Insights and Advances in Uterine Leiomyomas

William H. Catherino, M.D., Ph.D.

“The miracle of the seed and the soil is not available by affirmation; it is only available by labor.” Jim Rohn

Much has been written on optimizing the oocyte, the spermatocyte, and the embryo. However, the potential of the implanted embryo is threatened by a hostile environment. The negative impact of uterine leiomyomas on reproduction has been well documented, particularly when such tumors impact the uterine cavity. Furthermore, leiomyomas can cause such severe morbidity that definitive intervention with hysterectomy may be encouraged despite the continued desire for childbirth. If the past 50 years have been the era where therapy for leiomyomas moved from mortal threat to morbid threat, the past 10 years have foreshadowed therapy that will be targeted to specific patients with specific subtypes of uterine leiomyomas. These therapies have proven ability and potential promise to minimize therapeutic morbidity, eliminate disease morbidity, and protect reproductive options for women suffering from uterine leiomyomas.

In this issue of Seminars in Reproductive Medicine, we focus on cutting-edge insights and advances in uterine leiomyomas. The first section addresses mechanisms that result in leiomyoma growth, focusing specifically on the fibrotic process that defines the leiomyoma phenotype. Indeed, in the absence of excessive extracellular matrix (ECM) production, leiomyomas would remain a subclinical disease. Malik and colleagues summarize the data on disruptions in ECM formation that result in aberrant fibrosis, and they provide insight into the mechanism of current and future medical therapy options for inhibiting matrix production and stimulating matrix dissolution. Chegini reviews the cytokines that are produced by the leiomyoma cell and stored in the aberrant matrix that can impact both the cellular phenotype as well as the maintenance of the tumor phenotype.

The section that follows addresses the societal impact of human leiomyomas. Laughlin and colleagues review the world's literature on leiomyoma prevalence and provide a valuable cumulative pregnancy estimate based both on age and race. Olive and Pritts then evaluate the current data on the role of leiomyomas in patients attempting conception and childbirth, noting both the clinical insights that these studies provide as well as the limitations of the current literature. Such a review provides fertile direction for organizing future studies to answer critical questions.

The final section addresses the explosive advances in therapeutic options for women suffering from uterine leiomyomas. Agdi and Tulandi review advances in minimally invasive laparoscopic interventions, providing technical pearls for surgeons moving from laparotomy to laparoscopy. Freed and Spies provide a significant update of the advances in uterine artery embolization, which has progressed dramatically even over the 6 years since the last publication on uterine artery embolization in this journal. Al Hilli and Stewart review the data on high-frequency ultrasound therapy guided by magnetic resonance imaging for uterine leiomyomas, which is currently under study for the treatment of women interested in future fertility. Yu and colleagues review the role of receptor tyrosine kinases in hormonal regulation, providing novel insight into hormonal regulation of uterine leiomyomas. Finally, Yoshida and colleagues review exciting data on the use of selective progesterone receptor modulators as therapeutic options for women suffering from uterine leiomyomas. These compounds have proven clinical efficacy, regulate multiple cellular mechanisms, and alter ECM production.

With such a high prevalence in reproductive-age women combined with significant morbidity and disruptions in normal pregnancy, scientific investigation of uterine leiomyomas is expanding rapidly beyond the area of reproduction. They impact all facets of gynecologic care, transcending specialty and subspecialty. In addition, internationally recognized bench scientists, bioethicists, epidemiologists, and other experts are providing valuable contributions for the many women impatiently waiting for continued advances that will ultimately rid them and their progeny of these debilitating tumors.