Deep Dive: How Sex Hormones Affect More Than Just PMS

What do these hormones do outside of the uterus and ovaries? A lot.

Dear readers: welcome to another deep dive from Inner Workings. Today we are focusing on female sex hormones, what they are and how they affect the whole body system. This one’s long but packed with info that will make you (or at least, it made me) go WTF?! I came away from this research feeling like I had a better understanding of myself, and I hope you will too! (or a better understanding of the cycling people in your life, if you do not happen to be a person with an ovulatory cycle!)

I am using the word “women” in this essay as shorthand to refer to people with menstrual cycles. If you are a woman who does not have menstrual cycle, or if you do menstruate but don’t identify as a woman, you are still most welcome here. This conversation about hormones is for all of us.

Illustration by Stephanie Davidson, written by Rae Katz

In the last few years I’ve been suddenly surrounded by conversations about female sex hormones. It seems my cohort hit our mid-thirties and suddenly everyone said, wait a second, this seems kind of important, and I don’t know anything about it. Until this time, the extent I had heard or spoken about estrogen and progesterone, the two primary female sex hormones, was the phrase “I’m PMSing,” which exists as sort of an excuse, sort of an apology, and sort of an insult. 

Then. Then women around me started trying to get pregnant and, for the first time in many of our lives, became very aware of our ovulatory cycles. Then I did IVF and spent months injecting and ingesting and inserting a cocktail of hormones. Then people around me started getting pregnant and going through the hormonal roller coaster of the postpartum period. Then my friend Breena got breast cancer in her mid-thirties (and turned her cancer scans into art!), and her subsequent estrogen-suppressing medication put her into temporary early menopause. Then multiple friends’ investigations into chronic conditions revealed hormone imbalances of various types. At one point a friend and I compared notes and found that we had both been prescribed what we understood to be progesterone, one of us in order to stop our period, and one of us in order to get our period to start (this still baffles me). Suddenly, all the women around me, myself included, were becoming aware of our sex hormones for the first time. We were aware of their effect, the many situations where we "didn't feel like ourselves" but couldn't quite put a finger on why. Because, what does it mean to be hormonal?

I’ve said it before, “I’m so hormonal,” but what was I actually saying? I have rarely heard the experience described, and before this I had never looked deeply into the mechanics behind it. Here’s one version of the experience: It’s like something bad just happened and I’m not sure what. It’s a jittery feeling, like being forced to walk across a high balance beam. My chest feels tight, my arms feel heavy. Everything is heightened, the bad things all around are more evident, the little annoyances barge into my brain and live there, huge. I want things I can’t have. I want to leave. I don’t want to go for that walk. I don’t want to talk to you. My internal environment is zipping, it is flashing neon green and then black. It’s hectic and unpleasant and exhausting to be in. There’s a loud pounding beat that won’t stop. I would like to leave—I’ve had more than enough of these strobe lights—but I can’t. 

And here’s the thing, I’m pretty sure that there is a huge range of experiences of “being hormonal,” experiences which start to make sense once we understand the wide-ranging impacts of sex hormones in the body, but otherwise seem unrelated and kind of ridiculous…and maybe a little fake? I also have learned that there are plenty of much more positive versions of “being hormonal,” which we tend to discount or ignore or frame as negative. Men can also “be hormonal,” in the sense that their behavior is impacted by fluctuations of sex hormones, though I’ve never heard someone say, “he’s so hormonal.” Given the extent of my ignorance, I wanted to put together this little primer on female sex hormones that goes deeper than “PMSing.” I wanted to learn what I should have learned in health class about the cascading effects of sex hormones.

As with all my investigations into genuine medical topics, like this one on Hashimoto’s, I will say up front that I am no expert. I am doing my best to sift through the information and put together a succinct and accurate synthesis. If this is your area of expertise and you see an inaccuracy, please do let me know. Even if I miss the mark at times, I still think it’s worth trying, because we must make this type of information more accessible.

Female sex hormones 101

Hormones are made in organs throughout the body, including the pituitary, thyroid, pancreas, and adrenal glands, as well as the ovaries in women and the placenta during pregnancy. They are then released into the blood and circulated throughout the body, binding to any cells that have receptors for that specific circulating hormone and prompting a response in those cells and the tissues and organs they comprise. In this way, hormones are designed to send a consistent message across the whole body, at a pace that is relatively slower and less targeted than the firing of the nervous system. They are useful for messages that need to be consistently communicated across all parts of the organism (like, “we’re having sex now”). This whole operation of glands and hormones is called the endocrine system, and it makes me think of the traffic or weather channels on the radio, where important information can be aired and cells throughout the body tune in to get information to inform coordinated actions.

You may remember that hormones were also a big topic in my investigation into my Hashimoto’s disease, a condition which results in underproduction of thyroid hormones. In that case I was shocked to find that almost every cell in the body has receptors for thyroid hormones, explaining why the symptoms of Hashimoto’s can seem so random and unrelated and varied between people.

Well, I shouldn’t have been shocked this time, but still was, to learn that female sex hormones also bind with billions of cells all over the body, including in the GI tract, bones, liver, skin, and brain. Key brain regions have a particularly high density of progesterone and estrogen receptors, and we will dig into the implications of this shortly. For now, suffice it to say that it is abundantly clear that any of the many hormone-influencing experiences mentioned above—menstruating, certain chronic illnesses, infertility, pregnancy, menopause, taking the birth control pill and many more—will have wide-reaching impacts across multiple body systems, and especially in the brain. These impacts may also seem random and unrelated, given the broad reach of these hormones, and will vary widely between women. This seems like some real 101 info that everyone should, I dunno, learn at some point. And yet I lived for three decades as a woman without really being conscious of any of this.

Estrogen and progesterone in the ovulatory cycle

The ovulatory cycle is a great place to begin this discussion, since the adult female body proceeds through this ebb and flow of hormones and accompanying physiological changes every month for decades. (I am using the term “ovulatory cycle” rather than “menstrual cycle,” taking a cue from the research community. “Ovulatory cycle” takes the emphasis off periods and focuses more accurately on the full scope of changes across the whole cycle). The ovulatory cycle begins on the aptly named “cycle day 1,” which is the first day of full menstrual bleeding, and lasts an average of 28 days plus or minus. A discussion of the phases and hormonal changes involved in the ovulatory cycle can become encyclopedic, so for now we will just cover the most basic structure of the cycle. 

• In the first half, from about day 1 to day 14 or so, the body is preparing to ovulate, or to release a mature egg from a follicle in the ovary. This process is orchestrated by an increase in estrogen. 

• After ovulation, estrogen declines rapidly and the empty follicle that just released an egg begins producing progesterone. The increase in progesterone triggers physiological preparations for a potential pregnancy, including thickening the uterine lining for implantation.

So, from an absolutely bare bones reproductive perspective, that’s what the two hormones do: estrogen increases to cause the maturation of an egg for ovulation, and progesterone increases to cause the uterus to prepare for pregnancy. However, because the impacts of these hormones are not at all confined to the four or five square inches around the ovaries and uterus, there are many other impacts of the cycling hormones, the most well-known one being the progesterone-induced irritation, frustration, impatience, and jitteriness dismissively and derisively referred to as PMS. There are now a smattering of women’s health-focused media articles and women’s health brands highlighting the other half of the cycle, dominated by estrogen, when women tend to feel more energetic and optimistic. The sum total of this coverage, in my reading of pop media articles on the subject, is that we women are encouraged to exercise more during that estrogen-dominant phase because we have more energy, and by the way there’s an app that can help us. 

But let’s actually get into it. Why does estrogen cause an energetic and up-beat feeling? What does it actually mean that progesterone is depressive? This is going to get a little technical for a second, but bear with me.

Sex hormones and the brain

Here was my first big lightbulb moment: