342382341.

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Pretreatment of Leiomyoma with GnRH

Agonists/Antagonists B of Any Value
R. BLACKWELL
University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.

Introduction
Leiomyomata (fibroids) are the most common tumors of the female genital tract,
occurring in one out of 4-5 women in the United States. They occur with increasing
frequency in the later reproductive years and as women delay childbearing, myomectomy
is likely to become a more common treatment for individuals who wish to retain
reproductive potential.
The first myomectomy was performed by Amussta of Paris in 1842, and the first
series reported by Kelly and Cullen in 1906. Subsequently, a significant variation was
reported in the results of myomectomy with regard to pregnancy rates (26-79%) and
recurrence (5-35%). Two studies have included preoperative uterine size as a factor in
their evaluation. Buttram and Reiter, in 1983, evaluated 14 patients. Seven of 12 patients
conceived with uteri less than 12 weeks, and 0 or 6 conceived with uteri 12 weeks or
greater in size. Smith and Uhiir in 1990 evaluated 64 patients, 37 of 64 had uterine sizes as
an indication for surgery with an overall 40% pregnancy rate. The number of fibroids or
weight of the tumors was equivalent between groups that conceived and those that did
not. As a result of these studies, a dogma has developed that women with fibroids and a
Alarge uterus@ 16 weeks size or greater are not considered candidates for myomectomy,
only hysterectomy. In our own experience as presented in Table 1, we found that women
with uterine size 12-16 weeks had a 55% conception rate and a 57% live birth rate. Those
with uteri greater than 16 weeks had a 45% conception rate and a 43% live birth rate.
The central question of this controversy centers on whether the use of preoperative
GnRH analogs used before hysterectomy or myomectomy facilitates surgery. The reader is
directed to an excellent review in The Cochran Library by Lethaby A, Vollenhoven B, and
Sowter M. Reviewers are from New Zealand and 26 citations are included in the review.
The main results are as follows: APre- and postoperative hemoglobin and hematocrit were
significantly improved by GnRH analog therapy prior to surgery and uterine volume,
uterine gestational size, and fibroid volume were all reduced. Pelvic symptoms were also
reduced, however, some adverse effects were more likely during GnRH analog therapy.
Hysterectomy appeared to be easier after pretreatment with GnRH analog therapy. There
was reduced operating time, a greater proportion of hysterectomy patients were able to
have a vaginal rather than an abdominal procedure. Duration of hospital stay was also
reduced. Blood loss and the rate of vertical incisions were reduced for both myomectomy
and hysterectomy. Evidence for increased risk of fibroid occurrence after GnRH analog
pretreatment in myomectomy patients was equivocal, and few data were available to
assess changes and postoperative fertility. Lynestrenol did not offer any advantage over
GnRH analog therapy before fibroid surgery. The increased costs associated with GnRH
therapy were not assessed.@ The reviewers= conclusions, AThe use of GnRH analogs
for 3-4 months prior to fibroid surgery reduced both uterine volume and fibroid size. They
are beneficial in the correction of preoperative iron deficiency anemia if present, and
reduced intraoperative blood loss. If uterine size is such and a midline incision is planned,
this can be avoided in many women with the use of GnRH analogs. For the patients

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undergoing hysterectomy a vaginal procedure is more likely following the use of these
agents.@
This analysis would seem to suggest that the use of GnRH analogs is a beneficial
adjunct to surgery. Our group was involved in the original evaluation of leuprolide acetate
for the treatment of fibroids. A limited patient population demonstrated a reduction in
fibroid size, that averaged 47% as evaluated by MRI. About half the patients had a longterm remission, the other half ended up with either myomectomy or hysterectomy. Our
experience with these patients as well as those mentioned in our myomectomy series did
not alter our surgical treatment. One always has to consider that when evaluating an
unidentified pelvic mass that the diagnosis of fibroids may be wrong. I have had the
opportunity to see two patients who had previous myomectomies and were lost to followup. These women presented a number of years later with what they believed to be a
recurrence of their fibroids. Surgery ultimately demonstrated that both of these patients
had stage III ovarian cancer. Further, we have seen a number of cases of sarcoma or
carcinosarcoma which masqueraded as fibroids. This raises the question of the type of
incision that should be used for a large lesion, and in general, I would suggest that any
mass near the umbilicus should be approached with either a vertical or Maylard incision.
Either of these incisions would allow adequate exposure for removal of the mass and node
sampling. Further, in the case of fibroids, such an incision allows the delivery of the uterus
from the abdominal cavity, and allows the assistant surgeon to adequately occlude the
vascular supply so that blood loss is minimal.
The use of GnRH analog therapy prior to endoscopic treatment of fibroids would
seem to be a reasonable course of action. When vascularity is decreased, any reduction in
the size of the lesion should facilitate surgery whether myomectomy, myolysis, or
transcervical resection is contemplated. The issue of whether the use of GnRH analogs
facilitates a vaginal hysterectomy appears to me to be problematic, as one suspects that
many of the patients undergoing surgery did not have strong indications for the operation.
Many of these patients are frequently in a perimenopausal transition, they have problems
with bleeding, the fibroid is picked up on clinical examination, and hysterectomy is carried
out. I would submit that the judicious use of transvaginal ultrasonography clearly
demonstrates whether the fibroid impinges on the uterine cavity, and if no cavitary
involvement is demonstrated most of these bleeding problems can be handled with cyclic
hormonal replacement therapy.
The issue of pharmacoeconomics of preoperative GnRH therapy is an important
one. All brands of GnRH are expensive, at least in the United States, which adds to the
overall cost of therapy. If GnRH analogs are used it is suggested that 2-3 months will give
maximum results and minimize the cost of therapy. On the other hand, a GnRH analog can
frequently be used to defer surgery for a long period of time and, in fact, are a reasonable
alternative for surgery in certain patient groups; for instance, the young student or the
patient with impending menopause.
Conclusion
GnRH analogs are a useful adjunct for the treatment of fibroids and should
probably be used by surgeons who do not routinely perform large myomectomies and
resulting uterine reconstruction. The highly experienced surgeon who routinely operates
on large lesions may not find this adjunctive therapy to be of great benefit. One must
weigh patient preference, side-effects, cost, and complications when deciding to use these
agents as a surgical adjunct.

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Results
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Table 1