Oxytocin: Its Role in Sexual Function and Autism
by Tiffany Spudich, PharmD, Consultant Pharmacist
August 26, 2010
WHAT IS OXYTOCIN?
Oxytocin is a peptide hormone that regulates
a wide variety of behaviors including social memory, recognition,
bonding, love, trust, maternal behavior, childbirth, and lactation.
It is made by neurons in the hypothalamus and also peripherally
in the uterus, placenta, corpus luteum, testis, and heart. Oxytocin
has only one type of receptor, often called OTR or OXTR, and it
works in the body both peripherally and centrally. Both oxytocin
and OXTR expression is usually higher in females.
Peripherally, oxytocin is released from the posterior pituitary,
from where it enters the circulation by release into the portal
capillaries. Peripheral actions of oxytocin are commonly associated
with smooth muscle contraction, particularly within the female and
male reproductive tracts. Within the central nervous system, oxytocin
is expressed by the neurons of the hypothalamus that project into
higher brain centers. The OXTR is highly distributed throughout
the brain.
Oxytocin and Sexual Function
Plasma oxytocin levels significantly correlate
with higher levels of during sexual arousal, and orgasm significantly
raises levels in men and women. A study in 10 healthy male subjects,
intranasal inhalation of 24 units oxytocin significantly increased
plasma oxytocin and epinephrine levels (Burri et al, 2008). Oxytocin
levels stayed elevated after administration throughout the whole
experiment, which was greater than 60 minutes. Data indicates that
intranasal oxytocin administered during coitus may treat anorgasmia
in men in cases where medical conditions, drug abuse, and psychological
issues have been ruled out. (Ishak et al, 2008).
Studies have also shown steroid hormones to have an essential role
in sexual responsiveness to oxytocin. In males, the OXTR can be
found in the corpus cavernosum and epididymis of the penis, and
binding to the OXTR in this region may affect contractility. Data
has demonstrated that that oxytocin does not act alone to bring
about penile erections. Oxytocin was unable to induce erections
without testosterone and estrogen, and data has demonstrated that
OXTR binding was increased in the brain of male rats by estrogen
and testosterone administration and decreased by castration. Castration
eliminated erections even with administration of oxytocin and apomorphine,
but could later be re-established with co-administration of testosterone
(Melis et al, 1994). In addition, deprivation of endogenous estrogens
by using the aromatase inhibitor letrozole was shown to induce oxytocin
hypo-responsiveness - suggesting a new function of estrogen in males
(Vignozzi et al,2004). Studies have also shown that female rats
given oxytocin were more sexually receptive when also given estrogen,
or estrogen and progesterone (Caldwell et al, 1989a; Gorzalka and
Lester, 1987; Caldwell et al, 1986b; Arletti et al, 1985).
OXYTOCIN in AUSTISM
The potential role of oxytocin in autism spectrum
disorder addresses social deficits of the disorder, for which there
is currently limited pharmacological treatment. Data suggests oxytocin
therapy could potentially help individuals with autism to recognize
emotions or to eliminate the repetitive, obsessive behaviors linked
to the disorder. Some data has shown that children with autism manifest
lower plasma oxytocin levels than those of normal children and those
children with autism show alterations in the endocrine oxytocin
system - suggesting that deficits in oxytocin peptide processing
may be important in the development of autism. Several studies also
indicate that mutations in the OXTR genes are linked with autism
spectrum disorders. However, data from a recent study did not support
the role of common genetic variation in OXTR in the etiology of
autism spectrum disorders (Tansey et al, 2010).
A study in adults with autism and Asperger's disorder who received
intravenous infusion oxytocin, all 15 participants in the study
experienced a significant reduction in both the number and severity
of repetitive behaviors such as repeating, self-injury, and touching,
and increased ability to comprehend and remember the affective component
of spoken words such as whether they were happy, indifferent, angry,
or sad (Hollander et al., 2003). A recent double-blind, randomized,
placebo-controlled study in 15 male youth aged 12 to 19 who were
diagnosed with Autistic or Asperger's Disorder showed improvement
in emotion recognition after receiving a dose of 18 or 24 units
of oxytocin nasal spray (Guastella et al,2010).
CONCLUSION
There are still many questions to be answered
regarding the potential role of oxytocin in anorgasmia and autism
spectrum disorder. Since oxytocin is a peptide, it has poor blood
brain barrier penetration; once it is released peripherally it cannot
re-enter the brain. Intranasal administration has been shown to
pass through the barrier. However, intravenous administration may
or may not pass through this barrier and also this route of administration
is not realistic for most patients to use on a recurrent basis.
In addition, oxytocin has a short elimination half-life; Pitocin®,
a synthetic commercial brand of oxytocin often used in childbirth,
has a half-life of 1-5 minutes. Currently there is some investigation
into the development of non-peptide molecules that act as selective
agonists of the OXTR. The best way to both administer and dose oxytocin
is still under question, and more large, double-blind, randomized,
placebo-controlled studies are still needed that address multiple
populations including children with autism as well as women with
anorgasmia.
This article is not a substitute for medical advice. Always
contact your own physician or other professional healthcare provider
if you have a question concerning your or your family's health.
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