CPD Endometriosis management for general practice nurses

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Reference: March-April 2026 | Issue 2 | Vol 19 | Page 14

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GPNs are often the first clinicians to encounter individuals with symptoms suggestive of endometriosis. Their role in early recognition, education, symptom monitoring, safety-netting, and referral is therefore pivotal

Endometriosis: An introduction

Learning objectives

After completing this CPD module, the reader should be able to:

• Describe the epidemiology and public health burden of endometriosis.
• Explain the normal menstrual cycle and the pathophysiology of endometriosis in clear, patient-centred terms.
• Recognise typical and atypical clinical presentations and red flags.
• Understand how pharmacological treatments work and why they are used.
• Explain the role and rationale of non-pharmacological interventions.
• Apply evidence-based management, monitoring, and referral pathways in general practice.
• Understand the impact of endometriosis on fertility, cancer risk, and surgical decision-making.

Endometriosis is a chronic, inflammatory, oestrogen-dependent condition characterised by the presence of endometrial-like tissue outside the uterine cavity.¹ It is associated with dysmenorrhoea, chronic pelvic pain, dyspareunia, bowel and urinary symptoms, fatigue, subfertility, and significant impairment in quality of life.²

Despite affecting approximately one in 10 women of reproductive age, endometriosis remains under-recognised and under-diagnosed, with symptoms frequently normalised within healthcare encounters.¹

Across Europe, the average diagnostic delay is seven to nine years.³ This delay is associated with disease progression, psychological issues, and increased healthcare utilisation.⁴ The publication of the Irish National Clinical Practice Guideline: Assessment and Management of Endometriosis (2025) represents a major advance in standardising evidence-based care pathways.⁵

Epidemiology: Endometriosis is one of the most prevalent chronic gynaecological conditions worldwide. Contemporary estimates suggest that 10-15 per cent of individuals of reproductive age are affected globally, equating to around 190 million people.¹^,⁶ True prevalence is difficult to determine due to historical reliance on surgical diagnosis, symptom heterogeneity, and disparities in access to specialist services.⁷

Age of onset and life-course perspective: Endometriosis is increasingly recognised as a life-course disease. Up to two-thirds of individuals with confirmed endometriosis report symptom onset during adolescence, often within a few years of menarche.¹ Symptoms may persist into perimenopause and post-menopause, particularly in individuals with residual disease or severe historical endometriosis.⁸

Socioeconomic and public health impact: Endometriosis is associated with significant educational, occupational, and economic consequences. European cost-of-illness studies demonstrate that indirect costs related to absenteeism and reduced productivity often exceed direct medical costs.⁹ Quality of life impairment is comparable to that experienced in other chronic diseases such as diabetes and rheumatoid arthritis.¹⁰

Diagnostic delay as an epidemiological feature: Diagnostic delay remains a defining feature, with mean delays of seven to nine years, and even longer delays observed in adolescents and/or those with bowel-predominant symptoms.³^,¹¹ Delayed diagnosis is independently associated with poorer pain outcomes, psychological distress, and chronic pain syndromes.⁴

The menstrual cycle: Foundation for understanding endometriosis pathophysiology

A clear understanding of normal menstrual physiology is essential to understand the pathophysiology of endometriosis. Endometriosis develops within the context of normal cyclical hormonal signalling, and disruption of these regulatory pathways underpins symptom generation.

The menstrual cycle is regulated by the hypothalamic-pituitary-ovarian (HPO) axis. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in a pulsatile manner, stimulating the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinising hormone (LH).

These gonadotropins act on the ovaries to regulate follicular development, ovulation, and steroid hormone production. Ovarian oestradiol and progesterone exert both negative and positive feedback on the hypothalamus and pituitary, maintaining cycle regularity. A typical cycle lasts approximately 28 ± 4 days and consists of three interrelated phases.¹²

Menstrual phase (approximately days 1-5)
Menstruation represents the shedding of the functional layer of the endometrium when implantation has not occurred. Falling progesterone and oestrogen levels trigger vasoconstriction, tissue breakdown, and prostaglandin release – producing uterine contractions and menstrual bleeding. Prostaglandins also contribute to menstrual pain and gastrointestinal symptoms in susceptible individuals.

Follicular phase (approximately days 1-14)
FSH stimulates the recruitment of ovarian follicles. The dominant follicle produces rising oestradiol, which promotes proliferation and thickening of the endometrium in preparation for potential implantation. Oestradiol also alters cervical mucus to facilitate sperm survival. When circulating oestradiol reaches a critical threshold, positive feedback triggers a surge in LH.

Ovulation
The LH surge induces rupture of the dominant follicle and release of the oocyte. Ovulation represents the peak fertile window and marks the transition to the luteal phase.

Luteal phase (approximately days 15-28)
Following ovulation, the ruptured follicle forms the corpus luteum, which secretes progesterone and smaller amounts of oestrogen. Progesterone stabilises the endometrium, suppresses further proliferation, and modulates immune activity to support potential implantation. If pregnancy does not occur, corpus luteum regression leads to declining progesterone and oestrogen, initiating the next menstrual bleed.

Relevance to endometriosis
Progesterone normally counterbalances oestrogen-driven proliferation and inflammation. In endometriosis, progesterone-resistance impairs this protective effect, while local oestrogen production within lesions sustains inflammatory activity.¹^,¹³ Cyclical hormonal fluctuations therefore drive repeated activation of ectopic tissue, contributing to pain, inflammation, and disease persistence.

Clinical presentation²

Common and atypical symptoms include:

• Severe dysmenorrhoea
• Chronic pelvic pain
• Deep dyspareunia
• Dyschezia (difficulty/painful defaecation)
• Cyclical urinary symptoms
• Fatigue and cognitive impact
• Subfertility or infertility
• Anxiety and depression¹⁴
• Atypical neuropathic pain patterns.

Pathophysiology

Endometriosis is best understood as a chronic, systemic inflammatory condition that is hormonally driven and neurologically complex – rather than simply the presence of ectopic tissue.¹ The interaction between endocrine dysregulation, immune activation, neuroangiogenesis (the simultaneous growth of new nerve fibres and new blood vessels into tissue), and central nervous system sensitisation (when the brain and spinal cord become over-responsive to pain signals after repeated or prolonged pain, so that normal sensations or mild stimuli are perceived as painful) explains why symptoms can be severe, persistent, and poorly correlated with lesion size or surgical stage.¹

Hormonal dysregulation: Oestrogen dependence and progesterone resistance: In the normal menstrual cycle, oestrogen stimulates the proliferation of the endometrium while progesterone stabilises and limits excessive growth. In endometriosis, ectopic lesions demonstrate progesterone resistance, meaning progesterone signalling pathways are downregulated or dysfunctional.¹³ As a result, the normal suppressive effect of progesterone is reduced, and oestrogen-driven proliferation continues unchecked.

Inflammation and immune dysfunction: Endometriosis is associated with a chronic inflammatory pelvic milieu. Activated macrophages, mast cells, and ectopic stromal cells release cytokines (eg, interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and prostaglandins that promote pain, fibrosis, angiogenesis, and tissue remodelling.¹⁵ Instead of clearing ectopic tissue, immune dysregulation sustains lesion persistence.

Neuroangiogenesis and pain generation: Endometriosis lesions actively promote the growth of new blood vessels and sensory nerve fibres, increasing local pain signalling.¹⁶

Central sensitisation: Repeated nociceptive input can remodel central pain pathways, resulting in central sensitisation.⁴ Patients develop amplified pain responses, reduced pain thresholds, and persistent pain, even when peripheral disease activity is reduced or surgically removed.

Why do symptoms not match the surgical stage? Pain severity reflects nerve involvement, inflammatory burden, and nervous system sensitisation rather than lesion volume alone.¹^,¹⁷

Diagnosis in primary care

There is currently no single definitive non-invasive biomarker for endometriosis. Contemporary guidelines support early clinical diagnosis and initiation of treatment based on symptoms, rather than delaying care until surgical confirmation.⁵^,¹¹

Clinical assessment
Assessment should include a detailed menstrual history (age at menarche, cycle regularity, bleeding pattern), pain characteristics (onset, cyclical pattern, severity, radiation, functional impact), gastrointestinal and urinary symptoms, sexual function, fertility intentions, psychosocial impact, and family history. Validated pain scores or symptom diaries support objective monitoring.

Imaging
Transvaginal ultrasound is first line for the detection of ovarian endometriomas and deep infiltrating disease when performed by experienced operators. High-resolution ultrasound can identify features such as hypoechoic nodules, site-specific tenderness mapping, and reduced organ mobility.

Magnetic resonance imaging (MRI) is recommended for mapping complex disease, suspected deep infiltrating endometriosis, bowel or bladder involvement, ureteric disease, and preoperative surgical planning. MRI provides superior soft tissue contrast, allows assessment of disease depth and relationship to adjacent organs, and supports multidisciplinary surgical planning.

Computed tomography (CT) is not routinely used for the primary diagnosis of endometriosis due to limited soft tissue discrimination and radiation exposure. However, CT may be utilised in acute presentations to exclude alternative diagnoses (eg, bowel obstruction, perforation, malignancy) or to assess complications when MRI is not immediately available.

Role of laparoscopy: Diagnostic laparoscopy is reserved for individuals with refractory symptoms, diagnostic uncertainty, suspected complications, or before complex surgical management. Histological confirmation remains the gold standard, but is no longer required before initiating treatment.⁵^,¹¹

Emerging diagnostics: Saliva-based microRNA testing
The Endotest salivary microRNA assay analyses differential expression of microRNA signatures associated with endometriosis. Prospective validation studies demonstrate high sensitivity and specificity, including detection of early-stage disease and non-ovarian phenotypes.^18,19

Potential advantages include non-invasive sampling, reduced diagnostic delay, and improved access for adolescents. Limitations include cost, limited real-world implementation data, and evolving regulatory pathways.

While promising, current Irish guidance does not recommend the use of any biomarkers for diagnosing endometriosis, and the National Institute for Health and Care Excellence (NICE) advises against CA-125 for diagnosis – therefore, salivary miRNA testing is not currently recommended for routine diagnostic use in these guidelines.^5,11

Disease classification and staging of endometriosis

Accurate classification supports communication between clinicians, surgical planning, research comparability, and predicting fertility outcomes. Importantly, symptom severity does not reliably correlate with ‘stage’.¹^,¹⁷ The European Society of Human Reproduction and Embryology (ESHRE) guideline recommends a structured phenotype/anatomical description and recognition of limitations of existing staging systems.²

1) Revised American Society for Reproductive Medicine (rASRM) classification
The rASRM system categorises disease into four stages (I-IV) using a point score based on implants and adhesions. Limitations: Correlates poorly with pain and quality of life outcomes.¹^,¹⁷

2) Enzian classification (deep infiltrating and multi-compartment disease)
The Enzian system provides a compartment-based description of deep disease and has been adapted for imaging and operative reporting.²⁰ Clinical value: Supports mapping, multidisciplinary planning, and standardised follow-up.²⁰^,²¹

3) American Association of Gynaecologic Laparoscopists (AAGL) 2021 Endometriosis Classification (surgical complexity)
The AAGL 2021 system was designed to grade operative complexity more reliably than rASRM and support benchmarking and service planning.²²

4) Endometriosis Fertility Index (EFI)
The EFI is a validated post-surgical score that estimates the likelihood of spontaneous pregnancy following operative management for endometriosis. Evidence supports its prognostic value, and it can help guide counselling about how long to try naturally before referral for fertility treatment.²³

Non-pharmacological management

Endometriosis pain is multifactorial (nociceptive, inflammatory, myofascial, neuropathic, and centrally mediated). Non-pharmacological strategies target mechanisms that hormonal therapy may not fully address, particularly pelvic floor dysfunction, fear avoidance, sleep disruption, mood symptoms, and central sensitisation.⁴

Education, validation, and self-management skills: Education and validation reduce uncertainty, improve adherence, and can reduce pain-related distress.²⁴ Practical self-management includes pacing, flare plans, sleep hygiene, and symptom tracking.

Pelvic health physiotherapy: Targets pelvic floor overactivity, myofascial trigger points, dyspareunia, posture, and movement avoidance. Evidence supports clinically meaningful pain reduction with multimodal physical therapy in chronic pelvic pain, and physiotherapy techniques may improve pain in endometriosis-associated pelvic pain.²⁵^,²⁶

Psychological interventions: Cognitive behavioural therapy (CBT) helps patients reframe catastrophic thoughts, reduce hypervigilance, and build coping skills.²⁷

A systematic review with meta-analysis reported that psychological interventions improve pain, quality of life and mental health outcomes in endometriosis.²⁸ A randomised trial of CBT in endometriosis reported improvements in coping, psychological outcomes, and pain perception.²⁹

Yoga and mind-body movement: A randomised controlled trial of hatha yoga in endometriosis reported reductions in chronic pelvic pain and improvements in quality of life domains.³⁰

Acupuncture: A 2023 systematic review and meta-analysis reported improvements in pelvic and menstrual pain outcomes, though certainty varied by outcome and study quality.³¹ Earlier clinical literature also supports cautious interpretation due to limited trial size and heterogeneity.³²

GPN practice point: Support non-pharmacological management by educating patients about multimodal pain strategies, encouraging self-management skills, promoting realistic goals focused on function as well as pain reduction, signposting and coordinating referrals to services such as pelvic health physiotherapy and psychological supports, and monitoring progress over time.

Pharmacological management

Pharmacological therapy aims to suppress ovarian oestrogen production, reduce inflammatory activity, and modulate pain pathways.⁵

• Combined hormonal contraception (CHC): Suppresses the HPO axis, inhibits ovulation, and stabilises cyclical hormonal fluctuations – continuous regimens reduce withdrawal bleeding and prostaglandin release.²^,¹¹
• Progestogens: Induce decidualisation/atrophy of ectopic tissue and counteract oestrogen-driven proliferation and inflammatory signalling.^13,37
• Levonorgestrel intrauterine system (LNG-IUS): Reduces endometrial activity and pelvic inflammatory stimuli.³³
• GnRH antagonists: Reduce pituitary stimulation and ovarian oestradiol production – add-back therapy reduces hypo-oestrogenic adverse effects while maintaining analgesic benefit.³⁴^,³⁵
• Non-steroidal anti-inflammatory drugs (NSAIDs): Inhibit cyclooxygenase enzymes, reducing prostaglandin synthesis and dysmenorrhoea-related pain – adjunctive rather than disease-modifying.³⁶
• Neuromodulators: May be used within multidisciplinary chronic pain pathways for neuropathic features/central sensitisation.⁴

Endometriosis and fertility

Endometriosis is associated with subfertility in approximately 30-50 per cent of affected individuals.² The relationship is multifactorial and extends beyond mechanical distortion of pelvic anatomy. Inflammatory mediators may impair folliculogenesis, oocyte quality, tubal function, fertilisation, and implantation.²

Surgical management

Surgery may be indicated for refractory pain, suspected deep infiltrating disease, organ compromise, or fertility optimisation. Decision-making should be individualised and guided by symptom burden, disease distribution, previous surgery, and reproductive goals.

ESHRE recommends that complex disease be managed in specialist centres with multidisciplinary expertise.²^,³⁸ Excision is preferred for deep lesions where feasible.²

Post-operative hormonal suppression reduces recurrence when pregnancy is not immediately desired.² Persistent pain following surgery may reflect central sensitisation or comorbid pain conditions rather than surgical failure alone.⁴

Key red flags, clinical significance, and rationale

Early identification of red flag features is essential. National guidance emphasises safety-netting and low thresholds for investigation or referral when symptoms are atypical, progressive, or discordant with previous patterns.

• Postmenopausal bleeding or new pelvic pain after menopause: Postmenopausal bleeding is not a feature of benign endometriosis and may indicate endometrial hyperplasia or malignancy. New pelvic pain after menopause may reflect malignant transformation of residual disease or unrelated pelvic pathology. Urgent gynaecology assessment and imaging are required.¹¹^,³⁹
• Unexplained weight loss, anorexia, persistent fatigue, or anaemia: These features warrant prompt blood tests and referral rather than empirical hormonal escalation.¹¹
• Palpable pelvic or abdominal mass, rapidly enlarging adnexal lesion, or persistent ovarian cyst in peri- or post-menopause: Enlarging or complex masses raise concern for neoplastic change, torsion or haemorrhage, and should trigger urgent specialist review.¹¹
• Haematuria, rectal bleeding, bowel obstruction symptoms or severe cyclical urinary/bowel dysfunction: Although deep infiltrating endometriosis can involve bowel or bladder, visible bleeding or progressive change may indicate alternative pathology and requires investigation.¹¹
• Rapid escalation of pain, new neurological symptoms, or asymmetric pain distribution. Prompt evaluation is required.¹¹
• Failure to respond to appropriate first-line therapy or progressive deterioration despite adherence.

Reassessment of diagnosis and consideration of alternative pathology is indicated.¹⁴

Safety netting in general practice: GPNs should document red flag advice and advise urgent re-presentation if new bleeding, systemic symptoms, rapidly worsening pain, neurological symptoms, or mass effects develop.¹¹

Quick clinical summary – when to escalate urgently
Urgent referral is indicated if any of the following are present:

• Postmenopausal bleeding or new pelvic pain after menopause
• Unintentional weight loss, persistent fatigue, or unexplained anaemia
• Palpable pelvic/abdominal mass or rapidly enlarging ovarian cyst
• Visible haematuria, rectal bleeding, bowel obstruction symptoms
• Rapid escalation of pain, neurological symptoms, or asymmetric pain
• Failure to respond to appropriate first-line therapy

Endometriosis and cancer

Endometriosis is associated with a small but statistically significant increased risk of clear cell and endometrioid ovarian cancers, though the absolute risk remains low.⁴⁰^,⁴¹ Routine cancer screening does not differ from the general population – new postmenopausal symptoms, rapidly enlarging masses, or systemic symptoms warrant investigation.¹¹

Monitoring and follow-up

Ongoing monitoring supports treatment optimisation, early identification of adverse effects, and patient-centred care. Validated quality of life tools such as the Endometriosis Health Profile-30 support structured assessment of symptom burden and functional impact.⁴²

GPN clinical monitoring domains:

• Pain and function: Pain severity, flare patterns, work/school participation, sleep quality.
• Mental health: Screening for anxiety, depression, and pain catastrophising, where indicated.
• Medication safety: Blood pressure, weight, bleeding pattern, bone health for prolonged hypo-oestrogenic therapy.
• Reproductive goals: Regular review of fertility intentions and referral timing.
• Adherence and tolerability: Side effect burden, persistence with therapy.

Conclusion

Endometriosis is a complex, chronic, systemic condition with significant physical, psychological, reproductive, and socioeconomic consequences. Delayed diagnosis remains a major contributor to disease burden and long-term morbidity.

Understanding normal menstrual physiology and the multifactorial mechanisms driving endometriosis-associated pain allows nurses to explain symptoms clearly, validate patient experiences, and support early intervention.

GPNs occupy a pivotal position in the care pathway. Through comprehensive assessment, safety-netting, education, monitoring of treatment response, and coordination of referrals, they directly influence diagnostic timelines, treatment adherence, and patient empowerment.Recognition of fertility implications, appropriate use of imaging, awareness of disease classification systems, vigilance for red flags, and balanced counselling regarding cancer risk further strengthen holistic care delivery.

Integration of pharmacological and non-pharmacological strategies, informed by national and international guidelines, supports long-term symptom control and functional recovery. As emerging diagnostics and therapeutic innovations evolve, ongoing professional development remains essential to ensure safe, equitable, and evidence-based care for individuals living with endometriosis.

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