In recent years, there has been increased public scrutiny of health care professionals downplaying and dismissing concerning symptoms brought up by patients, which is a phenomenon called medical gaslighting.1 When it comes to birth control withdrawal, lack of scientific research investigating the side effects associated with stopping hormonal contraceptives exacerbates medical gaslighting.2 Females (both human and animal) have been historically underrepresented in scientific research, and funding for female-predominated diseases continues to be disproportionately small compared with the burden of disease.3 While studies investigating the hormonal and physiological effects of birth control exist, many of them are from the 1980s, predating the powerful tools of contemporary biology. Little research on the topic has been conducted since.4,5,6 What’s more is that, aside from fertility-related studies, few scientific studies have investigated the effects of stopping birth control.2,7,8 As a result, issues pertaining to female reproductive health are especially vulnerable to medical gaslighting.
While medical gaslighting can happen to anyone, Black women are often affected the most.9,10 Unfortunately, the maltreatment of Black women in reproductive health care has a history that dates back to the origins of gynecology. The so-called Father of Gynecology, J Marion Sims, is infamous for using enslaved Black women to repeatedly perform gruesome experimental surgeries — choosing to forgo anesthesia on his Black test subjects, but not on the white patients he would later treat.11,12 Lucy, Anarcha and Betsey — the most well-documented women who underwent Sims’ experiments — are now named the Mothers of Gynecology, as modern gynecology would not exist without their exploitation.13 Nearly 180 years later, Black women are still particularly vulnerable to suffering needlessly at the hands of those who were meant to care for them. Disparities in health care are major contributing factors toward pregnancy-related deaths being three times more prevalent in Black populations compared with white populations in the United States.14 Although modern gynecology would not have existed without the sacrifice of Black women, they are still undermined by the medical industry.
The Mothers of Gynecology contributed to the development of procedures that restored fertility, but gynecology today is just as focused on preventing unwanted pregnancies. The IUD (intrauterine device) is among the most popular forms of birth control in the world, with almost 160 million users worldwide.15 An IUD is a T-shaped device, measuring about 1.25 inches in size, that is inserted inside the uterus.16 IUDs come in both hormonal and nonhormonal varieties. The most commonly used IUD in the U.S. — Mirena — is hormonal.17 It continuously releases a small dose of synthetic progesterone over a period of up to eight years.16,18,19 Progesterone is a sex hormone involved in menstruation. Notably, dropping progesterone levels signal the uterus to shed its lining, thus causing a period.20 The hormonal release of progesterone into the uterus thins the uterine lining, preventing implantation (a crucial step marking the beginning of pregnancy) in the rare event that the egg becomes fertilized.16,18 This, paired with the mechanical effects of the hormonal IUD, which thickens the cervical mucus membrane,17 significantly reduces the chance of pregnancy.
In some cases, removal of hormonal IUDs could lead to unwelcome physical and emotional side effects known as Mirena crash — named after the Mirena IUD. This phenomenon describes a set of birth control withdrawal symptoms including depression, anxiety, nausea, weight gain and fatigue.21,22 Because birth control withdrawal is rarely studied, little is known about what causes Mirena crash.2 Furthermore, despite numerous reports online about Mirena crash, Mirena’s manufacturer, Bayer, refuses to acknowledge its existence,21 and no clinical studies have directly investigated the side effects of stopping hormonal IUDs.2 Unfortunately, this leads health care professionals to dismiss contraception-related side effects.23 Although Mirena crash does not affect all IUD users, acknowledging and studying the side effects some people experience after hormonal IUD removal is important to ensure everyone receives the best care. Thus, it is notable that a recent preprint of a scientific paper might finally bring insights to why birth control withdrawal affects physiology, cognition and behavior.24
While it is commonly believed that the hormonal effects of IUDs are contained locally within the uterus, several studies indicate this is not true. Those with hormonal IUDs had lower blood progesterone levels at specific points in their menstrual cycle.4 Additionally, breast MRIs show that when individuals are on the hormonal IUD, they have higher background parenchymal scores (hormone-associated changes in breast tissue) compared to when they are off it.25 Furthermore, side effects of hormonal IUDs include acne, weight gain, depression and decreased libido.16 All of these point to the systemic effects hormonal IUDs have on the entire body, challenging the belief that they only affect the uterus. Understanding the systemic effects of hormonal IUDs is important because sex hormones don’t just affect the reproductive system. The same receptors that sense progesterone in the uterus also exist in the brain!26,27 In fact, throughout the menstrual cycle, dramatic synaptic plasticity (changes in the brain’s neural connections) occurs as a result of hormonal fluctuations.28,29 This means that changing progesterone levels — for example, by taking hormonal birth control — will not only affect the reproductive system, but can also lead to psychological consequences.26,30
Specifically, changes in progesterone are linked to negative mental health outcomes. Pausing oral contraceptives, which also contain synthetic progesterone, causes negative emotional states similar to premenstrual syndrome (PMS), including anxiety and depression.31 In both humans and rodents, dips in progesterone or progesterone metabolites are linked to depressive symptoms in PMS.32,33 Additionally, dropping progesterone levels during childbirth, a phenomenon known as progesterone withdrawal, might contribute to postpartum depression.34 It is evident that there is a common link between progesterone and negative mental health outcomes, most likely as a result of changes in progesterone in the brain. Because blood progesterone levels are also altered by hormonal IUDs during parts of the menstrual cycle,4 could changes in progesterone in the brain contribute to the depressive symptoms of Mirena crash?
While progesterone has been implicated in mood changes associated with pausing oral contraceptives, PMS and postpartum depression, the exact mechanism of why this happens is not well understood. But, a recent preprint of a study from Fordham University offers a potential explanation. The researchers think a gene regulator called early growth response protein 1 (Egr1) may be the culprit. Early growth response protein alters gene expression across the menstrual cycle, which leads to changes in synaptic plasticity and behavior.35 Estrogen, another sex hormone involved in menstruation, increases early growth response hormone levels, while progesterone decreases early growth response hormone levels.36 The researchers found that progesterone and early growth response protein peak at the same phase of the estrous cycle (the mouse equivalent of the menstrual cycle). When they increased the levels of early growth response protein in mice, the female mice showed less anxiety and depression behavior. Notably, they did not observe the same effect in male mice, suggesting there is sex-specific sensitivity to early growth response protein.24
The researchers attributed this behavioral change to gene expression changes, as they also noticed more genes related to synaptic plasticity and fear response were activated in the female mice with increased early growth response protein levels. Interestingly, increasing early growth response protein levels in male mice also affected gene expression, but many of the genes they affected were different.24 Depression is often associated with lower levels of synaptic plasticity,37 so the effects of early growth response protein on boosting synaptic plasticity may explain its anti-depressive benefits in female mice. These findings shed a light on the relationship between progesterone levels, which are likely altered after hormonal IUD removal, and depressive and anxiety symptoms.
This paper gets us one step closer to pinpointing what causes these undesired side effects. While accounts of Mirena crash are widely reported online, no scientific investigation nor medical acknowledgement has validated this experience. Thus, research investigating the mechanisms of hormone-related changes in the brain and body may not only help legitimize historically discounted birth control withdrawal symptoms, but may also lead to birth control options that have reduced side effects.
The decision of whether or not to take hormonal birth control, and which type to choose, is a personal decision that comes with weighing many pros and cons. Overall, hormonal IUDs are safe to use, but they can come with side effects that are worth considering.18,22 The key is to make a well-informed decision when choosing between birth control options based on what fits your personal needs best.
Further research on the cause of Mirena crash and similar phenomenon will help bridge the gap between personal and medical wisdom. This will not only guide prospective birth control users toward making better-informed choices, but it will simultaneously provide pharmaceutical insights on creating birth control options with minimized side effects.
Citations
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The concept of medical gaslighting, particularly in reproductive health, underscores the importance of validating and addressing patients' concerns. It's encouraging to see emerging research, like the study on early growth response protein, that could offer a scientific explanation for experiences like Mirena crash. This kind of progress is vital not just for understanding these symptoms but for empowering individuals to make informed decisions about their health while pushing for more inclusive and comprehensive medical research.