FACTS Mental Health Awareness Series
The Effect of Levonorgestrel-Releasing IUDs on Mental Health
By Sunny Lee
Editor’s Note: As we continue our series highlighting Mental Health Awareness Month, we are featuring a patient interview that makes clear the dual need for comprehensive contraceptive counseling in modern medicine and compassionate care for patients with mental health issues. It also highlights an often unrecognized problem, the trauma many women experience at the hands of the medical community when their concerns are not adequately addressed. Sunny Lee, a medical student who participated in the FACTS elective, interviewed a 28-year-old woman who experienced psychiatric symptoms after insertion of a hormonal IUD.
This is a true story about a 28-year-old female and her experience with a hormonal intrauterine device (IUD). Though commonly prescribed and advertised as a safe, reliable form of contraception, hormonal IUDs may have overlooked adverse drug reactions involving mood symptoms, such as depression, anxiety, and panic disorder. I was inspired to write about this woman’s story in hopes of giving a voice to those with a similar experience and raising awareness when counseling patients on various forms of contraception. The patient agreed to be quoted under the pseudonym “Bella” to protect her privacy.
Like many newlyweds, Bella and her husband desired a reliable form of contraception. After reviewing her options, she was most interested in the hormonal IUDs due to their common use and high efficacy. However, she had some apprehension because of her history of depression, anxiety, and a series of depressive episodes from oral contraceptive pills. At the time, her mood was stable with a daily 50-mg dose of sertraline, and she did not have any other medical problems or take any other medications. When Bella shared these concerns with her OB-GYN during her IUD insertion appointment, her physician reassured her that the IUD would act locally and not be absorbed systemically — suggesting it was highly unlikely she would develop any mental health symptoms. However, one study showed locally released levonorgestrel-releasing IUDs lead to endometrial concentrations that are 200 to 800 times those found after daily oral use [1]. According to the criteria of the World Health Organization drug monitoring center and researchers Edwards, Aronson, and Naranjo, the levonorgestrel-releasing IUD can be classified as a “possible” cause or “probably/likely” to play a role in the development of psychiatric symptoms [2],[3],[4].
In December 2020, Bella had the Skyla IUD placed. For the next several months, she experienced daily spotting, as expected. However, starting in February of 2021, she began to notice changes in her mood. She became very anxious and started experiencing palpitations at night. Bella visited her OB-GYN to discuss these new symptoms but was told that the IUD was not the cause of her worsening mental health. She also pursued a cardiology workup for her new-onset palpitations, which found nothing amiss. With the reassurance of her doctors, she told herself that she was just stressed and that everything would go away on its own.
“She became very anxious and started experiencing palpitations at night. Bella visited her OB-GYN to discuss these new symptoms but was told that the IUD was not the cause of her worsening mental health.”
By March, Bella’s anxiety and panic symptoms increased in both frequency and severity, hindering her daily quality of life. She said, “I was crying every single night to my husband that I felt trapped and that I didn’t feel okay… I had racing thoughts about dying. It was all so intense. Just remembering all of this is bringing tears to my eyes.”
She began seeing a psychiatrist who shared anecdotally that he had worked with a few female patients who experienced worsening mood symptoms with hormonal IUDs. Her sertraline was increased to 75 mg that month and again to 100 mg the next month without improvement. Her symptoms continued worsening despite this adequate medical treatment, so Bella eventually decided to have the IUD removed in May. “I had thought the worst was over, but it was only the beginning,” she recalled.
Despite the initial relief, Bella began to experience a new set of symptoms starting in June. During the days preceding her menses, she experienced horrible migraines and intense panic attacks that occurred multiple times in a day. After her menses, she woke up every night with a tingling and burning sensation all over her body, hot flashes, and shortness of breath. During the day, she began to experience bloating, dry mouth, and a metallic taste.
“I truly can’t even remember fully who I was during these times because I had become a shell of who I once was,” she said. “Life felt like a torture. And whenever I would talk to people about how I felt, I noticed that many thought I was crazy or I was making this up or that I was exaggerating. I can’t express how lonely it was.”
But Bella wasn’t alone. Emerging research has shown an increase in first-time depression diagnose [5], suicide attempts [6], and anxiety and sleep disturbances [7] associated with levonorgestrel- releasing IUDs. However, many of these patients’ fears about their symptoms were dismissed as groundless [8]. There is a similar case of a 41-year-old female with onset of mood symptoms after IUD replacement who had resolution of her symptoms shortly after the IUD removal. Zeiss et al. suggests that, much like gynecologists would use an ultrasound to confirm the positioning of an IUD, it should be equally common to examine the patient’s mental health after IUD placement. [9]
“Emerging research has shown an increase in first-time depression diagnoses, suicide attempts, and anxiety and sleep disturbances associated with levonorgestrel- releasing IUDs.”
During the months that followed, Bella pursued multiple treatments and workups without a clear explanation and little to no improvement in her symptoms. She was at her maximum tolerable dose of sertraline and had carcinoid or other tumors ruled out. Extensive labs showed everything was normal, except for her vitamin D and B12 levels, for which she then started taking supplements. A one-time progesterone was 18.5ng/dL (HIGH) and estrogen was 696pg/mL (HIGH), which were drawn right after her menses. She underwent a pelvic ultrasound to evaluate for a functional cyst to explain her elevated estrogen, which was negative. After a repeat estrogen of 90 at the beginning of her next menses, the workups ceased.
Following this series of lab testing, Bella was told by her physicians that she did not have a hormonal or anatomic etiology of her symptoms. However, they had not performed a targeted hormone evaluation based on her probable day of ovulation to measure her post-ovulatory progesterone and estrogen levels. As I have learned during the FACTS elective, this is one of the most important things to do to accurately assess hormonal imbalances.
Today, Bella reports feeling better, but still is not back to her normal self yet: the hot flashes, body tingling, dry mouth, and pre-menstrual migraines continue to this day. Her symptoms are concerning, as they may indicate an ongoing, unidentified hormonal imbalance. I encouraged Bella to visit with an FABM-trained physician to learn about charting and to further assess her condition. Understandably, she was not interested in seeing any more clinicians or considering any hormonal therapies at the time. As a future physician, I felt devastated learning what Bella had gone through and her resulting distrust in the medical community. Knowing what I know now from taking the FACTS elective, I cannot help but wonder how different her story would have been if she had connected with a FABM-trained clinician prior to, or even after, her IUD insertion.
“I hope sharing all of this will make it so that the next time a woman is experiencing this, there will be a medical professional somewhere out in the world who will believe her and not just reduce her to her past medical history or brush off anxiety as if it is something so simple to deal with,” Bella said.
References
[1] Attia AM, Ibrahim MM, Abou-Setta AM. Role of the levonorgestrel intrauterine system in effective contraception. Patient Prefer Adherence. 2013;7:777-785. Published 2013 Aug 9. doi:10.2147/PPA.S36948
[2] The Uppsala Monitoring Centre. The use of the WHO-UMC system for standardised case causality assessment. https://www.who.int/medicines/areas/ quality_safety/safety_efficacy/WHOcausality_assessment.pdf?ua=1 (accessed 25 Aug2020).
[3] Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet (2000) 356:1255–9. doi: 10.1016/S0140-6736(00)02799-9
[4] Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberst EA, et al. DJ G. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther (1981) 30:239–45. doi: 10.1038/clpt.1981.154
[5] Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry (2016) 73:1154. doi: 10.1001/jamapsychiatry.2016.2387
[6] Skovlund CW, Mørch LS, Kessing LV, Lange T, Lidegaard J. Association of hormonal contraception with suicide attempts and suicides. Am J Psychiatry (2018) 175:336–42. doi: 10.1176/appi.ajp.2017.17060616
[7] Slattery J, Morales D, Pinheiro L, Kurz X. Cohort study of psychiatric adverse events following exposure to levonorgestrel-containing intrauterine devices in UK general practice. Drug Saf (2018) 41:951–8. doi: 10.1007/s40264-018- 0683-x
[8] Bitzer J, Rapkin A, Soares CN. Managing the risks of mood symptoms with LNG-IUS: a clinical perspective. Eur J Contracept Reprod Heal Care (2018) 23:321–5. doi: 10.1080/13625187.2018.1521512
[9] Zeiss R, Schönfeldt-Lecuona C, Gahr M, Graf H. Depressive Disorder With Panic Attacks After Replacement of an Intrauterine Device Containing Levonorgestrel: A Case Report. Front Psychiatry. 2020;11:561685. Published 2020 Aug 28. doi:10.3389/fpsyt.2020.561685
ABOUT THE AUTHOR
Sunny Lee
Sunny Lee is a graduate from Kansas City University and will soon be a first-year OB-GYN resident at the Cleveland Clinic. She participated in an FABM elective during her fourth year to learn more about fertility awareness in hopes of empowering and providing holistic care to her future patients.
