Dihexa for Endometriosis Brain Fog & Endo-Associated Cognitive Dysfunction: Neuroinflammation, BDNF, Central Sensitisation, Ryeqo NICE TA1057, the 2026 Women’s Health Strategy & the UK Review

Around 1.5 million UK women live with endometriosis (~10% of women of reproductive age) on Endometriosis UK and NHS England figures. The UK average diagnostic delay is 9 years and 4 months (Endometriosis UK 2024 survey of 4,371 patients), up from 8 years and 10 months in 2023 and 8 years in 2020 — rising to 11 years for diverse ethnic communities. In that 2024 survey, 47% of women had visited their GP 10 or more times before anyone named the condition, and 78% reported being dismissed by a doctor. 2025-2026 has been the most consequential window in endometriosis policy and brain science in a generation. In November 2025, Suzy Mahony, Philippa Saunders, Lucy Whitaker and Andrew Horne at the University of Edinburgh’s EXPPECT centre published 'The overlooked symptom in endometriosis: brain fog' in The Lancet Obstetrics, Gynaecology & Women’s Health — the first major journal commentary to formally name brain fog as a neglected cardinal symptom of endometriosis. In April 2025, the Horn, Sherman, Pehlivan et al. Macquarie / Sydney Journal of Health Psychology FACT-Cog survey of 1,239 individuals with endometriosis reported ~80% perceived cognitive impairment across attention, working memory, processing speed and executive function. In March 2025, NICE TA1057 approved Ryeqo (relugolix-estradiol-norethisterone, Gedeon Richter) as the first daily oral GnRH-antagonist combination pill for long-term endometriosis symptom management on the NHS, with approximately 1,000 women per year initially eligible. In April 2024, NICE NG73 on endometriosis diagnosis and management was substantively updated. In April 2026, the renewed UK Women’s Health Strategy for England was published with 117 action points and an explicit pledge to "eliminate the diagnostic odyssey facing women" with endometriosis and fibroids; the 5 March 2026 Westminster Hall Hansard debate aired cross-party concern about diagnostic delay and BSGE-centre access. The February 2026 Endometriosis UK 'State of Endometriosis Care' roadmap quantified the gaps. The mechanistic picture is converging: the 2023 Journal of Neuroinflammation paper from Erin Greaves’ group reported CNS-wide glial activation across thalamus, hippocampus and cortex in a mouse model; the 2025 Frontiers in Immunology JAK-STAT / mast cell activation paper formalised the neuroinflammation-pain axis; the Wu, Hu, Liang 2022 BMC Women’s Health paper documented elevated BDNF and TrkB in endometriosis patients correlating with dysmenorrhea severity; the 2017 Frontiers in Endocrinology BDNF-in-endometriosis-pain review consolidated the BDNF-elevated-in-peritoneal-fluid story — the central directionality paradox for any synaptogenic-peptide claim in endometriosis. Against this backdrop, does Dihexa have anything to offer the UK’s 1.5 million women with endometriosis — or is there a real theoretical risk that more BDNF / TrkB synaptic plasticity could consolidate rather than relieve the central-sensitisation pain-and-cognition pathology that drives endo brain fog? This rigorous 2026 UK review covers what is actually known, what is speculation, and where the evidence is genuinely absent. Readers may also want to read the closely related Dihexa for Fibromyalgia & Fibro Fog review (25% endometriosis-fibromyalgia comorbidity), the Dihexa for Migraine review (3x more common in endometriosis), the Dihexa for ME/CFS review (post-viral fatigue and chronic-pain overlap), the Dihexa for Long COVID Brain Fog review (parallel neuroinflammation-driven brain fog), the Dihexa for Menopause Brain Fog review (oestrogen-fluctuation overlap), the Dihexa for Anxiety & Stress review (~50% comorbidity), and the Dihexa for Depression & Mood review (~50% comorbidity).

Endometriosis in the UK in 2026: Scale, Diagnostic Delay & Why Brain Fog Matters

Endometriosis is a chronic inflammatory condition in which tissue similar to the endometrium (the lining of the womb) grows outside the uterus — on the ovaries, fallopian tubes, peritoneum, bowel, bladder, ureters, and in rarer cases the diaphragm, lungs and brain. Endometriosis UK and NHS England estimate that around 1.5 million women in the UK are affected — approximately one in ten women of reproductive age. The condition is one of the largest unmet needs in women’s health: the House of Commons Library briefing CBP-10591 on access to endometriosis services documented the systematic underfunding and under-recognition of the condition.

The 2024 Endometriosis UK survey of 4,371 women with a confirmed endometriosis diagnosis reported the UK average diagnostic delay had risen to 9 years and 4 months (up from 8 years and 10 months in 2023 and 8 years in 2020), broken down as 8 years 10 months in England and Scotland, 9 years 5 months in Northern Ireland, and 9 years 11 months in Wales, rising to 11 years for diverse ethnic communities. Of those surveyed, 47% had visited their GP 10 or more times before anyone named the condition; 78% reported being dismissed by a doctor; and a substantial minority were told that severe period pain was "normal" or attributed to anxiety. The diagnostic gold standard remains laparoscopy with histological confirmation, but the April 2024 NICE NG73 update places much greater emphasis on transvaginal ultrasound and MRI for initial diagnosis, in line with the ESHRE 2022 guideline.

Brain fog and cognitive symptoms are extraordinarily common in endometriosis — and have been chronically under-recognised. The April 2025 Macquarie / Sydney survey of 1,239 individuals with endometriosis by Horn, Sherman, Pehlivan and colleagues, using the Functional Assessment of Cancer Therapy — Cognitive Function (FACT-Cog) instrument, reported approximately 80% perceived cognitive impairment, with affected domains spanning attention, working memory, processing speed and executive function. Comparable rates have been reported in UK-based qualitative studies. The November 2025 Lancet O&G/WH commentary by Mahony, Saunders, Whitaker and Horne at the University of Edinburgh’s EXPPECT centre formally named brain fog as the "overlooked symptom" — arguing that cognitive dysfunction should be integrated into NICE NG73, the ESHRE 2022 guideline, and into all future endometriosis clinical trials as a patient-reported outcome.

Disease Staging: rASRM, ENZIAN & the Deep-Infiltrating Subtype

Endometriosis is conventionally staged using the revised American Society for Reproductive Medicine (rASRM) classification (1996, updated) — a four-stage system (minimal, mild, moderate, severe / I-IV) based on laparoscopic visualisation of lesion location, depth, size and adhesions. The system is well-recognised as a poor predictor of pain or fertility outcomes — a Stage I patient may have crippling pain, a Stage IV patient may be asymptomatic. The ENZIAN classification, originally for deep infiltrating endometriosis (DIE), provides more granular description of retrocervical, rectovaginal, sigmoid, ureteric and bladder involvement.

Three subtypes are clinically distinguished: (1) superficial peritoneal endometriosis, the commonest, found on the pelvic peritoneum; (2) ovarian endometrioma ("chocolate cysts"), the form most easily diagnosed on transvaginal ultrasound; and (3) deep infiltrating endometriosis (DIE), defined as >5mm penetration below the peritoneal surface, often involving the uterosacral ligaments, rectovaginal septum, bowel, bladder or ureters — the form requiring multidisciplinary surgical management at a BSGE-accredited endometriosis centre. Adenomyosis — endometrial tissue within the myometrium of the uterus itself — is a distinct but very commonly co-existing condition (estimated ~80% overlap with endometriosis on careful imaging).

The Endometriosis Brain Fog Evidence: From Patient Reports to The Lancet

For over a decade, endometriosis patient organisations have reported cognitive symptoms as a defining feature of living with the disease, alongside pelvic pain, dysmenorrhea, dyspareunia, dyschezia, dysuria, fatigue and infertility. Clinicians and researchers were slow to take cognitive complaints seriously. That has now substantively changed:

November 2025: The Lancet "Overlooked Symptom" Commentary

The Mahony, Saunders, Whitaker and Horne commentary in The Lancet Obstetrics, Gynaecology & Women’s Health — from the University of Edinburgh’s EXPPECT centre for endometriosis and pelvic pain research, the flagship UK academic centre in the field — consolidated the emerging mechanistic story and called for cognitive symptoms to be integrated into NICE / ESHRE guidelines, into clinical-trial endpoints, and into routine endometriosis assessment. Andrew Horne and Philippa Saunders are also responsible for the ROSE Repository of Stories of Endometriosis and have been central to UK-wide pelvic pain research over the last decade.

April 2025: The Horn FACT-Cog Survey

Mary Horn, Kerry Sherman, Melissa Pehlivan and colleagues at Macquarie / Sydney (2025, Journal of Health Psychology) ran a large online survey of 1,239 individuals with self-reported endometriosis using the validated FACT-Cog instrument. They reported ~80% scoring at clinically meaningful cognitive-impairment thresholds, with effects strongest for perceived processing speed and working memory and largely independent of analgesic use, age, education and depression score. The findings closely mirror cognitive-impairment data in fibromyalgia, long COVID brain fog and ME/CFS — the chronic-pain / chronic-fatigue / neuroinflammation triad.

2024 Endometriosis UK Patient Survey

The Endometriosis UK 2024 survey of 4,371 women established that brain fog, mental fatigue and concentration difficulty were among the top patient-reported quality-of-life burdens — alongside pain, fatigue and the cumulative impact of the 9-year diagnostic odyssey. The February 2026 'State of Endometriosis Care' roadmap formally documented the gap between patient need and current NHS commissioning.

The Modern Mechanistic Picture: Cytokines, Microglia, BDNF/TrkB, Central Sensitisation & HGF/c-Met

Peripheral Inflammatory Cytokines & the Blood-Brain Barrier

Endometriotic lesions are sites of chronic local inflammation that release TNF-alpha, IL-1-beta, IL-6, IL-8, prostaglandin E2 and a range of chemokines into the peritoneal fluid and systemic circulation. Peripheral CRP and IL-6 are elevated in many patients. These cytokines do not stay in the pelvis — they cross the blood-brain barrier (especially when BBB integrity is compromised by chronic peripheral inflammation), activate microglia, and produce the constellation of cognitive slowing, mental fatigue, memory lapses and concentration difficulty recognised in sickness-behaviour neuroinflammation models. The same neuroinflammatory narrative explains long COVID brain fog, fibro fog and ME/CFS cognitive dysfunction.

CNS-Wide Microglial & Astrocyte Activation: The 2023 Greaves Paper

The 2023 Journal of Neuroinflammation paper from Erin Greaves’ group used a surgically induced mouse model of endometriosis and reported CNS-wide glial activation (microglia and astrocytes) extending well beyond classical pain-processing areas to the thalamus, hippocampus and cerebral cortex, tracking with the development of pain-like behaviour. This is the strongest preclinical evidence that endometriosis is genuinely a CNS-wide neuroinflammatory condition — not a purely pelvic disease. The hippocampal involvement is particularly relevant to the cognitive complaints and to the directionality question for any synaptogenic peptide.

JAK-STAT & Mast Cell Activation

The 2025 Frontiers in Immunology review formalised the role of JAK-STAT signalling and mast-cell activation in endometriosis pain pathogenesis — supplying a mechanistic rationale for the off-label use of JAK inhibitors (and for the overrepresentation of mast cell activation syndrome / MCAS in endometriosis cohorts). This is biologically convergent with the JAK-STAT story in lupus and other autoimmune-adjacent conditions.

BDNF & TrkB: The Central Directionality Paradox

BDNF is elevated, not deficient, in endometriosis — and that single fact is the most important biological observation for any synaptogenic-peptide claim in this indication. The 2022 Wu, Hu, Liang BMC Women’s Health paper measured BDNF and TrkB expression in eutopic and ectopic endometrial tissue and reported significantly elevated expression in endometriosis patients, correlating with dysmenorrhea severity. The 2017 Frontiers in Endocrinology review by Hu and colleagues consolidated the literature: BDNF is significantly elevated in both peritoneal fluid and plasma in endometriosis, and is a key mediator of the transition from acute to chronic pelvic pain via central sensitisation. The same elevated-BDNF pattern is observed in migraine (Tanure 2010), in fibromyalgia (Polli 2020) and in chronic low back pain — the central-sensitisation BDNF biomarker has emerged as a unifying signature across chronic pain conditions.

The implication is the central uncomfortable question for Dihexa in endometriosis: if BDNF is already chronically elevated and is mediating maladaptive central sensitisation that consolidates pain and cognitive dysfunction, then pharmacologically pushing BDNF/TrkB signalling higher with a synaptogenic peptide is the wrong pharmacological direction. It is the same directionality concern that applies in fibromyalgia, migraine and OCD. Read more on the BDNF biology in our Dihexa & BDNF review.

Central Sensitisation: The Hippocampus-Amygdala-PFC Network

Central sensitisation is the unifying concept tying endometriosis pain, brain fog and the cluster of comorbid pain conditions together. Sustained nociceptive signalling from endometriotic lesions drives synaptic plasticity in spinal cord dorsal horn, brainstem and forebrain that amplifies pain processing and recruits cognitive networks. Functional MRI studies in chronic pelvic pain show altered connectivity across prefrontal cortex, anterior cingulate, insula, hippocampus and amygdala. This is the same network rewiring documented in migraine (see our migraine review), fibromyalgia and chronic low back pain. Importantly, the hippocampus is both a target of central sensitisation and a key cognitive structure — explaining why pain rewiring and cognitive dysfunction co-occur.

HGF/c-Met in Endometriosis: The Ectopic Lesion Proliferation Concern

HGF / c-Met signalling has been documented in endometriotic lesion vascularisation, angiogenesis and proliferation in multiple papers since the late 1990s. HGF is elevated in peritoneal fluid in endometriosis and is implicated in the establishment and maintenance of ectopic endometrial lesions. The mechanism overlaps with the broader cancer-biology concern around c-Met as an oncogenic driver in multiple solid tumours. The implication for Dihexa is significant: pharmacologically augmenting HGF / c-Met signalling could theoretically promote rather than suppress endometriotic lesion growth and vascularisation. This concern is separate from, and additional to, the central-sensitisation BDNF concern.

Iron Deficiency, Sleep Fragmentation, Analgesia & Depression Cognitive Cost

Beyond the neuroinflammation-BDNF-central-sensitisation core mechanism, endometriosis brain fog is multiply determined by: iron-deficiency anaemia from heavy menstrual bleeding (HMB) — producing fatigue, slowed processing and reduced working memory; sleep fragmentation from nocturnal pain and from comorbid sleep disturbance; analgesic burden from opioids, gabapentinoids, amitriptyline, NSAIDs and anticholinergics — all of which have cognitive side effects; the cognitive cost of co-existing depression and anxiety (present in approximately 50% of endometriosis patients per the 2025 PMC review of neuroimmune mechanisms in endometriosis-associated depression and anxiety); and the additive cognitive cost of comorbid migraine, fibromyalgia, ME/CFS and IBS. Addressing the modifiable contributors — iron repletion, sleep, analgesia rationalisation, mood treatment — is the appropriate first step before any nootropic consideration.

The 2026 UK Treatment Landscape: NICE NG73, TA1057 Ryeqo, BSGE Surgery & the Women’s Health Strategy

UK endometriosis management is anchored by the April 2024 update of NICE NG73 (endometriosis: diagnosis and management), supplemented by the ESHRE 2022 guideline by Becker, Bokor, Heikinheimo and colleagues and the Royal College of Obstetricians and Gynaecologists clinical framework. The pathway has five pillars:

1. Conservative First-Line: Analgesia & Hormonal Suppression

Simple analgesia (paracetamol, NSAIDs) is the first step. Hormonal suppression to induce amenorrhoea is the mainstay first-line medical therapy: the combined oral contraceptive pill (often continuously, eliminating the pill-free week); oral progestins (dienogest 2mg daily / Visanne (Bayer) is widely used, with VLIBRA trial data; medroxyprogesterone; norethisterone); the levonorgestrel intrauterine system (Mirena IUS), especially valuable in adenomyosis-overlap; or depot medroxyprogesterone (Depo-Provera). All work by suppressing cyclical oestrogen-progesterone hormonal shifts and inducing decidualisation or atrophy of endometriotic tissue.

2. Second-Line: GnRH Analogues & the New GnRH Antagonists

GnRH agonists — subcutaneous goserelin (Zoladex) 3.6mg monthly or 10.8mg three-monthly; intramuscular leuprolide / leuprorelin (Prostap) — downregulate pituitary GnRH receptors after an initial flare and produce a reversible medical menopause. They are highly effective for pain but unsuitable for long-term use without HRT add-back because of bone loss, hot flushes and mood effects.

GnRH antagonists are the newer class. Relugolix-estradiol-norethisterone (Ryeqo, Gedeon Richter) is the first daily oral GnRH-antagonist plus add-back HRT combination pill: NICE TA1057 was published in March 2025 recommending Ryeqo for long-term endometriosis symptom management on the NHS, with approximately 1,000 women per year initially eligible. The pivotal evidence base is the SPIRIT-1 and SPIRIT-2 24-week Phase 3 trials. NICE described it as a "transformational" daily pill — the first long-term endometriosis treatment of its kind. Linzagolix (Yselty, Ferring) holds EMA approval. Elagolix (Orilissa, AbbVie) is FDA-approved but was rejected by NICE.

3. Surgical Management: Laparoscopic Excision at BSGE-Accredited Centres

For symptomatic disease unresponsive to medical management, or for deep infiltrating disease, large endometriomata, or infertility, surgical management is indicated. Laparoscopic excision — cutting out the lesions — is preferred over ablation (burning or diathermy) per BSGE and ESHRE consensus, particularly for deep infiltrating disease. The British Society for Gynaecological Endoscopy (BSGE) runs the UK’s accreditation programme for endometriosis centres; BSGE-accredited centres meet defined standards for multidisciplinary team working (gynaecology, colorectal, urology, pain management, fertility), surgical volume and audit. Patients with deep infiltrating disease (rectovaginal, bowel, bladder, ureteric involvement) should be referred to a BSGE-accredited centre. Hysterectomy with bilateral salpingo-oophorectomy is the most definitive surgical option but recurrence still occurs in ~10% of patients, and is reserved for women who have completed family or are post-menopausal-considering.

4. Chronic Pelvic Pain Multidisciplinary Management

For patients with refractory pain after medical and surgical management, multidisciplinary chronic pelvic pain services provide pelvic floor physiotherapy and biofeedback; neuropathic pain modulators (gabapentin, pregabalin, amitriptyline, duloxetine); chronic pain CBT and acceptance-commitment therapy; and pain neuroscience education. The RCOG green-top guideline on chronic pelvic pain and the Pelvic Pain Support Network provide the framework. The cognitive dysfunction component is rarely addressed directly but improves indirectly when pain, sleep, analgesia and mood are optimised.

5. The April 2026 Renewed Women’s Health Strategy for England

On 14 April 2026, the UK Government published the renewed Women’s Health Strategy for England with 117 action points, including the explicit pledge to "eliminate the diagnostic odyssey facing women" with conditions including endometriosis and fibroids. The reforms most relevant to endometriosis are: a single gynaecological referral point; ringfenced funding to reduce gynaecology waiting lists; a national audit of endometriosis services; expansion of BSGE-accredited endometriosis centre capacity; integration of endometriosis education into GP training; and a commitment to reduce the UK average diagnostic delay. The 5 March 2026 Westminster Hall Hansard debate on Women’s Health Strategy: Endometriosis and Fibroids aired cross-party concern about ongoing diagnostic delay and BSGE access. Brain fog is not yet a named outcome in the strategy or in NICE NG73 — the November 2025 Lancet "overlooked symptom" paper was published precisely to push for that inclusion.

Where Could Dihexa Theoretically Fit in Endometriosis Biology?

The honest summary: endometriosis is a condition where the directionality risk for a synaptogenic peptide is acute. The dominant pain-and-cognition pathology is central sensitisation, the dominant peripheral biomarker is elevated BDNF, and the dominant ectopic-lesion driver includes HGF / c-Met. Each of these axes points to Dihexa pushing in the wrong direction. There is no clean BDNF-deficit case to motivate augmentation, and there is an additional lesion-proliferation concern that does not apply in most CNS conditions.

Risks & Theoretical Concerns Specific to Endometriosis

Beyond the generic risks in the Dihexa side-effects review, endometriosis-specific concerns include: central-sensitisation consolidation (the central directionality concern - augmenting BDNF/TrkB and NMDA-dependent plasticity in a brain already in a central-sensitisation state); ectopic lesion proliferation (HGF/c-Met has documented roles in endometriotic lesion vascularisation and growth; pharmacologically augmenting could theoretically worsen disease); oncogenicity (c-Met is an oncogenic driver in multiple cancers; endometriosis carries a small but real elevated background risk of clear cell and endometrioid ovarian cancer); pregnancy / contraception (endometriosis affects reproductive-age women, many of whom are trying to conceive or are pregnant; teratogenicity of Dihexa is unstudied; pregnancy is a strict contraindication); oestrogen-progesterone interaction (most endometriosis patients are on hormonal suppression therapy; potential pharmacokinetic and pharmacodynamic interactions with Ryeqo, dienogest, GnRH analogues and combined oral contraceptive are entirely unstudied); polypharmacy (patients with severe endometriosis are often on hormonal therapy, NSAID, opioid, gabapentinoid, antidepressant and anti-anxiety medication concurrently; drug-drug interactions are unstudied); iron-deficiency anaemia masking (cognitive improvement falsely attributed to a peptide when the true cause is concurrent iron repletion); delayed appropriate care (any time spent on an unproven peptide is time not spent on NICE NG73 / TA1057 Ryeqo / BSGE-centre referral, exactly the diagnostic odyssey the April 2026 strategy is trying to eliminate).

The Comorbidity Cluster: Migraine, Fibromyalgia, IBS, ME/CFS, Depression & Anxiety

Endometriosis is rarely a single-system disease. The most clinically important comorbidities, each of which independently contributes to cognitive symptom burden, include:

• Migraine — approximately 3x more common in endometriosis than in the general female population; see our Dihexa for Migraine review.
• Fibromyalgia — approximately 25% comorbidity; shared central-sensitisation biology; see our Dihexa for Fibromyalgia & Fibro Fog review.
• IBS / functional bowel disorders — approximately 50% overlap; shared visceral hypersensitivity biology.
• ME/CFS / chronic fatigue syndrome — substantial overlap, particularly in the severe and treatment-refractory endometriosis subset; see our Dihexa for ME/CFS review.
• Depression & anxiety — approximately 50% comorbidity (PMC 2025 neuroimmune mechanisms review); see our Dihexa for Depression and Dihexa for Anxiety reviews.
• Adenomyosis — approximately 80% co-existence on careful imaging.
• Hypermobility (hEDS) and mast cell activation syndrome (MCAS) — overrepresented in endometriosis cohorts.
• Long COVID — emerging signal of post-COVID worsening of pelvic pain and brain fog; see our Dihexa for Long COVID review.
• Perimenopause & menopause — the cognitive symptoms of perimenopausal oestrogen fluctuation overlap with endometriosis brain fog in midlife; see our Dihexa for Menopause Brain Fog review.

Addressing comorbidities is often the highest-yield route to cognitive symptom improvement — migraine prevention, fibromyalgia management, sleep, mood treatment, iron repletion, hormonal optimisation, and pain rationalisation. None of this is replaced by a peptide.

UK Resources, Charities & Specialist Services for Endometriosis

National charities: Endometriosis UK (helpline 0808 808 2227); The Endometriosis Foundation UK; Pelvic Pain Support Network; Versus Arthritis (for fibromyalgia comorbidity); Mind (mood comorbidity); Samaritans 116 123.

NHS specialist services: GP referral to consultant gynaecology under NICE NG73; BSGE-accredited endometriosis centres for deep infiltrating disease (the BSGE website lists all accredited UK centres); tertiary referral options include the Edinburgh EXPPECT centre (Andrew Horne, Philippa Saunders, Lucy Whitaker); the Oxford Endometriosis CaRe Centre (Krina Zondervan, Christian Becker); the Birmingham endometriosis service; and BSGE-accredited centres in London (UCLH, St Bart’s, Chelsea & Westminster), Manchester, Newcastle, Belfast, Cardiff and Glasgow.

Research & professional bodies: NIHR Be Part of Research for open endometriosis trials; BSGE; Royal College of Obstetricians and Gynaecologists (RCOG); ESHRE (European Society of Human Reproduction and Embryology); the All-Party Parliamentary Group on Endometriosis.

The 2026 Bottom Line

Endometriosis brain fog is finally being recognised after a decade of patient advocacy and clinical inattention — but the appropriate 2026 UK pathway is not an unproven synaptogenic peptide. The November 2025 Lancet "overlooked symptom" paper from the Edinburgh EXPPECT group, the April 2025 Horn FACT-Cog 1,239-patient survey, the March 2025 NICE TA1057 approval of Ryeqo (relugolix combination therapy), the April 2024 NICE NG73 update, the April 2026 renewed Women’s Health Strategy with 117 action points and an explicit pledge to "eliminate the diagnostic odyssey", the March 2026 Westminster Hall debate, and the February 2026 Endometriosis UK "State of Endometriosis Care" roadmap collectively represent the most consequential window for endometriosis policy and brain-science in a generation — none of which involves any role for an unapproved peptide. No clinical trial of Dihexa in any endometriosis, adenomyosis, chronic pelvic pain or dysmenorrhea population has been conducted, registered, or planned. The directionality risk is real: BDNF is elevated, not deficient, in endometriosis; central sensitisation is the dominant pain-and-cognition pathology; and HGF/c-Met is implicated in ectopic lesion proliferation. A peptide augmenting BDNF/TrkB signalling and HGF/c-Met activation is pointing in the wrong direction on all three axes. The evidence-based 2026 UK pathway is GP-led ultrasound and gynaecology referral under NICE NG73, hormonal suppression first-line (combined oral contraceptive, dienogest, Mirena IUS), NICE TA1057 Ryeqo for eligible patients, BSGE-accredited centre referral for deep infiltrating disease, and multidisciplinary chronic pelvic pain management for refractory symptoms — with Endometriosis UK and the Endometriosis Foundation for navigation support. The Lancet has formally named brain fog; the answer is to fund the research and the services, not to self-experiment with research peptides.

Selected References & External Sources

1. Mahony S, Saunders PTK, Whitaker LHR, Horne AW (2025). The overlooked symptom in endometriosis: brain fog. The Lancet Obstetrics, Gynaecology & Women’s Health. — Lancet O&G/WH
2. Horn M, Sherman KA, Pehlivan MJ, Basson M, Lin Z, Duckworth TJ (2025). Perceived cognitive functioning difficulties in individuals living with endometriosis. Journal of Health Psychology. — SAGE
3. Greaves E et al. (2023). Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis. Journal of Neuroinflammation. — J Neuroinflammation
4. Neuroinflammation in endometriosis — targeting JAK-STAT and mast cell activation (2025). Frontiers in Immunology. — Frontiers Immunology
5. Wu J, Hu C, Liang Y et al. (2022). BDNF and TrkB expression levels in patients with endometriosis and their associations with dysmenorrhoea. BMC Women’s Health. — PMC8932107
6. Role of brain-derived neurotrophic factor in endometriosis pain (2017). Frontiers in Endocrinology. — PubMed 28954602
7. Cognitive functioning in females with endometriosis-associated chronic pelvic pain: a literature review (2025). — PMC12290884
8. Depression and anxiety in patients with endometriosis-associated chronic pain: neuroimmune mechanisms (2025). — PMC12531961
9. Multiple lesion inductions intensify central sensitization driven by neuroinflammation in a mouse model of endometriosis (2025 bioRxiv). — bioRxiv
10. Non-hormonal strategies in endometriosis: targets with future clinical potential (2025). — PMC12295211
11. NICE NG73 (April 2024). Endometriosis: diagnosis and management. — nice.org.uk/guidance/ng73
12. NICE TA1057 (April 2025). Relugolix-estradiol-norethisterone (Ryeqo) for treating symptoms of endometriosis. — nice.org.uk/guidance/ta1057
13. NICE news (March 2025). First daily pill for endometriosis approved for NHS use. — NICE press
14. NICE updated guideline to improve the diagnosis of endometriosis. — NICE news
15. ESHRE Guideline: Endometriosis (2022). Becker, Bokor, Heikinheimo et al. — Human Reproduction Open
16. House of Commons Library briefing CBP-10591: Access to endometriosis services. — Commons Library
17. Hansard (5 March 2026). Westminster Hall debate: Women’s Health Strategy: Endometriosis and Fibroids. — Hansard
18. Endometriosis UK (February 2026). The State of Endometriosis Care: a roadmap. — Endometriosis UK PDF
19. Endometriosis UK statement on SMC: Ryeqo. — Endometriosis UK
20. Endometriosis UK: NICE guidance and quality standards on endometriosis. — Endometriosis UK
21. Endometriosis UK responds to renewed Women’s Health Strategy. — Endometriosis UK
22. Women’s Health Strategy for England (April 2026 renewal). — gov.uk
23. Neuropsychiatric and cognitive manifestations of endometriosis: 'endometriosis brain' (2025). — ResearchGate
24. SMC2666 relugolix-estradiol-norethisterone (Ryeqo) - Scottish Medicines Consortium. — SMC PDF
25. Benoist CC et al. (2014). HGF/c-Met dependence of Dihexa procognitive / synaptogenic effects. JPET. — PubMed 24403718
26. Wright & Harding (2015). Brain HGF/c-Met system. — PubMed 25711386
27. British Society for Gynaecological Endoscopy (BSGE). — bsge.org.uk
28. Royal College of Obstetricians and Gynaecologists (RCOG). — rcog.org.uk
29. ESHRE (European Society of Human Reproduction and Embryology). — eshre.eu
30. Endometriosis UK (helpline 0808 808 2227). — endometriosis-uk.org
31. Edinburgh EXPPECT centre for endometriosis and pelvic pain. — University of Edinburgh
32. NIHR Be Part of Research. — bepartofresearch.nihr.ac.uk
33. Pharmaceutical Journal: NICE recommends first combination pill for long-term treatment of endometriosis. — Pharm Journal