Uterine fibroids - Emerging treatments

Ulipristal

Ulipristal is a selective progesterone receptor modulator, for which there is moderate evidence to show that it effectively reduces the size of fibroids and reduces bleeding symptoms.[82] However, the European Medicines Agency (EMA) and UK Medicines and Healthcare products Regulatory Agency (MHRA) have recommended that the use of ulipristal be restricted as a result of cases of serious liver injury.[144][145] Ullipristal was first authorised in 2012 for intermittent or pre-operative treatment of moderate to severe symptoms of uterine fibroids in women of reproductive age. In 2018, the EMA reviewed the benefits and risks of ulipristal for the treatment of uterine fibroids following reports of serious liver injury, including liver failure leading to transplantation, and measures were implemented to minimise the risk.[146] However, as these cases were followed by another case of severe liver damage resulting in liver transplantation, despite adherence to measures to minimise the risk, the EMA started a new safety review in early 2020.[147] The UK MHRA also issued a drug safety update for ulipristal providing similar advice.[148] The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended revoking the drug’s marketing authorisation for this indication in Europe.[149] But, after careful consideration, they confirmed the benefits of ulipristal in controlling uterine fibroids might outweigh this risk in women who have no other treatment options. Therefore, they now recommend that the drug remains available to treat pre-menopausal women who cannot have surgery (or for whom surgery had not worked). Ulipristal must not be used for controlling uterine fibroids in women who are awaiting surgical treatment. The UK MHRA agreed that the temporary suspension should be lifted and the use of ulipristal should be further restricted to intermittent therapy of women with moderate to severe uterine fibroid symptoms before the menopause if surgical procedures (including uterine fibroid embolisation) are unsuitable or have failed.[145] The US Food and Drug Administration (FDA) has delayed a decision to approve ulipristal for the treatment of abnormal bleeding in women with fibroids and has asked the manufacturer to submit additional information, citing concerns around liver safety. Ulipristal is, therefore, not recommended for the treatment of uterine fibroids in the US. Ulipristal is approved as a single-dose medication for emergency contraception in some countries; these restrictions do not apply to this indication.

Linzagolix

Linzagolix is the third oral GnRH antagonist to become available in some countries. The EMA has approved linzagolix for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. It is not available in the US as yet, but the FDA are currently reviewing the application for approval.

Vilaprisan

A selective progesterone receptor modulator. According to a phase 2B trial, vilaprisan is a potentially safe and effective agent to treat uterine fibroids for women in whom surgery is not an option.[150]

Combination therapy

The use of a GnRH agonist in combination with a selective progesterone receptor modulator prior to surgery for uterine fibroids has been shown to be beneficial. Combination therapy can reduce the complexity of the surgical procedure, lessen blood loss, and decrease the incidence of anaemia. The improvement of surgical outcomes is important as it reduces the risk of potential complications (which can be debilitating and even fatal), improving recovery time and the need for prolonged hospital stay.[151]

Aromatase inhibitors and selective oestrogen receptor modulators

Other less-studied options for the treatment of uterine fibroids include aromatase inhibitors (e.g., letrozole) and selective oestrogen receptor modulators (e.g., tamoxifen, raloxifene). Aromatase inhibitors block the synthesis of oestrogen. Limited data have shown that aromatase inhibitors help to reduce fibroid size as well as decrease menstrual bleeding, with adverse effects including hot flushes, vaginal dryness, and musculoskeletal pain. Overall, there is insufficient evidence to support the use of aromatase inhibitors for the treatment of uterine fibroids.[152][153][154] Selective oestrogen receptor modulators act as partial oestrogen receptor agonists in bone, cardiovascular tissue, and the endometrium. In a small prospective trial of 18 patients, tamoxifen did not reduce fibroid size or uterine volume, but did reduce menstrual blood loss by 40% to 50% and decrease pelvic pain compared with the control group. Based on its adverse effects (e.g., hot flushes, dizziness, endometrial thickening), the authors concluded that its risks outweigh its marginal benefits for fibroid treatment. Another selective estrogen receptor modulator, raloxifene, has also shown inconsistent results, with two of three studies included in a Cochrane review showing significant benefit.[155][156]

Magnetic resonance-guided focused ultrasound (MRgFUS)

High-intensity focused ultrasound combines high-energy sound waves to focus intense heat to precisely targeted areas, thereby causing irreversible cell damage in deep tissue while sparing skin and adjacent normal tissue. Precision and assessment of tissue destruction is facilitated by the use of real-time MRI. The first MRgFUS system for the treatment of uterine fibroids was approved in the US by the Food and Drug Administration in 2004. Initial series of patients employing stringent safety and inclusion criteria, including uterine fibroid size ≤10 cm and total uterine size ≤24 weeks, showed good efficacy, rare complications, and high patient satisfaction.[157] Presence of more than five fibroids limits the success of MRgFUS/high-intensity focused ultrasound therapy; the indication to treat fibroids exceeding 10 cm in diameter should be reviewed critically. A 2019 consensus report of an expert meeting stated that MRgFUS is a safe and effective thermoablative technique to treat fibroid-related symptoms.[158] However, the evidence is limited because of a lack of randomised trials. Options following treatment failure of minimally invasive treatment techniques, including MRgFUS, always include surgical options of myomectomy or hysterectomy.

Nd:YAG laser

The use of Nd:YAG laser is still controversial. At present, there is insufficient evidence about efficacy and safety (particularly long-term safety) to warrant routine clinical use. Therefore, this treatment should only be given in the context of clinical trials in research institutions.[159]

Cryotherapy

The destruction of fibroids by freezing is still controversial. At present, there is insufficient evidence about efficacy and safety (particularly long-term safety) to warrant routine clinical use. Therefore, this treatment should only be given in the context of clinical trials in research institutions.[159]

Acupuncture

Acupuncture has been suggested as an alternative treatment for problems associated with fibroids such as heavy periods. However, currently, there is a lack of randomised controlled trials and no reliable evidence of effectiveness of acupuncture for treating uterine fibroids.[160]

Vitamin D

Administration of vitamin D3 may reduce the size of leiomyomas, and studies have found it to be a safe and effective treatment.[161]

Herbal remedies

One Cochrane review found that current evidence neither supports nor refutes the use of herbal preparations for treating uterine fibroids.[162] Epigallocatechin gallate (EGCG), the major catechin in green tea, exhibits several useful biological effects, including anti-inflammatory, antiproliferative, and antioxidant effects. EGCG has been shown to inhibit key pathways of tumour growth, and reduce the mean total fibroid volume. EGCG treatment has shown a significant safe and effective response in symptomatic uterine fibroid cases.[163]