Effective treatments for uterine fibroids and abnormal uterine bleeding

Effective treatments for uterine fibroids and abnormal uterine bleeding | Image Credit: © smolaw11 - © smolaw11 - stock.adobe.com.

In a recent review published in Fertility and Sterility, investigators highlighted current treatment methods for abnormal uterine bleeding (AUB) caused by uterine fibroids (UFs).¹

Approximately 70% of reproductive-aged women are impacted by UFs, with approximately 30% of UFs diagnosed during routine pelvic examination. AUB, heavy menstrual bleeding (HMB), pelvic pain, and infertility are common symptoms of UFs that significantly impact patients’ quality of life.

The International Federation of Gynecology and Obstetrics has classified AUB caused by UFs as AUB leiomyoma.² Significant increases in health care costs occur from symptomatic UFs with HMB, highlighting the need for adequate management.¹ This requires a balance of different medical, surgical, or radiologic treatment options.

Investigators conducted a review to summarize current medical, surgical, and radiological treatment methods used in patients with UFs. While experts have hypothesized a connection between UFs, AUB, and HMB, data about the pathophysiology involved in AUB in conditions such as UFs is currently lacking.

Alterations in the endometrial vascular architecture and function are caused by UFs, leading to increased angiogenesis. AUB and HMB presenting during UFs may also be explained by an increase in the surface area of the endometrium and the size of the uterine cavity, dilated blood vessels on UFs, and impaired myometrial contractility.

Medical treatment options, such as nonhormonal and hormonal drugs, are considered first-line methods for managing AUB or HMB linked to UFs. While data has not indicated superiority from a singular compound, certain drugs have displayed increased efficacy for AUB and HMB management.

Nonhormonal therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid. NSAIDs reduce prostaglandin synthesis at the endometrial level through inhibition of cyclooxygenase, decreasing dysmenorrhea.

Tranexamic acid blocks plasminogen, inhibiting fibrinolysis. This method has been indicated as more effective than NSAIDs alone, with a reduction in menstrual blood loss of 26% to 50%.

For hormonal options, combined oral contraceptives may be used to treat AUB and HMB, though data about the efficacy of this method remains limited. Alternatively, patients may use a 52-mg-levonorgestrel intrauterine system. This method has a local impact on the endometrium, reducing endometrial proliferation while increasing apoptosis.

Selective progesterone receptor (PR) modulators may be used as full PR agonists and antagonists. These can lead to apoptosis by impeding the cellular proliferation of leiomyoma cells. Certain selective PR modulators, such as ulipristal acetate, have shown a similar efficacy toward reducing fibroid size as gonadotropin-releasing hormone (GnRH) analogs.

Selective estrogen receptor modulators may act as agonists or antagonists, leading to tissue-specific changes in gene expression. However, this option is not recommended for treating symptomatic UFs because of minimal benefits. Aromatase inhibitors, another potential treatment method, also do not have adequate evidence proving its benefits.

GnRH agonists have been proven to decrease the volume of UFs while increasing preoperative hemoglobin levels. This is accomplished through down-regulation of pituitary GnRH receptors, leading to a reduction in gonadal steroid levels. However, long-term use has been associated with bone loss and decreased bone mineral density (BMD).

In comparison, oral GnRH antagonists immediately suppress gonadotropin release. Oral GnRH antagonists indicated as effective for controlling UFs-related HMB include elagolix, relugolix, and linzagolix. Additionally, BMD is preserved when using GnRH antagonists in combination with add-back therapy.

Globally, UF-related symptoms are most often treated through surgical methods. Myomectomy is a conservative option for patients wishing to conceive in the future but may carry a risk of recurrence because of uterine preservation. Additionally, larger fibroids may require a more complex procedure, increasing the risk of intraoperative complications.

While UFs are the primary indication for hysterectomy, this method should mainly be considered in patients with symptomatic UFs not desiring to retain their uterus. Investigators recommend discussions of all available options and short- and long-term goals.

Finally, radiologic options are available for patients unable or unwilling to receive medical and surgical options. These options include uterine artery embolization, magnetic resonance high-intensity focused ultrasound, high-intensity focused ultrasound, and radiofrequency ablation.

This data highlights the need for an individualized approach when managing UFs-related AUB and HMB. Investigators concluded, “the ultimate goal of treatment should be to relieve UF symptoms while preserving the uterus.”

References

1. Vannuccini S, Petraglia F, Carmona F, Calaf J, Chapron C. The modern management of uterine fibroids-related abnormal uterine bleeding. Fertility and Sterility. 2024;122(1):20-30. doi:10.1016/j.fertnstert.2024.04.041
2. Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018;143(3):393-408. doi:10.1002/ijgo.12666