The role of fibroid tumors in infertility is controversial. Many of the studies examining the relationship between these tumors and infertility are retrospective and non- randomized. Current evidence suggests that submucosal and intramural fibroid tumors that distort the uterine cavity can impair in vitro fertilization attempts.21 The impact of intramural and subserosal fibroid tumors that do not distort the intrauterine cavity is unclear. Despite the lack of clear evidence of their role in conception problems, submucosal fibroid tumors, intramural fibroid tumors that distort the uterine cavity, fibroid tumors larger than 5 cm, and multiple fibroid tumors are often treated in patients with otherwise unexplained infertility.22 The possible role of fibroid tumors in early miscarriage is also controversial. Given the conflicting data and potential observational bias and methodologic problems in studies examining this association, a causal relationship should not be assumed.23
Diagnosis
The bimanual examination is often the first indication that a patient may have uterine fibroid tumors. Several studies, including transvaginal ultrasonography, sono- hysterography, hysteroscopy, and magnetic resonance imaging (MRI), may be helpful in evaluating these tumors. Transvaginal ultrasonography has the lowest sensitivity and specificity, but it is the best initial test based on its noninvasive nature and cost-efficiency. MRI is preferred when precise myoma mapping is required (usually for surgical purposes), but it is the most expensive modality for evaluating fibroid tumors. Sonohys- terography and hysteroscopy can be used to evaluate the extent of submucosal fibroid tumors, but these tests are relatively invasive.24
Management
Knowing the full range of treatment options enables family physicians to counsel patients about the optimal management of symptomatic uterine fibroid tumors. The number of treatment options is increasing and includes expectant management, surgery, uterine artery embolization, ablative techniques, and medical management
(Table 2). Clinical guidelines have been created to assist patients and physicians in choosing appropriate management options25 (Table 3). However, a systematic review by the Agency for Healthcare Research and Quality emphasized the paucity of evidence to support specific procedures and treatments based on individual patient characteristics.26,27
Expectant Management
Expectant management with observation is increas- ingly recognized as a reasonable course for women with asymptomatic small and large fibroid tumors. Even rap- idly growing tumors should not be removed routinely because the risk of a malignant leiomyosarcoma is small percent in one study).28,29
Surgical Treatments
Selected patients may benefit from surgery. One of the biggest challenges is identifying malignant leio- myosarcomas; rapid growth alone is not an adequate marker. There is evidence that combining dynamic MRI (i.e., MRI enhanced by gadopentetate dimeglumine) and measurement of serum lactate dehydrogenase levels is useful in distinguishing leiomyosarcoma from benign fibroid tumors.29 This approach may be useful in evaluating selected patients, such as postmenopausal women with enlarging tumors. Other patients who may benefit from surgery include those with persistent abnormal uterine bleeding or symptoms resulting from uterine bulk that do not respond to conservative measures.26
Hysterectomy. The presence of uterine fibroid tumors is the most common indication cited for hysterectomy, accounting for more than 30 percent of these procedures.26 Although most hysterectomies in women with fibroid tumors are performed for symptomatic relief, the procedure is sometimes recommended to asymptomatic women whose uterine size is estimated to be greater than that at 12 weeks" gestation. Common justifications for this recommendation include the risk that tumors of this size could potentially mask other adnexal pathology, increase operative morbidity rates, and become malignant. Current evidence does not support the treatment of fibroid tumors in asymptomatic women.25-27
The Maryland Women"s Health Study30 and the Maine Women"s Health Study31 were large, prospective studies designed to measure the outcomes and effectiveness of hysterectomy for benign conditions. The most common indication for surgery in both studies was uterine fibroid tumors (48.1 and 35 percent, respectively). These studies demonstrated that hysterectomy substantially improves symptoms and quality of life in women with multiple and severe symptoms associated with gynecologic disorders. The Maine study enrolled a comparison group of women who received nonsurgical medical treatment.31 Medical therapy for abnormal bleeding and chronic pelvic pain produced significant improvements, but one quarter of the nonsurgical group subsequently under- went hysterectomy. Women with uterine fibroid tumors who continued with nonsurgical treatment reported no significant changes in symptoms or quality of life over the one year follow-up. Not all women who are treated surgically report improvement. In the Maryland study, almost 8 percent of women had more or the same number of symptoms 24 months after hysterectomy.30 Baseline depression, therapy for emotional problems, annual income of less than $35,000, and bilateral oophorectomy were significantly associated with poorer out- comes. Some women in the Maine study reported new symptoms after hysterectomy (e.g., hot flashes, weight gain, depression).31 Most studies evaluating the effect of hysterectomy on sexuality are poorly designed, but the available evidence suggests that hysterectomy does not adversely affect sexuality.32
Myomectomy. Myomectomy (i.e., surgical removal of fibroid tumors while preserving the uterus) traditionally has been performed by laparotomy. Endoscopic myomectomy is now a treatment option for many women, and hysteroscopic myomectomy may be considered in women with symptomatic submucosal fibroid tumors. Ultimately, however, the choice of surgical approach is largely dependent on the expertise of the physician. Although elective cesarean delivery traditionally has been recommended for women who become pregnant after myomectomy (especially when the uterine cavity has been entered), data to support this recommendation are limited.33
Uterine Artery Embolization. Uterine artery embolization is performed under intravenous sedation. Using a femoral approach, a microcatheter is introduced into the uterine artery. Polyvinyl alcohol foam particles or other occluding agents are then injected. Complete occlusion of both uterine arteries initially was the goal of this treatment, but recent data suggest that incomplete embolization may produce effective infarction of myomas with less severe pain.34 The Fibroid Registry for Outcomes Data was formed in 1999 to collect prospective data on more than 3,000 women undergoing embolization for fibroid tumors. Short-term outcomes in women included in this database have been encouraging. In the first 30 days after treatment, the incidence of adverse effects was low, and major complications in the hospital and 30 days postdischarge were uncommon (0.66 and 4.8 percent, respectively).35 Future data will address long-term out- comes of uterine artery embolization.
Myolysis. Myolysis (i.e., delivering energy to tumors to desiccate them directly or disrupt their blood supply) is most often performed with the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser or bipolar needles. Combination treatment with myolysis and endometrial ablation may reduce the need for subsequent procedures in patients with persistent bleeding.36
MEDICAl TREATMENTS
Medical therapy is available for women with symptomatic fibroid tumors who prefer conservative management.
Gonadotropin-Releasing Hormone Agonists. Gonado- tropin-releasing hormone (GnRH) agonists are the most well-established therapy for medical management, causing amenorrhea and a rapid reduction in the size of the tumor. However, the benefits of GnRH agonists are tempered by significant side effects resulting from hypoestrogenism (e.g., hot f lashes, vaginal dryness, bone demineralization). Because GnRH agonists are not appropriate for long-term use, this therapy is best suited for women in the perimenopausal or preoperative periods.37
Hormone Therapy. Hormone therapy with cyclic or noncyclic estrogen–progestin combinations appears to be ineffective in alleviating the symptoms of fibroid tumors and limiting tumor growth.26 Studies have found no evidence that low-dose contraceptives cause the growth of uterine fibroid tumors; thus, these tumors are not a contraindication to the use of these contraceptives. A small study found significant improvement in bleeding after treatment with depot medroxy- progesterone acetate (Depo-Provera) in 20 African women with menorrhagia attributed to uterine fibroid tumors.38 A review of six clinical trials with a total of 166 women demonstrated that treatment with mifepristone (Mifeprex) resulted in reduced tumor size and improvement in symptoms.39 However, none of the studies were placebo controlled or blinded, and a notable adverse effect was the development of endometrial hyperplasia. Better-quality clinical trials are needed before recommendations can be made.
Other Therapies. The selective estrogen receptor modulator raloxifene (Evista) has been shown in one small study to decrease tumor size in postmenopausal women; however, there was no effect on uterine bleeding.40 Small trials have provided insufficient evidence to assess the effectiveness of nonsteroidal anti-inflammatory drugs in the management of uterine fibroid tumors.41 A noninvasive treatment using a combination of MRI and ultrasonography (ExAblate 2000) has been approved by the U.S. Food and Drug Administration.42 This treatment focuses high-intensity sound waves on the tumor, inducing coagulation necrosis. The main advantage is that it is an out- patient procedure with a short recovery time. Long-term follow-up and additional studies are needed to identify women who will benefit most from this treatment.
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Navy Medical Department or the U.S. Navy at large.
REFERENCES
1. Lurie S, Piper I, Woliovitch I, Glezerman M. Age-related prevalence of sonographically confirmed uterine myomas. J Obstet Gynaecol 2005;25:42-4.
2. Lethaby A, Vollenhoven B. Fibroids (uterine myomatosis, leiomyomas). Am Fam Physician 2005;71:1753-6.
3. Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T, et al. Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene. Gynecol Obstet Invest 1995;40:204-8.
4. Chalas E, Constantino JP, Wickerham DL, Wolmark N, Lewis GC, Berg- man C, et al. Benign gynecologic conditions among participants in the Breast Cancer Prevention Trial. Am J Obstet Gynecol 2005;192:1230-7.
5. Wise LA, Palmer JR, Stewart EA, Rosenberg L. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women"s Health Study. Obstet Gynecol 2005;105:563-8.
6. Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uter- ine leiomyomas. Racial differences in severity, symptoms and age of diagnosis. J Reprod Med 1996;41:483-90.
7. Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT. Risk
factors for uterine fibroids: reduced risk associated with oral con- traceptives [Published correction appears in Br Med J (Clin Res Ed) 1986;293:1027]. Br Med J (Clin Res Ed) 1986;293:359-62.
8. Ligon AH, Morton CC. Leiomyomata: heritability and cytogenetic stud- ies. Hum Reprod Update 2001;7:8-14.
9. Chiaffarino F, Parazzini F, La Vecchia C, Marsico S, Surace M, Ricci E. Use of oral contraceptives and uterine fibroids: results from a case-control study. Br J Obstet Gynaecol 1999;106:857-60.
10. Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M, Vudhika- mraksa N, Werawatakul Y. Protective effect of depot-medroxyproges- terone acetate on surgically treated uterine leiomyomas: a multicentre case-control study. Br J Obstet Gynaecol 1996;103:909-14.
11. Boynton-Jarrett R, Rich-Edwards J, Malspeis S, Missmer SA, Wright R. A prospective study of hypertension and risk of uterine leiomyomata. Am J Epidemiol 2005;161:628-38.
12. Lumsden MA, Wallace EM. Clinical presentation of uterine fibroids. Baillieres Clin Obstet Gynaecol 1998;12:177-95.
13. Stewart EA, Nowak RA. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update 1996;2:295-306.
14. Warner PE, Critchley HO, Lumsden MA, Campbell-Brown M, Douglas A, Murray GD. Menorrhagia I: measured blood loss, clinical features, and outcome in women with heavy periods: a survey with follow-up data. Am J Obstet Gynecol 2004;190:1216-23.
15. Marino JL, Eskenazi B, Warner M, Samuels S, Vercellini P, Gavoni N, et al. Uterine leiomyoma and menstrual cycle characteristics in a popula- tion-based cohort study. Hum Reprod 2004;19:2350-5.
16. Oelsner G, Elizur SE, Frenkel Y, Carp H. Giant uterine tumors: two cases with different clinical presentations. Obstet Gynecol 2003;101 (5 pt 2):1088-91.
17. Courban D, Blank S, Harris MA, Bracy J, August P. Acute renal failure in the first trimester resulting from uterine leiomyomas. Am J Obstet Gynecol 1997;177:472-3.
18. Chaparala RP, Fawole AS, Ambrose NS, Chapman AH. Large bowel obstruction due to benign uterine leiomyoma. Gut 2004;53:386, 430.
19. Monga AK, Woodhouse CR, Stanton SL. Pregnancy and fibroids caus- ing simultaneous urinary retention and ureteric obstruction. Br J Urol 1996;77:606-7.
20. Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyo- mas in pregnancy. Am J Obstet Gynecol 1989;160(5 pt 1):1212-6.
21. Rackow BW, Arici A. Fibroids and in-vitro fertilization: which comes first? Curr Opin Obstet Gynecol 2005;17:225-31.
22. Bajekal N, Li TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update 2000;6:614-20.
23. Cooper NP, Okolo S. Fibroids in pregnancy—common but poorly understood. Obstet Gynecol Surv 2005;60:132-8.
24. Griffin KW, Ellis MR, Wilder L, DeArmond L. Clinical inquiries. What is the appropriate diagnostic evaluation of fibroids? J Fam Pract 2005;54:458, 460, 462.
25. Lefebvre G, Vilos G, Allaire C, Jeffrey J, Arneja J, Birch C, et al., for the
Clinical Practice Gynaecology Committee, Society for Obstetricians and Gynaecologists of Canada. The management of uterine leiomyomas. J Obstet Gynaecol Can 2003;25:396-418.
26. Myers ER, Barber MD, Gustilo-Ashby T, Couchman G, Matcher DB, McCrory DC. Management of leiomyomata: what do we really know? Obstet Gynecol 2002;100:8-17.
27. Matchar DB, Myers ER, Barber MW, Couchman GM, Datta S, Gray RN, et al. Management of uterine fibroids. Evidence Report No. 34. Rock– ville, Md.: Agency for Healthcare Research and Quality, 2001.
28. Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994;83:414-8.
29. Schwartz PE, Kelly MG. Malignant transformation of myomas: myth or reality? Obstet Gynecol Clin North Am 2006;33:183-98, xii.
30. Kjerulff KH, Rhodes JC, Langenberg PW, Harvey LA. Patient satisfaction with results of hysterectomy. Am J Obstet Gynecol 2000;183:1440-7.
31. Carlson KJ, Miller BA, Fowler FJ Jr. The Maine Women"s Health Study: I. Outcomes of hysterectomy. Obstet Gynecol 1994;83:556-65.
32. Farrell SA, Kieser K. Sexuality after hysterectomy. Obstet Gynecol 2000;95(6 pt 2):1045-51.
33. American College of Obstetricians and Gynecologists. ACOG prac- tice bulletin. Surgical alternatives to hysterectomy in the manage- ment of leiomyomas. Number 16, May 2000. Int J Gynaecol Obstet 2001;73:285-93.
34. Marshburn PB, Matthews ML, Hurst BS. Uterine artery embolization as a treatment option for uterine myomas. Obstet Gynecol Clin North Am 2006;33:125-44.
35. Worthington-Kirsch R, Spies JB, Myers ER, Mulgund J, Mauro M, Pron G, et al. The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short-term outcomes [Published correction appears in Obstet Gynecol 2005;106:869]. Obstet Gynecol 2005;106:52-9.
36. Goldfarb HA. Myoma coagulation (myolysis). Obstet Gynecol Clin North Am 2000;27:421-30.
37. Rackow BW, Arici A. Options for medical treatment of myomas. Obstet Gynecol Clin North Am 2006;33:97-113.
38. Venkatachalam S, Bagratee JS, Moodley J. Medical management of uterine fibroids with medroxyprogesterone acetate (Depo Provera): a pilot study. J Obstet Gynaecol 2004;24:798-800.
39. Steinauer J, Pritts EA, Jackson R, Jacoby AF. Systematic review of mife- pristone for the treatment of uterine leiomyomata. Obstet Gynecol 2004;103:1331-6.
40. Sammartino PS, Di Carlo C, Affinoto P, Zullo F, Nappi C. Effects of ral- oxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril 2001;76:38-43.
41. Lethaby A, Vollenhoven B. Fibroids (uterine myomatosis, leiomyomas).
Clin Evid 2005:(14):2264-82.
42. Stewart EA, Gedroyc WM, Tempany CM, Quade BJ, Inbar Y, Ehrenstein T, et al. Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol 2003;189:48-54.
PATRICIA EVANS, MD,
Georgetown University-Providence Hospital Family Practice Residency Program, Colmar Manor, Maryland
SUSAN BRUNSELL, MD,
National Naval Medical Center, Bethesda, Maryland
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