leiomyomas
LEIOMYOMAS

Leiomyomas or uterine fibroids are benign tumors of the uterus that consist of smooth muscle and extracellular matrix collagen and elastin.

Most common solid pelvic tumors and one of the most frequent clinical conditions encountered in gynecologic practice.

They tend to grow during the reproductive years and usually regress during menopause.

 

Principles of Therapy

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

Pharmacotherapy

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 are 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: Pre- and post-operative hemoglobin and hematorcit (Hb and Hct) are significantly improved. Studies reported shrinkage of the fibroid with a reduction in median uterine volume of 31-39% and myoma volume decreased by 23-27%
  • 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: Asoprisnil, Proellex, epigallocatechin gallate, Pirfenidone, Tranilast, curcumin, and vitamin D
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