Hormonal contraception and PMS Inger Sundström Poromaa Department of Women s and Children s Health Uppsala University
Definitions Premenstrual syndrome (PMS) ICD 10: Two symptoms, at least one psychological, regularly recurring in the premenstrual week Prevalence 17-18% Premenstrual dysphoric disorder (PMDD) DSM-5: Five symptom, at least four psychological, regularly recurring in the premenstrual week Prevalence 3% Treatment studies primarily done in PMDD
Prevalence of premenstrual symptoms
Progesterone causes the symptoms Mood symptoms with hormonal contraception Mood symptoms during sequential HRT resemble PMS GnRH agonists alleviate symptoms Progesterone treatment ineffective
RCTs on antidepressants Stone AB, et al. Fluoxetine. Psychopharmacol Bull. 1990; Veeninga AT, et al. Fluoxetine. Psychopharmacology (Berl). 1990; Stone AB et al. Fluoxetine. J Clin Psychiatry. 1991. Sundblad C et al. Clomipramine. Acta Psychiatr Scand. 1992 Wood SH et al. Fluoxetine. Obstet Gynecol. 1992 Sundblad C et al. Clomipramine. Neuropsychopharmacology. 1993 Eriksson E et al. Paroxetine. Neuropsychopharmacology. 1995. Steiner M et al. Fluoxetine. N Engl J Med. 1995 Halbreich U and Smoller JW. Sertraline. J Clin Psychiatry. 1997 Pearlstein TB et al. Fluoxetine,. J Clin Psychopharmacol. 1997 Su TP et al. Fluoxetine. Neuropsychopharmacology. 1997 Yonkers KA et al. Sertraline. JAMA. 1997 Wikander I et al. Citalopram. J Clin Psychopharmacol. 1998 Young SA et al. Sertraline. J Clin Psychiatry. 1998 Freeman EW et al. Fluoxetine. J Clin Psychopharmacol. 1999 Freeman EW et al. Fluoxetine. Arch Gen Psychiatry. 1999 Jermain DM et al. Sertraline. Arch Fam Med. 1999 Freeman EW et al. Venlafaxine. Obstet Gynecol. 2001 Cohen LS et al. Fluoxetine. Obstet Gynecol. 2002 Halbreich U et al. Sertraline. Obstet Gynecol. 2002 Hunter MS et al. Fluoxetine. J Psychosom Obstet Gynaecol. 2002 Miner C et al. Fluoxetine. Clin Ther. 2002 Cohen LS et al. Paroxetine. Psychosom Med. 2004 Freeman EW et al. Sertraline. Am J Psychiatry. 2004 Freeman EW et al. Escitalopram. J Clin Psychiatry. 2005 Steiner M et al. Paroxetine. Am J Obstet Gynecol. 2005 Yonkers KA et al. Sertraline. J Affect Disord. 2005 Kornstein SG et al. Sertraline. J Clin Psychiatry. 2006 Yonkers KA et al. Sertraline. J Clin Psychopharmacol. 2006 Landen M et al. Paroxetine. Neuropsychopharmacology. 2007. Eriksson E et al. Escitalopram. J Clin Psychopharmacol. 2008 Steiner M et al. Paroxetine. J Clin Psychiatry. 2008 Wu KY et al. Paroxetine. Psychiatry Clin Neurosci. 2008 Yonkers et al. Sertraline. JAMA Psychiatry. 2015
Antidepressant use in PMDS Higher response rate than in depression (60-90% responders) Response within 48 hours Cyclic treatment 10-14 days before menses All serotonergic antidepressants work chose the one you know
How about hormonal contraception? Combined oral contraceptives Mirena? Esmya?
Yasmin for PMS/PMDD Drosperinone similar to spironolactone 82 women with PMDD Placebo-controlled RCT Significant improvement in appetite, acne and food cravings Freeman, 2002.
YAZ and PMDD 2 placebo-controlled studies 328 PMDD women, parallel Improved with YAZ (24/4) Yonkers et al, Obstet Gynecol 2005 25 PMDD women, cross-over Improved with YAZ (24/4) Pearlstein et al, Contraception 2005
Cross-over study YAZ DRSP Sum Score 75 70 65 60 55 50 45 40 35 30 Baseline End of Treatment Period 1 End of Washout Phase End of Treatment Period 2 Group 1 - Placebo) (YAZ Group 2 (Placebo - YAZ) Pearlstein T et al. Contraception 2005;414-421
Parallel study - YAZ 0 depressed anxious mood swings angry less interest concentration lethargic appetite sleep out of control physical -1-2 -3-4 -5-6 -7 ** *** *** *** ** *** ** ** ** ** *** YAZ Placebo Kimberley A. et al, Obst & Gynecol 2005; Vol 106 :492-501
BUT the PMDD women often complain they cannot tolerate combined hormonal contraception
Placebo-controlled RCT in healthy women Lundin C, Danielsson KG, Bixo M, Moby L, Bengtsdotter H, Jawad I, Marions L, Brynhildsen J, Malmborg A, Lindh I, Sundstrom Poromaa I. Psychoneuroendocrinology. 2017;76:135-143.
Mirena? Leminen A et al. Acta Obstet Gynecol Scand 2012;91(3):318-25
Mifepristone? Halbreich U. Psychiatry. 1990 Nov;53(4):407-9.
Mifepristone? Two small published studies on single-dose mifepristone One unpublished study with positive results Some studies on high-dose mifepristone on psychotic depression
Esmya, ongoing trial in women with PMDD
Conclusion Low-dose 24/4 combined oral contraceptives can be used to treat PMDD Be ware of increased symptoms in the intermenstrual phase SSRI appear superior in the clinic but head-to-head comparisons are lacking