Pharmacology of Sexual Function

140

Practical Urology: EssEntial PrinciPlEs and PracticE

mechanisms. But in eugonadal men the amount

Most studies describe a periovulatory increase

of circulating testosterone exceeds the neces-

in sexual desire or activity whereas during preg-

sary to maintain sexual arousability in the brain.

nancy a significant lowering in sexual function

This can lead to the assumption that for periph-

with progression of pregnancy is stated. Studies

eral effects of testosterone higher levels are

observing sexual function under oral contra-

needed. Centrally, it has positive influence on

ceptives are not conclusive but hinting at induc-

the NO release synthase in the medial preoptic

ing no negative effect.

area whereby NO release and consecutively dop-

The impact of endogenous androgens on

amine release is stimulated. To allow the dop-

sexuality is also not clear by now: one large

amine release, testosterone has to be, at least

cross-sectional study showed no correlation,

previously to this, present.7 Estrogens seem to

whereas some case-control studies did let see

play an important role too as they are involved

that low androgens in women were associated

in control of gonadotropin secretion, fertility,

with sexual dysfunction. Even worse is the situ-

and psychosexual behavior.8 The different rela-

ation in case of testosterone therapy in pre-

tion of androgens and estrogens in males com-

menopausal women: no clear dose-response

pared to females could help to elucidate the

effect was detected. An important impact on

distinctions in sexual arousal and the response

this may be the great difficulty of the measure-

cycle between both genders.9

ment of the testosterone level in women. Sex

Hypogonadism has severe impact on the

hormones for sure showed a modifying effect

quality of life of an (aging) male and also on

on sexual function but also social influences

his morbidity and mortality. The ESPRIT study

and learned responses. The conclusion of all

(Energy, Sexual desire, and body PropoRtions

this is that further studies are urgently

wIth AndroGel, Testosterone 1% gel therapy),

required.13 ThisissupportedbytheAPHRODITE

a 6-month, multinational, open label, observa-

and other studies, where in postmenopausal

tional study in hypogonadal men being treated

women, treated with testosterone patches, at

with transdermal AndroGel, tries to search for

least a modest improvement of sexual function

the effects and safety of replacement therapy.10

could be detected but with uncertain long-term

Treatment with Tamoxifen, an estrogen blo-

effects.14,15

cker, can decrease libido, whereas estrogens

increase libido and frequency of sexual

acting.11

Neurohormones

Steroids in the Female

This group includes the peptide hormones oxy-

tocin, ß-endorphin, vasopressin, and prolactin.

In the female, the situation is much more com-

Their role in sexual arousal is complex and still

plex, which can be explained by their reproduc-

unclear originating from sometimes contrary

tive endocrine system. To obtain sexual arousal

functions in different places. Bancroft et al.

the presence of estrogen is necessary, but also

described excitatory and inhibitory effects for

testosterone seems to play an important role.

oxytocin and b-endorphin whereas prolactin

Wallen suggests a synergistic effect.12 In the fol-

was thought to work as a direct inhibitor of

licular phase, testosterone levels typically rise to

dopaminergic activity, but with inconclusive

a maximum in the middle third of the cycle.

evidence.16 Westheide et al. showed that the

Afterwards there is a decline in the final third to

sexual dysfunction caused by antipsychotics

a minimum in the beginning of the follicular

cannot be explained by heightened prolactin

phase of the next cycle.

levels alone.17 On the other hand, it has been

What complicates the situation is the fact that

proven that continuously high prolactin levels

not only testosterone is high in the mid-cycle

are of negative influence of sexual behavior.

but also estradiol, which makes it difficult to dif-

Because prolactin significantly decreases after

ferentiate the effects of the two hormones.

orgasm, Krüger et al. proposed that prolactin

General agreement exists upon the lowest

could function as a neuroendocrine reproduc-

sexual activity during menstruation period. But

tive reflex to the periphery or feedback to

then there are also nonhormonal explanations

dopaminergic neurons in the central nervous

for the drop in sexual activity.

system.18