Symptoms, root causes, and a thoughtful path toward balance

By Dr. Marie Andersson

Hormones are chemical messengers, and they coordinate nearly every system in the body: metabolism, mood, sleep, reproduction, and how you handle stress. When they fall out of balance, the effects rarely stay confined to one area of life. Here’s the good news, though: in my experience, hormone imbalance is rarely a mystery. It usually has identifiable causes, it often improves with some foundational lifestyle changes, and if you need more support than that, today’s hormone therapy is far more individualized (and far better studied) than the headlines from the early 2000s might have you believe.

Recognizing the Signs of Hormone Imbalance

Hormonal shifts look different for everyone, but a few patterns come up often enough in my practice that they’re worth watching for. If several of these sound familiar, it might be worth taking a closer look at your hormone health.

Many people don’t realize that hormonal changes often start years before menopause itself. This transition, known as perimenopause, can begin up to a decade earlier, usually sometime in a woman’s 40s, and it involves hormone levels that fluctuate unpredictably instead of declining in a straight line. That’s part of why a single blood test can look normal one day and off the next. It’s also why perimenopausal symptoms get missed or misattributed so often: mood changes get sent to a psychiatrist, sleep problems get sent to a sleep specialist, and nobody connects the dots back to hormones. As one longtime menopause specialist put it, “Menopause is easy. It’s perimenopause that’s tricky.”

For men, the decline is usually more gradual: testosterone typically drops by about 1 to 2% a year starting in the 30s, so the change is easy to miss or write off as normal aging until symptoms have been building for years.

In Women (Perimenopause & Menopause)

• Fatigue, low energy, and difficulty concentrating (“brain fog”)
• Irregular periods, hot flashes, and night sweats
• Weight changes
• Sleep disruption, independent of hot flashes
• Mood changes, including irritability, anxiety, or low mood
• Vaginal dryness, discomfort during intimacy, or urinary urgency
• Low libido and declining bone density
• Hormonally-linked migraines, especially around the menstrual cycle

In Men (Andropause / Low Testosterone)

• Reduced libido and erectile dysfunction
• Loss of muscle mass and strength despite consistent training
• Increased body fat, particularly around the midsection
• Fatigue, low motivation, and mood changes

Notably, fatigue, mood changes, and sleep disruption show up across almost every type of hormone imbalance I see. Part of the reason is mitochondrial: brain aging is increasingly understood as a process driven by cellular energy production, and the hormonal shifts of both menopause and andropause directly affect how efficiently brain cells generate that energy. When neurons can’t produce enough ATP, the result often shows up as brain fog, cognitive slowing, fatigue, and mood changes. That’s why I find looking at the broader picture, rather than fixating on a single symptom, tends to be the most reliable starting point.

What Drives Hormone Imbalance?

Aging is the most obvious driver (estrogen, progesterone, and testosterone all decline with age), but several everyday factors can speed up or compound that decline:

• Chronic stress: elevated cortisol suppresses the body’s production of progesterone and estrogen, and prolonged stress is linked to thyroid dysfunction and menstrual irregularities.
• Poor sleep: disrupted sleep impairs melatonin and growth hormone production and throws off the circadian rhythms that regulate cortisol and other hormones.
• Environmental toxin exposure: endocrine-disrupting chemicals in pesticides, plastics, and personal care products can mimic or block natural hormones.
• Diet and blood sugar swings: diets high in processed foods and added sugar disrupt insulin regulation, which in turn affects sex hormone balance.
• Gut health: specific gut bacteria (the “estrobolome”) produce an enzyme called beta-glucuronidase that can reactivate estrogen after the liver has already processed it for elimination. When gut balance is off, this can get in the way of healthy estrogen clearance.
• Underlying liver detox capacity: the liver’s two-phase detox pathways are what actually clear used hormones from the body. When those pathways are sluggish, hormones (and the byproducts left over from breaking them down) can build up.

Natural Ways to Support Hormone Balance

For many of my patients, foundational lifestyle changes make a real difference in symptoms, and in functional medicine, they’re always my starting point before (or alongside) any hormone therapy.

Lifestyle Foundations

• Diet: a whole-food, fiber-rich diet, especially one rich in cruciferous vegetables, supports healthy estrogen metabolism and insulin sensitivity. Cutting back on added sugar and processed foods also reduces the blood sugar swings that stress the endocrine system.
• Sleep: 7 to 9 hours of quality sleep supports the nightly rhythms of cortisol, melatonin, and growth hormone. Sex hormones also help maintain deep, restorative sleep, so their decline during menopause and andropause can fragment sleep beyond just hot flashes or night sweats, which matters for brain health specifically, since deep sleep is when the brain clears metabolic waste.
• Exercise: regular movement, particularly strength training, improves insulin sensitivity, supports healthy testosterone and growth hormone levels, and helps offset the muscle loss that’s common in both menopause and andropause.
• Stress management: mindfulness, breathwork, time outdoors, and consistent work-life boundaries all help regulate the HPA (stress) axis, which is closely intertwined with reproductive hormone balance.
• Gut health: a fiber-rich diet and a well-balanced microbiome support healthy beta-glucuronidase activity and, in turn, healthy estrogen clearance.

Supplements Worth Discussing With Your Clinician

Evidence quality varies quite a bit by supplement. Some are well-supported, others show more modest or mixed results, and none of them should replace personalized testing and guidance.

• Magnesium: one of the more consistently supported options. It’s involved in over 300 enzymatic reactions, including cortisol regulation and progesterone production.
• Vitamin D: functions as both a nutrient and a hormone precursor, with a well-established role in estrogen synthesis and insulin sensitivity. Correcting a deficiency here tends to be especially worthwhile.
• Omega-3 fatty acids: support insulin sensitivity and hormone receptor function, though the research base is thinner than it is for magnesium or vitamin D.
• DIM and calcium D-glucarate: used in functional medicine to support healthy estrogen metabolism and clearance. Calcium D-glucarate works in part by inhibiting beta-glucuronidase.
• Adaptogens (ashwagandha, maca): ashwagandha has reasonable evidence for lowering cortisol and supporting the stress response. Maca shows some benefit for menopausal symptom relief.

When Lifestyle Isn’t Enough: Considering Hormone Therapy

For some patients, particularly those with more significant menopausal or andropausal symptoms, hormone replacement therapy (HRT) becomes a reasonable next conversation. Here’s what I think is worth understanding before you have it.

Bioidentical vs. Synthetic Hormones

Bioidentical hormones, such as estradiol, estriol, and progesterone, are molecularly identical to the hormones your body naturally produces. That’s what allows them to bind to hormone receptors the way native hormones do. Synthetic hormones (like medroxyprogesterone acetate, the progestin used in the original Women’s Health Initiative study) have an altered molecular structure, and that structural difference can change how they behave in the body and shift their risk profile. My clinical approach favors picking the specific hormone molecule and delivery route that best matches your body’s own biology.

Potential Benefits

• Cognitive support: estrogen has real neuroprotective properties, acting as an antioxidant in the brain and supporting neuroplasticity, the brain’s ability to adapt, grow, and reorganize. Observational data suggest that starting HRT within about 10 years of menopause is associated with a lower dementia risk.
• Muscle and physical function: testosterone and growth hormone support muscle protein synthesis, and estrogen contributes to muscle health through antioxidant and metabolic effects. Together, an appropriately dosed HRT protocol can help offset the muscle loss that comes with menopause and andropause.
• Vascular support: estrogen improves endothelial function and can favorably shift LDL and Lp(a). This cardiovascular benefit does seem to depend heavily on starting therapy before significant atherosclerosis has developed, not after.
• Motivation and quality of life: many of my patients report that optimizing testosterone and estrogen restores the energy and mental clarity they need to sustain the broader lifestyle changes (exercise, diet, sleep) that support long-term health.

2025 Update: Reinforcing Why Timing Matters Most

A 2025 reanalysis of Women’s Health Initiative (WHI) data, published in JAMA Internal Medicine, focused specifically on women being treated for hot flashes and night sweats.

The researchers flagged an important limitation: the original WHI only tested oral conjugated equine estrogen (estrogen extracted from the urine of pregnant mares) with a synthetic progestin (or oral estrogen alone) — the formulations that were available roughly 30 years ago. Many of today’s options, including transdermal delivery and bioidentical micronized progesterone, are closer to what the human body produces versus taking hormones that are normal for horses.

There’s also no more “magic age” for stopping therapy. Leading researchers now describe continuing hormone therapy past 65 as a reasonable option for appropriate candidates with ongoing reassessment, especially with keeping an eye on liver function and detoxification capacity. As with everything in this newsletter, the same theme holds: there’s no one-size-fits-all answer, only an individualized one.

Without hormone replacement, the risk of both cardiovascular disease and osteoporosis rises after menopause. Neuroimaging research also shows menopause is associated with measurable changes in brain structure, including modest reductions in gray matter volume in regions tied to memory and emotional regulation, such as the hippocampus. The research here is still evolving: some studies find these changes stabilize or even partially reverse after the transition, while others find no acceleration beyond normal age-related decline.

Hot flashes are driven largely by estrogen withdrawal. As estrogen declines, it loses its normal calming effect on a group of neurons in the hypothalamus, the brain’s temperature-control center. Those neurons become overactive and narrow the body’s tolerance for temperature swings, so a small rise in core temperature triggers the flushing and sweating response we feel as a hot flash.

Estrogen Alone vs. Combined Therapy: A More Nuanced Risk Picture

Follow-up reanalyses of the WHI data have added important nuance to the original headlines. Women who took estrogen alone (typically those who no longer have a uterus, since estrogen-only therapy wasn’t used in women who still have one) and who had no strong family history of breast cancer showed a statistically significant reduction in breast cancer incidence in later analyses, and that protective effect persisted in longer-term follow-up. This finding appears specific to estrogen taken without a synthetic progestin. Women on combined estrogen-plus-progestin therapy didn’t show the same protective effect, and reanalyses still show a modest increased risk with that combination. Progestin is a synthetic hormone, not to be compared to bioidentical progesterone.

To put that risk in concrete terms: subsequent peer-reviewed analyses estimate the excess breast cancer incidence associated with combined estrogen-progestin therapy at roughly one additional case per 1,000 women per year of use, with no corresponding increase in breast cancer mortality. Menopause specialists have independently arrived at a similar figure, describing the actual increase as about eight additional cases per 10,000 women. Numbers like this are easy to lose in headlines about “increased risk,” which is exactly why I think absolute risk, not just relative risk, is the number worth asking your clinician about.

Risks, Safety, and Delivery Method

Route of administration matters almost as much as the hormone itself. Oral estrogen passes through the liver first, which can raise CRP and triglycerides and shift clotting factors (increasing prothrombin, decreasing antithrombin III). Those effects are tied to a real increase in clotting risk, most pronounced in the first year of treatment. Transdermal estrogen (patches, creams, gels) largely bypasses this liver effect and carries a meaningfully lower risk profile for clotting and stroke.

My Approach: Test First, Personalize Always

I don’t believe in reflexively adding hormones to a protocol. Safe estrogen clearance is a top priority to me, both for symptom relief and for long-term breast and endometrial health, and that starts with the gut and liver. Dysbiotic gut bacteria can produce high levels of an enzyme called beta-glucuronidase, which can reactivate estrogen the liver has already processed for elimination and send it back into circulation, so adding hormone therapy on top of that just recirculates excess estrogen rather than clearing it.

That’s why I sequence care in two phases. Phase 1 uses testing such as the Vibrant Wellness Gut Zoomer and Hormone Zoomer to check for environmental toxin burden, gut imbalance, and estrogen clearance markers (an elevated 4-OH estrogen metabolite pathway or high beta-glucuronidase activity, for example), and prioritizes gut and liver support first, opening up detoxification pathways. Phase 2 introduces hormone modulation, including bioidentical estrogen and progesterone, once those clearance pathways are functioning well. From there, I use comprehensive testing, including salivary cortisol curves, urinary estrogen metabolites, progesterone, and androgens, to guide dosing and monitor safety over time, with regular retesting to track your response and adjust as your needs change.

In my practice, that includes professional-grade bioidentical hormone replacement, and, when appropriate, medically supervised prescription estradiol, progesterone, and testosterone, along with peptides to support hormone balance. Every option is layered in only once testing shows it’s the right fit, and only ever alongside the foundational work.

Every hormone protocol I recommend is individualized to your labs, symptoms, and health history. There’s no one-size-fits-all dose or approach here.

Ready to Talk About Your Hormone Health?

If any of this resonates with you, I’d love to start with a conversation and comprehensive testing to understand what’s actually happening in your body, not guesswork. Reach out to schedule a consultation.

This newsletter is for educational purposes and is not a substitute for personalized medical advice. Please consult your clinician before starting or changing any supplement or hormone therapy regimen.