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Psychoneuroendocrinology. 2017 Jun;80:39-45. doi: 10.1016/j.psyneuen.2017.02.025. Epub 2017 Feb 28.

The levonorgestrel-releasing intrauterine device potentiates stress reactivity.

Author information

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.

KEYWORDS:

Adrenocorticotropic hormone; Affective disorders; Autonomic nervous system; Cortisol; Hypothalamus-Pituitary-Adrenal (HPA) axis; Levonorgestrel-releasing intrauterine device; Long-acting reversible contraception (LARC)

PMID:
28315609
DOI:
10.1016/j.psyneuen.2017.02.025
[Indexed for MEDLINE]

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