PMDD vs PMS: Hormonal Influence on Cognitive Function (Episode 589)

Full Transcript: Episode 589

Lisa Hendrickson-Jack:

In today’s episode, we are digging into PMDD. I am sharing a research study that looked at mood, cognitive performance, and appetite — how that changes for women with PMDD compared to women without PMDD. We are going to look at the study findings, what they measured in terms of hormone levels, what the implications are, and we’re going to talk a little bit about the strengths and weaknesses of their approach. So without further ado, let’s go ahead and jump into today’s episode with a focus on PMDD.

The title of today’s study: Changes in Mood, Cognitive Performance, and Appetite in the Late Luteal and Follicular Phases of the Menstrual Cycle in Women With and Without PMDD. This study was published in Hormones and Behavior. And I wanted to talk about it today because I feel like it really does highlight some of the differences between the way that the psychological and psychiatric community look at an issue like PMDD versus how you might look at PMDD if you track your menstrual cycles and are looking at the menstrual cycle as a really important factor.

What I find to be most interesting about this study, as we will dive into, is that they essentially dismiss the hormonal implications. And that’s really fascinating to me because by definition — how they define PMDD, how they define PMS — PMDD is characterized primarily by a cluster of mood symptoms, especially depression, tension, anxiety, irritability, and fatigue, with five or more symptoms present during the luteal phase. One of the things they’re looking for is the appearance of these symptoms during the five to seven days preceding the menstrual period. So these symptoms are specifically happening during that week before her period, and then they disappear in the follicular phase once the period is over.

So if you think about this just logically for a moment — if these symptoms are simply appearing at that specific time of the cycle, every time she is in that phase of the cycle, then logically you would think, well, there must be a hormone component. But as we’ll discuss, the researchers largely dismiss that component.

From my perspective, based on looking at the research around PMDD — PMDD, I often refer to as PMS’s cousin or something like that. It’s a really exacerbated version of PMS. In The Fifth Vital Sign, I talked about how 90% of women report some level of shifts in mood and energy during that time leading up to their period. Molimina refers to shifts that are manageable and that don’t disrupt your daily life. PMS is the moderate to severe situation. And PMDD is typically identified when the symptoms are debilitating. You can’t get to work. For a few days out of every cycle, you basically can’t function. That’s the distinction.

In this study, what they were trying to do is look at some of the symptoms that women commonly report with PMDD in a more systematic way — mood changes, cognitive function including memory recall tasks, balance, and food cravings. They used standardized testing questionnaires and they tracked hormones.

What they did — and this is the part I want to focus on — is they had these women identify ovulation with LH testing, which is very common for research studies. But LH testing, when we experience the LH surge, it is typically a precursor to ovulation. Once that LH surge takes place, ovulation is typically happening about 36 hours after. So LH by itself does not confirm that ovulation has taken place. And how they measured estrogen and progesterone — which was really astounding to me — is that they would do a salivary test once. Once in the pre-ovulatory phase, and once in the post-ovulatory phase. Literally one spot test on one day, and they base their study results on that.

That is astounding to me because when we look at the menstrual cycle, the estrogen output is not the same every hour of the day, let alone throughout the cycle. As a woman gets closer to ovulation, the estrogen levels significantly change and peak before the LH surge. And we don’t produce significant progesterone until after ovulation. But the progesterone level fluctuates throughout the post-ovulatory phase. After a woman ovulates, the progesterone levels start to rise significantly, and they tend to peak mid-luteal — about seven days after ovulation — and then they start to fall.

So logically: if we’re dealing with a woman that has PMS or PMDD, and this is literally defined by her having significant changes in her mood, cognition, and appetite specifically during the week before her period — wouldn’t it make logical sense to not just test progesterone one random day in the entire luteal phase? Wouldn’t it make sense to have full systematic tracking of the menstrual cycle where we actually have this woman charting? Test mucus. Test BBT. Have a few different markers to confirm ovulation. And then test progesterone every three days — three days after ovulation, six days, nine days — so that for each woman, you have a curve of progesterone that you can put on a graph for the entire luteal phase. So you can actually see what is happening during the period of time in question: the five to seven days leading up to their period.

These researchers tested progesterone once.

When they looked at the results for mood, cognition, and appetite, they did find that women with PMDD showed clear and consistent changes across mood, memory, and appetite in the luteal phase. They had significantly higher depression and anxiety scores. Their ratings were more negative compared to their own follicular phase scores. Compared to women without PMDD, there was a significant difference during that week before their period. Cognitively, performance dropped especially on delayed word and number recall tasks. And when it came to appetite, they consumed about 100 more calories at lunchtime, primarily from fat and protein.

In terms of the hormone findings, the researchers found and stated in their study that there was no significant difference between the estradiol levels and the progesterone levels of either group. All of the women had ovulatory cycles ranging from 23 to 33 days. Progesterone was higher in the luteal phase than the follicular phase — obviously, because we don’t produce significant progesterone until after ovulation. But beyond that shift, both groups were said to be the same.

And so it’s like — okay, conversation’s over. No hormonal component. They go on to suggest that, although these symptoms are worsening at a very specific point in the cycle over and over again, since they spot-tested once and there was no real difference between subjects, therefore it’s not hormonal. And so they recommend SSRIs. They’re suggesting psychiatric medication. They also dismiss the potential for progesterone replacement therapy. They say maybe it’s just that women with PMDD are more sensitive to hormones and that’s why they’re responding differently.

You cannot get an actual scientific comparison of hormones in a cycle when we know hormones fluctuate. We know there is a rise and fall. And when we look at research that has actually looked more deeply at that rise and fall, we can see that women who have PMS and PMDD symptoms are more likely to have an atypical progesterone pattern in the luteal phase. So when we don’t just check one random day, but do a systematic series of hormone testing, you can actually see women who have increased PMS symptoms potentially showing a drop instead of a gradual dip after mid-luteal. And when women are charting — when you have somebody tracking their temperature and their mucus — you also get this indirect view of what’s happening hormonally. It’s not uncommon for women who are having more significant PMS symptoms to show erratic temperatures, dropping temperatures, or a shorter luteal phase.

In this particular study, they didn’t measure the length of the follicular or luteal phases. They measured total cycle length. They estimated ovulation with LH testing. They did not identify whether the luteal phase was shorter in the PMDD group. They don’t know if there was premenstrual spotting. They don’t know if there were other symptoms correlated with low progesterone. This is potentially just the least scientific way to truly evaluate if this is a hormonal problem.

The implications are clear. Women are still experiencing these symptoms. But because we’re not looking at the menstrual cycle as a vital sign, we’re not really investigating it to the level it needs to be. You can have professionals say, “Well, there’s no hormonal component — this has been studied.” But you cannot make that conclusion based on this research. Not even close.

And what about bioidentical progesterone? That’s not something that can be patented. So there’s no financial incentive to fund the high-quality research that would actually test it properly. The way our system is designed, companies need to create something they can patent. You have to have a slight variation on a molecular structure that you can specifically patent in order to profit. So we have to look at research critically and really ask: who’s funding the studies, who benefits from the findings, and which industries rely on women not understanding this information.

The researchers in this study were not malicious. They thought they were following sound methodological standards. They did the LH testing. It didn’t occur to them to test progesterone more than once. But this is my point. When studies are being designed by individuals who are not knowledgeable around fertility awareness and body literacy and the menstrual cycle in general, they’re not thinking about the cycle the way we think about the cycle. There’s a systemic overconfidence in all things menstrual cycle in the medical and psychiatric fields — and it is reflected directly in how these studies are designed.

We have to be critical of the research. We have to be able to review it with a keen eye. And we have to keep building on it — demanding studies that are actually designed to investigate the luteal phase, that track progesterone across the full phase, that confirm ovulation with more than one marker. Until then, the conclusion that PMDD is not hormonal is not a conclusion at all.

As always, until next time — be well and happy charting.