Treat with Medical Therapy Not Hysterectomy

Although hysterectomy remains the most common procedure for treating fibroids and fibroids are the leading indication for hysterectomy, its long-term sequelae make less invasive alternatives the better choice for managing most of these myometrial masses, an invited clinical practice paper in the New England Journal of Medicine (NEJM) asserts. 

The practice summary also calls for earlier identification and treatment of fibroid disease and may raise awareness among general gynecologists and primary care physicians less familiar with newer treatments.

Based on a review of evidence and existing formal guidelines, the paper urges wider use of uterus-sparing approaches such as hormone therapy, uterine-artery embolization, focused ultrasound ablation, and radiofrequency ablation. Authored by ob/gyns Elizabeth A. Stewart, MD, and Shannon K. Laughlin ‑ Tommaso, MD, MPH, o f the Mayo Clinic in Rochester, Minnesota, the document also features textbook-style diagrams illustrating procedures.

“To clarify, this is not a new guidance but an invited clinical practice paper,” Laughlin-Tommaso told Medscape Medical News. “I believe NEJM recognized the gap in knowledge among all providers, for early diagnosis of uterine fibroids, especially in young patients and those presenting with anemia.”

The l ess invasive treatments highlighted in the paper can help women recover faster and resume their normal activities more quickly, said Laughlin-Tommaso. “Additionally, many studies have now shown that there are health benefits to keeping the uterus and the ovaries.”

Despite multiple uterine-sparing options, however, a recent study in a commercially insured population found nearly 60% of fibroid patients undergoing hysterectomy had never received a prior conservative treatment.

Why hysterectomy for a benign condition? Hysterectomy, which is universally available in ob/gyn practices, makes decision-making easier for medical providers and patients, Laughlin-Tommaso explained. “It’s the only treatment that is definitive in that patients will not have bleeding or fibroids in the future and providers don’t have to determine which fibroids to treat or remove.”

More common in Black women, fibroids affect up to 80% of persons with a uterus during their lifetime and up to 50% have symptoms such as heavy and prolonged menstrual bleeding, anemia-associated fatigue, pelvic pressure, and menstrual and nonmenstrual pain, the authors noted. These lesions can also compress nearby structures causing painful intercourse, constipation, and urinary frequency, urgency, or retention.

In 2021 the American College of Obstetricians and Gynecologists issued a practice bulletin on the management of symptomatic uterine leiomyomas, similarly endorsing individualized care that accounts for the desire to preserve fertility or the uterus, increase quality of life, and reduce symptoms. It, too, recommended medical management as first-line treatment for symptomatic fibroids.

“This paper will be helpful for clinicians by covering some of the newer options such as gonadotropin-releasing hormone antagonists introduced in the past 5 years and tailoring treatment to patients depending on whether they still want to conceive,” said Sandra M. Hurtado, MD, an ob/gyn and an assistant professor at UTHealth Houston Medical Center and McGovern Medical School in Houston, Texas, in an interview. “And the illustrations will be useful to doctors who are not gynecologists and will help to explain the interventional options to patients,” added Hurtado, who was not involved in the paper.

Offering another outside perspective on the paper, Charles J. Ascher-Walsh, MD, senior system vice chair for gynecology and division director of urogynecology in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology and Reproductive Science at Mount Sinai in New York City, called it a useful though not new summary. Reaching the wider audience of NEJM may raise awareness of newer fibroid therapies among general, nonspecialist ob/gyns, whose practices may concentrate largely on obstetrics, he added, “and the excellent illustrations clarify the treatment options.” In his view, broader awareness may increase much-needed funding for this neglected area of research.

Among the paper’s recommendations:

Diagnosis

Pelvic ultrasonography is the most cost-effective imaging method, providing information on size, location, and number of fibroids and ruling out adnexal masses. It is limited, however, by less-accurate resolution if the uterine volume is greater than 375 mL or if fibroids number more than four.

Medical Alternatives to Hysterectomy

Early diagnosis and first-line medical therapies are recommended.

Contraceptive hormones to control heavy menstrual bleeding are the first step in most algorithms for treating fibroid-related bleeding, despite low-quality evidence.

Nonsteroidal anti-inflammatory agents and tranexamic acid during menstruation also limit heavy menses but have more evidence of efficacy for idiopathic heavy menses.

Gonadotropin-releasing hormone (GnRH) agonists in depot form are approved for short-term preoperative therapy. While they cause amenorrhea in nearly 90% of patients and reduce uterine volume by 30%-60%, they have a high incidence of hypogonadal symptoms, including bone loss and hot flushes. They also cause a “steroidal flare” when the stored gonadotropins are released and cause subsequent heavy menstrual bleeding with the rapid decrease in estrogen levels. 

Oral GnRH antagonist combinations are a major therapeutic advance, pairing a GnRH antagonist (such as elagolix or relugolix, which rapidly inhibit ovarian steroidogenesis) with estradiol and progestin at doses equivalent to systemic levels in the early follicular phase of the menstrual cycle.

In clinical trials these combinations decreased heavy menstrual bleeding by 50%-75%, pain by 40%-50%, and bulk-related symptoms through a 10% decrease in uterine volume. Side effects are few, with hot flushes, headaches, and nausea occurring in fewer than 20% of participants.

Interventional Options

Smaller fibroids in the submucosal to intramural spaces can be treated transcervically, while larger lesions of any type or smaller subserosa fibroids are treated abdominally.

Uterine-artery embolization uses minimally invasive radiologically guided catheterization to release embolic particles directly into both uterine arteries. This process causes ischemic infarction of the fibroids and decreases bleeding, pain, and bulk-related symptoms. 

Other procedures shrink individual fibroids with energy that creates coagulative necrosis. These include focused ultrasound ablation (with MRI or ultrasound guidance) and radiofrequency ablation (with laparoscopic or transcervical ultrasound guidance).

Unlike uterine-artery embolization, which treats all fibroids concurrently, these therapies require individual targeting of fibroids. 

Radiofrequency ablation can be done concurrently with other surgical therapies, such as laparoscopic excision of endometriosis or hysteroscopic myomectomy. 

Myomectomy, or the surgical removal of fibroids, is most often used in persons actively seeking pregnancy or having very large fibroids in whom shrinkage would be inadequate. Most guidelines recommend surgical excision rather than shrinking procedures to optimize fertility. However, myomectomy often commits patients to future cesarean section, which increases pregnancy-related morbidity.

Although myomectomy is seen as superior to uterine-artery embolization for improving quality of life, both approaches provide substantial symptom relief.

Recurrence

Incidence of recurring fibroids is high, with, for example, new fibroids developing in approximately 50% of persons within 5 years of myomectomy. 

Earlier this year, a large cohort study reported that myomectomy was best for avoiding reintervention after surgical leiomyoma management.

Reintervention rates vary according to procedure, patient age, disease extent, and symptoms and can be as high as 33% up to 5 years after treatment, with lower percentages seen among persons older than 45 years of age.

Hysterectomy

Minimally invasive hysterectomy is recommended. Drawbacks to hysterectomy include perioperative risk and concomitant oophorectomy, which was common until the early 2000s when large cohort studies showed elevated risks of death, cardiovascular disease, dementia, and other illnesses compared with hysterectomy plus ovarian conservation. Oophorectomy but not hysterectomy rates have since decreased.

Still needing study, according to Laughlin-Tommaso are the underlying reasons for health disparities in fibroids, especially among Black and Latina individuals. “Some studies have found associations with vitamin D deficiency and with stress and racism,” she said.

Looking ahead, the authors stressed the need for a fibroid risk-prediction model, a staging system, and large randomized trials of treatment effectiveness. Also needed are methods for primary and secondary prevention. “Earlier screening and medical treatment in primary care settings could potentially minimize morbidity and the incidence of unnecessary hysterectomies, and primary care–based screening trials are warranted,” they wrote.

Case Study

In addition to procedural illustrations the practice document includes a vignette of a 33-year-old never-pregnant Black woman (but desiring motherhood) with heavy menstrual bleeding, abdominal bloating, and non–iron deficiency anemia. Evaluation for thalassemia and sickle cell anemia is negative, but ultrasonography reveals an enlarged uterus with multiple fibroids and normal ovaries.

In line with the clinical review, the authors prescribe oral GnRH agonist combination therapy, plus iron and multivitamin supplementation, and recommend annual reassessment — earlier if pregnancy is desired or if symptoms escalate. Since the patient prioritizes fertility, hysterectomy would be appropriate only if she had biopsy-proven cancer. 

The authors received no external funding for this practice paper, but both have funding from the National Institutes of Health for fibroid research. Laughlin-Tommaso reported royalties from UpToDate. Stewart reported research support from the Agency for Healthcare Research and Quality, and speaking, data-monitoring, and consulting fees for various private companies, including AbbVie, Anylam Pharmaceuticals, ASKA Pharma, and Movant Sciences. She holds a patent on treatment for abnormal uterine bleeding and has been involved in CME for various medical educational agencies. Hurtado and Ascher-Walsh had no relevant conflicts of interest to declare. 

Diana Swift is a freelance medical journalist based in Toronto, Canada.