GnRH Agonist Therapy

  1. Nature of the Drug  
    Lupron (leuprolide acetate), Synarel, Buserelin, and Zoladex are GnRH analogues (hormonal drugs) which are currently approved for treatment of prostatic cancer and pain associated with endometriosis. They are also useful in treating other conditions including fibroid tumors, and in conjunction with ovarian stimulation. Continuous daily administration decreases levels of FSH, LH, and estrogens to postmenopausal levels by acting as an inhibitor of pituitary hormone secretion. This effect is selective and reversible upon discontinuation of the drugs.
  2. Risk and/or Side Effects  
    • GnRH agonists have not been shown to cause major side effects in humans so far. The drugs are known to act primarily by suppressing pituitary hormone levels. The risks of therapy include:
      • Failure of the drug to produce the desired effect.
      • A chance of transient and mild worsening of symptoms early in treatment.
      • Discontinuation of menses.
      • Hot flashes, vaginal dryness, mood swings, headaches, and spotting.
      • Localized skin reaction at injection site.
    • In rats, large doses of this drug given over long periods of time caused enlargement of some benign tumors of the pituitary gland, but no signs of pituitary abnormality have been observed in human patients treated with leuprolide for 1 - 4 years of duration.
    • GnRH agonists have been taken inadvertently by more than 300 women in pregnancy. An increase risk of miscarriage was identified and potentially treated with progesterone supplementation. Long-term follow-up is not yet available to confirm other significant risk to the child.
  3. Potential Benefits  
    • Endometriosis To deprive endometriotic implants of the sex steroids that maintain them. Several studies have shown that endometriosis lesions may disappear or shrink while on medication.
    • Fibroids To induce fibroid shrinkage. This effect disappears after cessation of therapy. It may be advantageous preceding myomectomy (surgical removal of these uterine tumors).
    • Ovulation Induction To prevent a premature LH surge and to help induce uniform follicle development. A fairly high number of women undergoing ovarian stimulation with Bravelle, (20 -50 %) respond in an unsatisfactory manner. The number of oocytes retrieved, fertilization rates, and implantation rates may be improved. Lupron appears to decrease cancellation rates during ovulation induction and to increase pregnancy rates through uniform folliculogenesis.
  4. Alternative Therapy  
    • Endometriosis
      1. Danocrine or other medications
      2. Laser surgery to remove disease
      3. Major surgery to remove disease
    • Fibroids
      1. Myomectomy to remove the fibroid
      2. Hysterectomy to remove the uterus
    • Ovulation Induction
      1. Varying combinations of Clomiphene and Bravelle, without the use of Lupron.

Dosages of medication are relative to the individual patient and purpose of the therapy and are evaluated on an ongoing basis.

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