COMMENTARY

Medical Treatment of Fibroids and Related Heavy Menstrual Bleeding

Peter Kovacs, MD, PhD

Disclosures

November 19, 2018

Uterine Fibroids and Heavy Menstrual Bleeding

A typical menstruation occurs every 21-35 days (typically around 28 days) and lasts for 2-7 days. Excessive bleeding (heavy flow, clots) or menstruation that lasts longer than 7 days could cause anemia, affect quality of life, and lead to morbidity. Heavy menstrual bleeding requires proper evaluation and treatment.[1]

Bleeding disorders (von Willebrand disease), hormonal dysfunction (anovulation, thyroid disease) and anatomical defects may be responsible for heavy menstrual bleeding. Uterine fibroids may interfere with proper endometrial build-up, uterine contractility, and vascular function, resulting in heavy menstrual bleeding.[2]

Fibroids that distort the uterine cavity are typically managed surgically by resecting the myoma. Intramural fibroids can also be surgically managed (myomectomy, hysterectomy), or alternatively, radiologic interventions or medical therapy can be considered.

A new review by Donnez and colleagues[3] discusses the potential benefits of ulipristal acetate (UPA) for the medical management of heavy menstrual bleeding associated with uterine fibroids.

The Effectiveness of UPA

UPA, a selective progesterone receptor modulator, has direct effects on fibroids and endometrium. UPA reduces myoma volume and associated bleeding.

Short-term use (≤ 3 months) was associated with a significant reduction in menstrual flow in 90% of exposed women. The effect was seen as early as 5-7 days after initiation. It led to a one-third reduction in fibroid size, an effect that was maintained for up to 6 months.

Subsequently UPA was tested as extended use (3 months of UPA, then 2 months off UPA, repeated up to four times). Such use was associated with a reduction in fibroid size of 54%-67%, no heavy menstrual bleeding in 67%-81% of women, and significant improvement in quality of life.

UPA seems to have no adverse impact on subsequent fertility, although the number of pregnancies conceived after UPA treatment is limited at this point to draw firm conclusions. It may be associated with hot flushes and breast pain, but has no impact on thromboembolism risk. UPA is not recommended for women with liver disease.

The review concluded that a 5-mg dose of UPA used in repeated courses interrupted by drug-free intervals is effective in the management of large uterine fibroids and associated heavy menstrual bleeding.

Viewpoint

The usual medical treatments for heavy menstrual bleeding (eg, oral contraceptives) may not be effective when bleeding is associated with fibroids because they are hormone-sensitive. Gonadotropin-releasing hormone (GnRH) agonists can be offered to treat fibroid-related symptoms because they induce both a reduction in fibroid size as well as in the volume of bleeding. The hypoestrogenic side effects, however, limit the use of GnRH agonists to a maximum of 6 months, unless add-back therapy is also used. GnRH analogues are therefore usually prescribed as preoperative treatments.

UPA has been shown to be effective when used repeatedly with intermittent drug-free intervals. Hypoestrogenic side effects do not complicate the use of UPA.

Reports of liver toxicity have prompted the European Medicines Agency to review the safety of UPA. In a recent editorial,[4] the lead investigator of the UPA studies questions the significance of the liver toxicity reports because no such adverse effect was seen in the clinical trials.

If UPA is once again cleared, it should be a useful addendum to the medical therapies available to treat fibroids and fibroid-related heavy menstrual bleeding.

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