Associate Professor University of Maryland Medical Center, Maryland
Background & Introduction: Hot flashes, or vasomotor symptoms (VMS) of menopause affect up to 80% of women during the menopausal transition1. While symptoms of opioid withdrawal can vary widely, hot flashes and excessive perspiration are both commonly experienced and often significantly impact quality of life. Vasomotor symptoms (VMS) of menopause and opioid withdrawal hot flashes (OWHF) share overlapping features and neurobiological pathways. As such, their similarities can obscure diagnosis and delay appropriate treatment. In patients with opioid use disorder (OUD), such misattribution may perpetuate ongoing opioid use and increase risk of overdose. This case highlights the critical need for diagnostic clarity to ensure appropriate and timely treatment.
Case Description: Ms. M is a 46-year-old female who presented to an outpatient substance use treatment program requesting to re-initiate methadone. She had previously been on methadone for 15 years, until two years ago when she successfully weaned off the medication. Several months prior to presentation, she returned to use of non-prescribed opioids, specifically fentanyl. After her return to use, Ms. M began to experience symptoms she associated with opioid withdrawal, though her symptoms did not improve with increasing fentanyl use. The most prominent and distressing symptoms were hot flashes, irritability, and sleep disturbances. Notably, in the past, her most bothersome symptom of opioid withdrawal had been gastrointestinal upset. She attributed the lack of gastrointestinal symptoms at this time to a difference in the type of opioids that she was using. Ms. M was initiated on methadone and titrated to a dose of 50 mg daily, which helped to decrease her fentanyl use. However, the patient’s most distressing symptoms persisted. Her primary care physician suspected that these symptoms may be related to perimenopause and referred Ms. M to a gynecologist. Ms. M reported irregular menstrual cycles for the previous eight months, which she attributed to her return to opioid use. She began hormone therapy with 0.0375 mg transdermal estradiol weekly patch and 200 mg of micronized progesterone for ten days of the month. Ms. M returned to the office six months later and reported that her symptoms had completely resolved. She requested to continue the hormone therapy, stating, “It is more important than my methadone” for recovery. In retrospect, although her hot flashes, irritability, and sleep disturbances were identical to her previous withdrawal symptoms, she now recognizes them as symptoms of perimenopause.
Conclusion & Discussion: VMS and OWHF have overlapping characteristics. Both are likely mediated by norepinephrine pathways2. In fact, Simkins et al. proposed using precipitated morphine withdrawal in rats as a model for menopausal hot flashes due to the similarity in magnitude and duration of the skin temperature changes observed between the two3. This case highlights how VMS and OWHF can be difficult to distinguish, potentially delaying appropriate therapeutic management. It is important to note that if Ms. M had not been treated for VMS, she may have continued escalating fentanyl use to alleviate presumed withdrawal symptoms, increasing her risk of overdose. Menopausal transition is a natural and inevitable period for all women and therefore affects a large portion of patients with OUD. Further research is needed to understand the impact of this transition on women with OUD as well as to identify best practices for treatment when these conditions are co-occurring. In the interim, providers should reassess their differential diagnosis when withdrawal symptoms persist despite adequate medication for OUD. This case also highlights the need for collaboration across medical specialties, including gynecology and addiction medicine, to ensure comprehensive care.
References: 1 Avis NE, Crawford SL, Greendale G, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Internal Medicine. 2015;175(4):531. doi:https://doi.org/10.1001/jamainternmed.2014.8063 2 Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. American Journal of Obstetrics & Gynecology. 2007;196(2):97-106. doi:https://doi.org/10.1016/j.ajog.2006.05.056 3 Simpkins JW, Katovich MJ, Cheng Song I. Similarities between morphine withdrawal in the rat and the menopausal hot flush. Life Sciences. 1983;32(17):1957-1966. doi:https://doi.org/10.1016/0024-3205(83)90047-4 4 Bevry ML, Stogdill ER, Lea CM, et al. Addressing menopause symptoms in the primary care setting: opportunity to bridge care delivery gaps. Menopause. 2024;31(12):1044-1048. doi:10.1097/GME.0000000000002439 5 Brown L, Hunter MS, Chen R, et al. Promoting good mental health over the menopause transition. The Lancet. 2024;403(10430):969-983. doi:https://doi.org/10.1016/S0140-6736(23)02801-5
Disclosure(s):
Alia Capone, MD: No financial relationships to disclose
Katrina Mark, MD, FACOG, FASAM: No financial relationships to disclose
Learning Objectives:
Recognize that vasomotor symptoms of perimenopause may mimic opioid withdrawal in women with opioid use disorder.
Identify clinical features that should prompt reconsideration of presumed opioid withdrawal when symptoms persist despite adequate medication for opioid use disorder.
Understand how misattribution of menopausal symptoms to opioid withdrawal may contribute to continued opioid use and increase risk of adverse outcomes.
