Leiomyomas Treatment

Indications for Medical Treatment

• Preserve fertility in women with large leiomyomas prior to attempting conception
  • May include infertile women of reproductive age who wish to conceive or symptomatic women of reproductive age who wish to preserve their fertility but have no immediate desire for pregnancy
• Symptomatic patients who do not wish future fertility but want to preserve the uterus
• Treatment of women near menopause in an effort to avoid surgery
• Women with medical contraindications to surgery
• Personal or medical indications for delaying surgery
• Option as stand-alone treatment for temporary symptom relief
• Can be given as a preoperative adjunct to reduce the size of fibroids, control bleeding and improve hemoglobin levels

Gonadotropin Releasing Hormone (GnRH) Agonists

• Eg Goserelin, Leuprorelin (Leuprolide), Triptorelin
• Given to women in the perimenopausal or preoperative periods; operative and recovery time are both reduced
• Actions: Down-regulate GnRH receptors at the pituitary level resulting in significant reductions in follicle stimulating hormone (FSH), luteinizing hormone (LH) and ovarian steroids, thus producing a hypoestrogenic state
• Effects: Decrease uterine and myoma volume and improve menorrhagia
  
  • Maximal diminution of uterine and myoma size is achieved within the 1st 12 weeks of therapy
  • Menorrhagia or related anemia is controlled after the 1st month of treatment
  • Pressure symptoms are usually relieved in the 1st 2 months
  • May induce amenorrhea in some women depending on the duration of use

• Approximately half of the women treated will experience leiomyoma regrowth within a few months after treatment cessation
• Treatment duration should be no more than 6 months
• Significant side effects stem from the state of hypoestrogenism manifesting clinically as hot flushes, headaches, vaginal dryness, depression and bone demineralization
• Side effects can be alleviated by add-back therapy using estrogen, progestin, or both; however, addition of hormones may limit the effectiveness in treating myoma
  • Add-back therapy has not been shown to compromise the efficacy of GnRH agonists

Selective Progesterone Receptor Modulators (SPRMs)

• Eg Mifepristone, Ulipristal acetate
• Mifepristone reduces heavy menstrual bleeding and uterine and leiomyoma volume
• Ulipristal acetate is used for preoperative management of women with moderate to severe symptoms of uterine fibroids 
  • Significantly reduces bleeding and volume of leiomyoma
  • Patients with heavy menstrual bleeding may be offered up to 4 courses (long-term intermittent therapy) of Ulipristal acetate if with fibroids of >3 cm in diameter and hemoglobin level of <102 g/L
• Benign and reversible changes occur in the endometrial tissue [progesterone receptor modulator associated endometrial changes (PAEC)] with SPRM therapy

• Data showed SPRMs are non-inferior to GnRH agonist with less bone loss and menopausal side effects but with higher risk of amenorrhea

Pretreatment to Surgery

• Pretreatment with GnRH agonist for 2-4 months for uterine fibroids is recommended for patients with large uterus (>18 weeks size) or pre-op anemia
  
  • May be given in combination with oral iron therapy

• Effects: Preoperative hemoglobin is increased, and fibroid and uterine volume is decreased; in hysterectomy, blood loss, duration of operation and complication rates are also decreased
• Ulipristal acetate is given preoperatively for 3 months
  
  • Should also be considered in anemic patients prior to surgery

Other Medical Treatments of Leiomyomas

Gonadotropin Releasing Hormone (GnRH) Antagonists

• Eg Abarelix, Cetrorelix, Ganirelix
• Used as injectables, usually at doses of 5 mg twice daily for the initial 2 days followed by 0.8 mg twice daily for at least 3 months
• Action: Directly compete with endogenous GnRH for pituitary binding sites suppressing gonadotropin release
• Effect: Result in a rapid decrease in myoma and uterine volume with minor side effects; lacks the initial “flare” effect observed with GnRH agonist stimulation

Androgenic Agonists

• Eg Danazol, Gestrinone
• Can treat symptoms of fibroids but are related to frequent side effects

Antifibrinolytic Drug

• Eg Tranexamic acid
• Decreases uterine bleeding, including menorrhagia related to fibroids, but does not reduce volume of fibroids

Aromatase Inhibitors

• Eg Letrozole, Anastrozole, Fadrozole
• Clinical trials have shown reduction in size and symptoms of leiomyomas,though additional studies are needed to determine its cost effectiveness and duration of response

Hormonal Contraceptives

• Eg Levonorgestrel-releasing intrauterine system, exogenous progestins
• Reduce bleeding related to leiomyoma and provide contraception
• Do not appear to be effective in reducing bulk symptoms

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Used to treat pain, reduce blood loss from fibroids, but do not reduce volume of fibroids

Selective Estrogen Receptor Modulator (SERM)

• Eg Raloxifene
• May be given to women in the perimenopausal or preoperative periods

Other Therapeutic Options

• The following are undergoing clinical trials and laboratory investigations to determine their role in the management of leiomyomas: Elagolix, Relugolix, Asoprisnil, Telapristone, epigallocatechin gallate, Pirfenidone, Tranilast, curcumin, and vitamin D