Best Peptides for Endometriosis Research UK 2026: Ectopic Lesion Biology, Immune Privilege Disruption and Pelvic Pain Mechanisms

All peptides discussed in this article are intended strictly for laboratory and preclinical research purposes. They are not licensed medicines and are not approved for human therapeutic use. This content is addressed to researchers, scientists, and laboratory professionals operating under appropriate institutional oversight.

Endometriosis as a Research Biology Problem

Endometriosis affects an estimated 10% of women of reproductive age globally, yet its molecular pathogenesis remains incompletely understood and its treatments largely limited to hormonal suppression or surgical excision — neither of which addresses the underlying immune and inflammatory biology. The condition is characterised by the presence of endometrial-like tissue outside the uterine cavity, most commonly in the peritoneal cavity, ovaries, and fallopian tubes, with lesions capable of establishing their own vascular supply, evading immune clearance, and generating a chronic pelvic inflammatory microenvironment that drives both pain sensitisation and subfertility.

Research interest in peptide-based tools for endometriosis biology has grown substantially, driven by the recognition that ectopic lesion survival depends on three interlocking biological systems: immune privilege failure at the ectopic site, neovascularisation supporting lesion growth, and neurogenic inflammation generating central sensitisation and chronic pain. Peptide compounds with mechanisms spanning immunomodulation, angiogenesis regulation, and anti-inflammatory signalling offer research tools to probe each axis independently or in combination.

This hub reviews the preclinical research landscape across the most mechanistically relevant peptides for endometriosis biology, with specific attention to ectopic lesion models, peritoneal immune biology, pain pathway research, and fertility impairment mechanisms.

Endometriosis Pathobiology: Key Research Targets

The dominant mechanistic hypotheses for endometriosis establishment and persistence converge on several interconnected biological nodes that peptide research tools can interrogate. Retrograde menstruation — the reflux of endometrial cells and debris into the peritoneal cavity — occurs in the majority of menstruating individuals, yet endometriosis develops in only a subset. This selective implantation points to immune surveillance failure as a critical permissive factor.

In healthy individuals, peritoneal natural killer (NK) cells, macrophages, and T regulatory cells (Tregs) eliminate ectopic endometrial cells with high efficiency. In endometriosis, this immune clearance is impaired: peritoneal NK cell cytotoxicity is reduced, macrophages are skewed toward an M2-like tolerogenic phenotype that supports lesion vascularisation rather than elimination, and Treg populations are expanded at the ectopic site in a pattern that promotes immune tolerance of lesion antigens.

Established lesions recruit their own blood supply through VEGF-driven angiogenesis — a necessary step for growth beyond diffusion limits. They also establish innervation: sensory nerve fibres from spinal dorsal horn neurones grow into lesions, releasing substance P (SP) and CGRP that amplify local inflammation and contribute to peripheral sensitisation. Central sensitisation develops as chronic afferent nociceptive input remodels dorsal horn pain processing, explaining why pain severity in endometriosis often correlates poorly with lesion burden.

Fertility impairment in endometriosis occurs through multiple routes: inflammatory cytokines in peritoneal fluid directly impair oocyte quality and embryo development; altered peritoneal macrophage biology disrupts sperm and oocyte function; and endometrial receptivity is reduced through inflammation-driven suppression of HOXA10, LIF, and integrin αVβ3 expression during the implantation window.

LL-37 and Endometriosis Biology

The antimicrobial peptide LL-37, processed from its precursor hCAP18 by serine proteases including kallikrein-5/7 and PR3, is expressed in endometrial epithelial cells and is abnormally upregulated in ectopic endometrial lesions. Research into LL-37 in endometriosis reveals a biologically paradoxical role: while LL-37 at physiological seminal concentrations (3–5 µg/mL) drives endometrial macrophage M2 polarisation through FPR2 signalling — supporting implantation — its elevated expression in ectopic lesions appears to promote lesion survival through anti-apoptotic and pro-migratory effects.

In peritoneal LL-37 measurement studies, concentrations in endometriosis patients are reported at approximately 4.8 µg/mL versus 1.6 µg/mL in matched controls without endometriosis. In vitro modelling of ectopic endometrial stromal cells (ESCs) shows that LL-37 at concentrations mimicking the peritoneal microenvironment (5–10 µg/mL) reduces annexin V+ apoptotic fraction from approximately 24% to 14%, increases migration distance by 34%, and elevates IL-8 secretion by 1.6-fold — cytokine output that supports both angiogenesis and further immune deviation.

The FPR2 receptor mediates both the pro-resolving effects of LL-37 at low concentrations (lipoxin A4-like biology) and the pro-inflammatory/pro-survival effects at higher concentrations, with concentration-dependent pathway switching documented. This biphasic biology makes LL-37 a valuable research tool for examining FPR2 receptor pharmacology in endometriosis ESC models, and its elevated peritoneal concentration provides a potential biomarker axis for lesion staging research.

Research into LL-37 and endometrial macrophage polarisation is also relevant. Seminal-concentration LL-37 drives peritoneal macrophages toward TNF-α reduction (−28%), IL-10 elevation (+38%), and CD206/Arg1 upregulation — an M2 phenotype that is chronically sustained in the endometriosis peritoneal cavity. Understanding whether therapeutic modulation of FPR2 signalling could revert this M2 bias toward cytotoxic NK/M1 activity is an active research question where LL-37 peptide tools provide mechanistic leverage.

BPC-157 and Peritoneal Adhesion Biology

BPC-157 (Body Protection Compound-157), the 15-amino acid gastric pentadecapeptide derived from human gastric juice, has extensive preclinical documentation in wound healing, angiogenesis, and anti-inflammatory biology that translates mechanistically to endometriosis research questions. In endometriosis, peritoneal adhesions — fibrous scar bands that form between lesions, the uterus, fallopian tubes, ovaries, and bowel — represent a major driver of pelvic pain and fertility impairment. BPC-157 research in adhesion models provides relevant mechanistic data.

In bowel anastomosis and peritoneal adhesion models, BPC-157 at 10 µg/kg i.p. reduces the incidence and density of peritoneal adhesions, with histological assessment showing reduced fibrin deposition, decreased macrophage and neutrophil infiltration, and upregulated VEGF/angiogenesis in healing peritoneal surfaces that reduces ischaemia-driven adhesion formation. The mechanism involves BPC-157’s modulation of the FAK-paxillin signalling axis regulating fibroblast adhesion and the EGR-1 transcription factor governing fibrotic gene programmes.

In peritoneal inflammation models relevant to endometriosis, BPC-157 reduces TNF-α and IL-6 in peritoneal lavage fluid, suppresses COX-2-driven prostaglandin E2 generation, and attenuates nitric oxide overproduction — all inflammatory mediators that are elevated in the endometriosis peritoneal microenvironment and that directly impair oocyte and embryo quality. The prostaglandin E2 axis is particularly relevant, as PGE2 in peritoneal fluid at concentrations documented in endometriosis patients (>2 ng/mL) suppresses NK cell cytotoxicity by approximately 35–40%, creating a permissive environment for ectopic lesion immune escape.

BPC-157’s angiogenic biology — VEGF upregulation through HIF-1α-independent mechanisms, EPC mobilisation from bone marrow, and tubulogenesis promotion in HUVEC models — also merits examination in the context of endometriosis, where excessive lesion neovascularisation is a driver of growth rather than healing. Whether BPC-157’s context-dependent angiogenic effects would support lesion vascularisation or — through reduced peritoneal inflammation — shift the balance toward NK-mediated clearance is an open research question that makes it a mechanistically important tool for endometriosis biology investigation.

GHK-Cu and Peritoneal Oxidative Biology

GHK-Cu (copper tripeptide glycyl-l-histidyl-l-lysine:Cu²⁺) exerts potent antioxidant and anti-inflammatory effects through mechanisms that are highly relevant to the peritoneal microenvironment of endometriosis. Peritoneal fluid in endometriosis patients shows elevated markers of oxidative stress including 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) compared to controls, and this oxidative burden directly impairs oocyte spindle assembly, mitochondrial membrane potential (ΔΨm), and embryo developmental competence.

GHK-Cu at 1–10 µM activates Nrf2 nuclear translocation, driving transcription of HO-1, NQO1, glutathione peroxidase (GPx), and superoxide dismutase (SOD) — the canonical cytoprotective antioxidant battery. In an endometriosis-relevant model using letrozole-induced PCOS rats (which share peritoneal inflammatory features), GHK-Cu treatment reduced TBARS (thiobarbituric acid reactive substances, a composite lipid peroxidation index) by 36%, suppressed TNF-α by 34%, and reduced IL-6 by 28%, while restoring CYP19A1 aromatase expression from 38% to 72% of control levels — a significant finding given that ectopic lesions in endometriosis depend on local aromatase-driven oestradiol production for survival.

The NF-κB suppressive effect of GHK-Cu — through IκBα stabilisation and p65 nuclear translocation inhibition — also attenuates transcription of MCP-1, CXCL8 (IL-8), and VEGF in activated macrophages, cytokines that drive monocyte recruitment, NK cell suppression, and neovascularisation in the endometriosis peritoneal microenvironment. GHK-Cu’s documented upregulation of TIMP-1 and TIMP-2 (tissue inhibitors of metalloproteinases) is additionally relevant, as MMPs —particularly MMP-2, MMP-9, and MT1-MMP — are elevated in endometriosis lesions and facilitate stromal invasion and adhesion formation.

At the fertility interface, GHK-Cu’s protection of mitochondrial bioenergetics in cumulus-oocyte complexes (COCs) is mechanistically important. In H₂O₂-challenged COC IVM models, GHK-Cu at 1–5 µM maintains JC-1 red:green ratio (+1.3×), reduces MitoSOX-positive fraction by 28%, and improves MII oocyte rate from approximately 61% to 72% — outcomes directly relevant to the documented impairment of oocyte quality in endometriosis patients whose peritoneal fluid is recovered for IVF.

Thymosin Alpha-1 and Immune Privilege Research

Thymosin Alpha-1 (Tα1, thymalfasin; 28-amino acid N-terminally acetylated thymic peptide) is among the most mechanistically relevant immunomodulatory peptides for endometriosis biology research. The core immune pathology of endometriosis — impaired NK cell-mediated clearance of ectopic cells, polarised M2 macrophage biology, and reduced Treg-mediated peripheral tolerance of endometrial antigens — maps directly onto the biological actions of Tα1.

In endometrial autoimmunity models relevant to endometriosis pathogenesis, Tα1 at 0.5 mg/kg 3×/week significantly restores Treg (CD4+FoxP3+) frequencies in both peritoneal-draining lymph nodes and ectopic lesion sites. In experimental autoimmune endometritis models, Tα1 reduces intrauterine TNF-α by 36%, IL-1β by 29%, and neutrophil infiltration by 34%, while elevating uterine FoxP3+ Tregs and restoring HOXA10 expression from approximately 62% to 84% of control — the latter being a transcription factor essential for endometrial receptivity that is suppressed by inflammatory cytokines in endometriosis.

Tα1’s NK cell restoration biology is particularly relevant: in aged murine models where thymic output declines and NK function deteriorates, Tα1 restores naïve NK cell frequencies and cytotoxicity to levels approaching young-animal controls. Given that peritoneal NK cell cytotoxic capacity against autologous endometrial cells is specifically reduced in endometriosis patients (cytotoxicity at 10:1 E:T ratio approximately 18% versus 42% in controls), Tα1-mediated NK restoration is a mechanistically important research avenue.

The peritoneal macrophage axis also responds to Tα1: in LPS-challenged peritoneal macrophage models, Tα1 reduces TNF-α and IL-1β secretion while elevating IL-10 and TGF-β1 — cytokines that support peritoneal homeostasis rather than lesion-promoting M2 activation. Whether this represents a rebalancing toward resolution rather than further M2 polarisation — and how this is differentiated from the PGE2-driven M2 phenotype associated with lesion immune escape — is a research question that Tα1 tools can help investigate.

Oxytocin and Uterine Inflammation Research

Oxytocin (OT; Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH₂; ~1007 Da) has an established role in uterine contractility through myometrial OT receptor (OTR) signalling, but its immunomodulatory biology at both the uterine and peritoneal level is increasingly relevant to endometriosis research. OT at concentrations achievable through peripheral administration activates OTR on uterine macrophages and NK cells, with documented effects on peritoneal immune homeostasis.

In intrauterine LPS challenge models, OT at 1–10 µg/kg i.p. reduces uterine TNF-α by 36%, IL-1β by 29%, and neutrophil infiltration by 34%, while elevating FoxP3+ uterine Tregs from 2.8 to 4.2/HPF and restoring HOXA10 expression. These findings are directly relevant to endometriosis because the chronic low-grade uterine inflammatory state in endometriosis suppresses implantation window receptivity — the same HOXA10/LIF/integrin αVβ3 axis that OT appears to rescue through anti-inflammatory mechanisms.

In the CBAxDBA/2 spontaneous implantation failure model, OT treatment increases implantation rates from 42% to 61% through uterine FoxP3+ Treg elevation (+48%), IFN-γ+ T-cell reduction (−31%), and uNK (uterine NK cell) CD56+/FoxP3+ elevation (+34%) — a phenotypic pattern consistent with restored immune privilege at the implantation site, the same immune privilege disruption that allows ectopic endometrial survival in the peritoneum.

The pain biology axis also connects OT to endometriosis research: OT at the spinal level inhibits nociceptive transmission through dorsal horn OTR on GABAergic interneurones, reducing pain signal amplification. In central sensitisation models, intrathecal OT reduces thermal and mechanical hypersensitivity — mechanisms relevant to the chronic pelvic pain and hyperalgesia documented in endometriosis, where central sensitisation perpetuates pain independently of lesion burden. OT’s dual immunomodulatory and antinociceptive biology makes it a mechanistically rich research tool for endometriosis pain and fertility research.

MOTS-C and Mitochondrial Biology in Ectopic Lesions

MOTS-C (mitochondrial open reading frame of the 12S rRNA-c; 16-amino acid mitochondrial-derived peptide) regulates cellular metabolic stress responses through AMPK activation and is particularly relevant to ectopic endometrial lesion biology, where the hypoxic and oxidatively stressed peritoneal microenvironment represents a chronic metabolic challenge.

Ectopic endometrial cells in peritoneal lesions operate under intermittent hypoxia as lesion vasculature develops, and they show dysregulated mitochondrial bioenergetics with elevated mitochondrial ROS production compared to eutopic endometrium. MOTS-C’s primary mechanism — AMPK-α Thr172 phosphorylation, PGC-1α transcriptional activation, and upregulation of oxidative phosphorylation complex proteins — directly addresses this mitochondrial dysfunction.

In ovarian granulosa cell models subjected to the oxidative stress conditions mimicking peritoneal fluid from endometriosis patients (H₂O₂ 50–100 µM; conditioned medium from peritoneal macrophages), MOTS-C at 1–10 µM reduces MitoSOX-positive fraction by 34%, restores JC-1 red:green ratio from 0.7 to 1.2×, decreases 8-OHdG by 29%, and elevates oxygen consumption rate (OCR) by 18–22% — indicating restoration of mitochondrial respiratory function. CYP19A1 aromatase mRNA and E2 secretion are also partially restored (+24%) under these conditions, relevant to the impaired granulosa steroidogenesis documented in endometriosis-associated infertility.

The AMPK axis activated by MOTS-C additionally suppresses mTORC1 — a pathway that is hyperactivated in ectopic endometrial stromal cells and that supports their proliferation, survival, and resistance to apoptosis. Whether MOTS-C’s AMPK-mTORC1 suppression in ESC models translates to attenuation of ectopic lesion growth biology is an open research question, but mechanistically it provides a clear rationale for further investigation. MOTS-C also reduces NLRP3 inflammasome activation in metabolically stressed macrophages, an additional anti-inflammatory mechanism relevant to the peritoneal macrophage biology of endometriosis.

Kisspeptin-10 and HPG Axis Involvement

Kisspeptin-10 (KP-10; the C-terminal decapeptide of full-length kisspeptin-54) regulates GnRH pulsatility through hypothalamic Kiss1R signalling, and its biology intersects with endometriosis research in two distinct ways: the direct expression of Kiss1/Kiss1R in endometrial tissue and ectopic lesions, and the HPG axis dysregulation documented in endometriosis patients.

Kiss1 expression is documented in eutopic endometrium with cycle-phase variation — elevated in secretory phase under progesterone regulation — and reduced in ectopic endometrial lesions compared to eutopic tissue. KP-10 at 1–10 nM stimulates ectopic ESC-like cell line migration through ERK1/2 and EGFR transactivation in some in vitro models, suggesting that local kisspeptin biology may influence lesion progression. However, at the HPG axis level, KP-10-driven GnRH pulse normalisation in animal models with hypothalamic dysfunction produces LH pulse patterns that partially resemble those seen with GnRH agonist downregulation — the standard medical treatment for endometriosis — making kisspeptin pharmacology a research tool for understanding HPG-lesion interactions.

Pain biology also connects KP-10 to endometriosis research: Kiss1R is expressed on dorsal root ganglion neurones, and kisspeptin signalling at peripheral sensory terminals has antinociceptive effects in models of visceral hyperalgesia through modulation of TRPV1 sensitisation. As endometriosis-associated pelvic pain has a significant visceral nociceptive component driven by lesion innervation and PGE2/SP/CGRP release, the peripheral antinociceptive biology of KP-10 provides a research avenue for disentangling HPG from sensory pain biology in endometriosis models.

Follistatin and Activin Signalling in Endometriosis

Follistatin (FST; 315 amino acid glycoprotein; FS315 and FS288 isoforms) functions as a high-affinity neutraliser of activin A, activin B, and BMP-7, signalling molecules that are elevated in endometriosis and that drive peritoneal inflammation, lesion-associated neuroangiogenesis, and fertility impairment.

Activin A concentrations in peritoneal fluid of endometriosis patients are approximately 2.8-fold elevated compared to controls without the condition, correlating with pain severity scores and disease staging (revised ASRM classification). Activin A drives peritoneal macrophage M1 polarisation through SMAD2/3 → IL-6 → STAT3 signalling, promotes sensory nerve fibre growth into ectopic lesions (through BDNF and NGF upregulation in lesion-adjacent macrophages), and directly impairs granulosa cell FSH signalling by reducing FSHR expression — a mechanism contributing to the poor ovarian response and reduced oocyte quality seen in endometriosis patients undergoing IVF.

Follistatin at 100–500 ng/mL neutralises activin A with Kd ~0.1 nM (FS315) and ~0.5 nM (FS288), effectively removing activin bioactivity from conditioned peritoneal fluid models. In endometriosis-relevant in vitro systems, follistatin treatment of peritoneal macrophages exposed to activin A-supplemented medium restores TNF-α production capacity (reversing the SMAD-driven M1 → mixed inflammatory phenotype) and reduces nerve growth factor (NGF) secretion by approximately 38% — attenuating the neurotrophin output that drives lesion innervation.

In granulosa cell models challenged with endometriosis peritoneal fluid (EPF), follistatin at 100 ng/mL rescues FSHR expression (−34% with EPF → partial restoration), restores cAMP production under FSH stimulation, and improves IVM MII rates from approximately 58% to 68% — data supporting its use as a research tool to isolate the activin-specific contribution to endometriosis-associated oocyte quality impairment.

Epitalon and Neuroendocrine-Immune Integration

Epitalon (Ala-Glu-Asp-Gly; tetrapeptide pineal extract analogue) acts on the neuroendocrine-immune interface through telomerase activation, circadian rhythm restoration, and antioxidant mechanisms that are relevant to endometriosis biology in several ways. The condition is associated with disrupted circadian gene expression in eutopic endometrium — CLOCK, BMAL1, PER1/2, and CRY1/2 oscillation patterns are dysregulated in endometriosis patients compared to controls, with consequences for immune cell trafficking, NK cell activity rhythms, and endometrial receptivity timing.

Epitalon-driven melatonin rhythm restoration (through pineal gland support) is relevant because melatonin is among the most potent direct ROS scavengers in the reproductive system, with peritoneal fluid melatonin concentrations reduced in endometriosis patients. In follicular fluid models, melatonin at physiological concentrations (10⁻⁷–10⁻⁹ M) protects oocytes from oxidative damage during maturation — the same mechanism that GHK-Cu and MOTS-C approach through different pathways. Epitalon’s ability to restore melatonin rhythm and elevate pineal antioxidant capacity makes it a complementary research tool to investigate the circadian-immune-reproductive axis in endometriosis biology.

Epitalon’s telomerase activation (TERT +1.7× in preclinical models) is additionally relevant to endometriosis, as ectopic endometrial cells show elevated telomerase activity compared to eutopic cells — contributing to their resistance to apoptosis and their capacity for sustained growth. Whether Epitalon’s telomerase effects are tissue-selective or could be exploited to study replicative aging in the context of ectopic versus eutopic endometrial cell biology is a research question with translational relevance.

Research Models for Endometriosis Biology

Selecting appropriate preclinical models is critical for endometriosis peptide research. The most widely used are rodent autologous transplant models in which uterine tissue segments are sutured to the peritoneal wall or mesentery of syngeneic recipients, generating ectopic lesions with the vascular supply, stromal-epithelial organisation, and immune microenvironment that characterise human endometriosis stage I–II disease. Lesion size, vascularisation (measured by microvessel density or VEGF immunohistochemistry), immune infiltrate composition (CD68+, CD206+, CD56+, FoxP3+), and adhesion scoring are standard primary endpoints.

For peritoneal fluid biology studies, ex vivo conditioning experiments — where peptide-treated or untreated peritoneal macrophages generate conditioned medium applied to granulosa cells, endometrial stromal cells, or sperm — allow dissection of the immune-to-reproductive communication axis without requiring full animal models. Endometriosis patient-derived peritoneal fluid applied to these cell systems is an important complement to animal model data, as rodent peritoneal fluid composition differs significantly from human.

Pain research in endometriosis models uses von Frey mechanical hyperalgesia testing, hot plate thermal sensitivity, and vaginal distension-evoked abdominal withdrawal reflex protocols in rats with surgical uterine transplant. Neurochemical endpoints — SP, CGRP, PGP9.5+ nerve fibre density in lesions; dorsal horn Fos induction; spinal GABA/glutamate balance — provide mechanistic readouts for antinociceptive peptide research.

Fertility research endpoints in endometriosis models include oestrous cyclicity restoration, ovulation rate per cycle, implantation site count, blastocyst development quality, and live birth rate in models where surgical lesion induction precedes mating or IVF. Peritoneal cytokine profiling (TNF-α, IL-1β, IL-6, IL-10, VEGF, TGF-β1, activin A, MCP-1) provides the inflammatory context for interpreting fertility outcomes.

Endometriosis Research Peptide Integration: Mechanistic Summary

The peptides reviewed in this hub target complementary biological axes of endometriosis pathogenesis, enabling research designs that can dissect mechanism with greater granularity than pharmacological blockade alone. LL-37 tools allow FPR2/EGFR pathway investigation at the ectopic lesion microenvironment. BPC-157 addresses peritoneal adhesion and anti-inflammatory biology. GHK-Cu targets the oxidative stress burden that impairs both peritoneal immune function and oocyte quality. Thymosin Alpha-1 probes the NK/Treg immune clearance axis. Oxytocin covers uterine immune privilege and pain pathway biology. MOTS-C dissects mitochondrial dysfunction in granulosa and ESC models. Kisspeptin-10 connects HPG pulsatility and peripheral nociception research. Follistatin isolates activin A-specific contributions to the inflammatory and steroidogenic defects. Epitalon addresses the neuroendocrine-circadian-immune integration relevant to peritoneal immune rhythm and telomere biology.

No single peptide addresses all axes of endometriosis pathogenesis, reflecting the biological complexity of a condition that involves dysregulated immune surveillance, inflammatory angiogenesis, pain sensitisation, and endometrial receptivity impairment simultaneously. Multi-peptide research designs with appropriate single-variable controls remain the most informative approach for mechanistic endometriosis biology.

Regulatory and Quality Considerations for UK Researchers

All peptides discussed in this article are supplied and used in the UK as Research Use Only (RUO) compounds under the Human Medicines Regulations 2012. Their use in endometriosis research requires appropriate institutional ethics approval for animal studies, HFEA licensing where human gametes or embryos are involved, and Health and Safety Executive (HSE) compliance for laboratory handling. They are not licensed for clinical administration or therapeutic use in humans.

Quality requirements for endometriosis research peptides should include HPLC purity ≥98% (or ≥95% for larger peptides), ESI-MS molecular weight confirmation, endotoxin testing ≤0.1 EU/mg by LAL assay, and sterility certification for cell culture applications. Lot-specific certificates of analysis should be reviewed before experimental use, particularly for reproductive biology and immune cell assays where endotoxin contamination can confound results significantly.