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Levonorgestrel intrauterine device (IUD) exacerbation of PMS symptoms

Francisco J. Appiani, MD

Asociación Civil para el Estudio y Desarrollo de las Neurociencias (ACEDEN), Buenos Aires, Argentina

Brendan T. Carroll, MD

Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio, USA, Chillicothe VA Medical Center, Chillicothe, Ohio, USA

KEYWORDS: depression, premenstrual syndrome, PMS



Premenstrual syndrome (PMS) is one of the most common health problems reported by women of reproductive age, with an estimated prevalence of 12.6% to 31% of menstruating women.1 Progestins—synthetic progestogens used for hormonal contraception—can produce or exacerbate PMS-like symptoms.2

Case report

Ms. N, age 40, has a long history of moderate PMS, according to criteria from the American Congress of Obstetricians and Gynecologists,3 but she did not fulfill DSM-5 criteria for premenstrual dysphoric disorder (PMDD)4 and prospective chart mood register.5 Nine months after her second child was born, Ms. N’s gynecologist suggested she use an intrauterine device (IUD) with the progestin levonorgestrel (Mirena) for contraception. After IUD insertion, Ms. N reported increased PMS symptoms, particularly irritability, tiredness, and being overwhelmed by her usual daily activities, but her symptoms did not disappear during the follicular phase. Ms. N consulted a psychiatrist 1 year after IUD insertion because of her exacerbated PMS symptoms. Although she could not identify another cause for her worsening symptoms, Ms. N did not associate her mood symptoms to the IUD. Because she could not tolerate oral contraceptives, Ms. N would not agree to remove the IUD, and was started on sertraline, 100 mg/d, to treat her PMS symptoms.


Ms. N immediately responded to sertraline treatment with significant improvement in mood and daily activity, which was similar to change in PMS symptoms seen with selective serotonin reuptake inhibitors. Ms. N was not taking any other medications, had normal hormone levels, and showed no signs of perimenopause. It is possible that Ms. N’s symptom profile represents a chronic exacerbation of PMS symptoms (irritability, tiredness, and feeling overwhelmed) that also are present in the follicular phase, rather than comorbid major depressive disorder. This hypothesis is supported by Ms. N’s clinical presentation and the time between response and pharmacological treatment. According to the Naranjo Scale, Ms. N’s symptoms probably were induced by levonorgestrel (6 points).6

Mirena is an intrauterine delivery system of low doses of levonorgestrel. Initially, levonorgestrel is released at approximately 20 mcg/d, which decreases progressively to half that value after 5 years.7 There are reports of psychiatric side effects induced by levonorgestrel-releasing contraceptive implants—particularly anxiety, nervousness, and depression.8

Ms. N’s case illustrates probable exacerbation of retrospective PMS symptoms spreading to the entire menstrual cycle after insertion of a levonorgestrel IUD. Despite local release of levonorgestrel, some patients may be more likely to develop psychiatric symptoms. Gynecologists and psychiatrists must be aware of patients’ histories of psychiatric symptoms— especially PMS or PMDD—when choosing a contraceptive method.

DISCLOSURE: The authors report no financial relationships with any company whose products are mentioned in this article, or with manufacturers of competing products.


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  2. Baker LJ, O’Brien PM. Potential strategies to avoid progestogen-induced premenstrual disorders. Menopause Int. 2012;18:73–76.
  3. Mishell D. Premenstrual Disorders: epidemiology and disease burden. Am J Manag Care. 2005;11: S473–S479.
  4.  Diagnostic and statistical manual of mental disorders, 5th ed. Washington DC: American Psychiatric Association; 2013.
  5. Endicott J, Nee J, Harrison W. Daily Record of Severity of Problems (DRSP): reliability and validity. Arch Womens Ment Health. 2006;9:41–49.
  6. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245.
  7.  Bayer HealthCare Pharmaceuticals Inc. MIRENA (levonorgestrel) intrauterine device. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=92231d6f-f4d8-43b0-aa95-f7cec1cc18c5#nlm34070-3. Accessed August 21 2013.
  8. Sivin I. Risks and benefits advantages and disadvantages of levonorgestrel-releasing contraceptive implants. Drug Saf. 2003;26:303–335.

CORRESPONDENCE: Francisco J. Appiani, MD, Asociación Civil para el Estudio y Desarrollo de las Neurociencias (ACEDEN), Arenales 2838 5 B (CP:1425), Buenos Aires, Argentina E-MAIL: Franciscoappiani@live.com.ar