1st Institute of Obstetrics and Gynecology, University of Bologna, 40138 Bologna, Italy
aColumbia Laboratories, Paris, France
bNyon Medical Center, Nyon, Switzerland
Address for correspondence: Carlo Bulletti, M.D., 1st Institute of Obstetrics and Gynecology, University of Bologna, Via Massarenti, 13, 40138 Bologna, Italy. Voice: 39.541.393844 or 39.541.705741; fax: 39.541.705741.
Bull{at}infotel.it
Spontaneous uterine contractility during the menstrual cycle
is required for menstruation, gamete transport, and, most likely,
embryo nidation. Abnormal uterine contractility has been linked
to dysmenorrhea, a condition associated with painful uterine
cramping. Based on previous studies with progesterone, we have
postulated the existence of a portal system that is responsible
for some degree of direct vagina-to-uterus transport of administered
compounds (i.e., the "first uterine pass effect"). It is possible
that treatment with uterorelaxing substances, particularly ß-adrenergic
agonists, may alleviate the uterine discomfort that accompanies
dysmenorrhea. However, side effects encountered with oral administration
of ß-agonists limit their utility. Alternatively,
vaginal delivery of ß-agonists could solve this dilemma
by enhancing their efficacy and reducing side effects. Therefore,
in the current study we used hysterectomy specimens and an
in vitro uterine perfusion system to test the vagina-to-uterus
transport of [
3H]terbutaline, a well-known ß-agonist.
With the use of autoradiographic and scintillation counting
techniques, our results clearly show progressive diffusion of
labeled terbutaline from the rim of vaginal tissue through the
uterus during the first 12 hours of perfusion. This indicates
that uterine targeting of terbutaline can be accomplished through
vaginal administration, suggesting a new therapeutic modality
in women's health care.
