Long-term treatment of uterine fibroids with ulipristal acetate☆

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Abstract

To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.

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Uterine leiomyomas (fibroids or myomas), benign tumours of the human uterus, are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women and cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, and, in rare cases, reproductive dysfunction. Thus, both the economic cost and the effect on quality of life are substantial. Surgery has been the mainstay of fibroid treatment, and various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Although medications that manipulate concentrations of steroid hormones are effective, side-effects limit long-term use. A better approach may be manipulation of the steroid-hormone environment with specific hormone antagonists. There has been little evidence-based evaluation of therapy. New research into the basic biology of these neoplasms may add new treatment options for the future as the role of growth factors and genetic mutations in these tumours are better understood.

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Characterization of uterine leiomyomas by whole-genome sequencing.

Pia Vahteristo, Esa Pitkänen, Netta Mäkinen … (2013)

Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. (Funded by the Academy of Finland Center of Excellence program and others.).

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Uterine myomas: an overview of development, clinical features, and management.

Edward E Wallach, Nikos Vlahos (2004)

To review the biology and the pathophysiology of uterine myomas, focus on options for management, and emphasize principles that will render the decision-making process as logical as possible. Literature review and synthesis of the authors' experience and philosophy. Uterine myomas are the most common solid pelvic tumors in women. There is increasing evidence that they have a genetic basis and that their growth is related to genetic predisposition, hormonal influences, and various growth factors. Treatment choices are wide and include pharmacologic, surgical, and radiographically directed intervention. Most myomas can be followed serially with surveillance for development of symptoms or progressive growth. The past century has witnessed development of highly sophisticated diagnostic and therapeutic technology for myomas. The tools currently at our disposal permit greater management flexibility with safe options, which must be tailored to the individual clinical situation.