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Medical therapy can in some cases reduce the need for an operation but often it is not a long term solution. The drugs used can be divided into 2 groups: oral non-hormonal and hormonal (in various formulations). Summary of the available choices for medical therapy is shown below:

Class of Drug Product Outcome on fibroid size Outcome on abnormal uterine bleeding Outcome on fertility
Non-Hormonal NSAIDs
& Tranexamic Acid
No effect on fibroid size Decrease by 30% No effect
Hormonal Combined Oral Contraceptive No data Decrease 20-30% Contraceptive
GnRHa (3 to 6 months duration of therapy) Decrease 30%
Decrease uterine volume by 35%
Decrease > 80% Contraceptive
Oral Progestins Decrease 30% Decrease > 60% Contraceptive
LARC (Long Acting Reversible Contraceptive (e.g. Depo-Provera, Implanon [etonogestrel]) Decrease uterine volume by 35% Breakthrough bleeding Contraceptive
Levonorgestrel Intrauterine Device (e.g. Mirena) Decrease 20-30 % Decrease 40%
Systemic side effects
Contraceptive
Selective progesterone receptor modulators (SPRM), specifically ESMYA Decrease 12 % on 5 mg daily for 13 weeks Decrease 91%
Require monitoring of liver function.
Contraceptive

Nonsteroidal anti-inflammatory drugs (NSAIDs)

They have been a typical answer for pain. NSAID in combination with hormones, either oestroprogestins or progestogens, acting on the endometrium such as the levonorgestrel intrauterine system (LNG-IUS) has been effective in reduces menstrual blood loss. In practice, this combination has been an excellent solution for mild and even severe bleeding when it is well tolerated.

Tranexamic acid

Tranexamic Acid is a procoagulant drug that has been shown effective in reducing blood loss during menstruation.In women with fibroids who have mild bleeding, 3 or 4 days per month treatment has been very useful.

GnRH (Gonadotropin releasing hormone) agonist & antagonist

Key features of GnRH treatments are shown below:

GnRH Agonist GnRH Antagonist
  • It reduces oestrogen and progesterone levels and blood flow to the fibroids to shrink them. It works by temporarily stopping the menstrual periods and put you in the menopausal state.
  • Often, GnRHa treatment is given 3 to 4 months to shrink the fibroids before myomectomy or hysterectomy (in order to avoid midline incision, anaemia, blood transfusion), and also as a "short-term" treatment for women nearing the menopause (i.e. late peri-menopause) to reduce the bulk. Clinical evidence showed that up 30% reduction in fibroid size was achieved after a 6 month treatment of GnRHa.
  • A temporary treatment only: Once GnRHa treatment stops, the fibroids will return to their former (original) size.
  • GnRHa also reduces blood loss and relieves pelvic pressure, urinary frequency, nocturia and constipation.
  • The most commonly prescribed GnRHa is Zoladex which is injected either every month or 3-monthly and can be given up to 6 months maximum.
  • The major side-effect is severe bone thinning leading to osteoporosis. Some clinicians prescribe tibilone, raloxifene as "add-back" to minimise this bone loss.
  • Other adverse effects include symptoms of menopause (hot flushes, headache and vaginal dryness), irregular bleeding, depression, hair loss and musculoskeletal stiffness.
  • Reduction in fibroid size occurs more quickly compared to GnRH agonist.
  • Commonly, it is used as pre-operative in young women and before peri-menopausal women.
  • A typical example: Cetrorelix.
  • Side effects include hot flushes, amenorrheic (absence of menstrual periods). Normal periods return within one month of discontinuation of treatment.
  • Short term therapy only.
  • Fibroid regrows after stopping the medication.

Male hormones (androgens)

They can slow or stop the growth of fibroids and offer symptoms relief. Drugs like Danazol can reduce the size of the fibroids and the womb, and stop the periods and anaemia. However, its side-effects are off-putting for many women. The side-effects include weigh gain, depression, anxiety, oily skin and hair, deepening of the voice, headache, fatigue, hair loss, growth of facial and body hair, blood clots and liver problems.

Exogenous progestins

Exogenous progestins, taken orally, are often used to reduce bleeding but have no effect on fibroid size.

(a) Medroxy-progesterone acetate (Provera) 5-10 mg once a day, or

(b) Megestrol acetate 10-20 mg daily.
Either one is prescribed in the first 10-14 days of the menstrual cycle. Usually, bleeding is regulated after 1-2 cycles.
Provera can also be administered as a single injection (150 mg intramuscular) once every 3 months (Depo-Provera). It is best to see first whether you show any adverse side effects (weigh gain, depression, and even irregular bleeding) to the oral dose before trying the injection, because the effect of one injection lasts three months.

Medicated IUS

  • Medicated IUS is only suitable for heavy bleeding caused by fibroids with the fibroid uterus (womb) size of less than 12-week pregnancy with no distorting intracavity fibroids.
  • Mainly, IUS treats heavy period symptoms.
  • The procedure involves inserting an IUS (coil) into the uterus. This device delivers the hormone to decrease the blood flow to the fibroid preventing it developing.
    It has not been proven effective in reducing the size of the fibroids.
  • It may reduce your chance of requiring surgery or other medical treatment.
  • Side effects include irregular bleeding which can last up to six months, acne, headache, breast tenderness and in rare cases your period may stop altogether.
  • MIRENA® is the most commonly fitted coil in UK for control of heavy bleeding in fibroid patients. It does NOT reduce the fibroid size.
    It is a plastic coil which slowly releases levonorgestrel into the womb. Mirena coil can only used in women with fibroid uteri (womb) that is not more than 12 weeks pregnancy size. Mirena is only licensed for heavy menstrual bleeding and NOT for fibroid treatment.

Selective progesterone receptor modulators (SPRM)

Mifepristone (MFP)

MFP, initially code-named as RU486, is the first in class of compounds known as SPRM to have been synthesized and utilized clinically.

The Cochrane Review 2012, concluded that MFP use relieves heavy menstrual bleeding, although there was no conclusive evidence for an effect on the fibroid volume. While other analysis concluded: MFP, in doses between 2.5 and 25 mg for 3–6 months, is effective in reducing uterine and fibroid volume, hypermenorrhea, MBL, pelvic pain, pelvic pressure, anemia, and dysmenorrhea. More recent data suggested a preferable lower oral dose of 5 mg daily.

Today, MFP is mostly used outside of Western Countries.

Ulipristal (UPA)- ESMYA®

Previously, it was known as CDB-2914 or VA-2914. UPA has similar chemical structure to mifepristone.

In March 2012, Ulipristal received a European wide medical licence permitting its use as a medical treatment of fibroids and being marketed as ESMYA.

Two clinical trials (PEARL 1, PEARL 2, published February 2012) showed ulipristal acetate, at a daily dose of 10 mg, to achieve reduction in fibroid size (42 %) and improvement in heavy menstrual bleeding (98 % reduced heavy periods, 89 % amenorrhoea/no periods) comparable to that achieved by GnRHa (Leuprolide Acetate, Prostap). A daily dose of 5mg ulipristal appears to marginally less effective than the 10 mg dose at achieving fibroid size reduction (36 %) and amenorrhoea (75 %), but these differences are not statistically significant.

Importantly, ulipristal was able to achieve symptom improvement by one week of treatment commencement (compared to three weeks for GnRHa) and had significantly less side effects than GnRHa (i.e. 10 % risk of hot flushes compared to 40 % risk of hot flushes with GnRHa).

ESMYA's ability to reduce fibroid volume and restore normal haemoglobin (Hb) level, on regimen of 5 mg daily up to 3 months, has gained widely acceptance as an effective pre-operative therapy.

Reports of rare but serious liver injury have been shown by the EMA Pharmacovigilance Risk Assessment Committee (PRAC) to be associated with Esmya. The PRAC, therefore, recommended measures to minimise liver injury, including not to be used when liver problems are known and liver tests before, monthly during the firsdt two courses, and 2-4 weeks after stopping treatment.

Notwithstanding the warning, on June 2018, EMA’s Committee for Medicinal Products for Human Use has recommended granting marketing authorisation for UPA in the preoperative treatment of uterine fibroids.


Sources
Manuela Farris, Carlo Bastianelli, Elena Rosato, Ivo Brosens, and Giuseppe Benagiano1. Uterine fibroids: an update on current and emerging medical treatment options.Ther Clin Risk Manag. 2019; 15: 157–178.



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Last updated on Friday 3 July 2020 11:25 am.