Contemporary management of uterine fibroids: focus on emerging medical treatments

Figures & data

Figure 1. Factors involved in UF formation and growth. Adapted from Islam et al. 201314.

Figure 2. Uterine fibroid subclassification within the FIGO abnormal uterine bleeding classification system. Intracavitary lesions are attached to the endometrium by a narrow stalk and are classified as Type 0, whereas Types 1 and 2 require a portion of the lesion to be intramural – with Type 1 having less than 50% involvement and Type 2 at least 50%. Type 3 lesions are totally extracavitary but abut the endometrium. Type 4 lesions are intramural UFs that are entirely within the myometrium, with no extension to the endometrial surface or to the serosa. Subserosal (Types 5–7) UFs represent the mirror image of the submucosal UFs – with Type 5 being at least 50% intramural, Type 6 less than 50% intramural, and Type 7 attached to the serosa by a stalk. An additional category, Type 8, is reserved for UFs that do not relate to the myometrium at all, and would include cervical lesions, those that exist in the round or broad ligaments without direct attachment to the uterus, and other so-called ‘parasitic’ lesions. Hybrid UFs are transmural and are classified by their relationship to both the endometrial and serosal surfaces. Two numbers are separated by a hyphen (e.g., 2–5); the first refers to the relationship with the endometrium, while the second refers to the relationship with the serosa. Reprinted with permission from Munro et al., 201131.

Table 1. Factors associated with the risk of uterine fibroids.

Factor
Age (30–50 years)
African descent
Nulliparity
Early age at menarche
Family history of UFs
Obesity
Hypertension
Diabetes

Table 2. Summary of treatment options for uterine fibroids.

Treatment	Description	Advantages	Disadvantages	Fertility preserved?	Relief of symptoms?	Tumor shrinkage?
Medical
GnRH agonists*	– Intramuscular injection, subcutaneous injection, or nasal spray; variable treatment duration	– Significant reduction in UF and uterine volume and alleviation of symptoms	– Reduction of estradiol levels – Medical menopause with symptoms – Bone loss with long-term monotherapy – Requirement for hormonal add-back therapy – Flare of symptoms at treatment initiation – Rapid UF regrowth following treatment discontinuation	Likely	Bulk HMB	Yes
Ulipristal acetate	Oral selective progesterone receptor modulator; taken daily for maximum of 3 months	– Oral administration – Faster control of uterine bleeding and more prolonged UF volume reduction than with GnRH agonist – Maintenance of estradiol levels – Health Canada approved	– Smaller decease in uterine volume vs. GnRH agonist – Non-physiological endometrial changes	Likely	Bulk HMB	Yes
Oral contraceptives*	Estrogen/progestin combination or progestin alone	– Oral administration – Potential for reduced risk of developing UFs	– Increased risk of a number of conditions, including myocardial infarction, thromboembolism, stroke, hepatic neoplasia and gallbladder disease	Likely	HMB	No
Levonorgestrel-releasing intrauterine devices*	Long-lasting intrauterine contraceptive	– Minimal systemic effects – Effective for a number of years following insertion	– Risk of expulsion – Vaginal spotting – Not appropriate when fibroids distort uterine cavity	Likely	HMB	No
Danazol*	Oral synthetic steroid originally used to treat endometriosis	– Oral administration	– Less effective than GnRH agonists – High risk of adverse events: weight gain, acne, and androgenic effects – Use discouraged in recent guidelines	Likely	HMB	No
Tranexamic acid*	Oral antifibrinolytic agent	– Oral administration – Acute control of uterine bleeding	– Reported risk of UF thrombosis and necrosis leading to pain and fever	Likely	HMB	No
Surgical
Hysterectomy	Surgical removal of the uterus and possibly the ovaries	– Definitive treatment for women who do not wish to preserve fertility – High patient satisfaction	– Surgical risks – Surgical menopause with ovary removal	No	Bulk HMB	Yes
Myomectomy	Surgical excision of fibroids	– Symptom resolution and preservation of fertility	– Risk of UF recurrence – Risk of intraoperative transition to hysterectomy – Risk of uterine rupture with pregnancy – Risk or postoperative adhesions	Likely	Bulk HMB	Yes
Myolysis	In situ destruction of tumors by ultrasound, laser, or cryotherapy	– Minimally invasive – Rapid recovery	– Limited to treating few and small UFs – Requires surgical expertise and specialized equipment	Uncertain	HMB	Yes
Uterine artery embolization	Injection of occluding agents into uterine arteries	– Rapid recovery – Minimally invasive	– Higher rate of minor complications – Relatively high reoperation rate – Requires interventional radiology expertise and specialized equipment	Uncertain	Bulk HMB	Yes
Endometrial ablation with/without myomectomy	Destruction of endometrial uterine lining using heat, or radiofrequency	– Rapid recovery – Minimally invasive	– Contraception required for women of reproductive age – Relatively high reoperation rate	Unlikely	HMB	No

HMB: heavy menstrual bleeding.

*No specific indication in management of UFs or UF symptoms.

Figure 3. Uterine fibroid treatment algorithm. Please refer to Table 2 for advantages and disadvantages of the different therapeutic approaches.

Islam MS, Protic O, Giannubilo SR, et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metabol 2013;98:921-34

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Munro MG, Critchley HO, Broder MS, Fraser IS; Figo Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;113:3-13

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