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Uterine Fibroid

Uterine Leiomyoma

Uterine fibroids are common benign tumors of myometrial origin. Symptomatic fibroids cause abnormal uterine bleeding.


Presentation

One of the main complaints of women with symptomatic fibroids is abnormal uterine bleeding, which is characterized by heavy blood loss. Also, these patients may experience acute or chronic pelvic pressure as the tumors enlarge, degenerate or twist. Furthermore, symptoms such as urinary frequency and urgency, and constipation may be observed. These are attributed to compression of bladder and intestines, respectively. In fact, large fibroids can reflect in abdominal fullness distorting the abdomen. Very large leiomyomata can project an outward appearance resembling that of pregnancy [18]. 

The size, number, and location of fibroid(s) contribute to the likelihood of a symptomatic clinical picture. That being said, many are actually small and symptomatic. Also, they can shrink or enlarge.

Anemia
  • Past Medical History: B.C. admitted she has not seen a physician in approximately 8 years, however, she did recall being previously diagnosed with anemia. She does not remember being given a reason for anemia.[de.slideshare.net]
  • Tips for preventing anemia Anemia occurs when your body cannot produce blood as fast as it is being lost. As a result, you have fewer red blood cells in the blood. A test called a complete blood count (CBC) can tell you whether you have anemia.[healthlinkbc.ca]
Intravenous Drugs
  • Uterine pyoma as a complication of pregnancy in an intravenous drug user. South Med J 1996;89:892-5. 12. Gupta A, Gupta GM, Manaktala U. Ascending infection causing pyomyoma in a young woman. Egypt J Radiol Nucl Med 2014;45:1017-20. 13.[archintsurg.org]
  • Prahlow JA, Cappellari JO, Washburn SA (1996) Uterine pyomyoma as a complication of pregnancy in an intravenous drug user. South Med J 89(9): 892-895.[medcraveonline.com]
Increased Susceptibility to Infections
Orthopnea
  • Results: A 53 year old Malay woman with a background of schizophrenia presented with a large abdominal mass complicated by orthopnea and exertional dyspnea.[morressier.com]
Constipation
  • The most common presenting symptoms of leiomyomas are menorrhagia, dysmenorrhea, subfertility, pelvic pain, dyspareunia and pressure symptoms from the bowel and bladder, e.g. constipation, frequency, chronic urinary tract infections [ 3, 4 ].[clinmedjournals.org]
  • A 48-year-old nulliparous presented with a two-day history of abdominal pain, bloating, constipation, and menorrhagia. Within eight hours, her distress level increased.[ncbi.nlm.nih.gov]
  • Clinical symptoms of the large myoma are: pain, distension, constipation, occurring more often menstrual bleeding and micturation and reproduction affect 3.[czytelniamedyczna.pl]
  • Case Report It is about a 42-year-old mother of two living children, who came for a consultation of chronic abdominal pains and constipation. Her last delivery occurred 10 years ago.[gynecology-obstetrics.imedpub.com]
  • This can include questions about urinary issues, constipation, fertility issues, abdominal pressure or pain, painful menses, and pain during intercourse.[medbroadcast.com]
Abdominal Pain
  • The patient reported abdominal pain and sudden onset of 'miscarriage-like' HMB with clots 2 days ago. On speculum examination there was a smooth round-shaped mass lying over the external cervical os.[ncbi.nlm.nih.gov]
  • Case Report The patient was a 33-year-old nulligravida who presented to our clinic with a 3 day history of severe lower abdominal pain with an abdominal mass, nausea, vomiting, fever, and history of a huge myoma.[archintsurg.org]
Pelvic Mass
  • mass Abdominal myomectomy 10 Karim et al. [ 19 ] 16 2010 Pelvic mass; increased abdominal volume Abdominal myomectomy 25 Khorrami et al. [ 7 ] 17 2011 AUB; refractory anemia Hysteroscopic myomectomy 3 Taskin et al. [ 5 ] 16 2011 Pelvic mass; mass protruding[doi.org]
  • Leiomyomas must be remembered as an important differential diagnosis of pelvic mass in adolescents.[ncbi.nlm.nih.gov]
  • MRI has shown to be extremely useful in the diagnosis of complex pelvic masses.[scielo.br]
Abdominal Mass
  • We discovered a median abdominal mass covered by intestinal and omental adhesions ( Figure 1 ). Figure 1: Abdominal mass with adhesions.[gynecology-obstetrics.imedpub.com]
  • Abstract A 35-year-old woman presented with an abdominal mass found incidentally on an ultrasound scan. On examination, the uterus was mobile and 14 weeks in size.[ncbi.nlm.nih.gov]
  • In 1981, Augensen et al. described the case of a 15 year old patient that presented with abnormal uterine bleeding, urinary retention and an abdominal mass [ 3 ].[doi.org]
  • Large abdominal mass due to a giant uterine leiomyoma. Mayo Clin Proc. 2006;81(11):1415. Panayotidis C, Salleh S, Martin J E, Hirsh P, Wynn J. Giant uterine leiomyomas: dilemmas in surgical management. Gynaecol Surg. 2006;3(1):37-40.[ijrcog.org]
Lower Abdominal Pain
  • We present a case of a 37-year-old white nullipara who presented in the emergency room with acute, lower-abdominal pain which reportedly started after riding over a bump on a motorcycle.[ncbi.nlm.nih.gov]
  • A 35-year-old woman presented with a history of lower abdominal pain and distension for a period of around 6 months. On abdominal examination, vague right abdominal fullness was felt. Per vaginal examination revealed an adnexal mass.[ijri.org]
  • abdominal pain; increase in size around the waist and change in abdominal contour...[emedicinehealth.com]
  • A 52-year-old postmenopausal multiparous woman (gravida 8, para 5, aborta 3) presented with a history of lower abdominal pain and distension for about 10 months.[clinmedjournals.org]
Macula
  • Eyes: PERRLA(-‐)APD, EOM’s: Full (-‐)Diplopia, CVF: Full 360degs OU, ONH: 0.2/0.2 (-‐)Disc Edema OU, Retina: (-‐)Heme/Exudate to mid-‐ periphery OU, Macula: Healthy OU, Ant Segment: WNL/Anicteric OU, (-‐)Subconjunctival or Petechial Hemes, VA: 20/20 OU[de.slideshare.net]
Low Back Pain
  • The patient was a 44-year-old woman who presented with low back pain and left leg pain. Examination suggested lumbar radiculopathy but lumbar magnetic resonance imaging was negative with the exception of a large mass in the pelvis.[ncbi.nlm.nih.gov]
  • A feeling of fullness in the lower abdomen Frequent urination resulting from a fibroid that compresses the bladder Pain during sexual intercourse Low back pain Constipation Chronic vaginal discharge Inability to urinate Severe menstrual cramps Infertility[my.clevelandclinic.org]
  • Pelvic pain and pressure, such as: Pain in the abdomen, pelvis, or low back. Pain during sexual intercourse. Bloating and feelings of abdominal pressure. Urinary problems, such as: Frequency urination. Leakage of urine (urinary incontinence).[palmvascular.com]
Pelvic Pain
  • Although most fibroids are asymptomatic, about 25% are associated with symptoms that can have a significant impact on patient's quality of life, including prolonged or excessive menstrual bleeding, pelvic pain or bulkiness, dyspareunia, increased urinary[ncbi.nlm.nih.gov]
  • When fibroids increase in size and number, they can cause problems for women, such as heavy bleeding and pelvic pain. Uterine fibroids are benign tumors that affect nearly 30% of women ages 30-45.[alatehealth.com]
Vaginal Bleeding
  • Recurrence of heavy vaginal bleeding and massive necrosis of a uterine leiomyosarcoma are reported in a 41-year-old female who was being treated with GnRH-a for a presumed uterine fibroid.[ncbi.nlm.nih.gov]
  • Menstrual bleeding soaking through more than 3 pads per hour Severe or prolonged pelvic or abdominal pain Dizziness, lightheadedness, shortness of breath, or chest pain associated with vaginal bleeding Vaginal bleeding associated with pregnancy or possible[emedicinehealth.com]
  • In both these cases, the patients had clinical symptoms (abnormal vaginal bleeding) and radiological abnormalities suggestive of a uterine malignancy.[wjgnet.com]
Enlarged Uterus
  • Pelvic magnetic resonance imaging revealed a markedly enlarged uterus with multiple fibroids. The patient had laparoscopic hysterectomy with postoperative resolution of patient's symptoms and improved uroflow studies.[ncbi.nlm.nih.gov]
  • Diffuse leiomyomatosis appears as an enlarged uterus with abnormal echogenicity.[emedicine.com]
  • Two of the most common uterine symptoms of premenopause syndrome are an enlarged uterus and uterine fibroids.[womenlivingnaturally.com]
Dysmenorrhea
  • UFs are usually asymptomatic but at times can produce symptoms such as excessive menstrual bleeding, intermenstrual bleeding, dysmenorrhea, pelvic pain, pelvic pressure, bloating, dyspareunia, urinary and bowel disturbance, subfertility, and pregnancy-related[ncbi.nlm.nih.gov]
  • She presented with one year history of increased menstrual blood loss and secondary dysmenorrhea and six months history of a mass protruding down the vagina, irregular bleeding per vagina and offensive vaginal discharge.[smjonline.org]
  • Hypermenorrhea Multiple 37 No II-3 M195V 28 Hypermenorrhea 1 28 Thyroid cyst II-5 M195V 30 No II-7 No 49 No 1 61 Endometrial adenocarcinoma, adrenal adenoma III-1 M195V 27 Hypermenorrhea Multiple 29 Polycystic ovaries III-2 27 No 2 No III-5 M195V 23 Dysmenorrhea[doi.org]
  • Primary dysmenorrhea occurs without an associated underlying condition, while secondary dysmenorrhea has a specific underlying cause, typically a condition that affects the uterus or other reproductive organs. [5] The most common cause of secondary dysmenorrhea[en.wikipedia.org]
  • Fibroids inside the uterus wall however may cause heavy bleeding (menorrhagia), painful periods ( dysmenorrhea ) as well as irregular or prolonged menstrual cycles ( oligomenorrhea ).[womens-health-advice.com]
Dyspareunia
  • Although most fibroids are asymptomatic, about 25% are associated with symptoms that can have a significant impact on patient's quality of life, including prolonged or excessive menstrual bleeding, pelvic pain or bulkiness, dyspareunia, increased urinary[ncbi.nlm.nih.gov]
  • Additionally, women with uterine fibroids may suffer more often from dyspareunia and non-cyclic pelvic pain [ 27 ].[dx.doi.org]
  • The most common presenting symptoms of leiomyomas are menorrhagia, dysmenorrhea, subfertility, pelvic pain, dyspareunia and pressure symptoms from the bowel and bladder, e.g. constipation, frequency, chronic urinary tract infections [ 3, 4 ].[clinmedjournals.org]
  • There was no history of heavy menstrual bleeding, dysmenorrhea, or dyspareunia and no urinary symptoms. The mass appeared after her last pregnancy 15 years prior to presentation.[tjogonline.com]

Workup

Any woman with increased uterine bleeding warrants a comprehensive history including detailed information about menstrual and bleeding pattern and quantity. Also, they should be assessed for anemia through history and exam findings. In addition, a bimanual exam is very important. A clinician may notice an enlarged uterus and/or palpate actual fibroids (if located on the outer uterus).

In patients with heavy bleeding (acute or chronic) and/or symptomatic anemia, obtain complete blood count to assess hemoglobin and hematocrit. Other laboratory work may be indicated as well.

Imaging is a key component of the workup. Vaginal and abdominal ultrasonography is the imaging of choice. Other modalities include sonohysterography, hysteroscopy, and MRI. Sonohysterography and hysteroscopy may be useful to visualize submucosal fibroids but they are invasive [19]. MRI can be beneficial in surgery planning since it provides precise mapping although images of the fibroids may be limited since they share attenuation features as the myometrium. Calcifications are also usually seen on CT.

Ovarian Mass
  • This was observed in the second case where a differential of an accidented ovarian mass was entertained, while previous reports observed that fibroid red degeneration could be mistaken for ovarian mass. [14] For all patients managed in this series, myomectomy[tjogonline.com]
  • The subserosal fibroid can develop a stalk or stem-like base, making it difficult to distinguish from an ovarian mass. These are called pedunculated. The correct diagnosis can be made with either an ultrasound or magnetic resonance (MR) exam.[thegvi.com]
  • They need to be differentiated from other abnormalities (eg, ovarian masses). When imaging is indicated, ultrasonography (usually transvaginal) or saline infusion sonography (sonohysterography) is typically done.[merckmanuals.com]
  • A giant uterine leiomyoma simulating an ovarian mass in a 16-year-old girl: a case report and review of the literature. Eur J Gynaecol Oncol. 2006; 27 (3):294–296. [ PubMed ] [ Google Scholar ] 6.[ncbi.nlm.nih.gov]

Treatment

There are numerous treatment options for women with symptomatic fibroids. These include both surgical and nonsurgical interventions. When planning management with the patient, a clinician should consider the severity of symptoms, whether the patient wants to seek treatment and which intervention she prefers. The clinician should determine whether the patient has completed childbearing, if she is seeking fibroid treatment for fertility purposes, whether she has had previous surgeries, and if the patient has any contraindications to surgery or medical therapy. Many patients will have comorbidities such as hypertension, diabetes mellitus or obesity which can influence the decision making. All of these factors will help clarify the best treatment plan for the patient.

Surgical interventions

Hysterectomy is typically the treatment for women who do not want to preserve childbearing. If the uterus is removed, the patient avoids recurrent fibroids [20]. This can be performed laparoscopically or abdominally. The former is minimally invasive.

There are uterine sparing interventions that are available for women whether they seek to protect their fertility or not [21]. Black women are found to favor this option [22]. Myomectomy involves resection of fibroids, which can debulk the uterus and improve bleeding. However, there is a risk of recurrence. In fact, 10 to 25% will needed additional fibroid surgery. Endometrial ablation an intra-uterine procedure that removes the uterus lining. While this does not remove or minimize the fibroid(s), it may reduce or stop bleeding altogether. Women who undergo ablation should not have future pregnancies.

Drug treatments

There are various drug options available for those who are poor surgical candidates or opt for medications. Nonsteroidal anti-inflammatory drugs (NSAIDs) are beneficial for alleviating cramps and heavy flow. In addition, gonadotropin-releasing hormone analogue (GnRH) therapy may be an alternative to surgery since it mimics a menopausal state and helps shrink the fibroids. Treat underlying anemia with iron supplements and monitor for improvement. 

Prognosis

Malignancy

Uterine leiomyomas are typically benign. They rarely undergo malignant transformation and develop into sarcomas. In fact, the exact number that do is not clear since fibroids are very common unlike sarcomas, which may emerge de novo. Estimated incidence is as low as 0.2%.

Fertility

While most women with fibroids do not experience fertility issues, the location of these tumors can affect reproduction. For example, fibroids in the uterine cavity can compromise the ability to conceive. In fact, they may cause miscarriages. Surgical resection of this type can result in successful fertility. Leiomyomata on the outer wall of the uterus mildly reduce fertility. However, surgical removal does not necessarily improve fertility. Fibroids do not usually result in pregnancy complications, but large fibroids greater than 5cm may.  

Etiology

While the cause of fibroids has not been fully elucidated, it seems that they arise from a unicellular origin [1]. Furthermore, monoclonal proliferation of smooth muscle cells is seen histologically. The composition of these benign tumors are smooth muscle and fibrous tissue.

Some women may have predisposing genes [2] [3]. There may be a genetic component in tumor development as mutations in uterine muscle have been suggested [4]. But there is a multifactorial component promoting the growth of leiomyomata.

Reproductive and environmental factors are linked to the risk of developing fibroids. For example, higher parity [5] [6] and the use of progestin only injectable contraceptives are factors associated with a reduced risk [5] [6] [7]. Conversely, early menarche and the initiation of oral contraceptives prior to 16 years of age are correlated with a greater risk of forming fibroids [5] [6] [7].

Dietary risk factors also exist. A decreased risk is found in patients who incorporate a diet rich with fruits, vegetables, and low fat dairy [8]. A high body mass index (BMI) elevates risk [9] and has been observed in patient with fibroids.

Epidemiology

Fibroids are the most common tumors in the female reproductive tract. Approximately 70% of women will have uterine fibroid(s) by the age of 45 years. 

Race

Increased incidence of fibroids in black women has been demonstrated [10]. Furthermore, black women exhibit bigger and more symptomatic fibroids than white women [11] [12] [13] [14] [15]. 50% of black women and 25% of white women experience symptoms.

Risk factors

Women with hypertension [16] and high BMI are observed to be at greater risk of fibroid formation.

Protective factors

Parturition and cigarette smoking are associated with decreased risk.

Sex distribution
Age distribution

Pathophysiology

These benign tumors emerge during reproductive age as evidenced by a complex interplay between estrogen and progesterone on the influence of fibroids. They develop and grow during fertility years but regress during menopause. Comparison of estrogen and progesterone receptors on fibroid cells and uterine cells showed that cells of the former exhibit more hormone receptors, hence they have a capability to increase in size [17]. In addition to these two hormones, insulin like growth factor (IGF-1) [4] and growth hormone also contribute to the development of leiomyomata.

Fibroids are categorized according to their location in the uterus. In order of decreasing frequency, they are called: subserosal, intramural, and submucosal fibroids. Subserosal fibroids may be pedunculated. In addition, this type is found on extrauterine sites. Generally, any type can undergo changes such as degeneration, atrophy, hemorrhage, calcification, or fibrosis.

There are varying sizes that range from very small to extremely large. Sometimes, fibroids develop in other parts of the reproductive tract such as the broad ligaments, fallopian tubes, or even cervix.

Prevention

Dietary modifications may help reduce the risk of developing leiomyomata. One study showed that intake of pork and beef is associated with these tumors whereas vegetables provided protection [8]. Furthermore, food with a high glycemic index (GI) such as white rice, white breads, donuts and others elevate serum glucose level. This leads to the increase in IGF-1. Note from earlier discussion that this can stimulate fibroid growth.

One study showed that vitamin D plays a role in inhibiting growth, thus insufficient amounts of this vitamin may raise the risk of developing the benign tumors [23]. Another study explored the fibroid risk with intake of fruits, vegetables, and carotenoids. The results showed a lower risk in women with higher intake of fruit and retinol [8]. Furthermore, lower dairy consumption may be associated with higher risk [24]. 

Modifying diet by consuming vegetables, fruits, and dairy products can reduce the risk of fibroid formation but additional benefits include potential weight loss and improvement in hypertension, thus addressing other risk factors. 

Summary

Uterine leiomyomas (or uterine fibroids) are the most common tumors in the female genital tract. They are benign and rarely become malignant sarcomas. Fibroids are composed primarily of smooth muscle as well as fibrous tissue. In fact, they basically grow from the uterine muscle.

While genetic mutations have been associated with development of this benign tumor, the cause is likely multifactorial. There are established risk factors such as black race, obesity, hypertension, nulliparity, and family history.

Fibroids are under the influence of estrogen and progesterone and hence occur during reproductive years. While many leiomyomata are small and asymptomatic, an increase in size and number of the benign tumors tends to cause symptoms. The clinical presentation consists of abnormal uterine bleeding, pelvic pressure, urinary and/or abdominal symptoms.

There are surgical and drug therapies available to treat symptomatic women. The management is tailored for each patient since medical and personal factors play in role in the decision making.

Patient Information

Uterine fibroids, also called uterine leiomyomas, are benign tumors that arise from the muscle of the uterus. They usually do not become malignant. Most women will have these tumors as they are very common in women of reproductive age. In fact, they are found in about 70% of women by age of 45. There are risk factors that increase the possibility of developing fibroids such as obesity, black race, never had children, positive family history, and having high blood pressure.

Many fibroids are small and do not produce symptoms. Patients with large and/or many fibroids have a higher chance of having symptoms. The biggest complaints include heavy bleeding, increased urinary frequency and/or urgency, constipation, abdominal fullness, and pelvic pressure or pain.

Diagnosis is done through an ultrasound that is performed vaginally and abdominally. Also, your doctor may be able to feel the fibroid(s) and diagnose this during a pelvic exam

There are a number of ways to treat fibroids that cause symptoms. In women who have completed child bearing, they can opt for a hysterectomy, which is a surgery in which the uterus is removed. The surgery could be done with minimal invasiveness. Women who want to keep their uterus and/or preserve fertility can have other procedures such as a myomectomy, which is removal of the fibroid. 

For those are not good candidates for surgery or just do not want it altogether, there may be drug therapies that can help shrink the fibroids. The patient and her doctor will discuss all appropriate options and together decide what the best plan is. 

References

Article

  1. 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. Gynecologic and Obstetrical Investigation. 1995;40(3):204–8.
  2. Mäkinen N, Mehine M, Tolvanen J, et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011;334(6053):252-255.
  3. Eggert SL, Huyck KL, Somasundaram P, et al. Genome-wide linkage and association analyses implicate FASN in predisposition to uterine leiomyomata. American Journal of  Human Genetics. 2012;91(4):621-628.
  4. Vollenhoven BJ, Herington AC, Healy DL. Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium. J Clin Endocrinol Metab. 1993 May;76(5):1106-10. 
  5. Marshall LM, Spiegelman D, Goldman MB, et al. A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertility and Sterility. 1998;70(3):432-439.
  6. Wise LA, Palmer JR, Harlow BL, et al. Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in African-American women: a prospective study. American Journal of Epidemiology. 2004;159(2):113-123.
  7. Hodge JC, T Cuenco K, Huyck KL, et al. Uterine leiomyomata and decreased height: a common HMGA2 predisposition allele. Hum Genetics. 2009;125(3):257-263.
  8. Wise LA, Radin RG, Palmer JR, Kumanyika SK, Boggs DA, Rosenberg L. Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata. American Journal of Clinical Nutrition. 2011;94(6):1620-1631.
  9. Wise LA, Palmer JR, Spiegelman D, et al. Influence of body size and body fat distribution on risk of uterine leiomyomata in U.S. black women. Epidemiology. 2005;16(3):346-354.
  10. Wise LA, Palmer JR, Stewart EA, Rosenberg L. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women's Health Study. Obstetrics and Gynecology. 2005;105(3):563–8.
  11. Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uterine leiomyomas. Racial differences in severity, symptoms and age of diagnosis. Journal of Reproductive Medicine. 1996;41(7):483–90.
  12. Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. British Medical Journal (Clinical research ed). 1986;293(6543):359-362.
  13. Ligon AH, Morton CC. Leiomyomata: heritability and cytogenetic studies. Human Reproduction Update. 2001;7(1):8–14.
  14. 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. British Journal of Obstetrics and Gynaecology. 1999;106(8):857–60.
  15. Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M, Vudhika-mraksa N, Werawatakul Y. Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case-control study. British Journal of Obstetrics and Gynaecology. 1996;103(9):909–14.
  16. Boynton-Jarrett R, Rich-Edwards J, Malspeis S, Missmer SA, Wright R. A prospective study of hypertension and risk of uterine leiomyomata. American Journal of Epidemiology. 2005;161(7):628–38.
  17. Andersen J, Barbieri RL. Abnormal gene expression in uterine leiomyomas. Journal for the Society of Gynecologic Investigation. 1995;2(5):663-672.
  18. Uterine fibroids. Cedars-Sinai website. http://www.cedars-sinai.edu/Patients/Health-Conditions/Uterine-Fibroids.aspx.
  19. Griffin KW, Ellis MR, Wilder L, DeArmond L. Clinical inquiries. What is the appropriate diagnostic evaluation of fibroids? Journal of Family Practice. 2005;54(5):458,460,462.
  20. Marret H, Fritel X, Ouldamer L, et al. Therapeutic management of uterine fibroid tumors: updated French guidelines. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2012;165(2):156-164.
  21. American College of Obstetricians and Gynecologists. ACOG practice bulletin: alternatives to hysterectomy in the management of leiomyomas. Obstetrics and Gynecology. 2008; 112(2 part 1):387-400.
  22. Stewart EA, Nicholson WK, Bradley L, Borah BJ. The burden of uterine fibroids for African-American women: results of a national survey. Journal of Women's Health (Larchmt). 2013(10);22:807-816.
  23. Sharan C, Halder SK, Thota C, Jaleel T, Nair S, Al-Hendy A. Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. Fertililty and Sterility. 2011;95(1):247-253.
  24. Wise LA, Radin RG, Palmer JR, Kumanyika SK, Rosenberg L. A prospective study of dairy intake and risk of uterine leiomyomata. American Journal of Epidemiology. 2010;171(2):221-232.

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Last updated: 2019-06-28 12:19