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Clinical Crossroads | Clinician's Corner

A 41-Year-Old Woman With Menorrhagia, Anemia, and Fibroids:  Review of Treatment of Uterine Fibroids

Bradley Van Voorhis, MD, Discussant
JAMA. 2009;301(1):82-93. doi:10.1001/jama.2008.791.
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Published online

Uterine fibroids are common tumors that can cause heavy menstrual bleeding, pelvic pressure symptoms, and reproductive disorders. The incidence of fibroids peaks in the fifth decade of age and they are more common in African American women. Often, fibroids are asymptomatic and require no treatment. However, the case of Ms P, a 41-year-old woman with recurrent uterine fibroids, menorrhagia, anemia, and fatigue who wishes to retain fertility, illustrates the symptoms that require treatment. Evaluation usually begins with a pelvic examination and an ultrasound to determine both the size and location of the fibroids within the uterus. Standard treatment of symptomatic fibroids is surgical removal by myomectomy or hysterectomy, depending in part on the desire for future fertility; new treatment options include uterine artery embolization via interventional radiologic techniques as well as various medical interventions. Several new therapies show promise but are still experimental at this time. The evidence for treatment options for Ms P and symptomatic patients with fibroids in general is discussed.

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Figure 1. Ms P’s Uterine Ultrasound
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A, Abdominal ultrasound shows large fibroids distorting the shape of the uterus. B, Illustration of anatomical structures in view. (See also interactive eFigure.)

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Figure 2. Normal Pelvic Anatomy, Locations of Uterine Fibroids, and Fibroid Tissue Histology
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Abnormal uterine bleeding is influenced by the size and location of fibroids. Larger fibroids and fibroids located in or near the endometrial cavity tend to cause more bleeding symptoms and reproductive disorders. In a representative tissue sample, a fascicular pattern of smooth muscle bundles can be seen, separated by vascularized connective tissue. Individual smooth muscle cells are elongated with eosinophilic cytoplasm, distinct cell membranes, and uniform “boxcar-shaped” nuclei. Mitoses, in this case and in most fibroids, are extremely rare and, if present, raise the possibility of leiomyosarcoma, a malignant tumor of smooth muscle origin.

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Figure 3. Uterine Artery Embolization (UAE)
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A, During UAE, a catheter is introduced along a guide wire into the femoral artery and advanced through the external iliac artery into the common iliac artery. The catheter is then guided into the internal iliac artery and then into the uterine artery. Microspheres injected through the catheter embolize the distal branches of the uterine artery that supply the fibroid and block perfusion, causing necrosis and shrinkage of the fibroid. B, Angiogram prior to UAE shows the blood supply of a large fibroid. After embolization of the uterine artery, absence of contrast in the distal branches confirms occlusion.

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Uterine fibroids: The disconnect between treatment options and patient expectations
Posted on December 30, 2008
Kristen A. Matteson, MD, MPH
Women and Infants Hospital, Alpert Medical School of Brown University
Conflict of Interest: None Declared
Treatment of uterine fibroids is guided by the patient's symptoms and their impact on her quality of life, her expectations for treatment, and her desires for future fertility. Ms P, who has symptomatic fibroids, is distressed by fatigue, presumably from severe anemia. She wants the fibroids "eradicated" without another "big" surgery and she wants to preserve her ability to bear children. A hysterectomy, the only option that will completely "eradicate" this patient's fibroids, is a "big" surgery that would eliminate her ability to bear children. A myomectomy, which would maintain her ability to have children, could eradicate many of the fibroids. Unfortunately, it would likely involve major surgery and remaining fibroids may grow and become symptomatic.
Uterine Artery Embolization (UAE) and Magnetic Resonance Imaging- Guided Focused Ultrasound Therapy (MRgFUS) are less invasive procedures that decrease symptoms associated with uterine fibroids.(1,2,3) However, in clinical trials, approximately one-quarter of women undergoing these procedures had a subsequent hysterectomy for persistent symptoms. Successful pregnancies after UAE and MRgFUS have been described, however the impact of these procedures on pregnancy and fertility has not been adequately evaluated.(1)
No medical therapies are approved for long-term treatment of uterine leiomyoma. Despite limited evidence, estrogen-progesterone combinations and progesterone only pills are widely used to treat heavy menstrual bleeding.(4,5,6,7) The utility of these agents in treating women with fibroids is uncertain.(1) The levonorgestrel intrauterine system (LNG IUS) may be effective in treating heavy menstrual bleeding in women with fibroids, though its effect on the fibroid size is unclear.(8)
GnRH agonists reduce myoma size and bleeding and are approved for use up to 3 months to allow symptomatic relief while preparing for surgery.(9) Postmenopausal symptoms and bone loss associated with GnRH agonists limit their use long-term and leiomyoma return to pre-treatment size after therapy cessation.(10) Other therapies, such as aromatase inhibitors and progesterone modulators may decrease fibroid size and symptoms but warrant further investigation.
Unfortunately for Ms P, it is not possible to eradicate her fibroids, avoid a major surgical procedure, and preserve her ability to bear children. Currently, these are mutually exclusive expectations of uterine fibroid treatment. Therefore, it is important to have a detailed conversation with this patient about the treatments available and set realistic expectations for treatment results and future fertility. If after these discussions, she wants to preserve her ability to bear children without surgical intervention, she could be managed with the LNG IUS or GnRH agonists while waiting to attempt pregnancy. However, she would need to be counseled that (a) these agents provide symptom reduction rather than eradication (b) evidence on the effectiveness of the LNG IUS in the treatment of fibroids is limited, and (c) GnRH agonist use beyond 3 months could involve substantial adverse effects. Not enough data on pregnancy after UAE and MRgFUS are available to offer these as options for this patient.
Ms P embodies a challenging case that is common in clinical practice. Uterine fibroids drastically affect the quality of life of women and better therapeutic options are needed.
1. ACOG Practice Bulletin Number 96, August 2008. Alternatives to Hysterectomy in the Management of Leiomyomas.
2. Volkers NA, Hehenkamp WJK, Birnie E, Ankum WM, Reekers JA. Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: 2 years' outcome from the randomized EMMY trial. Am J Obstet Gynecol; 196:519e.1-519.e11.
3. Stewart EA, Rabinovici J, Tempany CM, Inbar Y, Regan L, Gostout B, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids [published erratum appears in Fertil Steril 2006; 85:1072]. Fertil Steril 2006; 85:22-29.
4. Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for heavy menstrual bleeding. The Cochrane Database of Systematic Reviews 1997, Issue 2
5. Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. The Cochrane Database of Systematic Reviews 1998, Issue 4.
6. Hickey M, Higham J, Fraser IS. Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation. The Cochrane Database of Systematic Reviews 1998, Issue 3
7. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD002126. DOI: 10.1002/14651858.CD002126.pub2
8. Kaunitz AM. Progestin-releasing intrauterine systems and leiomyoma. Contraception 2007; 75: S130-S133.
9. Friedman AJ, Hoffman DI, Comite F, Browneller RW, Miller JD. Treatment of leiomyomata uteri with leuprolide acetate depot: a double- blind, placebo controlled, multicenter study. The Leuprolide Study Group. Obstst Gynecol 1991; 77:720-725)
10. Parker WH. Uterine myomas: management. Fertility and Sterility 2007; 88: 255-271
A 41-Year-Old Woman Suffering with Fibroids
Posted on December 9, 2008
John C Lipman, MD, FSIR
Director, Center For Image-Guided Medicine, Emory-Adventist Hospital, Atlanta, Georgia
Conflict of Interest: None Declared
The indication for treating women with fibroids should be to significantly improve or cure their symptoms, or to address a specific clinical concern (eg, difficulty conceiving or recurrent pregnancy loss). In this particular example, the patient has menorrhagia and subsequent iron-deficiency anemia. This has resulted in chronic fatigue, migraine headaches, decreased quality of life, and depression.
A study by Lee et al estimated that ½ million women in this country have clinically significant fibroids. These women have a diminished quality of life, and if untreated, have a poorer health status.(1) Therefore, expectant management of this patient is not a good option.
There are a number of possible therapeutic options for this patient. Medical management (eg, OCP, Mifepristone, Leonorgestrel-IUD) is often a first-line option, but her symptoms warrant a more definitive option. A Cochrane collaborative review from 2006 stated that "evidence-based reviews suggest that current medical therapies tend to give only short- term relief, and the crossover rate to surgical therapies is high."(2)
Uterine Artery Embolization (UAE) would be an excellent option for this patient. The August 2008 Practice Bulletin of the American College of Obstetricians & Gynecologists stated that based on long- and short- term outcomes, UAE is a safe and effective option for women who wish to retain their uteri. The patient would need to see an Interventional Radiologist for a second opinion. The benefits of a multidisciplinary approach to fibroid treatment is the subject of a recent Ob/Gyn publication.(3) The strengths of UAE are that it can be an outpatient procedure with high clinical success rates and high patient satisfaction.(4,5) The patient avoids the surgical risks and the longer surgical recovery. It is also a global therapy (i.e. treats all the fibroids) rather than a local therapy (eg, myomectomy and MR-guided Focused Ultrasound [MRgFUS]). In this particular case, the patient has seen that myomectomy did not provide long-term relief, and she has had a prompt return of her symptoms.
MRgFUS is also an option. There are short-term studies that show safety and efficacy, and improvements in UFS-QOL.(7) However, long-term studies are needed to see if the results are comparable to other treatment options beyond 2 years. If the 2 fibroids in the ultrasound image are the only fibroids to speak of, this therapy becomes more of an option than if there are numerous additional fibroids present in the uterus.
The patient’s desire to avoid another “big” surgery, and the capacity to bear children, eliminate hysterectomy, open myomectomy, and endometrial ablation from consideration. Laparoscopic myomectomy would be an option, although studies report recurrences from 12.7% at 1 year to 27% at 2 ½ years.(8) According to Reed et al, the cumulative risk for a second surgery (which is typically hysterectomy) after myomectomy is high (~5% per year).(9)
In summary, as stated in a report from the Agency for Healthcare Research and Quality (AHRQ) in 2007, “there is a remarkable lack of high quality evidence supporting the effectiveness of most interventions for symptomatic fibroids."(10) With that said, I would discuss the above options with the patient, but the two best in my opinion for this patient would be UAE or MR-gFUS. Of these two options, UAE is likely the more complete and durable procedure, but MRgFUS is an attractive option for selected patients with a limited fibroid burden who wish to have a non-invasive therapy. At this time, most insurers do not yet reimburse for MRgFUS, and therefore, her decision may need to be made with that in consideration.
John C. Lipman, MD, FSIR Director, Image-Guided Medicine, Emory-Adventist Hospital Atlanta, Georgia
References
1. American College of Obstetricians and Gynecologists. Uterine Fibroids. www.acog.org/publications/patient_education/bp074.cfm.
2. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database of Systemic Reviews 2006, Issue 2. Art. No.: CD003855. DOI: 10.1002/14651858.CD003855.pub2.
3. Fischer JH and Zurawin RK. Expert Exchange: How to Formulate the Relationship Between the Ob/Gyn and the Interventional Radiologist for the Treatment of Uterine Fibroids. Contemporary Ob/Gyn 2008; April: 1-8.
4. Hutchins F, Worthington-Kirsch R, Berkowitz R. Selective uterine artery Embolization as primary treatment for symptomatic leiomyomata uteri. J Am Assoc Gynecol Laparosc 1999; 6: 279-84.
5. Spies J, Ascher SA, Roth AR, et al. Uterine Artery Embolization for Leiomyomata. Obstet and Gynec 2001; 98: 29-34.
6. Stewart EA, Rabinovici J, Tempany CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril 2006; 85 (1): 22-9.
7. Viswanathan M, Hartmann K, McKay N, et al. Management of Uterine Fibroids: An Update of the Evidence. Agency for Healthcare Research & Quality US Dept of Health & Human Services. 2007 Contract # 290-02- 0016, July #154.
8. Rosetti A, Sizzi O, Soranne L, et al. Long-term results of laparoscopic myomectomy: recurrence rate in comparison with abdominal myomectomy. Hum Reprod 2001; 16 (4): 770-4.
9. Reed SD, Newton KM, Thompson LB, et al. The Incidence of Repeat Uterine Surgery following Myomectomy. J Women’s Health 2006; 15: 1046-52.
10. Viswanathan M, Hartmann K, McKay N, et al. Management of Uterine Fibroids: An Update of the Evidence. Agency for Healthcare Research & Quality US Dept of Health & Human Services. 2007 Contract # 290-02- 0016, July #154.
No relevant financial interests
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