LEPTIN LEVELS IN TREATING PREMATURE EJACULATIONM. ATMACA
Serum leptin levels in patients with premature ejaculation before and after citalopram treatment
M. ATMACA, M. KULOGLU, E. TEZCAN, B. USTUNDAG* and A. SEMERCIOZ†Departments of Psychiatry, *Clinical Biochemistry and †Urology, Firat University, School of Medicine, Elazig, TurkeyOBJECTIVE
serotonergic systems. In a previous study
between the groups at baseline; it increased
serum leptin levels were high in patients with
after 8 weeks of treatment with citalopram in
To evaluate serum leptin levels (an adipocyte
premature ejaculation. The present study
group I, to a mean (SD) of 209 (72.1) s, but not
in group II. No difference was detected in
ejaculation according to the Diagnostic and
leptin levels between the groups at baseline,
ejaculation before and after treatment with
Statistical Manual of Mental Disorders Third
but at 8 weeks they were lower in group I.
citalopram, a selective serotonin reuptake
Revised Version. Fifteen patients (group I)
inhibitor, with the hypothesis that leptin
CONCLUSION
citalopram treatment and the remainder (15,
group II) received no therapy. The patients
As hypothesized, leptin levels decreased in
patients with premature ejaculation after
PATIENTS AND METHODS
intravaginal ejaculation latency time, and
treatment with citalopram, and this decrease
seemed to be linked to the therapeutic effect.
The inhibitory effect of serotonin on libido,
measured at baseline and after 8 weeks.
Further experimental studies are needed.
ejaculation and orgasm is well documented. Although there is no direct evidence of an
KEYWORDS
association involving brain pathways which are related to sexual behaviour, there is an
There was no significant difference in the
leptin, premature ejaculation, serotonin,
mean intravaginal ejaculation latency time
INTRODUCTION
drugs is the enhancement of net serotonergic
leptin levels might become normal during this
transmission by blocking the presynaptic 5-
hydroxytryptamine uptake site [7]. Leptin is a
as uncontrolled ejaculation, the essential
fat-cell-derived hormone which signals the
feature of which is recurrent or persistent
PATIENTS AND METHODS
regulation of weight and sexual behaviour,
and so it is thought to lead to suppression of
The study comprised 30 married men (aged
appetite, weight loss and acceleration of
sexual maturation, and to stimulate energy
institution, and had been diagnosed with
expenditure [8,9]. Zhang et al. [10] reported
masturbation for considerably longer than
that it is a product of the ob gene. The
Diagnostic and Statistical Manual of Mental
Disorders Third Revised Version (DSM-III-R)
psychiatric disorders has been noted [11–14];
[17] and met the study admission criteria. The
The inhibitory effect of serotonin on libido,
moreover, there is an interaction between the
ejaculation and orgasm is well documented,
leptinergic and serotonergic systems in the
groups on a double-blind basis, determined by
CNS [15] and leptin has no significant effect
patients (group I) received citalopram for
neurotransmitter enhancing sexual function)
while leptin perfusion induces a significant
increase in 5-hydroxy indole acetic acid
therapy (behavioural or pharmacological).
metamphetamine (better known as ecstasy)
overflow from the hypothalamus [15,16]. In
induces serotonin and dopamine release with
Each patient was evaluated diagnostically in
a central action, and causes an increase in
significantly high serum leptin levels in
detail by one trained psychiatrist using the
libido and sexual satisfaction by dopamine
patients with premature ejaculation, after
Structured Clinical Interview for DSM-III-R
release, while causing delay and prominent
adjusting for body mass index or age. These
outpatient form [18]. Patients with any kind
serotonin activation [4]. Selective serotonin
whether there would be a change in serum
excluded. To be able to exclude organic sexual
reuptake inhibitors (SSRIs) are reported to be
leptin levels in patients with premature
dysfunctions, fasting glucose level, urine
effective for treating premature ejaculation
ejaculation before and after treatment with
analysis, complete blood count, sex hormones
citalopram, an SSRI, and we hypothesized that
2 0 0 3 B J U I N T E R N A T I O N A L | 9 1 , 2 5 2 – 2 5 4 | doi:10.1046/j.1464-4096.2003.04052.x
L E P T I N L E V E L S I N T R E A T I N G P R E M A T U R E E J A C U L A T I O N
between leptin levels and the duration of the
condition, at baseline, in both groups (r = 0.61
and 0.56 for groups I and II, respectively).
Citalopram was well-tolerated; there were 14
reports of adverse effects from eight patients,
the most frequent being gastrointestinal
complaints (four) and insomnia (three). No
patient withdrew from the study because of
DISCUSSION
The major findings of the present study are that citalopram treatment considerably
patients were free of all medication for at
least the previous 2 weeks. Patients were
of < 25 kg/m2. Serum leptin levels were
positive correlation between leptin levels and
excluded if: they had erectile dysfunction and
assayed at baseline and after treatment with
the duration of the condition. SSRIs have been
inhibited male orgasm, a severe physical
illness, a history of alcohol and substance
premature ejaculation [5,6]. In the present
abuse or dependence, a previous history of
The statistical analysis used independent-
study, citalopram, the most selective SSRI
sample and paired t-tests, analysis of
[19], produced considerable improvements in
endocrinological state. All participants were
covariance (ANCOVA) and Pearson's method of
patients with premature ejaculation, even
correlation, with differences considered
though the study had methodological limits,
significant at P <0.05 for all tests.
e.g. relatively few patients. The effect of
All patients were carefully assessed to exclude
serotonin on premature ejaculation and other
autoimmune, pulmonary, infectious diseases
sexual dysfunction was hypothesized from
and neoplasms. Their body mass index (BMI)
was calculated. They were asked to determine
the average intravaginal ejaculation latency
The characteristics of the two groups are
time (IELT) for three consecutive episodes of
inhibition of antidepressant-induced orgasm
coitus, verified by both patients and their
could be reversed by a nonselective serotonin
wives, using a chronometer. The IELT was
significantly after treatment with citalopram.
No patient had a significant weight change on
Fluoxetine, an SSRI, has been reported to
intromission and ejaculation. The patients and
citalopram; while one lost 0.6 kg and one
reduce the plasma leptin levels in rats [22],
their wives were encouraged to have coitus at
0.4 kg, three gained weight of 0.8, 0.6 and
which was supported by the present study
least twice per week. Patients in group I
using a different SSRI (citalopram); leptin
initially received 20 mg/day citalopram for
administration also stimulated serotonin
1 week; this was titrated up to 60 mg/day
At baseline, the leptin levels were high in nine
turnover [23]. In contrast, in another study
according to the patient's tolerability and
patients in group I and in eight in group II,
clinical response. In addition, they were asked
administration of fluvoxamine (an SSRI) and
to report adverse effects using an instrument
designed by the authors which included all
significant difference in serum leptin levels
influenced immunomodulation by clozapine
side-effects reported that were related to
between the groups at baseline, adjusted for
and some of its side-effects, the two together
antidepressant use. Thus, side-effects were
BMI (ANCOVA). At 8 weeks the mean leptin level
enhanced the clozapine-induced increase in
recorded as ‘present’ and ‘absent’. After
was significantly lower than baseline (ANCOVA
leptin plasma levels with no significant effect
describing the study to the patients, written
with BMI as the covariate, P < 0.05, adjusted
for BMI) in group I (P < 0.001), but not in
Hastings et al. [16] investigated the
and ethical permission obtained from the
local ethics committee of Firat University
neurotransmitter systems of the rat brain,
There was a positive correlation between
reporting that leptin had no significant effect
To determine the serum levels of leptin, all the
baseline (r = 0.62 and 0.56, P < 0.05 for
while leptin perfusion induced a significant
groups I and II, respectively) and at 8 weeks
increase in 5-hydroxy indole acetic acid
samples were drawn from an antecubital vein
(r = 0.58 and 0.54, both P < 0.05). Correlation
at 08.00 hours and leptin levels measured
analysis between leptin levels and age showed
using a radioimmunoassay kit (rat leptin kit,
no statistical significance in both groups
correlation between leptin levels and the
Linco Corp., St Charles, MO, USA) in a gamma
(respectively at baseline and 8 weeks, r = 0.08
duration of illness or the IELT; this suggest
counter (LKB Wallac 1261, Wallac Corp., Turku,
and 0.06 for group I, and 0.17 and 0.12 for
that an increased severity of illness affects
Finland). Normal values are <10 for males and
group II). There was also a positive correlation
leptin levels, and that as the illness becomes
2 0 0 3 B J U I N T E R N A T I O N A L
Yilmaz Y. The efficacy of fluoxetine in the
brain in vitro. Regul Pept 2002; 103: 67–
There are some limitations in the present
double-blind placebo controlled study. J
study; first, the lack of placebo control and
Urol 1996; 156: 1631–2 Diagnostic and Statistical Manual of
short duration of treatment, and second,
Mental Disorders. 3rd revised edn.
there were relatively few patients, who might
open clinical trial of fluoxetine in the
not be representative of those with premature
ejaculation. Moreover, we were unable to
J Clin Psychopharmacol 1996; 16: 379–
18 Spitzer RL, Williams JBW, Gibbon M, First
assess economic status, other psychosocial
factors and dietary differences which might
affect serum leptin levels. In summary, the
Biochemical effects of the antidepressant
present results provide further evidence that
ejaculation, although there were too few
Psychopharmacology 1987; 93: 193–
evaluation. Exp Opin Pharmacother 2001;
patients to permit clear conclusions. Leptin
2: 681–98
levels in patients with premature ejaculation
Prolo P, Wong ML, Licinio J. Leptin. Int J
20 DeCastros R. Reversal of MAOI-induced
decreased after treatment with citalopram, as
Biochem Cell Biol 1998; 30: 1285–90
anorgasmia with cyproheptadine. Am J
hypothesized, and this decrease seemed to be
Psychiatry 1985; 142: 783
linked to the therapeutic effect. However,
and promise in pharmacotherapy. Current
21 Sovner R. Impotence from the psychiatric
Drug Targets 2001; 2: 181–95
standpoint. BMJ 1984; 1: 697–9
of leptin and indices of serotonin are needed
10 Zhang Y, Proenca R, Malfei M, Barone M,
22 Dryden S, Brown M, King P, Williams G.
to determine the exact role of leptin in
Leopold L, Friedman JM. Positional cloning
premature ejaculation. Future studies with
homologue. Nature 1994; 372: 425–32
substance known to reduce leptin levels, but
11 Kraus T, Haack M, Schuld A, Hinze-Selch
fluoxetine. Horm Metab Res 1999; 31:
influence ejaculation, should be used.
normal body mass indices in patients with
23 Calapai G, Corica F, Corsonello A et al.Neuroendocrinology 2001; 73: 243–7
inhibition of brain nitric oxide synthesis.
REFERENCES J Clin Invest 1999; 104: 975–82 Diagnostic and Statistical Manual of
premature ejaculation. Arch Androl 2002;
Mental Disorders, 4th edn. Washington
48: 345–50
13 Atmaca M, Kuloglu M, Tezcan E, Ustundag
B, Gecici O, Firidin B. Serum leptin and
weight. Psychopharmacology 2000; 149:
attempters. Neuropsychobiology 2002;
dimethyltriptamine induced ejaculation in
the rat. Br J Pharmacol 1986; 87: 639–48
14 Atmaca M, Kuloglu M, Tezcan E, Gecici O,
Ustundag B. Serum cholesterol and leptin
(Euphrates) Üniversitesi, Firat Tip Merkezi,
side effects. Arch General Psychiatry
Psikiyatri Anabilim Dali, 23119 Elazig, Turkey.
1990; 47: 191–2
personality disorder. Neuropsychobiology
2002; 45: 167–71
15 Liebowitz SF, Alexander JT. Hypothalamic
Abbreviations: SSRI, selective serotonin
(‘Ecstasy’) on human sexual function. In
serotonin in control of eating behavior,
reuptake inhibitor; DSM-III-R, Diagnostic and Abstracts of the 149th Annual Meeting of
Statistical Manual of Mental Disorders Third
the American Psychiatric Association.
Psychiatry 1998; 44: 851–64
Revised Version; BMI, body mass index; IELT,
16 Hastings JA, Wiesner G, Lambert G, Morris
intravaginal ejaculation latency time; ANCOVA,
MJ, Head G, Esler M. Influence of leptin on
2 0 0 3 B J U I N T E R N A T I O N A L
Who is Gerry? We thank our lucky stars everyday that we have a man like Gerry in our lives. You may know him from his many years of dedicated service here at Caledon and in the industry. He has been our intrepid International Sales Manager for many years and in that role has made many friends all over the world and here at home too. Not too long ago however, we got the scare of our lives an