COMMENTARY

More Nonsurgical Options for Fibroids Becoming Available

Peter Kovacs, MD, PhD

Disclosures

December 02, 2014

Fibroid Growth and Medical Options for Treatment

Chabbert-Buffet N, Esber N, Bouchard P
Fertil Steril. 2014;102:630-639

Background

Fibroids are benign tumors originating from uterine small muscles. They can be solitary or multiple and can grow towards the uterine cavity or towards the abdominal cavity. They may produce symptoms or can remain asymptomatic. Symptoms are typically associated with their location and size. Those myomas that grow towards the uterine cavity will often result in bleeding abnormalities (menorrhagia, irregular bleeding). Larger fibroids may cause problems due to their size if they compress the bladder or bowel or grow to such size that may mimic a pregnant uterus.[1]

The occurrence and growth of fibroids are linked to reproductive factors. Longer steroid hormone exposure (early menarche, late menopause, oligo-ovulation) is a known risk factor, as are race and hereditary factors.[1]

Fibroids in general do not need to be treated. If they grow rapidly, and malignant transformation is suspected, their removal is recommended. Those associated with symptoms also require therapy. Fibroids that distort the uterine cavity or multiple large intramural fibroids lower the chance of successful reproduction; therefore, their removal is also recommended.[2]

This review summarizes the latest information on medical therapies.

Summary

The authors point out that fibroids develop from a single smooth muscle cell and, therefore, are classified as clonal disease. They can be detected in up to 70% of women, with the majority of them not producing clinically significant symptoms. Reproductive factors, prolonged estrogen, progesterone exposure, as well as genetic factors all play a role in their etiology.

The only curative therapy is surgery (hysterectomy), but there are destructive therapies using ultrasound or radiofrequency ablation, endometrial ablation, uterine artery embolization, and medical therapies that could all improve symptom severity and, through that, quality of life. Current medical therapies include progestins, gonadotropin-releasing hormone (GnRH) analogues, selective estrogen receptor modulators (SERMs), selective progesterone receptor modulators (SPRMs), and aromatase inhibitors:

Progestins alone (oral, intramuscular, or intrauterine) may control bleeding by reducing endometrial hyperplasia, but their use will not result in tumor shrinkage and may, in fact, induce tumor growth.

SERMs will induce either an estrogen agonist or antagonist effect depending on the tissue. Raloxifene (Evista®) has antiestrogenic uterine effects and slows down cell proliferation. Studies have reported conflicting results regarding their efficacy in fibroid management.

Aromatase inhibitors prevent androgen-estrogen conversion and, therefore, should lower estradiol levels; but in regularly cycling women, they induce multifollicular development and overall still lead to relatively high estradiol concentrations. Locally within the uterus/fibroid, their effect still may be a reduction in estradiol synthesis and, therefore, could result in tumor regression. More clinical information is needed regarding their effect before firm conclusions can be drawn.

GnRH analogues are effective in tumor size reduction. They are also associated with a significant reduction in bleeding; in fact, prolonged use induces amenorrhea. Their use is accompanied by low estradiol level and, therefore, often causes undesired side effects related to hypoestrogenism. Their effect is temporary; following discontinuation of treatment, the tumors regrow to pretreatment size. They can be combined with add-back therapy (progestin, estrogen-progestin combination, SERM) to minimize the side effects.

SPRMs (mifepristone [Mifeprex®], ulipristal acetate [Ella®], telapristone acetate [Proellex®]), and the investigational drug asoprisnil, are the latest medical treatment choices. They induce progesterone receptor agonist or antagonist effect in a tissue-selective manner. They were shown to induce an up-to-57% decrease in fibroid volume, and this effect was maintained for at least 6 months following treatment. Their effect develops faster when compared with GnRH analogues, and their use is not associated with hypoestrogenic side effects. Currently, ulipristal acetate is available as a 3-month regimen, but studies evaluating the impact of longer-term use are underway.

Herbal therapies and vitamin D supplementation are also being evaluated for their effect on fibroids.

Viewpoint

Fibroids can be detected in up to 70% of women.[1] Most tumors are picked up on ultrasounds or other imaging studies as incidental findings, but fibroids can induce symptoms that significantly interfere with well-being.

Submucosal fibroids, either themselves or by altering endometrial function, can cause significant bleeding that can result in anemia. Larger fibroids may compress the adjacent organs, may cause dyspareunia, and may interfere with normal reproduction. Definitive therapy is hysterectomy. Fibroids are the most common indication for hysterectomies, with hundreds of thousands of procedures done each year in the United States. Treatment expenses, related work loss, and obstetric expenses are in the billions, causing a significant healthcare burden.[3] There are cases when surgery should be avoided, though, such as desire for future fertility, surgical risk, and patient preference. For these women, conservative surgery via myomectomy, ablative and destructive therapies, or uterine artery embolization can be offered.

In the African-American population, myomas tend to occur at a younger age, but in other races they usually develop by the late reproductive years. In this latter group, fibroids will shrink once the woman enters menopause; therefore, not all require surgery. If menopause is close enough, a few months of medical therapy may eliminate the need for surgery.

There are several medical options to choose from—SERMs, SPRMs, GnRH analogues, and aromatase inhibitors. Their impact on tumor size and bleeding patterns is variable. Their side effect profiles differ too, sometimes limiting their clinical use.

SPRMs are the latest group of drugs for fibroid treatment. They induce rapid tumor regression and are associated with favorable bleeding pattern changes. They seem to have a long-lasting effect and may be available for extended use without harmful side effects.

Medical therapies could be used as adjuvant therapy prior to surgery if the patient has to be brought into a fit preoperative condition, but they may also offer long-term symptom relief for those who wish to avoid surgery. Results of studies with longer-term use and potential other growth-modulating drugs could revolutionize the medical management of leiomyomas.

Abstract

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