Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder

• Published in: Contraception (Stoneham) Vol. 85; no. 1; pp. 19 - 27
• Main Authors: Halbreich, Uriel, Freeman, Ellen W., Rapkin, Andrea J., Cohen, Lee S., Grubb, Gary S., Bergeron, Richard, Smith, Lynne, Mirkin, Sebastian, Constantine, Ginger D.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2012; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Continuous; Contraceptive Agents, Female - administration & dosage; Contraceptive Agents, Female - adverse effects; Depression; Double-Blind Method; Estrogens - administration & dosage; Estrogens - adverse effects; Ethinyl estradiol; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - adverse effects; Female; Female genital diseases; Genital system. Reproduction; Gynecology. Andrology. Obstetrics; Humans; Levonorgestrel; Levonorgestrel - administration & dosage; Levonorgestrel - adverse effects; Medical sciences; Middle Aged; Mood disorders; Non tumoral diseases; Obstetrics and Gynecology; Oral contraceptive; Pharmacology. Drug treatments; Premenstrual dysphoric disorder; Premenstrual Syndrome - drug therapy; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Treatment Outcome; Young Adult; Ethinyl estradiol; Oral contraceptive; Continuous; Premenstrual dysphoric disorder; Levonorgestrel; Mood disorder; Ethinylestradiol; Menstruation disorders; Estrogen; Oral administration; Depression; Female genital diseases; Progestagen; Contraceptive; Premenstrual syndrome
• ISSN: 0010-7824; 1879-0518; 1879-0518
• DOI: 10.1016/j.contraception.2011.05.008

The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD). In this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE ( n=186) or placebo ( n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP). Mean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (−30.52±1.73 [SE] vs. −22.47±1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (−26.77±1.83 vs. −20.89±1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (≥50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥1 improvement) at last on-therapy cycle (p=.025). Continuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD.