George A Vilos1, Jennifer L Marks-Adams2, Angelos G Vilos2, Ayman Oraif3, Basim Abu-Rafea4, Robert F Casper5. 1. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Western University, London, Ontario, Canada. Electronic address: george.vilos@lhsc.on.ca. 2. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Western University, London, Ontario, Canada. 3. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Western University, London, Ontario, Canada; Department of Obstetrics and Gynecology, King AbdulAziz University, Jeddah, Saudi Arabia. 4. Department of Obstetrics and Gynecology, Dalhousie University, Halifax, Nova Scotia, Canada. 5. Division of Reproductivve Sciences, Department of Obstetrics and Gynecology, University of Toronto, and Lunenfield-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Abstract
STUDY OBJECTIVE: Experience with low-dose intermittent danazol or prolonged gonadotropin-releasing hormone agonist (GnRH-a) with and without add-back therapy in endometriosis-associated ureteral obstruction. DESIGN: Retrospective case series (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS: Three women with endometriosis-associated ureteral obstruction. INTERVENTION: The regimen of GnRH-a alone or with add-back included (1) leuprolide acetate 3.75 mg intramuscularly monthly; (2) micronized 17α-estradiol 1 mg/day by mouth; (3) pulsed norethinedrone 0.35 mg/day by mouth, 2 days on and/or 2 days off; and (4) letrozole 2.5 mg by mouth for the first 5 days of the first GnRH-a injection. Danazol, 100 mg/day by mouth, was prescribed as a regimen of 3 months on, 3 months off, for 4 years. MEASUREMENTS AND MAIN RESULTS: The first case was a 50-year-old woman, gravida 3, para 3, body mass index (BMI) 27 kg/m(2), with multiple surgeries, including hysterectomy and bilateral salpingo-oophorectomy (HBSO), and history of a stroke. She presented with right-sided pain and hydro-uretero-nephrosis. Magnetic resonance imaging identified a right adnexal cyst (4.5 × 3.4 × 2.4 cm). She was treated with leuprolide acetate monthly injections and a ureteric stent. The cyst, pain, and hydro-uretero-nephrosis resolved after 12 months. The second case was a 45-year-old woman, G2P2, BMI 28 kg/m(2) with multiple surgeries, including HBSO. She presented with left-sided pelvic pain. Ultrasound identified a left adnexal cyst and hydronephrosis. After 3 months of leuprolide acetate and add-back therapy, the cyst, pain, and hydronephrosis resolved. The third case was a 46-year-old woman, G2P2, BMI 25 kg/m(2), who presented with left flank and pelvic pain. Magnetic resonance imaging indicated moderate left hydronephrosis and left adnexal pelvic side-wall involvement with possible endometriosis. Due to many previous surgeries, this patient was a high-risk surgical candidate, and therefore, she was offered medical therapy. After a normal serum liver and lipid profile, she was started on danazol, 100 mg/day for 3 months. After 3 months of therapy, there was complete resolution of the patient's hydronephrosis and pain. She was then advised to continue with a 3-month on, 3-month off regimen. She discontinued the danazol and remained asymptomatic with no recurrence of hydronephrosis at 3 years. CONCLUSIONS: Low-dose intermittent danazol or GnRH-a alone or with add-back, may be effective long-term therapies in endometriosis-associated ureteral obstruction when surgery is contraindicated, refused, or difficult to perform.
STUDY OBJECTIVE: Experience with low-dose intermittent danazol or prolonged gonadotropin-releasing hormone agonist (GnRH-a) with and without add-back therapy in endometriosis-associated ureteral obstruction. DESIGN: Retrospective case series (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS: Three women with endometriosis-associated ureteral obstruction. INTERVENTION: The regimen of GnRH-a alone or with add-back included (1) leuprolide acetate 3.75 mg intramuscularly monthly; (2) micronized 17α-estradiol 1 mg/day by mouth; (3) pulsed norethinedrone 0.35 mg/day by mouth, 2 days on and/or 2 days off; and (4) letrozole 2.5 mg by mouth for the first 5 days of the first GnRH-a injection. Danazol, 100 mg/day by mouth, was prescribed as a regimen of 3 months on, 3 months off, for 4 years. MEASUREMENTS AND MAIN RESULTS: The first case was a 50-year-old woman, gravida 3, para 3, body mass index (BMI) 27 kg/m(2), with multiple surgeries, including hysterectomy and bilateral salpingo-oophorectomy (HBSO), and history of a stroke. She presented with right-sided pain and hydro-uretero-nephrosis. Magnetic resonance imaging identified a right adnexal cyst (4.5 × 3.4 × 2.4 cm). She was treated with leuprolide acetate monthly injections and a ureteric stent. The cyst, pain, and hydro-uretero-nephrosis resolved after 12 months. The second case was a 45-year-old woman, G2P2, BMI 28 kg/m(2) with multiple surgeries, including HBSO. She presented with left-sided pelvic pain. Ultrasound identified a left adnexal cyst and hydronephrosis. After 3 months of leuprolide acetate and add-back therapy, the cyst, pain, and hydronephrosis resolved. The third case was a 46-year-old woman, G2P2, BMI 25 kg/m(2), who presented with left flank and pelvic pain. Magnetic resonance imaging indicated moderate left hydronephrosis and left adnexal pelvic side-wall involvement with possible endometriosis. Due to many previous surgeries, this patient was a high-risk surgical candidate, and therefore, she was offered medical therapy. After a normal serum liver and lipid profile, she was started on danazol, 100 mg/day for 3 months. After 3 months of therapy, there was complete resolution of the patient's hydronephrosis and pain. She was then advised to continue with a 3-month on, 3-month off regimen. She discontinued the danazol and remained asymptomatic with no recurrence of hydronephrosis at 3 years. CONCLUSIONS: Low-dose intermittent danazol or GnRH-a alone or with add-back, may be effective long-term therapies in endometriosis-associated ureteral obstruction when surgery is contraindicated, refused, or difficult to perform.