My PMDD Ruled My Life. Then I Got on Zepbound.
I had been taking Zepbound for about six months when it clicked. My period — the monster that turned me from a functioning person into a whimpering, tremulous piece of Jell-O carving a spot into the couch — had, somehow, lost its power. As I understood it, I had premenstrual dysphoric disorder, or PMDD. More than just “heavy PMS,” PMDD meant that the week before my period I suffered from a grab bag of severe mental and physical symptoms including a new, frightening one: suicidal ideation.
Now, however, things were different. My period didn’t rule my life anymore. In fact, there was little to no difference in my mood and energy no matter what time it was in my cycle. The only thing that had changed in my life was my weekly shot of Zepbound.
According to the International Association of Premenstrual Disorders, PMDD affects 5.5 percent of reproductive-age women, which translates to about 4 million women in the U.S. Misunderstood and understudied, it takes the average patient 12 years to get an accurate diagnosis; in one study, the IAPMD found that 34 percent of sufferers had attempted suicide during a PMDD episode. The cause of the disorder is unclear, and it can start during any stage in someone’s reproductive life. For me, it became severe and dangerous shortly after giving birth in October 2020. When my period returned, I started to feel paralyzed with depression for about three days a month during my luteal phase, or the time between ovulation and the start of my period. This wasn’t how I felt before I had given birth. I was a scary and strange new version of myself, one that felt listless, tired, and with an uncontrollable urge to binge food. Instead of losing any pregnancy weight, I was slowly gaining it, and soon I was the biggest I’d ever been, my prepregnancy clothes sitting in boxes in the back of my closet.
Six months postpartum, my mood was dark and dreary. I didn’t quite notice. I was busy with the baby. My husband suggested therapy, and my psychiatrist prescribed Wellbutrin. The drug barely made a dent. Of course, it didn’t help matters that my emotional and physical nadir coincided with a global pandemic. My initiation into motherhood was lonely. I was the primary caretaker for our daughter, as my husband worked full time as a Legal Aid attorney and pounded the pavement for his City Council campaign during nights and weekends. In those months before the vaccine, my only “friend” who I’d see regularly was Tyra Banks when I watched America’s Next Top Model: the complete series on Hulu, and she was no friend to women.
Maybe this was just what postpartum life felt like, I thought. I should be grateful to have a child at all. It was a long road to get there, marked by miscarriage and an accompanying cancer scare. Maybe I was just embodying that Fleabag quote, “Women are born with pain built in.” I hid from my moods as much as I could, something I’ve practiced my whole life as an Irish Catholic from Boston. I was also dealing with sleep apnea, made worse by weight gain, which combined with the typical late-night infant wake-ups was destroying my sleep. Dull and sapped, lacking the enthusiasm and optimism that felt inherent to my personality, I was an imitation of myself, going through the motions. Months passed, which turned to years, and suddenly my newborn daughter was a potty-trained, Bluey-loving toddler. Stuck in survival mode, I considered myself simply depressed. I didn’t have the energy to consider alternatives.
In early 2023, I texted a friend asking if this was a normal way to feel when you start weaning off breastfeeding. She punctured through my gloom with an illuminating “No, and this is worrying.” It was the reality check I needed. I started attending postpartum groups and individual therapy over Zoom. Sitting in front of a secondhand pink crib, talking into the glowing maw of my MacBook, is when my therapists first brought up the idea that I very likely had PMDD as well as C-PTSD related to that earlier miscarriage.
Treating PMDD is complex and uncertain: Once a diagnosis is made — based on symptoms both emotional (such as mood swings, depression, and suicidal ideation) and physical (such as marked changed in appetite or sleeping patterns, breast tenderness, and weight gain) — treatments range from SSRIs to hysterectomy. My psychiatrist recommended I take Zoloft for the luteal week before my period; given my lackluster experience on Wellbutrin, I was skeptical that taking another SSRI would help. My therapists didn’t have many other suggestions for how to help — nothing about lifestyle changes, weight loss, or surgery. The vagueness bothered me. I found myself scrolling through Reddit boards, where thousands of sufferers unsatisfied with their doctors’ answers crowdsourced solutions such as taking antihistamines like Benadryl or microdosing psychedelics for relief.
Answered prayers arrive in funny forms and, for me, finding PMDD salvation started with a bad heart scan. In January 2023, I paid a visit to my general practitioner for my first physical since the pandemic. My doctor looked at my apparently abnormal EKG reading and said, bluntly, “Did you have a heart attack?” It was a shocking thing to hear. My maternal grandma had died from a heart attack in her 50s, leaving my mom motherless at 17. My cholesterol was high, and my doctor prescribed a statin. Straightforward and to the point, she told me to lose weight. I said I eat mostly vegetarian and exercised and I wasn’t sure what I could do. I had a dim awareness of a tendency to binge during my period, but I didn’t see that as the source of my weight gain, just something that led to an empty pretzel bag hidden in the trash. On my husband’s suggestion, I followed up my worrisome physical with a visit to an endocrinologist. The blood work for that appointment had me at a pre-diabetic A1C. She suggested a GLP-1 drug for weight loss.
At first, I resented the doctor’s suggestion. I told myself that I was okay with my body, resigned to a permanent state of trying to lose weight, vaguely, at some point, and feeling guilty over my binges. But it didn’t take long to decide that — considering my heart, the statins, my grandmother — if a GLP-1 had the potential to make me healthier, then I had to give it a shot. My doctor prescribed Ozempic, but I couldn’t find it in stock anywhere. Same with Wegovy. But months later, Zepbound came on the market and I was first on line.
Little by little, the weight came off, about a pound a week. My formerly uncontrollable urges to snack right before my period — the kind where honey-mustard pretzels would tremble in my presence — had become nonexistent. I ate three square meals a day. I did strength workouts on my Peloton app. Never much of a drinker, save a social glass of wine with dinner, I completely stopped. My therapy appointments mellowed out, too, even in the historically wretched week leading up to my period. And I was more focused: Instead of scrolling on my phone at the playground while I pushed my daughter on the swing, lost in depressing thoughts, I noticed myself noticing how she navigates the playground, moving from the swing to big imaginary games about the princesses from Frozen, a movie she’s never seen. I was a little more present, and I had a little more energy. I was, finally, starting to feel like a good mother and a fully realized person too, less of a gremlin killing time in between binges.
I missed finding pleasure in food, like the delight of indulging in a great meal at a restaurant. But I was gaining alternate delights. Some of them were shallow and conditional. I fit in new sizes in my clothes. I looked happier and more confident. I felt like I could go out in the world and people would listen to me. There was some joy that came from that, even if I knew, intellectually, that it was a Pyrrhic victory, further proof that we live in a society that prioritizes and is kinder to smaller bodies. Then there were the substantial, important results at my next physical, like an A1C that wasn’t prediabetic and an improved cholesterol reading. Emotionally, I felt calmer, but it felt strange for happiness to become something like a permanent state of being, a smooth way to go through the world. I had gotten so used to the ups and downs of being a sensitive person in the world — the roller coaster of euphoria and despair — that I almost missed them.
The transformation felt so much bigger than weight loss. Was it possible that Zepbound was influencing how my brain responded to my menstrual cycle? I began searching PMDD Facebook groups to see if anyone else was having a similar experience. There’d be the rare post that would sound just like me, someone who started taking one of these drugs and found their symptoms lessened, what one such poster called a “refreshingly positive side effect.” But others would say that trying a GLP-1 made their depression, their PMDD, or their suicidality worse. Reddit boards featured similar extremes, as tends to be the case with Doctor Internet: people detailing why something they did was the best or worst thing ever with no recounting of the mundane experiences in the middle.
My therapist, my medication-management doctor, and my husband all affirmed that my mood was clearly brighter and happier. But I still didn’t really understand why Zepbound had seemingly affected my PMDD. My best friend, a doctor, and her husband, a psychiatrist, said that my experiences with Zepbound and PMDD were fascinating, but the drugs were too new to be hearing anything official to know why, exactly, I was being affected in this way. I wanted to figure out what was going on with my body and mind.
Maybe, I hoped, a PMDD expert would know more. I turned to Sandi MacDonald, the co-founder and executive director of the International Association of Premenstrual Disorders. For MacDonald, PMDD is best described as a sensitivity to hormone fluctuations: “Patients have that sensitivity where they just can’t handle it, their bodies can’t handle the rise and fall of the hormones and so their bodies and brains are reacting to it. That’s what makes PMDD so dramatic.” When MacDonald first started her group in 2013, a Google search would yield three results. These days, it’s 100,000. Anecdotally, MacDonald was hearing that PMDD patients taking Ozempic and Wegovy have been reporting muted symptoms with their PMDD. But it’s hard to figure out an explanation for how GLP-1’s could be affecting PMDD sufferers when the problem at hand is already under-defined. For example, I had read it theorized that GABA (the neurotransmitter that helps regulate your mood) signaling may play a role in PMDD. Separately, researchers have found GLP-1 receptors located on GABA neurons. Could there be some connection made between those two points that helps explain my personal experience? We simply don’t know enough about how PMDD works to say.
I also called up Dr. Karolina P. Skibicka, neuroscientist and associate professor at Penn State and professor of molecular medicine at Gothenburg University. She said that it’s too soon to know whether there is a connection between GLP-1 drugs and hormonal disorders like PMDD but affirmed that it’s a question that she and other scientists are trying to answer. Skibicka has been studying GLP-1 drugs for almost two decades and authored the first paper concluding that GLP-1’s affect the brain’s reward circuitry and appear to have the potential to reduce cravings from things other than food, such as alcohol. Her lab and others have shown that the GLP-1 hormone interacts with estrogen, which might explain why women tend to lose more weight on the drugs than men. Now, she’s interested in learning how these drugs affect emotionality in women. Specifically, she’s been studying how these drugs affect anxiety and depression “separate from obesity” and whether these drugs can affect the brain’s mesolimbic dopamine system. But it won’t be a simple question to answer, in part because of (you guessed it) the history of gender bias in scientific research.
“A lot, if not most, of what we know about the brain is based on male brain, irrespective of whether a given disease is more prevalent in men or women,” Skibicka explained. Historically, she continued, most neuroscience studies have used male rats. This has only started to change recently, beginning around 2016, when the National Institute for Health mandated that all new grants need a statement about how they will be using male and female species in their research. As a result, “we are only a decade into learning about neurochemical differences between men and women regarding things like food intake.” And of course, there is not a lot of funding for PMDD research, which Skibicka described as “snuck” into grant proposals.
In my private, one-woman human study, I have more working hypotheses than conclusions. Not only do I not know exactly what’s happening with my body, but leading experts don’t either — and we could be many years away from beginning to figure it out. I still don’t know if there’s a cure for PMDD, but with my symptoms lessened, I’m at least feeling some hope, and hope is something you can hold onto in the dark. I feel like a different person now, maybe closer to who I’m supposed to be. Life doesn’t have to feel at its absolute grim nadir forever. It’s not an answer to my question, but it’s a start.
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