Timetable of effects of testosterone administration to hypogonadal men
on variables of sex and mood
FRIEDRICH JOCKENHO¨VEL1, TIMO MINNEMANN2, MARKUS SCHUBERT2,
SUSANNE FREUDE2, DORIS HU¨BLER4, CHRISTINA SCHUMANN2, ARND CHRISTOPH2,
LOUIS GOOREN3, & MICHAEL ERNST4
1Evangelisches Krankenhaus Herne, Wiescherstraße 24, Herne, Germany, 2Klinik II und Poliklinik fu¨r Innere Medizin,
Klinikum der Universita¨t zu Ko¨ln, Ko¨ln, Germany, 3VUmc, Amsterdam, the Netherlands, and 4Jenapharm GmbH & Co.
KG, Otto-Schott-Straße 15, Jena, Germany
(Received 7 August 2009; revised 7 September 2009; accepted 9 September 2009)
Abstract
Introduction. The effects of testosterone have been extensively characterized, but little attention has been given to the
timetable of occurrence of the various effects of testosterone.
Methods. The timetables of effects on sexual and psychological variables in 40 hypogonadal men receiving treatment with
either parenteral testosterone enanthate (TE) or undecanoate (TU).
Results. Sexual thoughts/fantasies and sexual interest/desire/spontaneous morning erections emerged quickly and plateaued
after 3 weeks. Total erections rose to a maximum over 9 weeks and then plateaued. Ejaculations per week/satisfaction with
sex life rose over the first 3 weeks, increasing steadily to a plateau at 12 weeks. Depression scores decreased to reach a plateau
after 6 weeks. Aggressiveness did not change. Scores of concentration improved and reached a plateau after 3 weeks in the
group treated with TE and after 9 weeks in the group treated with TU. Good mood improved after 6–9 weeks. Positive effects
on self-confidence appeared between 3–6 weeks and on fatigue after 9–12 weeks.
Conclusion. Insight into the emergence of effects may be useful information for the patient and for the attending physician in
monitoring clinical effects of testosterone treatment of hypogonadal men.
Keywords: Testosterone, time, effects
Introduction
Treatment of hypogonadal men with testosterone is
rewarding, for the patients as well as the physician.
The patient experiences, to his satisfaction, profound
changes in his physical appearance and his mental
make-up. The attending physician observes the
changes the patient undergoes and rarely fails to be
fascinated by the multitude of functions testosterone
appears to have in process of masculinization in the
broadest sense.
Although the effects of testosterone have been
described in detail, relatively little attention has been
given to the timetable of the various effects of
testosterone. This seems relevant. To the attending
physician, monitoring the effects of administration of
testosterone will be facilitated when it is known when
certain effects can and should be expected. Patients
like to receive information when the effects will set in.
If patients have not been exposed to testosterone at the
usual time of puberty, they must be counseled about
the emergence of sexual thoughts and dreams, an
increase in erections and seminal emissions.
In this study the effects of two treatment modalities
of testosterone were analyzed: parenteral testosterone
enanthate (TE) or long-acting parenteral testosterone
undecanoate (TU). The latter is a rather novel
testosterone preparation [1,2]. Over a period of 30
weeks, every 3 weeks the effects of testosterone
administration on parameters of sexual functioning
and mood were analyzed.
Subjects and methods
The study analyzed the relationship of time following
administration vs. effects on sexual functioning and
mood in an open-label, randomized, prospective
clinical trial design [3]. Subjects received either the
traditional parenteral testosterone ester, TE or the
new parenteral long acting testosterone undecanoate.
Correspondence: Dr. Friedrich Jockenho¨vel, Evangelisches Krankenhaus Herne, Wiescherstraße 24, 44623 Herne, Germany. Tel: þ49-2323-498-2051.
Fax: þ49-2323-498-2485. E-mail: f.jockenhoevel@evk-herne.de
The Aging Male, December 2009; 12(4): 113–118
ISSN 1368-5538 print/ISSN 1473-0790 online  2009 Informa UK Ltd.
DOI: 10.3109/13685530903322858

Forty men were included in the study. Their ages
ranged between 18 and 65 years and their serum
testosterone levels at inclusion in the present study
were 55 nmol/L (normal range, 10–30 nmol/L)
following discontinuation of prior testosterone treat-
ment for at least 8 weeks, and, if testosterone pellets
had been used, for 12 months.
Seven patients had not received testosterone
therapy previously. To ensure that the patients were
meeting the inclusion criteria, they underwent two
initial screening visits 42 and 21 days prior to
randomization. If medical history, physical examina-
tion, and laboratory analysis at screening revealed
evidence of severe physical or mental illness, of
alcohol or drug abuse, or of any contraindication
against testosterone treatment such as severe lower
urinary tract symptoms, suspected malignancy of the
prostate, erythrocytosis, heart/liver/kidney failure),
patients were excluded from participation in the
study. All patients gave their written informed
consent to inclusion in the study. The study
protocols were approved by the Ethics Committee
of the University and the State Medical Board,
Cologne, Germany.
The study medication (testosterone undecanoate
(TU) (Nebido1) 1000 mg in 4 ml castor oil) and
Testosteron-Depot JENAPHARM1 Injektionslo¨-
sung (TE 250 mg in 1 ml oily solution)) were
manufactured by Jenapharm GmbH & Co. KG,
Jena, Germany. All i.m. injections were administered
into the gluteus medius muscle, starting on Day 0.
The first four TU injections were given at two
intervals of 6 weeks, the following after an interval of
9 weeks. All following injections were given at 12-
week intervals [18]. TE injections were administered
at 3-week intervals. Every 3 weeks during the
comparison study, patients presented for blood
sampling and assessment of individual study
variables.
The patients were randomly assigned (using the
SAS software) to treatment with either TU i.m.
(n¼ 20) or TE i.m. (n¼ 20) for 30 weeks. There
were no essential differences between the two
treatment groups regarding age, BMI, and baseline
serum testosterone levels.
The study was financially supported by Jenapharm
GmbH & Co KG, Jena, Germany.
For the assessment of possible psychosexual effects
a standardized questionnaire published by Behre
et al. [4,5] based on standardized questionnaires
[6,7], was used, assessing general mood and sexual
activity, as well as frequency of erections and
ejaculations and number of morning waking erec-
tions, sexual thoughts and fantasies, sexual interest
and desire, satisfaction with sexuality, as well as
questions of general well-being during the past 7
days. In our experience compliance with tasks for the
patients is best before a new visit to the clinic.
Therefore, the data were collected for three con-
secutive days before each clinic visit over the 30
weeks of the study when the effects of TU were
compared to those of TE. Patients were asked to rate
their state concerning 12 different items (sociability,
concentration, agitation, self-confidence, listlessness
(inertness), dizziness, activation, depression, fatigue,
anxiety, good mood, and aggressivity). The ratings
were performed by the patients using a 10-cm visual
analog scale, a horizontal line, on which a subject
indicated his response checking tick-marks on a scale
with two extremes designated ‘not at all’ and ‘very
strong’. The subjects marked a point between these
two extremes of ‘not at all’ and ‘very strong’ to
specify their level of agreement to a statement. This
method resembles a Likert-type scale, though in our
scale, points were not fixed as in the Likert scales
which commonly have a 5- or 7-point scale.
The ratings related to sexual fantasies, sexual
interest, and satisfaction with sex life were recorded
in the same way.
The answers were evaluated by measuring the
distance between the beginning of the line segment
(‘not at all’ and the mark made by the subject,
multiplying this value by 100 and dividing by the
length of the whole line segment.
Statistical analysis
For statistical analysis to examine the time-depen-
dent effects of exposure a weight function within a
generalized linear model was estimated. The shape of
the weight function, which is modeled as a cubic B-
spline, gives information about the impact of
exposure increments at different times [8].
Results
As reported earlier [3] in the TE group, mean trough
levels of serum T were always less than 10 nmol/l
before the next injection, whereas in the TU group,
mean trough levels of serum T were
14.1+ 4.5 nmol/l after the first two doses (6-wk
intervals) and 16.3+ 5.7 nmol/l after the 9-wk
interval at Week 30.
There were only a few minor statistically signifi-
cant differences between the two treatment modal-
ities with regard to their effects on the parameters of
the study and their timetables; they were apparent in
the non-sexual items of the effects of testosterone
administration. Sexual thoughts/fantasies and sexual
interest /desire rose quickly and plateaued 3 weeks
after start of testosterone administration (P5 0.05)
(Figure 1). Spontaneous morning erections showed a
similar pattern (P5 0.05). Total erections rose to a
maximum over 9 weeks (P5 0.05) and then pla-
teaued (Figure 2). Ejaculations per week rose over
the first 3 weeks (P5 0.05), and then increased
steadily to a plateau reached after 12 weeks (P5 0.05
when compared with values at 3 weeks) (Figure 2).
Satisfaction with sex life showed a similar trend
(P5 0.05) (Figure 1).
114 F. Jockenho¨vel et al.