- Email: [email protected]
Uterine artery embolization for symptomatic fibroids in postmenopausal women
Clinical Imaging xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Uterine artery embolization for symptomatic fibroids in postmenopausal women Shin Jae Lee, Man Deuk Kim ⁎, Gyoung Min Kim, Jong Yoon Won, Sung Il Park, Do Yun Lee Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
a r t i c l e
i n f o
Article history: Received 6 April 2015 Received in revised form 12 August 2015 Accepted 13 August 2015 Available online xxxx Keywords: Uterine artery embolization Menopause Uterine fibroid Magnetic resonance imaging
a b s t r a c t Purpose: The aim of the current study was to evaluate the efficacy of uterine artery embolization (UAE) for symptomatic fibroids in postmenopausal women. Materials and methods: Among 900 cases who underwent UAE between 2007 and 2013, a total of 9 postmenopausal women with symptomatic fibroids (n=6) and fibroid with adenomyosis (n=3) were included in this retrospective study. Ages ranged from 49 to 55 years (median of 52). The embolic agent was nonspherical polyvinyl alcohol particles. We evaluated 18 uterine arteries in nine patients and compared the size of the uterine artery relative to inferior mesenteric artery (IMA) in preprocedural magnetic resonance (MR) angiography. Magnetic resonance imaging (MRI) was performed before and 3 months after UAE. Predominant fibroid and uterine volumes were calculated from MR images. Results: Urinary frequency was the most common symptom, observed in seven patients (77.8%). Of two patients (22.2%) with vaginal bleeding from submucosal myomas, one patient had been on hormone replacement therapy (HRT). One patient underwent UAE due to growing leiomyoma after HRT. All of the 18 uterine arteries were bigger than the corresponding IMAs in MR angiography. Contrast-enhanced MRI revealed complete necrosis of the predominant fibroid in all patients. Eight (88.9%) of the nine participants demonstrated resolution of symptoms. The mean predominant fibroid and uterine volume reduction rates were 39.7% and 36.9%, respectively. Conclusions: In postmenopausal women, UAE was effective to treat symptomatic fibroids, and it could be considered as an alternative treatment to hysterectomy. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Uterine fibroids, the most common solid tumors of the female genital tract, develop in 20–40% of women [1,2]. Even though uterine artery embolization (UAE) is rapidly gaining acceptance as an effective alternative to hysterectomy and myomectomy [3–6], UAE is generally not recommended for the treatment of fibroids in postmenopausal women because regression of the uterine fibroid is expected. There are, however, some postmenopausal women who have continuing symptoms or, specifically, who develop symptoms while taking hormone replacement therapy (HRT) [7–9]. Therefore, reaching menopause can no longer be seen as the end of fibroid development in some patients. Additional factors need to be considered, e.g., postmenopausal women have different clinical settings than premenopausal women. The size of the uterine artery (UA) may be a concern in performing UAE, as uterine volume is significantly decreased after menopause [10]. There have been few reports of effectiveness of UAE for management of symptomatic fibroids in postmenopausal women [11,12]. The purpose of the current study is to evaluate the efficacy of UAE for ⁎ Corresponding author. Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea, 120-752. Tel.: + 82-2-2228-2355 (office); fax: + 82-2-393-3035. E-mail address: [email protected] (M.D. Kim).
symptomatic fibroids or adenomyosis in postmenopausal women and to describe the clinical characteristics. 2. Materials and methods The institutional review board of our institution approved this retrospective study. 2.1. Participants in the study A total of 900 cases underwent UAE for symptomatic fibroid or adenomyosis between 2007 and 2013 in our institute. Of these, a total of 9 postmenopausal women who met the Stages of Reproductive Aging Workshop criteria for menopause, defined as 12 months of amenorrhea after the final menstrual period, were enrolled in the present study [13]. Patient demographics are summarized in Table 1. Among nine patients, fibroids (n=6) and fibroids with adenomyosis (n=3) were diagnosed based on magnetic resonance imaging (MRI). Patients’ ages ranged from 49 to 55 years (median of 52). Duration of menopause before procedure ranged 1–7 years (median 4 years). Mean follow-up period was 11 months (range of 6–18 months). The mean diameter of predominant fibroids was 6.21±1.8 cm. Seven women presented with bulk-related fibroid symptoms, and two patients presented with vaginal bleeding. All patients were primarily cared for by
http://dx.doi.org/10.1016/j.clinimag.2015.08.010 0899-7071/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
2
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
and B were defined as minor complications, and grades C through F were defined as major complications.
Table 1 Patient demographics (n=9) Age range (years) Mean follow-up period (months) Median duration of menopause before procedure (years) HRT Symptoms Bulk-related symptoms Urinary frequency Pelvic heaviness Palpable mass Bleeding MRI Fibroids Fibroid and adenomyosis Adenomyosis Mean diameter of the predominant fibroid (cm)
49–55 (median, 52) 4 (3–9) 4 (1–7) 2 7 6 4 2 2 6 1 2 6.21±1.84
an interventional radiologist, who also conducted the clinical follow-up. Procedures were performed at the tertiary university hospital. 2.2. MRI All patients underwent preoperative MRI using a 3-T Signa HD/HDx (GE Healthcare; Milwaukee, WI, USA). Follow-up MRI at 3 months after UAE was recommended as routine clinical care. For contrast-enhanced magnetic resonance (MR) angiography, the Time Resolving of Contrast KineticS technique was used. A dose of 10 ml meglumine gadoterate (Dotarem; Guerbet, Villepinte, France) was administered at a flow rate of 2.5 ml/s, followed by 25 ml saline with the same injection parameters. Uterine volume was calculated by the volume equation for a prolate ellipse (length×width×height×0.5233) using measurements from the images [14]. 2.3. Angiographic procedures Unilateral right femoral artery access was used in all cases. A 5.0-F RHR catheter (Cook; Bloomington, IN, USA) was then placed in the internal iliac artery, and a Renegade microcatheter (Boston Scientific; Natick, MA, USA) was advanced into the UA. The embolic agent was nonspherical polyvinyl alcohol (PVA) particles (Contour, Boston Scientific; Natick, MA, USA) mixed with 60 ml of a 1:1 saline solution:contrast agent mixture. All patients underwent embolization initially with 355- to 500-μm PVA particles, followed by 500- to 700-μm PVA particles. Embolization was performed until complete cessation of blood flow was achieved in the ascending and transverse segment of the UA for 10 cardiac beats.
2.6. Statistical analysis Wilcoxon signed-rank test was used to compare effects of UAE on reduction of mean volumes of predominant fibroid and uterus. Differences were considered statistically significant when P was b.05. 3. Results The outcome of treatment by UAE in postmenopausal patients is summarized in Table 2. Seven patients had pressure symptoms including urinary frequency, pelvic heaviness, or palpable mass (Fig. 1). Two patients were treated by HRT; one became menopausal 3 years previously, experienced intermittent vaginal bleeding after 5 months of HRT, and presented submucosal myomas. The second patient entered menopause 7 years previously; she had been treated by HRT for 5 years, but recent growth of a myoma had led to urinary symptoms. Eight (88.9%) of nine patients demonstrated resolution of symptoms, and one patient demonstrated about 20% reduction in volume of predominant fibroid with little improvement in urinary symptoms, even if fibroids were completely infarcted at the 3-month follow-up MRI. The volume reduction rate of the uterus and the predominant fibroids after UAE were 39.7% and 37.0%, respectively. All of the 18 UAs were bigger than the corresponding IMAs in MR angiography. Catheterization of UAs was successful in all cases. One patient had minor (grade A) complications, and she experienced spontaneous vaginal passage of a submucosal fibroid. 4. Discussion Uterine fibroids are dependent upon the sexual steroid hormone (estrogen and progesterone); thus, they are expected to be resolved in women postmenopausally, when there is much less estrogen and progesterone in the body [3,15]. Therefore, health care providers have counseled patients that leiomyomas are a self-limiting problem that will resolve when a woman completes the transition to menopause. However, several studies have reported that some postmenopausal women may have continuing symptoms of the fibroid or growth of the fibroid even in menopause. Additionally, postmenopausal women undergoing HRT have been observed to develop symptoms of bleeding or growth of the fibroid or even development of new fibroids [8,9,16,17]. Indeed, an onset of new leiomyomas was observed in 5% of previously leiomyoma-free postmenopausal women after HRT [16]. The effect of HRT on uterine fibroid size is controversial because few data are available.
2.4. Size of the UA We evaluated 18 UAs in the 9 study participants and compared the size of the UA relative to inferior mesenteric artery (IMA) in preprocedural MR angiography. The UAs were categorized into three groups: bigger than, same as, or smaller than IMA. 2.5. Clinical follow-up Follow-up examination consisted of an outpatient visit and MRI 3 months after UAE. We evaluated if the patient still had symptoms or experienced a resolution of symptoms after the procedure. We classified complications from UAE into six grades, as previously reported [9,10]: grade A=no therapy, no consequence; grade B=nominal therapy, observation, no consequence; grade C=required therapy, unanticipated minor hospitalization (b48 h); grade D=major therapy, unplanned increased level of care, unanticipated prolonged hospitalization (N48 h); grade E=permanent adverse sequelae; and grade F=death. Grades A
Table 2 Outcomes of UAE in postmenopausal women (n=9) Characteristics
Number
Size of the UA relative to that of IMA Bigger Same Smaller Complete necrosis of the fibroid or adenomyosis Resolution of symptoms Uterus (n=9) Mean volume before treatment (cm3) Mean volume after UAE (cm3) Volume reduction rate Predominant fibroid (n=7) Mean volume before treatment (cm3) Mean volume after UAE (cm3) Volume reduction rate Vaginal passage of the fibroid
18 18 0 0 9/9 (100%) 8/9 (88.9%) 389.79±166.35 246.53±113.87 39.74% (P=.008⁎) 125.17±78.94 74.49±54.24 36.98% (P=.018⁎) 1
⁎ Wilcoxon signed-rank test.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
3
in the third year of treatment. Although 13.5% (5/37) of postmenopausal women experienced a significant increase in fibroid size after HRT, this occurred only in the first 2 years. The mechanism is unclear. However, several factors have been proposed, including the presence of estrogen and progesterone receptors in leiomyoma cells and stimulation of leiomyoma growth by estrogen and progesterone [18]. In our study, seven of nine patients had bulk-related symptoms of the fibroid. Since most patients had bulk-related symptoms, one of the goals of the procedure was simply to reduce the volume of fibroid or uterus. Among the seven patients with bulk-related symptoms, six (85.7%) showed improvement in these symptoms. One patient (14.3%) showed no improvement, i.e., only 22% reduction in volume of predominant fibroid and 20% reduction in volume of uterus, even multiple fibroids were completely infarcted at the 3-month follow-up MRI. Intrauterine structural abnormalities, leiomyomas in particular, have been linked to abnormal uterine bleeding in postmenopausal women undergoing HRT. When compared with women who had normal uterine cavities, the presence of submucosal myomas was associated with a 2-fold increase in the risk of abnormal withdrawal bleeding in postmenopausal women [8]. Chrisman et al. reported efficacy of UAE in postmenopausal patients with fibroid-related bulk symptoms. However, they excluded patients with abnormal uterine bleeding and thus were not able to determine if UAE is effective for bleeding in postmenopausal women [12]. We included two patients with bleeding in our study, one of whom was treated with HRT; the other had never been exposed to HRT, but she had a submucosal myoma protruding into the cervix. Our results indicated that UAE was effective, even in postmenopausal women, under the condition that MRI confirms that the cause of bleeding is submucosal fibroid. When complete necrosis of submucosal fibroids following UAE was achieved, the patients were able to continue treatment by HRT. A concern we had was whether the size of the UA was appropriately large enough to undergo UAE. The reason for the concern was that the size of UAs in menopausal women may be relatively small as uterine volume is known to decrease after menopause [10]. However, our results showed that all women in menopause with fibroids had UAs of sufficient size for performing UAE. For the analysis, we compared the size of UA relative to IMA, which was a standard shown in a previous study to predict ovarian artery embolization [19]. One of limitations of the present study was the relatively small number of patients, and further studies are needed. According to the American College of Obstetricians and Gynecologists guideline, we should have performed biopsy for both patients with vaginal bleeding. However, they only underwent MRI, which revealed typical submucosal fibroid, because they refused additional exam including biopsy. In conclusion, UAE showed itself to be effective in the study, and it can be considered as an alternative treatment in postmenopausal women who have symptomatic fibroids that may or may not have been affected by HRT. References
Fig. 1. A 50-year-old woman with multiple uterine leiomyomas. (A) T2-weighted sagittal images demonstrate multiple leiomyomas. (B) MR angiography shows tortuous and dilated uterine arteries (white arrows) bigger than IMA (black arrow). (C) Follow-up MRI 3 months after embolization reveals no contrast enhancement of leiomyomas and 49% reduction of the uterine volume, from 747 cm3 to 381 cm3.
Yang et al. showed that there is a trend toward increasing fibroid growth in postmenopausal women undergoing HRT [17]. This effect of HRT on fibroid growth is evident in the first year and reaches a maximum during the second year and then it is reduced or even disappears
[1] Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol 2004;104:393–406. [2] Ryan GL, Syrop CH, Van Voorhis BJ. Role, epidemiology, and natural history of benign uterine mass lesions. Clin Obstet Gynecol 2005;48:312–24. [3] American College of O, Gynecologists. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol 2008;112:387–400. [4] Lohle PN, Voogt MJ, De Vries J, Smeets AJ, Vervest HA, Lampmann LE, et al. Longterm outcome of uterine artery embolization for symptomatic uterine leiomyomas. J Vasc Interv Radiol 2008;19:319–26. [5] Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol 2008;31:73–85. [6] Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 2007;356:360–70. [7] Stewart EA. Uterine fibroids. Lancet 2001;357:293–8. [8] Akkad AA, Habiba MA, Ismail N, Abrams K, al-Azzawi F. Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities. Obstet Gynecol 1995;86:330–4.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
4
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
[9] Loffer FD. Hysteroscopic myomectomy in postmenopausal women. J Minim Invasive Gynecol 2005;12:323–5. [10] Merz E, Miric-Tesanic D, Bahlmann F, Weber G, Wellek S. Sonographic size of uterus and ovaries in pre- and postmenopausal women. Ultrasound Obstet Gynecol 1996;7:38–42. [11] McLucas B, Adler L, Perrella R. Uterine fibroid embolization: nonsurgical treatment for symptomatic fibroids. J Am Coll Surg 2001;192:95–105. [12] Chrisman HB, Minocha J, Ryu RK, Vogelzang RL, Nikolaidis P, Omary RA. Uterine artery embolization: a treatment option for symptomatic fibroids in postmenopausal women. J Vasc Interv Radiol 2007;18:451–4. [13] Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril 2001;76:874–8. [14] Broekmans FJ, Heitbrink MA, Hompes PG, Schoute E, Falke T, Schoemaker J. Quantitative MRI of uterine leiomyomas during triptorelin treatment: reproducibility of volume as-
[15] [16] [17] [18] [19]
sessment and predictability of treatment response. Magn Reson Imaging 1996;14: 1127–35. Society of O, Gynaecologists of C. SOGC clinical practice guidelines. Uterine fibroid embolization (UFE). Number 150, October 2004. Int J Gynaecol Obstet 2005;89:305–18. Polatti F, Viazzo F, Colleoni R, Nappi RE. Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT. Maturitas 2000;37:27–32. Yang CH, Lee JN, Hsu SC, Kuo CH, Tsai EM. Effect of hormone replacement therapy on uterine fibroids in postmenopausal women–a 3-year study. Maturitas 2002;43:35–9. Maruo T, Ohara N, Wang J, Matsuo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum Reprod Update 2004;10:207–20. Lee MS, Kim MD, Lee M, Won JY, Park SI, Lee do Y, et al. Contrast-enhanced MR angiography of uterine arteries for the prediction of ovarian artery embolization in 349 patients. J Vasc Interv Radiol 2012;23:1174–9.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Uterine artery embolization for symptomatic fibroids in postmenopausal women Shin Jae Lee, Man Deuk Kim ⁎, Gyoung Min Kim, Jong Yoon Won, Sung Il Park, Do Yun Lee Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
a r t i c l e
i n f o
Article history: Received 6 April 2015 Received in revised form 12 August 2015 Accepted 13 August 2015 Available online xxxx Keywords: Uterine artery embolization Menopause Uterine fibroid Magnetic resonance imaging
a b s t r a c t Purpose: The aim of the current study was to evaluate the efficacy of uterine artery embolization (UAE) for symptomatic fibroids in postmenopausal women. Materials and methods: Among 900 cases who underwent UAE between 2007 and 2013, a total of 9 postmenopausal women with symptomatic fibroids (n=6) and fibroid with adenomyosis (n=3) were included in this retrospective study. Ages ranged from 49 to 55 years (median of 52). The embolic agent was nonspherical polyvinyl alcohol particles. We evaluated 18 uterine arteries in nine patients and compared the size of the uterine artery relative to inferior mesenteric artery (IMA) in preprocedural magnetic resonance (MR) angiography. Magnetic resonance imaging (MRI) was performed before and 3 months after UAE. Predominant fibroid and uterine volumes were calculated from MR images. Results: Urinary frequency was the most common symptom, observed in seven patients (77.8%). Of two patients (22.2%) with vaginal bleeding from submucosal myomas, one patient had been on hormone replacement therapy (HRT). One patient underwent UAE due to growing leiomyoma after HRT. All of the 18 uterine arteries were bigger than the corresponding IMAs in MR angiography. Contrast-enhanced MRI revealed complete necrosis of the predominant fibroid in all patients. Eight (88.9%) of the nine participants demonstrated resolution of symptoms. The mean predominant fibroid and uterine volume reduction rates were 39.7% and 36.9%, respectively. Conclusions: In postmenopausal women, UAE was effective to treat symptomatic fibroids, and it could be considered as an alternative treatment to hysterectomy. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Uterine fibroids, the most common solid tumors of the female genital tract, develop in 20–40% of women [1,2]. Even though uterine artery embolization (UAE) is rapidly gaining acceptance as an effective alternative to hysterectomy and myomectomy [3–6], UAE is generally not recommended for the treatment of fibroids in postmenopausal women because regression of the uterine fibroid is expected. There are, however, some postmenopausal women who have continuing symptoms or, specifically, who develop symptoms while taking hormone replacement therapy (HRT) [7–9]. Therefore, reaching menopause can no longer be seen as the end of fibroid development in some patients. Additional factors need to be considered, e.g., postmenopausal women have different clinical settings than premenopausal women. The size of the uterine artery (UA) may be a concern in performing UAE, as uterine volume is significantly decreased after menopause [10]. There have been few reports of effectiveness of UAE for management of symptomatic fibroids in postmenopausal women [11,12]. The purpose of the current study is to evaluate the efficacy of UAE for ⁎ Corresponding author. Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea, 120-752. Tel.: + 82-2-2228-2355 (office); fax: + 82-2-393-3035. E-mail address: [email protected] (M.D. Kim).
symptomatic fibroids or adenomyosis in postmenopausal women and to describe the clinical characteristics. 2. Materials and methods The institutional review board of our institution approved this retrospective study. 2.1. Participants in the study A total of 900 cases underwent UAE for symptomatic fibroid or adenomyosis between 2007 and 2013 in our institute. Of these, a total of 9 postmenopausal women who met the Stages of Reproductive Aging Workshop criteria for menopause, defined as 12 months of amenorrhea after the final menstrual period, were enrolled in the present study [13]. Patient demographics are summarized in Table 1. Among nine patients, fibroids (n=6) and fibroids with adenomyosis (n=3) were diagnosed based on magnetic resonance imaging (MRI). Patients’ ages ranged from 49 to 55 years (median of 52). Duration of menopause before procedure ranged 1–7 years (median 4 years). Mean follow-up period was 11 months (range of 6–18 months). The mean diameter of predominant fibroids was 6.21±1.8 cm. Seven women presented with bulk-related fibroid symptoms, and two patients presented with vaginal bleeding. All patients were primarily cared for by
http://dx.doi.org/10.1016/j.clinimag.2015.08.010 0899-7071/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
2
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
and B were defined as minor complications, and grades C through F were defined as major complications.
Table 1 Patient demographics (n=9) Age range (years) Mean follow-up period (months) Median duration of menopause before procedure (years) HRT Symptoms Bulk-related symptoms Urinary frequency Pelvic heaviness Palpable mass Bleeding MRI Fibroids Fibroid and adenomyosis Adenomyosis Mean diameter of the predominant fibroid (cm)
49–55 (median, 52) 4 (3–9) 4 (1–7) 2 7 6 4 2 2 6 1 2 6.21±1.84
an interventional radiologist, who also conducted the clinical follow-up. Procedures were performed at the tertiary university hospital. 2.2. MRI All patients underwent preoperative MRI using a 3-T Signa HD/HDx (GE Healthcare; Milwaukee, WI, USA). Follow-up MRI at 3 months after UAE was recommended as routine clinical care. For contrast-enhanced magnetic resonance (MR) angiography, the Time Resolving of Contrast KineticS technique was used. A dose of 10 ml meglumine gadoterate (Dotarem; Guerbet, Villepinte, France) was administered at a flow rate of 2.5 ml/s, followed by 25 ml saline with the same injection parameters. Uterine volume was calculated by the volume equation for a prolate ellipse (length×width×height×0.5233) using measurements from the images [14]. 2.3. Angiographic procedures Unilateral right femoral artery access was used in all cases. A 5.0-F RHR catheter (Cook; Bloomington, IN, USA) was then placed in the internal iliac artery, and a Renegade microcatheter (Boston Scientific; Natick, MA, USA) was advanced into the UA. The embolic agent was nonspherical polyvinyl alcohol (PVA) particles (Contour, Boston Scientific; Natick, MA, USA) mixed with 60 ml of a 1:1 saline solution:contrast agent mixture. All patients underwent embolization initially with 355- to 500-μm PVA particles, followed by 500- to 700-μm PVA particles. Embolization was performed until complete cessation of blood flow was achieved in the ascending and transverse segment of the UA for 10 cardiac beats.
2.6. Statistical analysis Wilcoxon signed-rank test was used to compare effects of UAE on reduction of mean volumes of predominant fibroid and uterus. Differences were considered statistically significant when P was b.05. 3. Results The outcome of treatment by UAE in postmenopausal patients is summarized in Table 2. Seven patients had pressure symptoms including urinary frequency, pelvic heaviness, or palpable mass (Fig. 1). Two patients were treated by HRT; one became menopausal 3 years previously, experienced intermittent vaginal bleeding after 5 months of HRT, and presented submucosal myomas. The second patient entered menopause 7 years previously; she had been treated by HRT for 5 years, but recent growth of a myoma had led to urinary symptoms. Eight (88.9%) of nine patients demonstrated resolution of symptoms, and one patient demonstrated about 20% reduction in volume of predominant fibroid with little improvement in urinary symptoms, even if fibroids were completely infarcted at the 3-month follow-up MRI. The volume reduction rate of the uterus and the predominant fibroids after UAE were 39.7% and 37.0%, respectively. All of the 18 UAs were bigger than the corresponding IMAs in MR angiography. Catheterization of UAs was successful in all cases. One patient had minor (grade A) complications, and she experienced spontaneous vaginal passage of a submucosal fibroid. 4. Discussion Uterine fibroids are dependent upon the sexual steroid hormone (estrogen and progesterone); thus, they are expected to be resolved in women postmenopausally, when there is much less estrogen and progesterone in the body [3,15]. Therefore, health care providers have counseled patients that leiomyomas are a self-limiting problem that will resolve when a woman completes the transition to menopause. However, several studies have reported that some postmenopausal women may have continuing symptoms of the fibroid or growth of the fibroid even in menopause. Additionally, postmenopausal women undergoing HRT have been observed to develop symptoms of bleeding or growth of the fibroid or even development of new fibroids [8,9,16,17]. Indeed, an onset of new leiomyomas was observed in 5% of previously leiomyoma-free postmenopausal women after HRT [16]. The effect of HRT on uterine fibroid size is controversial because few data are available.
2.4. Size of the UA We evaluated 18 UAs in the 9 study participants and compared the size of the UA relative to inferior mesenteric artery (IMA) in preprocedural MR angiography. The UAs were categorized into three groups: bigger than, same as, or smaller than IMA. 2.5. Clinical follow-up Follow-up examination consisted of an outpatient visit and MRI 3 months after UAE. We evaluated if the patient still had symptoms or experienced a resolution of symptoms after the procedure. We classified complications from UAE into six grades, as previously reported [9,10]: grade A=no therapy, no consequence; grade B=nominal therapy, observation, no consequence; grade C=required therapy, unanticipated minor hospitalization (b48 h); grade D=major therapy, unplanned increased level of care, unanticipated prolonged hospitalization (N48 h); grade E=permanent adverse sequelae; and grade F=death. Grades A
Table 2 Outcomes of UAE in postmenopausal women (n=9) Characteristics
Number
Size of the UA relative to that of IMA Bigger Same Smaller Complete necrosis of the fibroid or adenomyosis Resolution of symptoms Uterus (n=9) Mean volume before treatment (cm3) Mean volume after UAE (cm3) Volume reduction rate Predominant fibroid (n=7) Mean volume before treatment (cm3) Mean volume after UAE (cm3) Volume reduction rate Vaginal passage of the fibroid
18 18 0 0 9/9 (100%) 8/9 (88.9%) 389.79±166.35 246.53±113.87 39.74% (P=.008⁎) 125.17±78.94 74.49±54.24 36.98% (P=.018⁎) 1
⁎ Wilcoxon signed-rank test.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
3
in the third year of treatment. Although 13.5% (5/37) of postmenopausal women experienced a significant increase in fibroid size after HRT, this occurred only in the first 2 years. The mechanism is unclear. However, several factors have been proposed, including the presence of estrogen and progesterone receptors in leiomyoma cells and stimulation of leiomyoma growth by estrogen and progesterone [18]. In our study, seven of nine patients had bulk-related symptoms of the fibroid. Since most patients had bulk-related symptoms, one of the goals of the procedure was simply to reduce the volume of fibroid or uterus. Among the seven patients with bulk-related symptoms, six (85.7%) showed improvement in these symptoms. One patient (14.3%) showed no improvement, i.e., only 22% reduction in volume of predominant fibroid and 20% reduction in volume of uterus, even multiple fibroids were completely infarcted at the 3-month follow-up MRI. Intrauterine structural abnormalities, leiomyomas in particular, have been linked to abnormal uterine bleeding in postmenopausal women undergoing HRT. When compared with women who had normal uterine cavities, the presence of submucosal myomas was associated with a 2-fold increase in the risk of abnormal withdrawal bleeding in postmenopausal women [8]. Chrisman et al. reported efficacy of UAE in postmenopausal patients with fibroid-related bulk symptoms. However, they excluded patients with abnormal uterine bleeding and thus were not able to determine if UAE is effective for bleeding in postmenopausal women [12]. We included two patients with bleeding in our study, one of whom was treated with HRT; the other had never been exposed to HRT, but she had a submucosal myoma protruding into the cervix. Our results indicated that UAE was effective, even in postmenopausal women, under the condition that MRI confirms that the cause of bleeding is submucosal fibroid. When complete necrosis of submucosal fibroids following UAE was achieved, the patients were able to continue treatment by HRT. A concern we had was whether the size of the UA was appropriately large enough to undergo UAE. The reason for the concern was that the size of UAs in menopausal women may be relatively small as uterine volume is known to decrease after menopause [10]. However, our results showed that all women in menopause with fibroids had UAs of sufficient size for performing UAE. For the analysis, we compared the size of UA relative to IMA, which was a standard shown in a previous study to predict ovarian artery embolization [19]. One of limitations of the present study was the relatively small number of patients, and further studies are needed. According to the American College of Obstetricians and Gynecologists guideline, we should have performed biopsy for both patients with vaginal bleeding. However, they only underwent MRI, which revealed typical submucosal fibroid, because they refused additional exam including biopsy. In conclusion, UAE showed itself to be effective in the study, and it can be considered as an alternative treatment in postmenopausal women who have symptomatic fibroids that may or may not have been affected by HRT. References
Fig. 1. A 50-year-old woman with multiple uterine leiomyomas. (A) T2-weighted sagittal images demonstrate multiple leiomyomas. (B) MR angiography shows tortuous and dilated uterine arteries (white arrows) bigger than IMA (black arrow). (C) Follow-up MRI 3 months after embolization reveals no contrast enhancement of leiomyomas and 49% reduction of the uterine volume, from 747 cm3 to 381 cm3.
Yang et al. showed that there is a trend toward increasing fibroid growth in postmenopausal women undergoing HRT [17]. This effect of HRT on fibroid growth is evident in the first year and reaches a maximum during the second year and then it is reduced or even disappears
[1] Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol 2004;104:393–406. [2] Ryan GL, Syrop CH, Van Voorhis BJ. Role, epidemiology, and natural history of benign uterine mass lesions. Clin Obstet Gynecol 2005;48:312–24. [3] American College of O, Gynecologists. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol 2008;112:387–400. [4] Lohle PN, Voogt MJ, De Vries J, Smeets AJ, Vervest HA, Lampmann LE, et al. Longterm outcome of uterine artery embolization for symptomatic uterine leiomyomas. J Vasc Interv Radiol 2008;19:319–26. [5] Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol 2008;31:73–85. [6] Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 2007;356:360–70. [7] Stewart EA. Uterine fibroids. Lancet 2001;357:293–8. [8] Akkad AA, Habiba MA, Ismail N, Abrams K, al-Azzawi F. Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities. Obstet Gynecol 1995;86:330–4.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010
4
S.J. Lee et al. / Clinical Imaging xxx (2015) xxx–xxx
[9] Loffer FD. Hysteroscopic myomectomy in postmenopausal women. J Minim Invasive Gynecol 2005;12:323–5. [10] Merz E, Miric-Tesanic D, Bahlmann F, Weber G, Wellek S. Sonographic size of uterus and ovaries in pre- and postmenopausal women. Ultrasound Obstet Gynecol 1996;7:38–42. [11] McLucas B, Adler L, Perrella R. Uterine fibroid embolization: nonsurgical treatment for symptomatic fibroids. J Am Coll Surg 2001;192:95–105. [12] Chrisman HB, Minocha J, Ryu RK, Vogelzang RL, Nikolaidis P, Omary RA. Uterine artery embolization: a treatment option for symptomatic fibroids in postmenopausal women. J Vasc Interv Radiol 2007;18:451–4. [13] Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril 2001;76:874–8. [14] Broekmans FJ, Heitbrink MA, Hompes PG, Schoute E, Falke T, Schoemaker J. Quantitative MRI of uterine leiomyomas during triptorelin treatment: reproducibility of volume as-
[15] [16] [17] [18] [19]
sessment and predictability of treatment response. Magn Reson Imaging 1996;14: 1127–35. Society of O, Gynaecologists of C. SOGC clinical practice guidelines. Uterine fibroid embolization (UFE). Number 150, October 2004. Int J Gynaecol Obstet 2005;89:305–18. Polatti F, Viazzo F, Colleoni R, Nappi RE. Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT. Maturitas 2000;37:27–32. Yang CH, Lee JN, Hsu SC, Kuo CH, Tsai EM. Effect of hormone replacement therapy on uterine fibroids in postmenopausal women–a 3-year study. Maturitas 2002;43:35–9. Maruo T, Ohara N, Wang J, Matsuo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum Reprod Update 2004;10:207–20. Lee MS, Kim MD, Lee M, Won JY, Park SI, Lee do Y, et al. Contrast-enhanced MR angiography of uterine arteries for the prediction of ovarian artery embolization in 349 patients. J Vasc Interv Radiol 2012;23:1174–9.
Please cite this article as: Lee SJ, et al, Uterine artery embolization for symptomatic fibroids in postmenopausal women, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.08.010