Women in Mid-life and the Biology of Grief
Part 2: I promised you biology – so let’s get into it.
When I was deepest in grief last year, I kept waiting – no, expecting – to feel better. I mean, I was trying – dragging myself out for walks, going to therapy, calling friends when I could make myself pick up the phone. But nothing was helping. My body felt … numb, disconnected. I was exhausted, but couldn’t really sleep. I ate more for stimulation and comfort than for nourishment. I knew how to act “okay” around people, but the effort it took was enormous. I kept thinking, “this is taking too long. Something must be wrong with me”.
As it turns out, something was happening – just not what I thought. Grief wasn’t just an emotional experience of a significant loss; it was a full-body biochemical event, happening on top of a hormonal landscape that was already in flux. Once I understood that, the way I felt started to make more sense. I hope it does for you, too.
TL;DR – Perimenopausal and post-menopausal women are specifically more vulnerable to Prolonged Grief Disorder, because the hormonal scaffolding that normally supports mood regulation, cognitive flexibility, stress resilience, and emotional processing – the communication pathways that help grief move through us rather than getting lodged – is already challenged. (Ask me how I know.)
The Tank is Already Running Low
Let’s talk for a minute about what’s already happening hormonally during the menopause transition – because context matters here.
Let’s start with estrogen: Rather than declining in a gradual arc (wouldn’t that be nice?), estrogen tends to ride a wild rollercoaster of spikes-and-dips as it trends downward, especially in early perimenopause.
Progesterone – which has calming, sleep-supportive, and mood-stabilizing effects – declines more steadily, but this decline begins earlier than most people realize.
Insulin sensitivity decreases, meaning blood sugar regulation becomes less of a given.
And cortisol – your “awake” hormone, also your primary stress hormone – may already be dysregulated from the increase of psycho-social-emotional pressures that often seem to peak in mid-adulthood. Cortisol is meant to spike in response to acute stress, then return to baseline levels when the stressor has passed. With chronic, “how-is-this-my-life?” stress, cortisol can remain elevated long-term … but then eventually flatline, leaving you completely depleted.
And wait - there’s more!
On top of all these hormonal shifts, the anti-inflammatory, neuroprotective, and limbic-regulating support systems that depend on these hormones are also declining. In other words, the very systems that help your brain and body buffer stress, regulate mood, and process difficult experiences are already operating with less hormonal scaffolding than they used to have.
And Then… Grief Shows Up
It’s normal that after a significant loss the body’s stress response kicks into high gear. Research consistently shows HPA axis dysregulation, heightened systemic inflammation, impaired immune responses, and gut disturbances in bereaved individuals. (We’ll come back to the gut in Part 3, because it’s a whole conversation.)
Remember cortisol, and the fact that it’s already potentially dysregulated in the menopause transition? We tend to see two cortisol patterns associated with grief:
The first is chronic elevation, wherein prolonged stress – often compounded by reduced food intake, btw – activates the release of corticotropin releasing hormone that stimulates chronic high cortisol.
The second is almost the opposite – a flattened cortisol curve, where the natural rise-and-fall rhythm of cortisol throughout the day becomes blunted. In this scenario, waking levels are often below normal range, meaning you start your morning with low cortisol levels that can leave you feeling wiped out before your day even begins.
Both patterns are impactful, just in different ways. Chronically elevated cortisol is inflammatory, metabolically disruptive, and makes restorative sleep elusive. Flattened cortisol is associated with fatigue, low motivation, emotional numbness, and difficulty getting going. (Fun fact: When I finally got my sh*t together enough to do a cortisol test last fall, my “curve” was a flat line at the bottom of the graph. Yikes.)
Here’s what makes this particularly relevant for mid-life women: both acute loss (like the death of someone you love) and chronic, ongoing difficulties (like, say, navigating a major hormonal transition while the world keeps demanding more of you) can increase systemic inflammatory responses. And research shows that the more severe the grief, the greater the levels of inflammatory cytokines. Perimenopause and grief are not just emotionally layered – they are biologically layered. Meaning allll this adds up over time.
Grief Can Get Stuck
Most people move through acute grief – not over it, not past it, but through it – in a way that allows them to gradually re-engage with life. But for some, the healing process gets impeded. This is what’s known as Complicated Grief (CG), a syndrome characterized by the kind of intense, drawn-out grief that doesn’t seem to soften with time the way it’s “supposed” to.
CG symptoms include separation distress – intrusive thoughts about the person you’ve lost, difficulty accepting the reality of the loss – as well as traumatic distress, which can include avoidance, shutting down, and difficulty processing the loss. When these symptoms become maladaptive and ongoing, a formal diagnosis of Prolonged Grief Disorder (PGD) or Persistent Complex Bereavement Disorder (PCBD) may be made by the appropriate medical or mental health professional.
I want to take a step back and offer this reminder: Sadness is so, so normal and expected after a loss – and also, sadness, depression, and grief can all exist simultaneously. While grief and depression are clinically distinct, loss can trigger either (or both simultaneously). They can look similar from the outside and feel similar from the inside, which is one reason why grief that has “gone wrong” can be so hard to identify and address.
It’s not about weakness or poor coping skills. It’s about biology meeting circumstance at a particularly vulnerable intersection. When your neurological and hormonal buffers are diminished, grief has less to push up against (and more room to take root).
The “Bonding Hormone” and Grief
You probably know oxytocin as the “bonding hormone”. It’s the one that floods new mothers during skin-to-skin contact, the one that surges during moments of deep connection and intimacy. It’s essentially the body’s biological language for I am safe, I am loved, I belong.
What you may not know is that oxytocin tracks closely with estrogen. The two hormones have significant overlap in their functions, too – think mood and sleep regulation, bone health, metabolic health – and as estrogen declines during the menopause transition, oxytocin tends to follow. Studies indicate that this declining hormonal cocktail may predispose some women to mood disturbances, particularly those who have experienced early life trauma.
Now add grief to that picture. Grief is a profound experience of disconnection – perhaps from a person you’ve lost, from your sense of the future, and sometimes from yourself. And here’s where it gets biologically interesting: research has found that circulating levels of oxytocin are actually elevated in people with CG/PGD. Which raises the question – is this the body, in all its wisdom, mounting a kind of rescue effort? Is flooding the system with the very hormone associated with connection and healing an attempt to counteract the devastation of loss?
It’s a compelling idea. Oxytocin does have anxiolytic and antidepressant effects, and it interacts with serotonin, dopamine, and the HPA axis in ways that are broadly protective.
But there’s a catch. Oxytocin is also anorexigenic, meaning it suppresses appetite. Elevated oxytocin in the presence of grief may help explain something many grieving people experience but rarely connect to a biological cause: the loss of interest in food, the reduced appetite, the way hunger and satiety cues can be blunted when you’re in the thick of loss. It’s not just sadness; it’s biochemistry (also, more on why this matters nutritionally in Part 3).
You Can, in Fact, Die of a Broken Heart
It’s not just a cliché.
Takotsubo cardiomyopathy – sometimes called ‘broken heart syndrome’ – is a mostly reversible, stress-induced cardiomyopathy triggered by intense emotional or physical stress. A person experiencing Takotsubo presents with cardiac abnormalities, including chest pain, shortness of breath, and in some cases, heart failure – all in the complete absence of clogged arteries. It mimics an acute myocardial infarction in presentation, but the underlying mechanism is entirely different.
In Takotsubo, norepinephrine and epinephrine - the catecholamines released in extreme stress – are elevated to 7-34 times their normal levels. 7-34 times!! Essentially, the heart is flooded with stress hormones, and yet the cardiac enzymes that would typically be released from damaged heart muscle are not present. The heart is in crisis, but not for the reasons a standard cardiac workup would reveal.
Here’s the statistic that stopped me cold when I first read it:
9 out of 10 cases of Takotsubo syndrome occur in women, and the majority of those women are menopausal or perimenopausal.
Let that land for a minute.
Takotsubo cardiomyopathy is mostly reversible, and awareness is protective – but it profoundly illustrates how loss, stress, and grief live in your physical body. Women in mid-life already navigating a hormonally-challenged stress response system are often hit hardest by this reality.
Now you know a bit more about what’s happening inside your body when grief and perimenopause collide. It’s a lot.
In Part 3, we’re going to talk about food, lifestyle, eating behavior, the gut-brain connection, and some specific practices that can genuinely be supportive.
See you there!
About The Author
Stephanie Thompson is a New Orleans-based functional nutrition specialist who specializes in helping people alleviate frustrating (often mysterious) health symptoms with dietary guidance, targeted nutrients, and lifestyle modifications. She digs deep into the biochemical pathways and interconnected organ systems to find the root causes of her clients' issues for specific and sustainable relief!
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