Advertisement
Original research article| Volume 85, ISSUE 1, P19-27, January 2012

Download started.

Ok

Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder

  • Author Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Uriel Halbreich
    Correspondence
    Corresponding author. Biobehavior Program, University of Buffalo School of Medicine and Behavioral Sciences, Hayes Annex C, Ste 1, 3435 Main St. Bldg 5, Buffalo, NY 14214. Tel.: +1 716 829 3811, +1 716 829 3808; fax: +1 716 829 3812.
    Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Affiliations
    Departments of Psychiatry and Gynecology and Obstetrics, University of Buffalo (SUNY-AB), Buffalo, NY; 14214, USA
    Search for articles by this author
  • Ellen W. Freeman
    Affiliations
    Department of Obstetrics and Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, PA; 19104, USA
    Search for articles by this author
  • Andrea J. Rapkin
    Affiliations
    Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California��Los Angeles, Los Angeles, CA; 90095, USA
    Search for articles by this author
  • Lee S. Cohen
    Affiliations
    Department of Psychiatry, Harvard Medical School, Boston, MA; 02114, USA
    Search for articles by this author
  • Author Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Gary S. Grubb
    Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Affiliations
    Pfizer, Inc., Collegeville, PA; 19426, USA
    Search for articles by this author
  • Richard Bergeron
    Affiliations
    Departments of Psychiatry and Cellular and Molecular Medicine, Ottawa Health Research Institute, Ontario, Canada, CAN K1H 8L6
    Search for articles by this author
  • Lynne Smith
    Affiliations
    Pfizer, Inc., Collegeville, PA; 19426, USA
    Search for articles by this author
  • Sebastian Mirkin
    Affiliations
    Pfizer, Inc., Collegeville, PA; 19426, USA
    Search for articles by this author
  • Author Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Ginger D. Constantine
    Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.
    Affiliations
    Pfizer, Inc., Collegeville, PA; 19426, USA
    Search for articles by this author
  • Author Footnotes
    1 Employees of Wyeth Research, which was acquired by Pfizer in October 2009, at the time of the study.

      Abstract

      Background

      The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD).

      Study Design

      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).

      Results

      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).

      Conclusions

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hylan T.R.
        • Sundell K.
        • Judge R.
        The impact of premenstrual symptomatology on functioning and treatment-seeking behavior: experience from the United States, United Kingdom, and France.
        J Womens Health Gend Based Med. 1999; 8: 1052
        • Johnson S.R.
        • McChesney C.
        • Bean J.A.
        Epidemiology of premenstrual symptoms in a nonclinical sample. I. Prevalence, natural history and help-seeking behavior.
        J Reprod Med. 1988; 33: 340-346
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 2000: 771-774
        • Yang M.
        • Wallenstein G.
        • Hagan M.
        • Guo A.
        • Chang J.
        • Kornstein S.
        Burden of premenstrual dysphoric disorder on health-related quality of life.
        J Womens Health (Larchmt). 2008; 17: 113-121
        • Kroll R.
        • Rapkin A.J.
        Treatment of premenstrual disorders.
        J Reprod Med. 2006; 51: 359-370
        • Lopez L.M.
        • Kaptein A.A.
        • Helmerhorst F.M.
        Oral contraceptives containing drospirenone for premenstrual syndrome.
        Cochrane Database Syst Rev. 2009; (CD006586)
        • Brown J.
        • O'Brien P.M.
        • Marjoribanks J.
        • Wyatt K.
        Selective serotonin reuptake inhibitors for premenstrual syndrome.
        Cochrane Database Syst Rev. 2009; (CD001396)
        • Archer D.F.
        • Kovalevsky G.
        • Ballagh S.A.
        • Grubb G.
        Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen.
        Contraception. 2009; 80: 245-253
        • Endicott J.
        • Nee J.
        • Harrison W.
        Daily Record of Severity of Problems (DRSP): reliability and validity.
        Arch Womens Ment Health. 2006; 9: 41-49
        • Lerner D.
        • Rogers W.H.
        • Chang H.
        The work limitations questionnaire.
        Qual Life Newsl. 2002; 28: 9-10
        • Halbreich U.
        Selective serotonin reuptake inhibitors and initial oral contraceptives for treatment of PMDD: effective but not enough.
        CNS Spectr. 2008; 13: 293-300
        • Landen M.
        • Eriksson O.
        • Sundblad C.
        • Andersch B.
        • Naessen T.
        • Eriksson E.
        Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.
        Psychopharmacology (Berl). 2001; 155: 292-298
        • Halbreich U.
        • Bergeron R.
        • Yonkers K.A.
        • Freeman E.
        • Stout A.L.
        • Cohen L.
        Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder.
        Obstet Gynecol. 2002; 100: 1219-1229
        • Halbreich U.
        • O'Brien P.M.
        • Eriksson E.
        • Backstrom T.
        • Yonkers K.A.
        • Freeman E.W.
        Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?.
        CNS Drugs. 2006; 20: 523-547
        • Landen M.
        • Nissbrandt H.
        • Allgulander C.
        • Sorvik K.
        • Ysander C.
        • Eriksson E.
        Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.
        Neuropsychopharmacology. 2007; 32: 153-161
        • Teichmann A.
        • Apter D.
        • Emerich J.
        • et al.
        Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial.
        Contraception. 2009; 80: 504-511
        • Archer D.F.
        • Jensen J.T.
        • Johnson J.V.
        • Borisute H.
        • Grubb G.S.
        • Constantine G.D.
        Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: Phase 3 study results.
        Contraception. 2006; 74: 439-445