Understanding PMDD: How we’re oversimplifying a complex disorder as a hormone issue

Have you been diagnosed with PMDD or do you experience significant, often debilitating mood changes in association with your menstrual cycle? If yes, you’re probably thinking something is wrong with your hormones. For most women, testing hormones results in the crushing weight of being told everything is normal which, though I believe not intentional, invalidates the suffering that women like you and me can experience. Certainly there is something hormonal in nature occurring, and I’d agree with this, too. But it’s not as simple as we might think.

What is PMDD?

Premenstrual dysphoric disorder (PMDD) is diagnosed according to the DSM-5 when a person has at least 5 of 11 specific symptoms that occur during the week before onset of menses, improve within a few days after the onset of menses, and are minimal or absent post-menses (at least one symptom must be affective and at least one must be behavioral/cognitive).

Affective symptoms:

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

2. Marked irritability or anger in increased interpersonal conflicts)

3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts

4. Marked anxiety, tension, and/or feelings of being keyed up or on edge

Behavioral/cognitive symptoms:

1. Decreased interest in usual activities

2. Subjective difficulty in concentration

3. Lethargy, easy fatiguability, or marked lack of energy

4. Marked change in appetite, overeating or specific food craving

5. Hypersomnia or insomnia

6. A sense of being overwhelmed or out of control

7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of bloating or weight gain

I want to mention that in the context of this article (and in my practice), it does not matter to me whether or not a patient meets criteria for PMDD according to the DSM-5. The depth of assessment and understanding of the underlying pathology are just as important to me for someone with significant menstrual-related mood changes that does not meet criteria for PMDD. I like to let my patients name their own experiences rather than having me invalidate their pain by disagreeing with a naming of PMDD. In reality, PMS can feel just as severe as PMDD as can premenstrual exacerbation (PME) of an existing mood disorder.

What is really causing PMDD?

During the luteal phase, or approximately second half of the menstrual cycle, estrogen and progesterone levels increase and remain elevated until menstruation. But it isn’t these hormones themselves that exert biological effects in the brain that influence our moods and emotions. Due to several factors, our brains can actually have abnormal responses to “normal” levels of circulating hormones.

Altered metabolism of allopregnanolone and GABA

Our limbic system, comprised mostly of the amygdala and hippocampus, is the region of the brain most involved in our behavioral and emotional responses. It’s this area of the brain that contains the highest concentration of receptors that respond to products of estrogen and progesterone. Both hormones have limited biological activity before they are broken down into active metabolites in the brain and other parts of the body.

Progesterone’s active metabolite, allopregnanolone, is the key metabolite of importance when it comes to understanding progesterone’s indirect role in menstrual-related mood changes. When allopregnanolone binds to its receptors on limbic system structures, these brain cells increase production of a hormone called GABA, our primary inhibitory neurotransmitter. GABA creates a calming, sedative effect with an anti-anxiety, anti-depressive and sleep-promoting outcome. It’s actually GABA receptors which bind benzodiazepines like Xanax and Klonopin, though allopregnanolone does so with ten times greater affinity. Without a sufficient flow of GABA, our ability to stay grounded, regulate our responses to stress and give rest to our nervous systems will plummet.

Both impaired metabolism of progesterone to allopregnanolone and slower production of GABA can result in symptoms of PMDD. In other words, so what if there’s enough fuel in the tank if it’s the engine that needs repair.

Limbic system sensitivity

Another factor that plays a major role in the biological underpinnings in PMDD is sensitivity. Women with PMDD likely have increased sensitivity of limbic system receptors to estrogen products and/or decreased sensitivity to allopregnanolone. The downstream effects of progesterone offset the effects of estrogen in the limbic system. In other words, rising estrogen levels during the luteal phase decrease our capacity for nervous system regulation, making challenges feel harder and emotions feel heavier.

Before we pathologize this receptor sensitivity as a genetic curse, let’s look at the other side. It’s my strong belief that humans with higher biological sensitivity have been blessed with a tremendous gift. Sensitivity imparts greater capacity for empathy and creativity, a gift not only for the individual but for humankind. I come back to this topic often in my practice and in my writing, as it is one near and dear to my heart as a highly sensitive person myself. 

A multi-angled approach to a complex disorder

The first piece of support in helping my patients with PMDD is classical homeopathy to modulate limbic system receptor sensitivity to the effects of circulating estrogen and progesterone metabolites. We now know that homeopathic remedies, when prescribed accurately to the individual needs of the body, alter gene expression on a cellular level and promote adaptive changes. In other words, they lower a person’s susceptibility to experiencing symptoms of PMDD.

In many cases, homeopathic remedies alone are sufficient to significantly reduce or eliminate symptoms. In other cases, specific nutritional support may be necessary to increase cellular metabolism of progesterone to allopregnanolone and increase production of GABA. Vitamin B6, for example, is a critical cofactor in the production of GABA and often helpful in supplemental form throughout the entire cycle or just during the luteal phase.    

Lastly, I never neglect the power of a regulated nervous system in creating bottom-up neuroendocrine changes. Our limbic system may sit at the top of our nervous system (and be the focus of this article,) but it does represent just a small component of our vast emotional regulatory soft-wiring. And we can’t talk about the nervous system without talking about trauma. Trauma sensitizes our nervous system to overactivation of survival responses – meaning a greater tendency toward persistent states of anxiety, depression, overwhelm, etc. Somatic practices to create felt safety in our body send messages directly to our brain that down-regulate limbic system activity. Even in the context of heightened sensitivity to cyclical hormone changes, conscious embodiment has profound ability to shift susceptibility to PMDD overtime.

Why women with PMDD don’t always find healing in conventional progesterone therapy

It might be obvious by this point that prescription of synthetic progesterone therapy, which is sometimes suggested in PMDD, is often incorrect and oversimplified. But what’s more unfortunate is that is can also be detrimental. The reason behind this is that synthetic progesterone, unlike biological progesterone, does not get metabolized to allopregnanolone. And because the body down-regulates biological hormone production in the presence of synthetic hormone, limbic system receptors end up receiving even less allopregnanolone than they otherwise would, resulting in lower GABA levels, and so on.

Something else to keep in mind

Women are not men. End of story. We cycle monthly. Even in a state of hormone balance, we can’t bring the same thing to the table at different phases in our cycle. Unfortunately, we live in a society that does not make space for the cyclical fluctuations that women experience each month. With this in mind, feelings of overwhelm, sadness and anger can be quite normal to experience if you’re in a body that is misunderstood by the system placing demands on it. Yes, we need to address the biological and psychological susceptibility occurring in PMDD and menstrual-related mood disorders. But true healing requires collective shifts in understanding towards empathically holding space for experiences that are different than ours – which is what I’m also hoping to do here.

With love,

Dr. Kayla Amin

https://www.mcimh.com