Jurate Aleknaviciute1, Joke H M Tulen2, Yolanda B De Rijke3, Christian G Bouwkamp4, Mark van der Kroeg5, Mirjam Timmermans6, Vincent L Wester7, Veerle Bergink8, Witte J G Hoogendijk9, Henning Tiemeier10, Elisabeth F C van Rossum11, Cornelis G Kooiman12, Steven A Kushner13. 1. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: j.aleknaviciute@erasmusmc.nl. 2. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: j.h.m.tulen@erasmusmc.nl. 3. Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: y.derijke@erasmusmc.nl. 4. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: c.bouwkamp@erasmusmc.nl. 5. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: m.vanderkroeg@erasmusmc.nl. 6. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: m.timmermans.1@erasmusmc.nl. 7. Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: v.wester@erasmusmc.nl. 8. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: v.bergink@erasmusmc.nl. 9. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: w.hoogendijk@erasmusmc.nl. 10. Departments of Child and Adolescent Psychiatry and Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl. 11. Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: e.vanrossum@erasmusmc.nl. 12. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: kooiman@cgkooiman.nl. 13. Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: s.kushner@erasmusmc.nl.
Abstract
BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. METHODS: We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. RESULTS: Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P<0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P<0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P<0.0001). CONCLUSIONS: Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions.
BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. METHODS: We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. RESULTS:Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P<0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P<0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P<0.0001). CONCLUSIONS: Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions.
Authors: Carolin A Lewis; Ann-Christin S Kimmig; Rachel G Zsido; Alexander Jank; Birgit Derntl; Julia Sacher Journal: Curr Psychiatry Rep Date: 2019-11-07 Impact factor: 5.285