Preoperative Hormonal Treatment Before Laparoscopic Approach for Uterine Fibroids: Do We Need It?

We recently have read the narrative review by Marín-Buck et al. [1], describing the most recent advances in minimally invasive approaches for performing myomectomy. Overall, asymptomatic women affected by small fibroids may benefit from expectant management, particularly those approaching menopause. Although hysterectomy and myomectomy have been the traditional gold standard curative therapies for symptomatic fibroids, not all women wish to undergo a surgery, and some may have an elevated risk of surgical complications. However, in the last years, the number of the gynecological surgical laparoscopic procedure has sharply increased, and, today, they peak 80% of all gynecological procedures. With particular regard to myomectomy, it has been demonstrated that when compared with traditional laparotomic or mini-laparotomic techniques, laparoscopic approach tends to improve intraoperative blood loss, postoperative hemoglobin drop, postoperative pain and length of hospitalization [2].

We would focus the attention on the preoperative medical treatment options for treating uterine fibroids, topic which the authors briefly discussed in this interesting overview of the literature [1]. In general, surgical management for uterine fibroids can be directly performed in women having adequate hemoglobin levels; otherwise, in case of anemia, preoperative menstrual suppression and iron supplementation may be advisable in order to improve the outcomes of surgery. In fact, laparoscopic myomectomy can be complicated by extensive peri-operative bleeding; therefore, blood transfusions and eventually reoperation may be necessary for treating some patients, especially if they had previous low levels of hemoglobin. Preoperative hormonal therapy for uterine fibroids aims to correct preoperative anemia, decreasing uterine abnormal bleeding related to their presence and to decrease intraoperative blood loss, reducing fibroid vascularization and volume [3]. The preoperative hormonal therapy may be advantageous in all women undergoing laparoscopic myomectomy but particularly in those patients affected by large and/or multiple fibroids, which likely have a higher risk of intraoperative blood loss. Obviously, better postsurgical levels of hemoglobin can allow for a quicker return to social activities, among which work. Moreover, a decrease in myoma volume due to the use of a preoperative drug may theoretically allow the performance of less invasive surgical procedures; for example, in case of large uteri requiring morcellation for laparoscopic abdominal or vaginal removal, a decrease of uterine size can reduce the need of an eventual intrabdominal morcellation.

Until now, the most investigated preoperative hormonal options for uterine fibroids have been gonadotropin releasing hormone analogs (GnRH-as) and selective progesterone receptor modulator (SPRMs). The choice of most appropriate therapy should consider the characteristic of myomas (size, location and number), efficacy and safety profiles of each drug, route of administration as well as preference of both patients and surgeons. Nevertheless, we have to consider that all these preoperative drugs share some potential drawbacks such as cost, delay in the surgical approach, additional consultations, and onset of drug-related adverse events.

Traditionally, GnRH-as have been routinely employed in this setting, as they have demonstrated to reduce abnormal uterine bleeding before surgery, increasing hemoglobin levels, as well as to reduce size of fibroids and uterus. However, a not negligible issue is related to the fact that under the administration of these hormonal drugs, patients can experience a not negligible rate of menopausal-related adverse events, which may limit adherence to the schedule [4].

Ulipristal acetate (UPA) is a SPRM that can be preoperatively considered in patients potentially eligible for undergoing any type of surgery for myomas. This drug confers clinical advantages similar to GnRH-as while awaiting surgery, but it is characterized by a better safety-profile in comparison to the previous: in fact, the majority of adverse events experienced under UPA therapy (i.e. headache, breast tenderness and hot flushes) tend to be mild to moderate in intensity and they do not usually cause the interruption of treatment [5]. Anyway, after four recent cases of serious liver injury (three of which ended in liver transplantation), the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency (EMA) recommends to put in place several measures in order to minimize the rare eventual risk of hepatic toxicity during UPA therapy. Anyway, in the literature, the data about this topic are controversial.

In general, there is a good evidence that UPA decreases the uterine bleeding as well as improves the preoperative hemoglobin level in patients affected uterine fibroids; furthermore, this drug also decreases intraoperative blood loss and, therefore, the risk of a subsequent intra- and postoperative transfusion. Secondarily, UPA may facilitate minimally invasive surgical procedures (such as laparoscopic or hysteroscopic myomectomy) by shrinking the myomas. At least, UPA does not seem to worse the overall technical feasibility of laparoscopic myomectomy [6]. The major concern of laparoscopic surgeons is that the preoperative therapy with UPA may complicate myomectomy because of a modification in consistency of fibroids, which are presumed to become softer after this hormonal treatment. This can lead to a higher difficulty in adequately grasping the benign mass, considering the relevance of the traction maneuvers during laparoscopic myomectomy; additionally, a softer consistency of the fibroids may theoretically worse the differentiation of these lesions from the surrounding endometrium/myometrium. Until now, contradictory results have been reported in the current literature on this topic and further studies are needed.

Overall, it should be under scored that until now few studies on surgical outcomes after UPA administration are available in the literature [7–9]; similarly, not sufficient data on the comparison between preoperative SPRMs and other hormonal therapies in patients undergoing laparoscopic myomectomy can be found [4]. Moreover, further trials should be planned for evaluating long-term outcomes such as frequency of myoma recurrence, recovery time and post-surgical quality of life after laparoscopic myomectomy with preoperative UPA use. Not less importantly, future research should draw conclusion about cost-effectiveness of this treatment, helping to distinguish between groups of women with fibroids who would most benefit.

Recently, a systematic review by Cochrane have analyzed the data available in the literature on the preoperative medical therapy for myomas: when compared with UPA, GnRH-as are associated with a greater reduction in uterine volume but are more likely to cause AEs, such as hot flushes. Moreover, there is no a clear difference in bleeding reduction or hemoglobin levels among the two hormonal options [10]. In the near future, new randomized prospective studies with larger sample size are necessary in order to confirm these positive preliminary results. Importantly, it should be performed an accurate comparison between preoperative UPA and GnRH-as. Additionally, among studies more homogenous end-points should be established in order to allow a future accurate meta-analysis on this topic.

DECLARATION OF INTEREST

The authors have no conflict of interest.