IUD and Norethindrone Acetate for Treatment of Endometriosis

Endometriosis is a major source of morbidity for U.S. females, affecting ~49% of adolescents with chronic pelvic pain and 10% of all women of reproductive age. This percentage translates into approximately 176 million women worldwide who may suffer from endometriosis. Annual health care costs are estimated to be over $22 billion in the US alone. Over 50% of adults with endometriosis report onset of severe pelvic pain during their adolescence. Symptoms result in decreased quality of life, negative socioeconomic consequences, impaired reproductive potential, and diminished mental health. Endometriosis is a chronic disease that progresses over time in more than half of patients. Endometriosis has no cure. For adolescents in particular, this means that the impact of endometriosis and its symptoms can last for decades. Appropriate management involves not only prompt initiation of therapy, but also the maintenance of therapy for a protracted length of time. Medical therapy for endometriosis typically includes oral progestins or contraceptive pills. Though often effective, these options are associated with systemic side-effects which may further affect compliance and preclude long-term use. Furthermore, the need for repeated or regular administration compromises compliance and therefore efficacy. The levonorgestrel-releasing intrauterine system (LNG-IUD) has been evaluated as a promising treatment for endometriosis in adult women. The LNG-IUD 52 mg (Mirena) delivers levonorgestrel (LNG) to the uterine cavity at a steady rate of 20 µg/day over 5 to 6 years. The LNG causes atrophy and pseudo decidualization of the uterine lining, along with apoptosis of endometrial glands and stroma. As the LNG-IUD requires no further patient action following insertion, patient compliance is excellent. While continuation of the device is generally very good in adults, unfavorable uterine bleeding patterns are the most frequent reason for early device removal, particularly within the first 6 months. Anecdotal clinical experience suggests that combining use of the LNG-IUD with low-dose oral progestin therapy may maximize effectiveness and continuation of the LNG-IUD device in adolescents. The investigators will recruit 80 adolescents for participation in a double-blind, randomized trial of NETA (n=40) vs. placebo (control group, n=40) for adjunct treatment to the levonorgestrel-containing IUD for pelvic pain due to endometriosis. It is believed that a combination of the locally-acting LNG-IUD plus systemic NETA may be the optimal combination to effectively treat endometriosis pain, minimize side effects, provide contraception, and control bleeding for adolescents with endometriosis.