Hormonal contraception and PMS. Inger Sundström Poromaa Department of Women s and Children s Health Uppsala University

Transcription

1 Hormonal contraception and PMS Inger Sundström Poromaa Department of Women s and Children s Health Uppsala University

2 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

3 Prevalence of premenstrual symptoms

4 Progesterone causes the symptoms Mood symptoms with hormonal contraception Mood symptoms during sequential HRT resemble PMS GnRH agonists alleviate symptoms Progesterone treatment ineffective

5 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 Sundblad C et al. Clomipramine. Acta Psychiatr Scand Wood SH et al. Fluoxetine. Obstet Gynecol Sundblad C et al. Clomipramine. Neuropsychopharmacology Eriksson E et al. Paroxetine. Neuropsychopharmacology Steiner M et al. Fluoxetine. N Engl J Med Halbreich U and Smoller JW. Sertraline. J Clin Psychiatry Pearlstein TB et al. Fluoxetine,. J Clin Psychopharmacol Su TP et al. Fluoxetine. Neuropsychopharmacology Yonkers KA et al. Sertraline. JAMA Wikander I et al. Citalopram. J Clin Psychopharmacol Young SA et al. Sertraline. J Clin Psychiatry Freeman EW et al. Fluoxetine. J Clin Psychopharmacol Freeman EW et al. Fluoxetine. Arch Gen Psychiatry Jermain DM et al. Sertraline. Arch Fam Med Freeman EW et al. Venlafaxine. Obstet Gynecol Cohen LS et al. Fluoxetine. Obstet Gynecol Halbreich U et al. Sertraline. Obstet Gynecol Hunter MS et al. Fluoxetine. J Psychosom Obstet Gynaecol Miner C et al. Fluoxetine. Clin Ther Cohen LS et al. Paroxetine. Psychosom Med Freeman EW et al. Sertraline. Am J Psychiatry Freeman EW et al. Escitalopram. J Clin Psychiatry Steiner M et al. Paroxetine. Am J Obstet Gynecol Yonkers KA et al. Sertraline. J Affect Disord Kornstein SG et al. Sertraline. J Clin Psychiatry Yonkers KA et al. Sertraline. J Clin Psychopharmacol Landen M et al. Paroxetine. Neuropsychopharmacology Eriksson E et al. Escitalopram. J Clin Psychopharmacol Steiner M et al. Paroxetine. J Clin Psychiatry Wu KY et al. Paroxetine. Psychiatry Clin Neurosci Yonkers et al. Sertraline. JAMA Psychiatry. 2015

6 Antidepressant use in PMDS Higher response rate than in depression (60-90% responders) Response within 48 hours Cyclic treatment days before menses All serotonergic antidepressants work chose the one you know

7 How about hormonal contraception? Combined oral contraceptives Mirena? Esmya?

8 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.

9 YAZ and PMDD 2 placebo-controlled studies 328 PMDD women, parallel Improved with YAZ (24/4) Yonkers et al, Obstet Gynecol PMDD women, cross-over Improved with YAZ (24/4) Pearlstein et al, Contraception 2005

10 Cross-over study YAZ DRSP Sum Score 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;

11 Parallel study - YAZ 0 depressed anxious mood swings angry less interest concentration lethargic appetite sleep out of control physical ** *** *** *** ** *** ** ** ** ** *** YAZ Placebo Kimberley A. et al, Obst & Gynecol 2005; Vol 106 :

12 BUT the PMDD women often complain they cannot tolerate combined hormonal contraception

13 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:

14 Mirena? Leminen A et al. Acta Obstet Gynecol Scand 2012;91(3):318-25

15 Mifepristone? Halbreich U. Psychiatry Nov;53(4):407-9.

16 Mifepristone? Two small published studies on single-dose mifepristone One unpublished study with positive results Some studies on high-dose mifepristone on psychotic depression

17 Esmya, ongoing trial in women with PMDD

18 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