthermore, a larger sample size may
have unmasked a confounding relationship between testos-
terone and libido.
In summary, we have found that elevated serum levels of
estradiol are associated with increased libido in men on TST.
We recommend judicious use of aromatase inhibitors for
indications such as gynaecomastia. Indiscriminate prescrip-
tion for the sole purpose of reducing serum oestrogen may
EUROPEAN UROLOGY 65 (2014) 1224–1225
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Table 1 – Predictors of libido in men on testosterone
supplementation therapy: univariate analysis
Odds ratio (95% CI)
p
value
Age
1.02 (1.01–1.04)
0.001
FSH
1.07 (1.02–1.12)
0.004
LH
1.17 (1.06–1.28)
0.002
Estradiol level
>
5 ng/dl vs
<
5 ng/dl
2.22 (1.47–3.38)
<
0.001
Testosterone level
>
300 ng/dl vs
<
300 ng/dl
2.37 (1.47–3.83)
<
0.001
Free testosterone
1.00 (1.00–1.00)
0.282
SHBG
1.01 (1.00–1.02)
0.130
CI = con±dence interval; FSH = follicle-stimulating hormone; LH = luteinising
hormone; SHBG = sex hormone-binding globulin.
Table 2 – Predictors of libido in men on testosterone
supplementation therapy: multivariable analysis
Odds ratio (95% CI)
p
value
Age
1.01 (1.00–1.03)
0.093
FSH
1.01 (0.93–1.10)
0.853
LH
1.10 (0.92–1.33)
0.290
Estradiol level
>
5vs
<
5 ng/dl
2.13 (1.35–3.36)
0.001
Testosterone level
>
300 vs
<
300 ng/dl
1.63 (0.97–2.75)
0.064
CI = con±dence interval; FSH = follicle-stimulating hormone; LH = luteinising
hormone.
0302-2838/$ – see back matter
#
2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.