Macarena Alpañés1, Francisco Álvarez-Blasco1, Elena Fernández-Durán1, Manuel Luque-Ramírez1, Héctor F Escobar-Morreale1. 1. Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, Madrid, Spain.
Abstract
OBJECTIVE: We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). DESIGN: We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). METHODS: The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension). A complete anthropometric, biochemical, hormonal and metabolic evaluation was conducted every three months and data were submitted to intention-to-treat analyses. RESULTS: Twenty-four patients were assigned to COC plus spironolactone and 22 patients to metformin. Compared with metformin, COC plus spironolactone caused larger decreases in hirsutism score (mean difference 4.6 points, 95% CI: 2.6-6.7), total testosterone (1.1 nmol/L, 0.4-1.7), free testosterone (25 pmol/L, 12-39), androstenedione (5.5 nmol/L, 1.8-9.2) and dehydroepiandrosterone sulfate (2.7 μmol/L, 1.4-4.0). Menstrual dysfunction was less frequent with COC plus spironolactone (OR: 0.06, 95% CI: 0.02-0.23). No differences were found in frequencies of abnormal glucose tolerance (OR: 1.7, 95% CI: 0.7-4.4), dyslipidemia (OR: 0.6, 95% CI: 0.2-1.8) or hypertension (OR: 0.3, 95% CI: 0.5-2.0). No major adverse events occurred and biochemical markers were similarly safe with both treatments. CONCLUSIONS:COC plus spironolactone was more effective than metformin for symptoms of PCOS showing similar safety and overall neutral effects on cardiometabolic risk factors.
RCT Entities:
OBJECTIVE: We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). DESIGN: We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). METHODS: The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension). A complete anthropometric, biochemical, hormonal and metabolic evaluation was conducted every three months and data were submitted to intention-to-treat analyses. RESULTS: Twenty-four patients were assigned to COC plus spironolactone and 22 patients to metformin. Compared with metformin, COC plus spironolactone caused larger decreases in hirsutism score (mean difference 4.6 points, 95% CI: 2.6-6.7), total testosterone (1.1 nmol/L, 0.4-1.7), free testosterone (25 pmol/L, 12-39), androstenedione (5.5 nmol/L, 1.8-9.2) and dehydroepiandrosterone sulfate (2.7 μmol/L, 1.4-4.0). Menstrual dysfunction was less frequent with COC plus spironolactone (OR: 0.06, 95% CI: 0.02-0.23). No differences were found in frequencies of abnormal glucose tolerance (OR: 1.7, 95% CI: 0.7-4.4), dyslipidemia (OR: 0.6, 95% CI: 0.2-1.8) or hypertension (OR: 0.3, 95% CI: 0.5-2.0). No major adverse events occurred and biochemical markers were similarly safe with both treatments. CONCLUSIONS: COC plus spironolactone was more effective than metformin for symptoms of PCOS showing similar safety and overall neutral effects on cardiometabolic risk factors.
Authors: Eloise Fraison; Elena Kostova; Lisa J Moran; Sophia Bilal; Carolyn C Ee; Christos Venetis; Michael F Costello Journal: Cochrane Database Syst Rev Date: 2020-08-13