Why HRT is not working and what you are missing

Helen, 48 — on HRT, and still not herself

Helen came to me at 48, on HRT that had been increased to 50 mg, and still — in her words — feeling awful. Hot flushes and night sweats that flared the moment she was stressed, anxiety, broken sleep, brain fog, joint pain, low energy, low libido and weight gain, none of it settling on the HRT. Her bloods told the story the dose could not reach: blood sugar running high, an underactive thyroid, low vitamin D, B12 and folate, and inflammation — all against a long background of stress. Each of her symptoms had a driver in there, and not one of them was a shortage of oestrogen.

We worked on the drivers underneath — steadying her blood sugar, easing the load on her stress system, healing her gut, and correcting what was depleted. Four weeks later her overall symptom score, measured on the same scale at the start and the end, had fallen by 80%. Her hot flushes had resolved, her sleep had deepened, the brain fog had lifted, and her joint pain was gone. She came off HRT during this time and felt well.

“Having struggled with just awful peri-menopause symptoms for a few years and feeling more and more at a loss as to how best to support my health, I took the plunge and booked Sandra 1:1 to get me back on track. She provided a detailed health review, testing and a healthy eating guide. I felt better almost within a week, and four weeks later symptoms almost gone! My vitality is back! It has made me feel like I’m back in the driving seat of my well-being. Transformative.” — Helen

Helen’s result is her own, and every woman’s picture is different. But it shows the pattern this article describes: symptoms that persisted on HRT because their drivers were never oestrogen, settling once those drivers were addressed. Read Helen’s full story →

Are you in a similar situation?

The symptoms came, and you started HRT — oestrogen as a patch or gel, and progesterone as a pill to balance it. Perhaps it helped at first. Perhaps the dose has been raised once or twice since, and the patch swapped for a gel or vice versa. The hot flushes maybe quieter, but the brain fog, the low mood, the fatigue, and the wired-but-tired nights still with you. On paper you are treated. You still do not feel like yourself.

The usual next step is to adjust the dose again. Sometimes that helps. When it does not, the better question is a different one: what if the symptoms that remain, though the oestrogen decline set them off, are now driven by something else? If they are, more oestrogen will not reach them.

For some women that opens a larger question: if HRT is not the whole answer, is it worth staying on? That is for you and your doctor to decide — but it is a decision better made from understanding what your body is doing. That understanding is what the rest of this is for.

What HRT does, and what it does not

Start with the name. HRT stands for hormone replacement therapy — and that word, replacement, carries an assumption that turns out to be wrong: that something is missing and needs replacing. The ovaries winding down is a programmed transition, not a fault — nothing has broken, and nothing has been lost that the body was meant to keep. There is no oestrogen deficiency at menopause. So HRT is really a misnomer: it does not replace something missing, it extends — it extends the amount of time you are exposed to oestrogen.

That matters for understanding what it can and cannot reach. The symptoms of menopause are not the falling oestrogen itself. They come downstream of it — the decline is the trigger that sets off a cascade of changes in metabolism and the nervous system, and it is in those changes that the symptoms arise. Extending oestrogen holds off some of those downstream effects, and where a symptom follows closely from the decline — classically the hot flushes and night sweats, and often vaginal and urinary changes — that works, and works well. The relief is real, and for many women it is reason enough to take it.

Oestrogen in patch or gel form is licensed — by the medicines regulator, the MHRA — for hot flushes and night sweats; and where bone protection is the main concern, treatments other than HRT are usually considered first [14]. NICE, the body that guides how the NHS uses medicines, has since gone further, recommending it for the low mood that arises with menopause too [13]. But in practice it is prescribed more widely still — for fatigue, brain fog and general wellbeing — beyond both the licence and that guidance, to the point NICE itself advises against using it to prevent heart disease or dementia [13]. So a woman can be on HRT for symptoms it was never licensed, or firmly shown, to fix. When those are the symptoms that remain, that is part of the reason.

What extending oestrogen does not do is undo the changes running underneath. Menopause is a whole change in how the body runs — how it fuels itself, how it handles stress, how it holds oestrogen in the tissues. Extension speaks to one part of that. The rest keeps moving, whatever your dose.

The Oestrogen Shift: the androgen side HRT leaves untouched

The Oestrogen Shift is a change in where oestrogen is made. Before menopause, the ovaries make most of it. As they wind down, the tissues take over, making their own oestrogen locally — and for that they need a raw material from the adrenal glands: DHEA.

As the ovaries slow, the adrenals step up their DHEA production [7, 8, 9]. DHEA then does double duty: the body uses it to build the tissues’ local oestrogen, and to build testosterone. So one adrenal supply sits behind two things at once — the oestrogen the tissues now make for themselves, and the testosterone behind libido, drive, wellbeing, and mental sharpness.

HRT restores neither. Over a year, modern HRT — transdermal oestradiol with progesterone — left DHEA and testosterone unchanged; only DHEA itself raised them [11]. Older oral oestrogen lowered them further [10]. HRT adds oestrogen to the bloodstream and leaves the DHEA and testosterone side where it was. This is why the “therapy” keeps needing more added to it: first oestrogen, then the progesterone to balance it, and now testosterone — each step an admission that the one before was not the whole picture. It is the same lesson arriving slowly: menopause is not one missing hormone to replace, but a whole supply the body has to re-source.

So the symptoms that lean on that side do not lift with more oestrogen — low libido, flat mood and drive, and the share of brain fog that is a testosterone shortfall rather than an oestrogen one. The evidence linking testosterone to memory and concentration is still limited [12], but the pattern is clear: what depends on DHEA and testosterone is what extending oestrogen was never going to reach. In Helen’s case, this was the side behind her low libido and flat drive. I develop this axis in The Oestrogen Shift →.

The Energy Shift: fuel HRT cannot top up

As oestrogen falls, the brain is meant to shift from running mainly on glucose toward using more ketones, the fuel the liver makes from fat. That transition is normal. It stalls when insulin stays high — kept up by a diet high in sugar and refined carbohydrates, and by the insulin resistance that builds over years — because ketones are only made when insulin is low. The brain is then left short of steady fuel, and the result is hot flushes, brain fog, fatigue, low mood, and waking in the night — the brain, short of fuel, rousing you to raise your blood sugar.

Oestrogen does help the brain use glucose. But the thing holding this shift up is not oestrogen — it is a fuel supply blocked by high insulin, which comes from diet and metabolism. Extending oestrogen does not lower your insulin or steady your blood sugar. So where these symptoms are running off the Energy Shift, adding oestrogen leaves the block in place.

This was the heart of Helen’s case. Her blood sugar ran high, holding the fuel switch shut — and out of that stalled Energy Shift came her brain fog, her fatigue, the weight that would not move, and the waking in the small hours when her fuel ran low, whatever her dose.

The Emotional Shift: from tend-and-befriend to challenge-and-disrupt

For decades, oestrogen has supported the systems that keep the nervous system settled and connection easy — the oxytocin, and the GABA calm (helped by progesterone) behind what researchers call the tend-and-befriend response. As oestrogen and progesterone fall in perimenopause, that buffering withdraws. The fight-or-flight axis, held quiet for years, comes closer to the surface, and with it a sharper edge — a short fuse for dynamics long absorbed without complaint, a rise of feeling that can seem out of proportion to its trigger. In my work I read this less as a disorder to be corrected than as a nervous system changing mode — often registering, accurately, what has been costing too much for too long. That same rise in fight-or-flight keeps cortisol and blood sugar up, feeding the fuel block of the Energy Shift, so the two run together.

As the transition goes on and oestrogen falls relative to testosterone, the balance tips further. I think of it as move to challenge-and-disrupt — more inclined to set boundaries, question old arrangements, and follow one’s own direction than to organise everything around others’ comfort. Extending oestrogen can soften the edges of this, but it does so by damping a signal that is often meaningful, and it leaves the testosterone side of the change untouched. Neither the rupture nor what comes after it is a shortage of oestrogen to be topped up. I develop this in The Emotional Shift →.

Helen lived the near side of this. Years of stress had left her fight-or-flight axis loaded and her fuse short, reactive to pressures she had carried for years — and that same loaded stress kept pushing her blood sugar up, tightening her fuel block from the other direction, so her two shifts fed each other.

Why some symptoms lift, and the rest stay — and what reaches them

Look at which symptoms settled on HRT and which did not, and a pattern appears. The flushes and sweats are usually the ones HRT settles most reliably — they fire at the brain’s thermostat, and oestrogen steadies it directly. The fog, the fatigue, the flat mood, the broken sleep, the weight that will not move are the ones that tend to linger. Oestrogen reaches part of them — it helps the brain take up glucose, so HRT can lift the fog a little — but it cannot open the blocked ketone side of the fuel supply, or undo the insulin resistance beneath it. So these ease only partly, or not at all: the block holding them is not one oestrogen controls.

Helen’s case shows how far this can go. Even her flushes — the symptom HRT usually settles — kept firing, flaring the moment she was under stress, because her blood sugar and her stress load ran high enough to tip the thermostat against the oestrogen she was taking. The dose was never the missing variable. The drivers underneath were.

This is not a sign the HRT is failing at its job. It is doing exactly what it does — restoring oestrogen, and reaching what oestrogen reaches. The symptoms that remain persist because part of what drives them sits outside oestrogen’s reach. What reaches them are the levers that act on fuel and stress:

• Steadying insulin — bringing down refined carbohydrates and sugar, with enough protein and quality fat, so the fuel switch can work and the brain is no longer left short.
• Taking the load off cortisol — through stress, sleep and caffeine, so the nervous system can settle out of its reactive state.
• Correcting what is depleted — B12, folate, vitamin D, iron, thyroid function; all common, all able to hold symptoms in place when low, and all findable on a blood panel.
• Supporting the gut — since it absorbs the nutrients the rest of the work depends on.

Helen’s joint pain traced the same way — to inflammation and a low vitamin D, not to her hormone dose. Worked on together, her drivers gave way: four weeks of steadying her blood sugar, easing her stress load, correcting what was depleted and healing her gut, and the symptoms her HRT had never reached settled — the fog, the fatigue, the anxiety, the joint pain, the flushes. None of it had been an oestrogen shortage.

Why “more HRT” does not fix a problem that is not about oestrogen

This is where the dose-chasing begins: symptoms persist, so the dose goes up, or the delivery changes, or another hormone is added. Where the remaining symptom really is oestrogen-driven, that can help. Where it is not — where it is fuel, or cortisol, or gut, or a nutrient the body is short of — more oestrogen has nothing to act on. The symptom stays, and the search for the right dose continues, because the dose was never the variable that mattered for that symptom.

The model that blames low oestrogen for every menopause symptom, and reaches for more oestrogen when they persist, is too small for what menopause is. Symptoms have more than one driver. The ones HRT leaves behind usually have a different one.

Work with me

If you are on HRT, still not yourself, and you want to come off it, this is the work I do. The medication itself stays with you and your prescriber — my work is the body underneath it: addressing the drivers HRT has been covering over, so that as the oestrogen comes down, your own systems can hold steady and the symptoms are less likely to come flooding back.

The discovery call is free, thirty minutes, no obligation. We go through your symptoms, your history, and what you have already tried, and you leave with a clear picture of what is driving the symptoms that remain.

Book a discovery call →

References

1. Harlow SD, et al. The Study of Women’s Health Across the Nation (SWAN): a longitudinal cohort of the menopausal transition. Menopause.(Menopause symptoms are heterogeneous and cluster in patterns, supporting multiple underlying drivers rather than a single hormonal cause; SWAN investigators, including Nanette Santoro, have argued against an oversimplified model that attributes all symptoms to low oestrogen.)
2. Aras SG, Grant AD, Konhilas JP. Clustering of symptom logs reveals distinct pre, peri, and menopausal phenotypes. Sci Rep. 2025;15:640. doi:10.1038/s41598-024-84208-3. (Symptoms co-occur in consistent patterns — vasomotor, sleep, mood and cognitive — consistent with shared underlying mechanisms.)
3. Athar F, Gregory S, Houston EJ, Templeman NM. Insulin levels early in perimenopause inform vasomotor symptom incidence across the menopausal transition. J Clin Endocrinol Metab. 2026. doi:10.1210/clinem/dgaf699. (Higher insulin early in perimenopause predicts earlier and longer vasomotor symptoms — evidence of a metabolic driver independent of oestrogen status.) Brinton RD, Yao J, Yin F,
4. Mack WJ, Cadenas E. Perimenopause as a neurological transition state. Nat Rev Endocrinol. 2015;11(7):393–405. doi:10.1038/nrendo.2015.82. (Menopause involves a shift in brain fuel use from glucose toward ketones — a metabolic transition alongside the hormonal one.)
5. Mosconi L, et al. Perimenopause and emergence of an Alzheimer’s bioenergetic phenotype in brain and periphery. PLoS One. 2017;12(10):e0185926. (Reduced cerebral glucose metabolism across the menopausal transition, underpinning cognitive and energy symptoms.)
6. Fruehwald-Schultes B, et al. Hyperinsulinemia, but not hypoglycemia, acutely increases hypothalamic-pituitary-adrenal axis activity in humans. J Clin Endocrinol Metab. 1999. (Insulin and the stress axis interact — high insulin raises cortisol — linking the metabolic and nervous-system drivers.)
7. McConnell DS, Stanczyk FZ, Sowers MR, Randolph JF Jr, Lasley BL. Menopausal transition stage-specific changes in circulating adrenal androgens. Menopause. 2012;19(6):658–663. PMID 22415570. (A shift toward Δ5 adrenal steroid production — DHEA, androstenediol — occurs in ~85% of women, beginning after the menopausal transition starts; the DHEAS rise is adrenal, seen even in ovariectomised women.)
8. Lasley BL, Chen J, Stanczyk FZ, El Khoudary SR, Gee NA, Crawford S, McConnell DS. Androstenediol complements estrogenic bioactivity during the menopausal transition. Menopause. 2012;19(6):650–657. PMID 22415563. (Androstenediol, produced by the Δ5 shift, has oestrogenic activity — a route by which the body maintains local oestrogen effect as ovarian output falls.)
9. Moran FM, Chen J, Gee NA, Lohstroh PN, Lasley BL. Dehydroepiandrosterone sulfate levels reflect endogenous luteinizing hormone production and response to human chorionic gonadotropin challenge in older female macaque. Menopause. 2013;20(3):329–335. PMID 23435031. (Adrenal DHEAS output tracks LH and responds to gonadotropin (hCG) challenge — the basis for the gonadotropin-driven model of the Δ5 shift. Primate data; the gonadotropin-drive in women is inferred, and coexists with the classical ACTH-driven view of adrenal DHEA.)
10. Wood CE, Cline JM, Anthony MS, Register TC, Kaplan JR. Adrenocortical effects of oral estrogens and soy isoflavones in female monkeys. J Clin Endocrinol Metab. 2004. (In ovariectomised (postmenopausal) monkeys, oral oestrogen therapy lowered adrenal androgens — DHEA-S ~29–35% and testosterone ~41–52% — while cortisol rose. Primate data, oral conjugated oestrogens; transdermal oestradiol may differ.)
11. Pluchino N, Ninni F, Stomati M, et al. One-year therapy with 10 mg/day DHEA alone or in combination with HRT in postmenopausal women: effects on hormonal milieu. Maturitas. 2008;59(4):293–303. (Over 12 months, transdermal oestradiol (50 µg) plus oral micronised progesterone did not raise DHEA, DHEAS, androstenedione or testosterone; DHEA supplementation raised androgens and oestrogens and lowered cortisol. Modern transdermal HRT leaves the adrenal androgen/DHEA tone unchanged — human data. Hormone-level changes; the symptom benefit of DHEA is separately mixed.)
12. Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019;104(10):4660–4666. PMID 31498871. (Testosterone is a biologically active hormone in women, with actions in the brain, and the only evidence-based indication for testosterone therapy is low sexual desire (HSDD). Evidence for testosterone in cognition is rated insufficient — not negative; the panel called for adequately powered trials.)
13. National Institute for Health and Care Excellence. Menopause: identification and management (NG23). (Offer HRT for vasomotor symptoms associated with menopause; consider HRT for low mood arising as a result of menopause; offer vaginal oestrogen for genitourinary symptoms. Do not offer combined or oestrogen-only HRT for the primary or secondary prevention of cardiovascular disease, or for dementia prevention.)
14. British National Formulary — Sex hormones: Hormone replacement therapy. NICE/BNF. (HRT licensing at normal menopausal age is for symptomatic control — vasomotor and vaginal symptoms — not disease prevention; where osteoporosis is the main concern, alternatives to HRT should be considered.)