Leiomyomas Treatment
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 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