Uterine leiomyoma

Estrogen- and progesterone-dependent noncancerous tumors of the uterus and are the most common type of benign tumor in women of reproductive age, affecting up to 70% of Caucasian women and up to 80% of African American women by age 50 years. 

Progestogens promote the growth of uterine fibroids.

Risk increases with nulliparity , early menarche, and in African-American women.

Pregnancy reduces the risk.

Obesity increases the risk presumably fro increases estrogen production in adipocytes.

Accounts for 40% of abdominal hysterectomies.

Accounts for approximately 160,000 hysterectomies per year in the U.S.

Are the most common indications for hysterectomy.

20%-50% produce symptoms that include menorrhagia, pelvic pain or pressure, infertility, recurrent pregnancy loss and impingement on adjacent organs that causes constipation, urinary frequency, or hydronephrosis.

Occur 2-3 times as often in in black females compared to white or Asian women.

Most common between ages 35 and 49 years.

Typically resolve after the menopause.

There are no known preventive strategies for the development of fibroids.

Typically presents with multiple tumors, with an estimated average of 6-7 lesions (Cramer SF, Patel A).

Classified based on their location: submucosal lesions are the least common, intramural fibroids grow within the uterine wall, and subserosal fibroids develop on the outer portion of the uterus.

Submucosal fibroids lie in the submucosal and near the endometrial cavity.

Submucosal fibroids are associated with heavy and prolonged menstrual periods and with an increased miscarriage rate.

Submucosal fibroids may be pedunculated and may prolapse into the cervix.

Growth of intrauterine fibroids can cause symptoms related to a mass affects with abdominal distension and urinary frequency.

Subserosal fibroids may be pedunculated and can grow into the abdomen or into the ligaments of the uterus and cause abdominal distension and bladder compression.

Most patients are asymptomatic and lesions are typically noted during routine clinical examination.

Most common symptom is is abnormal uterine bleeding.

Most common manifestations are menorrhagia and iron deficiency which may lead to chronic fatigue.

30% of women with leiomyomas develop menorrhagia.

Pelvic pain and pelvis pressure present in 30% of women with leiomyomas.

Pain may be cause by the outgrowing of the blood supply, and the development of necrosis.

Large fibroids may increase abdominal girth and may cause pressure on adjacent organs such as the bladder or bowel and cause urinary frequency, urinary urgency, and constipation.

Maybe associated with iron deficiency anemia secondary to menorrhagia..

Leiomyomas may be associated with infertility.

Occasionally associated with dysmenorrhea, dyspareunia or post coital bleeding.

Diagnosis is often delayed with 1/3 of patients, taking up to five years and some patients more than eight years.

Delays in diagnosis, adversely affects quality of life and fertility.

95% of people with symptomatic fibroids report, psychological sequelae, including depression, worry, anger, and body image distress.

Pelvic ultrasound is the first imaging modality use for diagnosis, and it can provide accurate information about uterine size, fibroid number, size, and location within uterus.

50-72% of persons who receive a diagnosis of uterine fibroids on the basis of ultrasound are not previously aware that they had fibroids.

Initial therapy for symptomatic leiomyomata typically is medical management with a variety of hormonal agents including progestins, oral contraceptives, and gonadotropin releasing hormone agonists.

The estimated prevalence of unexpected leiomyosarcoma at the time of surgical treatment for presumed fibroids ranges from less than one to 13 per 10,000 surgeries, and the risk increases with age and individuals who are Black.w22

Treatment options for symptomatic leiomyoma include hysterectomy, myomectomy, myolysis hysteroscopic resection, endometrial ablation,uterine fibroid embolization and MRI guided focused ultasound.

Focused ultrasound with use of MRI or ultrasoundguidance and radiofrequency ablation with the use of laparoscopic or transcervical ultrasound can reduce heavy menstrual bleeding and bulk related symptoms, however, these therapies require individual targeting of each fibroid.

Leiomyoma management includes expectant, medical and surgical procedure options.

Expectant management is appropriate for asymptomatic patients with normal laboratory findings, for those trying to conceive, or those who have symptoms, but are not willing to initiate therapy.

Medical treatments are divided into hormonal or non-hormonal.

Most medical treatments are addressing fibroid related bleeding, anemia and pain, but not the fibroids themselves.

Non-hormonal treatments include non-steroidal anti-inflammatory drugs, tranexamic acid and iron supplementation.

Hormonal treatments include oral contraceptives, progestins, progestin releasing uterine systems, and gonadotropin releasing hormone analogues which address heavy bleeding by causing endometrial thinning.

Contraceptive hormones to control heavy menstrual bleeding is the usual first step for the treatment of fibroid related, heavy menstrual bleeding, despite low quality evidence.

Elective uterine artery embolization indicated, provided there is no premalignant or malignant disorder, is symptomatic, postfertility patients with substantial anemia or pelvic pain who have failed to respond to medical therapy and who decline surgery or are poor surgical candidates.

Uterine artery embolization is used infrequently in women of reproductive age because of concern about potential adverse effects on fertility.

Endometrial ablation involves destruction of endometrial tissue, but does not impact the fibroids themselves.

Definitive treatment is often surgical and consists of hysterectomy or myomectomy in patients who wish to preserve the uterus.

Fewer than 0.1% of all leiomyomas undergo malignant transformation.

Intervention is guided by the patient’s age and desire to preserve fertility and avoid hysterectomy.

Contraceptives are the first line medical treatments, but the quality evidence for the use is low.

Gonadotropin releasing hormone agonists (GnRH) can be used as bridging for free surgical treatments and create an artificial menopausal state with production in uterus and fibroid volume, but cause hot flashes and may decrease bone mineral density.

Gonadotropin releasing hormone (GnRH) agonist leuprolide acetate stops bleeding in 85% of patients with anemia before myoma surgery.

Gonadotropin releasing hormone (GnRH) agonists are approved for short term, preventative therapy for fibroids and cause a menorrhea in nearly 90% of patients, and can reduce uterine volume by 30 to 60%; they are accompanied by high incidence of hypo gonadal symptoms, such as bone loss and hot flashes can cause a steroid flare with heavy bleeding when estrogen levels decrease rapidly.

GNRH agonists such as leuprolide are affective, however hypoestrogenic sequelae limit their duration of use or lead to additional hormonal therapy to mitigate side effects.

Progestin usage is often associated with breakthrough bleeding when used for uterine fibroids, and they also may promote their proliferation.

Levonorgestrel releasing intrauterine system can be used for patients with small fibroids, but irregular bleeding and expulsion of the device is common.

Ulipristal acetate randomly assigned to symptomatic women with fibroids with excessive uterine bleeding revealed effective control of bleeding and reduction in the size of fibroids (Donnez J et al).

Injectable depot formulations of gonadotropin-releasing hormone agonists can be prescribed for heavy menstrual bleeding associated with uterine fibroids, however they induce long lasting gonadal suppression resulting in adverse hypoestrogenic effects.

Elagolix, and oral gonadotropin releasing hormone antagonist results in rapid, reversible suppression of gonadotropins and ovarian sex hormones in women.

Elagolix Is effective in reducing heavy menstrual bleeding in women with uterine fibroids.

Oriahnn contains elagolix, , estradiol and norethindrone acetate for premenopausal bleeding heavy menstrual bleeding from uterine fibroids.

In a double-blind non-inferiority trial 307 patients with symptomatic bleeding fibroids randomly assigned to receive 3 months of daily therapy with early ulipristal or once monthly intramuscular ejections of leuprolide: both 5mg and 10 mg daily doses of ulipristal were not inferior to once monthly leuprolide in controlling uterine bleeding and were significantly less likely to cause hot flashes (Donnez J et al).

Surgical management includes myomectomy or hysterectomy.

Hysterectomy is the only definitive treatment for leiomyoma.

Myomectomy can be performed hysteroscopically, abdominally via laparotomy or by a minimal invasive surgical approach with laparoscopic robotic assistance.

Many women seek an effective alternative to hysterectomy: seeking pregnancy, maintenance of bodily integrity and faster recovery.

Large lleiomyoma can be removed by a minilaparotomy, vaginally by colpotomy, or by electric power morcellation to fragment the leiomyoma.

Morcellation has the potential to disseminatie cancer if the leiomyoma is associated with unrecognized cancer.

The overall risk of malignancy associated with electric power morcellation at the time of myomectomy is one in 1073 (Wright JD et al).

Advanced age is the strongest risk factorfor pathological abnormalities associated with the use of electric power morcellation for myomectomy and should be used with caution and older women.