Is hormone replacement therapy (HRT) safe for patients with uterine fibroids?

Hormone Replacement Therapy in Patients with Uterine Fibroids

Hormone replacement therapy (HRT) can be used cautiously in patients with uterine fibroids, but requires careful monitoring as it may cause fibroid growth in some cases, particularly with higher doses of progestogens.

Safety Considerations for HRT in Patients with Fibroids

• The natural history of fibroids is typically shrinkage and symptom resolution during menopause due to decreased circulating estrogen 1
• HRT may influence fibroid growth, but available data are conflicting and do not suggest that fibroids represent an absolute contraindication to HRT 2
• The location and type of fibroids matter - subserosal fibroids are less likely to be problematic than intramural or submucosal fibroids 1
• Postmenopausal patients with fibroids and abnormal bleeding should undergo endometrial biopsy to rule out malignancy before considering HRT 1

HRT Regimen Recommendations

• If HRT is necessary, use the lowest effective dose of progestin to minimize potential fibroid growth 2
• Consider transdermal estrogen with 2.5mg medroxyprogesterone acetate (MPA) rather than higher doses, as 50μg transdermal estradiol with 5mg MPA has been shown to increase fibroid size 3
• Selective estrogen receptor modulators (SERMs) like raloxifene may be better alternatives for women with asymptomatic fibroids due to their tissue-specific actions 4
• Tibolone is another option that has been evaluated for women with fibroids, though results are variable 2

Monitoring Recommendations

• Women with uterine fibroids on HRT should be periodically examined with ultrasound to monitor for fibroid growth 2
• Consider measuring the pulsatility index of uterine arteries as a possible screening tool before initiating HRT, as low resistance index is associated with increased risk of fibroid growth 4
• Discontinue HRT if fibroids appear to increase significantly in size or become symptomatic 2

Alternative Management Options

• For patients with symptomatic fibroids who wish to avoid surgery, GnRH agonists with add-back therapy (low-dose estrogen and progestin) can be an effective approach 1, 5
• GnRH antagonists (elagolix, linzagolix, relugolix) with add-back therapy are FDA-approved for fibroid-related heavy menstrual bleeding 1
• Progesterone receptor modulators like ulipristal acetate show promise in reducing both bleeding and bulk symptoms, though reports of hepatotoxicity have limited approval in the US 1

Special Considerations

• In perimenopausal women with fibroids, intermittent courses of progesterone receptor modulators may help transition into menopause while avoiding surgery 1
• For postmenopausal women with symptomatic fibroids not responding to medical management, hysterectomy provides definitive resolution and allows pathologic evaluation to confirm absence of malignancy 1
• The risk of unexpected uterine sarcoma increases with age, from lower risk in younger patients to up to 10.1 per 1,000 in patients 75-79 years of age 1

Common Pitfalls to Avoid

• Never initiate HRT in postmenopausal women with abnormal uterine bleeding without first ruling out endometrial cancer or sarcoma 1
• Avoid high doses of progestogens in combination therapy as they may increase the risk of fibroid growth and formation of new fibroids 4
• Don't assume all fibroids will respond similarly to HRT - response varies based on size, location, and individual factors 1, 2