elevation of intracellular cyclic AMP, which acts

ches of premature ejaculation,31 but medical

similar to cGMP and also at least partly via

treatments have received increasing attention in

opening of K+ channels, but does not require

the past decade. Knowledge on the neurobiology

input from endogenous nerves. Even further

of premature ejaculation is limited and largely

down-stream, and also independent of endoge-

has been derived by indirect conclusions from

nous nerves and NO, would be somatic gene

clinical data. The central neurotransmitter sero-

therapy to enhance expression of relevant K+

tonin appears to play a key role as it is released

channels.28

in the anterior lateral hypothalamus at the time

While all of the above mechanisms are based

of ejaculation, where it apparently reduces dop-

on the enhancement or mimicking of endogenous

amine release.6,32 This conclusion is largely based

pro-erectile signals, at least theoretically it would

on the observation that various drugs enhanc-

also be possible to act by inhibition of endoge-

ing serotonin concentrations in the synaptic

nous anti-erectile mechanisms. This would make

cleft, that is, selective serotonin reuptake inhibi-

a case for the use of a1-adrenoceptor antagonists.

tors (SSRI) such as paroxetine or citalopram but

Despite limited evidence for a moderate efficacy

also tricyclic antidepressants, have repeatedly

of yohimbine (probably acting centrally) and

been shown to be effective in its treatment.While

phentolamine (probably acting centrally and

the clinical effectiveness of SSRI in the treatment

peripherally), selective a1-adrenoceptor antago-

of depressive disorders, their primary indica-

nists have proven to be too weak to provide effec-

tion, requires their use over several weeks, they

tive treatment of erectile dysfunction.29

can be effective in treating premature ejacula-

tion upon on-demand administration. Based on

Ejaculatory Function

such findings a short-acting SSRI, dapoxetine,

has been developed specifically for the on-

demand treatment of premature ejaculation,

Ejaculation is a necessary step to allow semen to

and it has been registered for this indication in

several European countries but not the USA.32

reach female oocytes and hence to allow fertil-

The opioid receptor agonist tramadolol, the

ization. However, disorders of ejaculation can

PDE5 inhibitor sildenafil, and the a1-adrenocep-

not only affect reproductive function but can

also lead to psychologically less fulfilling sexual

tor antagonist terazosin have also shown prom-

ising results in some studies, implying opiod

experiences. Two main ejaculatory disorders

and a1-adrenergic receptors as well as cGMP in

exist, premature ejaculation and abnormal ejac-

ulation, the latter often being a side effect of

the pathophysiology of premature ejaculation.

However, in general, premature ejaculation is a

drug treatment or surgery.

research field where (often inconsistent) clinical

data have advanced more than the pathophysio-

Premature Ejaculation

logical understanding of the condition.

The International Society for Sexual Medicine

Abnormal Ejaculation

has defined premature ejaculation in 2007 as “a

male sexual dysfunction which is characterised

Retrograde ejaculation has long been known as

by ejaculation which occurs or nearly always

a possible adverse result of, for example, a tran-

occurs prior to or within about a minute of vagi-

surethral resection of the prostate.When similar

nal penetration, and the inability to delay ejacu-

effects were observed upon treatment with a1-

lation on all or nearly all vaginal penetrations

adrenoceptor antagonists, it was first assumed

and negative personal consequences, such as

that this was also due to retrograde ejaculation,

distress, bother, frustration and/or the avoid-

and many clinical studies code this adverse event

ance of sexual intimacy,” It is considered to

as “retrograde ejaculation,” However, more

involve psychological, environmental, endo-

recent studies have demonstrated that this actu-

crine, neurobiological, and perhaps even genetic

ally is a relative anejaculation,29 most likely due

factors.30 Of note, premature ejaculation often

to relaxation of vas deferens smooth muscle.33

coexists with erectile dysfunction.

While abnormal ejaculation can occur with each

Behavioral treatment is generally considered

a1-adrenoceptor antagonist, it is mostly seen

to be an important part of treatment approa-

with tamsulosin29and even more often with the