Synopsis: Premenstrual Dysphoric Disorder (PMDD) sounds a lot like Premenstrual Syndrome (PMS), but is a far more extreme condition than PMS. If you have PMDD or know someone who does, the good news is that there are treatments that work.

BY LEN LANTZ, MD / 12.29.22 (last updated 6.16.24); No. 63 / 14 min read

Disclaimer: Yes, I am a physician, but I’m not your doctor, and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post might also contain affiliate links. Please click this LINK for the full disclaimer.

What’s the difference between PMS and PMDD?

Premenstrual Dysphoric Disorder (PMDD) is a much bigger issue than most people realize. Even the name of the condition gives people a vague sense that they probably know what it is. Most don’t. PMDD can result in dramatic changes in mood, functioning, and relationships, so knowing more about it can help you deal with it more effectively for yourself and your loved ones.

The average person has heard of Premenstrual Syndrome (PMS) as the term PMS is everywhere. Comedians joke about it. People use it for an explanation or an apology, “I’m sorry. I’m just PMSing,” and there are many articles in the media on PMS and its remedies that help people to become aware of the condition. PMS has been studied since the 1930s and the term Premenstrual Syndrome was used as early as the 1950s. (Rapkin, A. Psychoneuroendocrinology. 2003).

PMS is common among women of reproductive age with a worldwide prevalence of 48% (Alwafa, et al. BMC Women’s Health. 2021) to 90% (Matsumoto, et al. Gynecological Endocrinology. 2013). In the 5 days before menses, PMS involves at least one of the following emotional and physical symptoms (ACOG, 2000):

• Depression (sadness, crying)

• Angry outbursts

• Irritability

• Anxiety

• Confusion

• Social withdrawal

• Breast tenderness

• Abdominal bloating

• Headache

• Swelling of extremities

If most people know what PMS is, then it makes sense that we would assume that we also know about Premenstrual Dysphoric Disorder. The word “dysphoric” sounds like something sad or bad, so people might guess that PMDD is severe PMS or “sad PMS.” That conclusion is not far off the mark. Even researchers suggest that PMDD is a severe form of PMS because there is significant symptom overlap – up to 79% symptom overlap – between PMDD and severe PMS (Freeman, et al. JAMA. 1995). However, most people are unaware of how much more severe PMDD is compared to typical PMS.

What is PMDD?

The symptoms of PMDD substantially interfere with work, social activities, and relationships. The symptoms must be present with most menses for over a year with at least 5 symptoms total in the week before menses (the symptoms must remit within days following the onset of menses):

• The 5 symptoms must include at least one of these emotional symptoms:

  • Marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection)

  • Marked irritability or anger or increased interpersonal conflicts

  • Markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts

  • Marked anxiety, tension, and/or feelings of being “keyed up” or “on edge”

• The 5 symptoms must include at least one of these symptoms:

  • Decreased interest in usual activities

  • Worsened concentration

  • Lethargy, easy fatigability, or marked lack of energy

  • Marked change in appetite, overeating, or specific food cravings

  • Excessive sleep or insomnia

  • A sense of being overwhelmed or out of control

  • Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating” or weight gain

In comparing PMS to PMDD, you can see how much more intense PMDD is than PMS. PMDD can result in extreme mood and anxiety changes and cause a much greater impact on functioning and relationships than PMS.

PMDD can be missed or even misdiagnosed as other conditions

One of the reasons PMDD can be missed is due to the general knowledge most people already have about Premenstrual Syndrome (PMS). Once we settle on an explanation, we often stop questioning or considering other possibilities. We might minimize or dismiss our own or someone else’s difficulties as “just PMS” or worse, “Well, she’s on her period but give me a break! Virtually all women just deal with it.” Easy explanations cause us to stop being inquisitive and we can ignore serious problems that are right in front of us.

PMDD can mimic other conditions. The “affective lability” seen in PMDD can look like rapid mood cycling that is seen in bipolar disorder mixed mood episodes. Without careful questioning by a doctor and careful monitoring by a woman experiencing PMDD, her rapid mood switches near her menses could be misdiagnosed as bipolar disorder. Some women with PMDD don’t experience sadness or irritability. For them, their predominant difficulty is anxiety, and the anxiety that they experience near their menses in PMDD is severe, mimicking an exacerbation of generalized anxiety disorder.

The level of emotional dyscontrol, suicidality, and relational conflict that occurs in some women with PMDD could also lead to an incorrect diagnosis of borderline personality disorder. While a woman can have both borderline personality disorder and PMDD, an accurate diagnosis of PMDD is critically important because the existing treatments that specifically help PMDD can help both disorders to improve. A woman can have both PMDD and any other mental health condition but knowing the cause (PMDD or other condition) of a recent episode of symptom worsening will help treatment to be more effective.

PMDD can dramatically worsen mood and anxiety disorders

Separate from the problems of an incorrect or missed diagnosis, PMDD can also severely worsen existing conditions, such as anxiety and mood disorders. Separating a new episode of worsening anxiety/OCD, major depressive disorder, or bipolar disorder from co-occurring PMDD is critical to effective and sustained improvement.

In untreated PMDD, each menstrual cycle can push symptoms from being in control to temporarily feeling out of control. This makes it much harder to deal with chronic symptoms of depression, anxiety, Posttraumatic Stress Disorder (PTSD), or Obsessive-Compulsive Disorder (OCD). Also, relationship conflict that occurs in PMDD symptom worsening makes it harder to cope with other conditions.

PMDD can affect kids too

I’m trained both as an adult and pediatric psychiatrist and I can tell you that kids can also experience PMDD. It can be a big problem for girls because the adolescent years are already filled with more intense emotional reactivity. Dismissing PMDD symptoms as teenage emotionality or “just PMS” is harmful to these adolescents and their families because PMDD is treatable. Finding a doctor who will listen to and respond effectively to girls with PMDD symptoms (and their parents) is absolutely necessary.

What you need to know if you are close to someone with PMDD

One of the first things that can be helpful if you know someone with PMDD is that they are going to have episodic intense emotional responses. The best initial strategy is not to ask, “Are you near your period?” One of the most helpful approaches is to respond in a supportive manner that encourages your loved one with PMDD to engage in self-care and not make major life decisions during intense symptoms. When your loved one with PMDD is in a good place emotionally, it might be helpful to check in with them if they notice intense emotional and physical changes near their menses and what strategies they have found to be helpful. Since you will be well informed from reading this article, you might mention that you heard about strategies that they might try, or you could share this article with them.

The proposed mechanism of action of PMDD

The human brain is an estrogen-sensitive organ of the body, so it should come as no surprise to us that many women struggle with PMDD symptoms. Research shows that PMDD affects 3-9% of menstruating women (Thakrarm, et al. Journal of Affective Disorders Reports. 2021). The mechanism by which reproductive hormones cause PMDD is still under active investigation and is not fully understood, but a heightened sensitivity to estrogen, progesterone, and metabolites of those reproductive hormones is suspected. Other possible causes or contributors to the development of PMDD include a history of exposure to stress/trauma (Hantsoo, et al. Current Psychiatry Reports. 2015) and cyclical fluctuations in calcium-regulating hormones (Thys-Jacobs, et al. Journal of Clinical Endocrinology & Metabolism. 2007).

The strategies that work for PMDD

Many strategies can help PMDD symptoms, but I’ll be highlighting the top 5 that have a research basis that shows efficacy.

Please Note: Consult your healthcare professional before trying any of these strategies. There are risks with both prescribed medications and over-the-counter (OTC) supplements.

SSRIs and other antidepressants

Selective serotonin reuptake inhibitors (SSRIs) have some of the strongest evidence in helping reduce or eliminate PMDD symptoms. The best studied is Prozac (fluoxetine) which can be helpful when taken continuously or near menses on an intermittent basis if the menstrual cycle is regular/predictable (Carr, et al. Annals of Pharmacotherapy. 2002). In November 2000, fluoxetine was FDA-approved for PMDD and temporarily marketed under the brand name Sarafem.

In addition to fluoxetine, other SSRI medications like Zoloft (sertraline), Lexapro (escitalopram), Paxil (paroxetine), and the SNRI Effexor (venlafaxine) have more evidence for effectiveness in treating PMDD compared to other categories of antidepressant medications, such as the NDRI Wellbutrin (bupropion) (Pearlstein, et al. Journal of Clinical Psychopharmacology. 1997.)

Combination birth control pills

Research shows that combined hormonal contraceptive (CHC) pills help alleviate PMDD symptoms. Birth control pills with the strongest evidence are 20 mcg ethinyl estradiol/ 3 mg drospirenone in a 24/4 extended cycle regimen (Rapkin, et al. Open Access Journal of Contraception. 2019). Common brand-name versions of these medications are:

• Beyaz (also contains levomefolate calcium)

• Gianvi

• Loryna

• Yaz

Similar brand-named combined oral contraceptive medications that include 30 mcg ethinyl estradiol/ 3 mg drospirenone include:

• Ocella

• Safyral (also contains levomefolate calcium)

• Syeda

• Yasmin

• Zarah

Other birth control pills, such as combined monophasic, extended cycle hormonal contraceptive pills with less androgenic progestins (i.e., drospirenone) might also be helpful, but these medications have less research evidence supporting their use. Copper intrauterine devices (IUDs) are recommended for women who desire or need non-hormonal contraception.

Keep in mind that some forms of birth control have the potential to worsen mood disorders (including PMDD) such as Depo-Provera (depot medroxyprogesterone acetate), Nexplanon (etonogestrel) implant, progestin-only pills (POPs), and the levonorgestrel IUDs (Mirena, Skyla, and Liletta) (Rapkin, et al. Open Access Journal of Contraception. 2019).

Cognitive Behavioral Therapy (CBT) and iCBT

CBT is one of the most thoroughly researched forms of psychotherapy that has efficacy for mood and anxiety disorders. CBT teaches skills for balancing thoughts and emotions and encourages people to engage in healthy and supportive activities (behavioral activation). iCBT stands for Internet-based Cognitive Behavioral Therapy, which is a computerized version of CBT that is delivered over the internet.

In a recent study, women with PMDD were enrolled in an 8-week therapist-guided iCBT program, which combined “classical CBT techniques with strategies to introduce lifestyle changes.” The lifestyle changes included improved coping with symptoms such as seeking support and engaging in activities that enhanced mood (“positive-affect-inducing activities”). Up to 78% of the women in the study reported an ability to improve impairment caused by PMDD and the treatment effects were stable for up to 6 months following iCBT (Weise, et al. Psychotherapy and Psychosomatics. 2019).

Elemental calcium

As calcium regulation is suspected to play a role in PMDD symptoms, it shouldn’t surprise us that daily calcium would reduce PMDD symptoms. A high enough dose of elemental calcium can be effective for PMDD.

So, what’s elemental calcium? It’s the amount of calcium listed on the bottle that you will actually get. For example, a bottle of calcium carbonate contains both calcium and carbonate, so you need to read the “supplement facts” panel on the bottle, see how many pills are in a “serving size” and how much elemental calcium a serving contains, and then do a little math to make sure that you are getting enough calcium if you are using this strategy. If you take acid-blocking medication, you need to take calcium citrate instead of calcium carbonate in order to absorb the calcium.

One of the earliest and most convincing research studies of using calcium to treat women with PMS/PMDD involved giving participants 1,200 mg of elemental calcium every day (Thys-Jacobs, et al. Am J Obstet Gynecol. 1998). The researchers looked at four different symptom factors: negative affect (sadness, anger, anxiety), water retention, food cravings, and pain. By their third menstrual cycle on calcium, the participants saw a 48% reduction in total symptom scores (beating the placebo at 30%), and all four symptom factors were significantly improved.

In a more recent study, women with PMS/PMDD were given a 500 mg daily dose of elemental calcium (Shobeiri, et al. Obstetrics and Gynecology Science. 2017). The women receiving calcium saw a substantial improvement by their second menstrual cycle on calcium in measures of anxiety, depression, emotional changes, water retention, and somatic changes. Women receiving the placebo pills saw much less improvement in their symptoms.

Exercise

Nearly every woman with PMDD that I’ve treated in my clinical practice has noticed an improvement in their symptoms when they exercise near their menses. I know that exercising regularly is easier said than done, but there is a strong and convincing body of research showing that exercise helps anxiety and is more effective for depression than most people realize (see my article, “The Surprising Results of Exercise for Depression”).

Exercise has also been researched and found to be effective for PMS/PMDD. In a meta-analysis of studies using exercise (minimum of 8 weeks duration) compared to no exercise, the exercise group had a notable improvement in reducing global PMS symptom scores (Pearce, et al. BJGP Open. 2020). The meta-analysis looked at a variety of exercise interventions including aerobic exercise, yoga, Pilates, water aerobics, and stretching and resistance exercise.

Bonus strategy #1: L-tryptophan

Please note: It might not be safe to combine L-tryptophan with an antidepressant.

L-tryptophan, an essential amino acid, is involved in the synthesis of serotonin, an important neurotransmitter system of the brain that likely influences depressive symptoms. Several research studies have shown that the rapid depletion of tryptophan worsens PMDD symptoms (Rapkin, et al. Open Access Journal of Contraception. 2019). It turns out that there also was a study on adding L-tryptophan to improve PMDD symptoms.

In a small placebo-controlled trial, women with PMDD were given 6 grams per day of L-tryptophan from ovulation until day 3 of menses. Compared to the placebo, the women who received L-tryptophan saw moderate improvements in irritability, mood swings, tension, and dysphoria (Steinberg, et al. Biological Psychiatry. 1999).

Some women who do not tolerate antidepressants due to sexual dysfunction or other side effects might find benefit from L-tryptophan as it is typically well-tolerated and not known to be associated with sexual dysfunction. Because it is a supplement, you would not need a prescription to try it.

Bonus strategy #2: Oxaloacetate

Oxaloacetate is an organic compound with a crystalline structure. It is a component in several crucial metabolic processes in the body and brain (in particular, gluconeogenesis). Researchers hypothesize that oxaloacetate impacts emotions through multiple mechanisms.

One study that compared oxaloacetate to placebo in the management of PMS showed that a combination of oxaloacetate and Vitamin C (ascorbic acid) was associated with improvements in depression, perceived stress, generalized anxiety, and aggression (Tully, et al. Obstetrics & Gynecology Science. 2020). Also, the women who participated in the study experienced an average 48% improvement in their suicidal thoughts on the oxaloacetate/Vitamin C combination, outperforming the placebo.

In the study, women took two pills of 100mg oxaloacetate (200mg total daily) and 150mg of Vitamin C (300mg total daily). Note: The primary role of Vitamin C was to improve oxaloacetate's stability (preventing breakdown at room temperature).

Women in the study took the supplements with breakfast (or lunch if they forgot earlier in the day). The study was short in that the women were on the placebo for one complete menstrual cycle and on the active ingredients of oxaloacetate/Vitamin C for one complete menstrual cycle. The researchers in the study did not provide a detailed list of side effects; however, they stated, “No side effects and/or adverse effects in the study population were reported with the oxaloacetate/vitamin C mix.”

So far, the scientific evidence supporting oxaloacetate for premenstrual mood symptoms is limited but promising.

Even more strategies…

While there is less robust research evidence on dietary changes, many women observe that eliminating sugar near their menses helps reduce their PMDD symptoms. This is hard to do because they might be craving sugar and desiring comfort food and sweet treats at the very time that they need to be avoiding sugar and highly processed foods.

There are more solutions for people with treatment-resistant PMDD symptoms but it is best to work with a gynecologist to discuss strategies such as shutting down the reproductive system with Lupron (leuprolide), which is associated with 60-70% PMDD symptom improvement (Pincus, et al. Journal of Psychiatric Research. 2011), or hysterectomy with removal of ovaries and postoperative hormone replacement therapy, which is associated with significant improvement in 96% of women with PMDD (Cronje, et al. Human Reproduction. 1994).

A story about finding solutions for PMDD

Jessica was 26 years old, and she really hated her period. It was particularly embarrassing and frustrating for her that she couldn’t control her emotional responses near her menses. She was smart, tough, and a great problem-solver. She usually felt like she could take on any challenge and overcome it, but starting before her period she felt helpless and uncertain until about day three of her menstrual flow.

Jessica noticed intense anxiety and irritability near her menses. She was in a great relationship with her significant other. They consistently supported each other and had so much in common! But about a week before her menses started, she would start feeling uncertain about the relationship. She would start responding irritably and they might bicker. As soon as that happened, her panic would settle in. She would start saying to herself, “This was a big mistake! I’m trapped in a worthless relationship. We’re all wrong for each other!” And then about 3-5 days after her menstrual flow started, it would feel like a veil was lifted from her emotions. Her anxiety and panic would resolve and she would return to the feeling that she and her partner were on solid ground. She’d say to herself, “We are so good for each other. A perfect match!”

She was tired of always feeling like a rug was pulled out from under her feet once a month around her period, so she decided to do some research. Of course, Jessica knew she had PMS but she hadn’t heard about PMDD. When she read through the symptoms of PMDD, she felt like they were describing her. She decided to start implementing some of the natural recommendations (taking a calcium supplement, exercising near her period, and cutting out sugar near her period), but that wasn’t enough.

She scheduled a meeting with her primary care provider to discuss birth control and fluoxetine. The birth control helped but she did not tolerate fluoxetine, so her provider referred her to a psychiatrist and a therapist. The therapist taught her some skills to use when she was having her menses and helped her to be accountable to herself in following through on the natural strategies. Jessica learned to take a step back from her intensely negative perspective before her period, to tell herself that, though it felt like the sky was falling, it probably wasn’t.

The psychiatrist helped explain what medications would be the most helpful for her PMDD and how to minimize side effects. The second medication that she took didn’t cause side effects, but it wasn’t particularly helpful. The third antidepressant that she tried offered the most benefit and it didn’t cause any side effects.

Jessica was proud of herself. She still hated that hormones could have such a big impact on her emotions, but she was satisfied with herself for taking action and finding solutions that worked well for most of her menstrual cycles. And she continued to build her self-confidence as the intelligent, resourceful, and effective woman she always was.

Learning about, understanding, and dealing with PMDD can help you and others

Premenstrual Dysphoric Disorder (PMDD) is far more severe, debilitating, and common than most people would expect. And it’s treatable. Anyone who is reading this probably knows or has regular contact with a woman who deals with PMDD. Identifying and getting effective treatment for PMDD can be life-changing. Effective treatment improves relationships, enhances functioning, and improves quality of life. If you have PMDD or know someone who does, consider what effective strategies could be started today!

For further reading, check out:

• Len’s Article, “A Stepwise Approach to Medications for Depression”

• Len’s Article, “How Record Keeping Can Help Treatment-Resistant Depression”

• Len’s Article, “Cognitive Behavioral Therapy (CBT) – the Most Effective Therapy?”

• Len’s Article, “How Good is Internet-based Cognitive Behavioral Therapy (iCBT)?”

• Len’s Article, “The Surprising Results of Exercise for Depression”

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