99130871
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
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women with the use of GnRH analogs. For the patients 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 long-term
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 follow-up. 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
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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.
Results
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Table 1