Gonadotropin-releasing hormone analogues GnRH analogues produce a hypogonadotrophic-hypogonadic state by downregulation of the pituitary gland. Goserelin and leuprolide acetate are the commonly used agonists. Efficacy is limited to pain suppression, and fertility rates may show no improvement. Winkel et al have claimed that GnRH therapy may lead to improvement in pain associated with endometriosis in 85-100% of women. Furthermore, the pain relief is believed to persist for 6-12 months after cessation of treatment. Treatment is usually restricted to monthly injections for 6 months. Loss of trabecular bone density caused by GnRH is restored by 2 years after cessation of therapy. Other prominent adverse effects include hot flashes and vaginal dryness. Add-back therapy and empiric therapy Much interest has been shown in whether estrogen/progestin add-back therapy should be instituted to prevent osteoporosis and hypoestrogenic symptoms. Hormone replacement therapy preparations, progestins, tibolone maleate, and bisphosphonates have all been shown to be effective. Add-back therapy has been shown to prevent loss in bone density and to relieve vasomotor symptoms without reducing the efficacy of GnRH regimens. GnRH agonists have been used for 12 months with norethindrone add-back therapy with good results. A clinical trial has shown that a 3-month empiric course of GnRH, based on a diagnostic algorithm without definitive laparoscopic diagnosis, is efficacious. However, long-term effects of GnRH analogues on bone density in this population remain unproven. Therefore, add-back therapy remains the standard of care while the patient is on GnRH treatment. Also, empiric treatment without a firm diagnosis could result in unnecessary treatment in patients with chronic pelvic pain, whose condition could be due to other causes. In Lings study, 13% of subjects were shown to not have endometriosis. GnRH therapy has also been proven to relieve the pain and bleeding associated with extrapelvic distant endometriosis. GnRH analogues vs danazol A Cochrane review comparing GnRH analogues with danazol treatment showed no difference in improvement of dysmenorrhea, dyspareunia, pelvic pain, or pelvic tenderness. Likewise, no difference in retrospective American Fertility Society (rRAFS) score was found at approximately 24 weeks follow-up. In contrast, studies that evaluated total pain resolution showed greater benefit from GnRH analogues compared with danazol. Side-effect profiles differed, with greater frequency of hot flushes and vaginal dryness with GnRH analogues, whereas danazol treatment resulted in a greater frequency of weight gain, acne, and headaches.
Posted on: Tue, 15 Oct 2013 22:04:06 +0000
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