Induratio Penis Plastica · A patient's account

I had Peyronie's
with a 40° bend.
Six months later, gone.

This is my personal experience of what happened, why each compound matters at the cellular level, and the published research behind it.

Read the account

Educational only. Not medical advice. Not affiliated with Dr. Paulis. Anyone considering this protocol should consult a qualified urologist or andrologist.

01 · Diagnosis

I never had pain. I never felt a nodule. One morning the bend was 40°.

The first signal was subtle, erections losing rigidity. No nodule I could feel through the skin, no pain, no warning. Then one morning I woke up with a sudden, hard 40° curvature and could no longer reach full rigidity: around 70% of normal, crookedly curved. That was day one of the visible disease.

I went to an andrologist who performed a penile Doppler ultrasound after intracavernous injection of a vasoactive drug, the very ICI-Doppler procedure critiqued in the clinicians' section of this page, and read the scan as parenchymal, inside the cavernous tissue, and as already in the chronic phase. He told me the only realistic option was surgery: the bend would cause buckling of the corpora during intercourse, buckling would induce more microtrauma and scarring, and that cycle would progressively damage cavernous tissue until I needed a penile prosthesis. Conservative therapy was, in his words, "proven ineffective." Both halves of his diagnosis were wrong. The plaque was septal, not parenchymal, sitting on the tunica albuginea between the two corpora cavernosa, the typical Peyronie location. And the disease was still in its active inflammatory phase, which is the phase in which conservative anti-oxidative / anti-fibrotic therapy works most reliably (Paulis has published regression even in plaques with calcification, but active-phase tissue is by far the easiest to turn around).

I refused surgery and spent two months reading the peer-reviewed literature. The consensus story online, surgery or nothing, was not the consensus in the journals. Dr. Gianni Paulis, andrologist at Regina Apostolorum Hospital in Rome, holds a degree in Medicine and Surgery from La Sapienza Rome (1982), a postgraduate specialty in Urology (Rome, 1985), a postgraduate specialty in Endocrinology, field of Andrology, from the University of Pisa (2002), and an additional University Masterclass in Andrological Ultrasonography also at Pisa. The University of Pisa is one of Italy's oldest universities and operates the most rigorous Endocrinology-Andrology specialty programme in the country, combining reproductive endocrinology, sexual medicine and dedicated andrological imaging training in one institution. That combination is what makes Paulis' diagnostic approach to Peyronie's distinctive: the same clinician thinks about hormones, tissue biochemistry, and ultrasound morphology of the tunica simultaneously, rather than handing each off to a different speciality. He directs the Centre for the Treatment of Peyronie's Disease at the Castelfidardo Medical Team in Rome and has been publishing on oxidative stress as the driver of plaque growth since the early 2010s. In 2022 he and his team reported complete plaque regression in three patients (J Med Case Rep 16:359); his 2017 review in Adv Urol is the mechanistic foundation. Both papers are referenced below; both are open access.

I travelled to Rome to be treated by Dr. Paulis personally. The control ultrasound was performed by Giovanni De Giorgio, an expert ultrasound and elastography operator who co-authored Paulis' 2012, 2022 and 2025 publications and who has separately published on combined ultrasound + elastography for detecting non-palpable, non-sonographically visualized Peyronie plaques. Paulis' 2022 case series explicitly stresses that this protocol depends on "accurate ultrasound assessment, performed using a sufficiently advanced machine by an experienced operator."

Initial imaging: 22 October 2025. Control imaging in Rome: 29 April 2026, six months on protocol. Plaque volume down 51% between the two scans. The residual plaque was elastic rather than fibrotic and rigid, evidence that the matrix had already started remodelling. Curvature on erection, 40° at peak during the active phase, was 7°. That 7° is my congenital baseline: the natural curve I had before the disease ever started. The Peyronie-driven curvature is gone. Erections are fully rigid. I am one data point. I am not a clinical trial. But the cellular story below is what I believe was happening, the compounds I used are linked directly to each mechanism, and every claim traces to the literature.

Documentary evidence

Side-by-side B-mode ultrasound scans of the tunica albuginea. Left column dated 22.10.25 shows the initial septal plaque. Right column dated 29.4.26 shows the same region after six months on protocol, with markedly reduced plaque volume.
B-mode ultrasound, 22 October 2025 (left) vs. 29 April 2026 (right). Same patient, same operator, same machine.
Two clinical ultrasonography reports issued in Rome. The earlier report records a plaque volume of 0.853 ml; the later report records 0.416 ml, a 51% reduction.
The corresponding reports from Rome. Plaque volume 0.853 ml → 0.416 ml, a measured −51%. Personal identifiers redacted.

Both scans performed by Giovanni De Giorgio at the Castelfidardo Medical Team, Rome. The numbers above are not a rhetorical claim; they are what the report says.

Many andrologists on earth will tell you that all roads lead to surgery. They do not. One of them leads to Rome.

02 · The protocol

What I took, and why each one matters

Six compounds, four oral, two topical. Each one targets a different node in the oxidative-inflammatory-fibrotic cascade. Tap any compound for verified ingredient list, exact dosing, and the mechanism it addresses.

03 · The cascade

Six steps from microtrauma to plaque

Six steps, one per process, each anchored to a real micrograph or peer-reviewed pathway diagram. Every term is hyperlinked to an authoritative non-Wikipedia source, UniProt, NCBI, Reactome, MedlinePlus or Kenhub, so doctors can verify and patients can drill into any concept.

Paulis 2017 pathogenesis flow diagram of Peyronie's disease: tunica albuginea trauma → fibrin deposition → inflammatory infiltrate → cytokine release (TGF-β1, PDGF, IL-1, bFGF) → fibroblast recruitment and myofibroblast transformation → plaque formation, with oxidative stress and free radicals feeding the loop.
Figure 1 (Pathogenetic mechanisms of Peyronie's disease) from Paulis G, Romano G, Paulis L, Barletta D. Recent Pathophysiological Aspects of Peyronie's Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment. Adv Urol. 2017;2017:4653512 (open access, CC BY 4.0; full text via Europe PMC PMC5514334). The six steps below trace this same cascade, annotated with the per-node intervention points of the protocol.
  1. Anatomical 3-D rendering showing the tunica albuginea layer covering the corpora cavernosa of the penis.
    Tunica albuginea anatomy, Manu5, Wikimedia Commons (CC BY-SA 4.0).

    01 · Trigger

    Mechanical microtrauma to the tunica albuginea

    The tunica albuginea is a two-layer collagen sheath: an inner circular layer and an outer longitudinal layer, with elastic fibres weaving between. During buckling stress , sudden axial load on a partially erect penis, or repeated sub-clinical micro-trauma, the inner layer shears against the outer. Subtunical microvessels rupture, fibrin deposits at the lesion, platelets degranulate, and resident tunical fibroblasts release alarm cytokines. The fibrin clot itself is strongly chemotactic, recruiting neutrophils, macrophages and mast cells into the lesion. Platelets and incoming macrophages co-release TGF-β1 and PDGF (platelet-derived growth factor), both of which independently attract more fibroblasts. In parallel, infiltrating macrophages secrete elastase, which degrades the tunica's elastic fibres; the elastin-derived peptides are themselves chemotactic, feeding more inflammatory cells back into the lesion (Paulis 2017). In men with the genetic / lifestyle susceptibility profile, Paulis lists competitive sports, smoking, vigorous intercourse and high-fat diets as facilitating factors, that local injury fails to resolve cleanly and ignites a chronic inflammatory loop.

    What the protocol does at this node

    Nothing direct. Microtrauma is an event, not a pathway, and no oral or topical compound can prevent buckling. But two things de-risk this step in practice:

    • NO/cGMP support via L-citrulline (Alpavir Uno), keeps cavernous smooth muscle compliant and full erections rigid, lowering the probability of buckling during intercourse. Same axis acted on by PDE5 inhibitors (Cialis, Viagra), via the nitric-oxide / cGMP pathway.
    • Local anti-inflammatory cover at the plaque (diclofenac spray + Sclero-Hyal cardiospermum / glycyrrhetinic acid), damps the local fibrin / cytokine response when minor trauma does occur.

    In effect: the protocol cannot stop the trigger, but it can keep the trigger from arming the cascade.

    Devine CJJ et al., J Urol 1997, trauma hypothesis for PD lesion. Somers & Dawson, J Urol 1997, fibrin deposition in the plaque.

  2. Three-dimensional electron tomographic reconstruction of mitochondrial cristae, the inner-membrane folds where Complex I and III generate ROS.
    Mitochondrial cristae tomogram, Terrence G. Frey, PLoS ONE (CC BY 3.0).

    02 · Oxidative ignition

    NADPH oxidase + mitochondrial Complex I/III generate ROS

    Two reactive-oxygen-species factories light up at the lesion. NADPH oxidase (Nox2 / Nox4) on the inflammatory-cell membrane pumps electrons onto extracellular oxygen, generating superoxide (O₂⁻·). Inside fibroblast and macrophage mitochondria, electron leak from Complex I and Complex III (the cristae-embedded respiratory complexes shown above) does the same. Once superoxide meets nitric oxide, the product is peroxynitrite (ONOO⁻), which nitrates tyrosine residues on collagen, inactivates manganese superoxide dismutase, and oxidises thiol switches on regulatory enzymes. The membrane consequence is lipid peroxidation: PUFA chains get oxidised into 4-HNE and malondialdehyde, signalling molecules that propagate the damage long after the original superoxide is gone. In Paulis' clinic this is measured by the oxidative-stress index (OSI), elevated in plaque tissue and peripheral blood across his 2017, 2022 and 2025 cohorts.

    What the protocol does at this node

    This is where the multimodal protocol is densest, because every downstream pathology is fed from here.

    • Superoxide dismutase (Peyflog, 11,000 IU/g), direct catalytic dismutation of O₂⁻· to H₂O₂. Catalytic, not stoichiometric, one enzyme molecule clears thousands of superoxide radicals.
    • Coenzyme Q10 (Peyflog), restores electron-transport efficiency at Complex III, reducing the upstream electron leak that creates mitochondrial superoxide in the first place. Mechanism reviewed by ScienceDirect Topics.
    • L-acetyl carnitine (Peyflog), fatty-acid carnitine shuttle keeps β-oxidation feeding the electron transport chain on its preferred substrates, so the mitochondrion is not running on backup substrates that leak more electrons.
    • Vitamin E (Peyflog + Alpavita EC + Sclero-Hyal, ~600 mg/day in Paulis' published protocol, 300 mg twice daily after meals), donates a hydrogen atom to lipid peroxyl radicals, breaking the chain reaction in membranes; vitamin E metabolites also have anti-COX2 activity (Paulis, 2014 interview).
    • Vitamin C (Peyflog + Alpavita EC), aqueous-phase scavenger; recycles oxidised α-tocopherol back to active vitamin E, allowing one Vitamin E molecule to neutralise many lipid radicals.
    • Bilberry anthocyanins (Peyflog, 25% titre), protect endothelial cells against peroxynitrite-induced apoptosis; inhibit iNOS and COX-2 expression (Paulis, 2014).
    • Propolis flavonoids (Peyflog + Sclero-Hyal, 10% galangin titre), quench peroxynitrite, suppress NF-κB-driven iNOS / COX-2 expression.

    Paulis G et al., Adv Urol 2017;2017:4653512 · Paulis G, De Giorgio G, Paulis L, Int J Mol Sci 2022;23:15969 · Sikka & Hellstrom, Int J Impot Res 2002;14:353.

  3. Diagram of canonical and non-canonical NF-κB signaling: receptor activation, IKK complex, IκB phosphorylation, p65/p50 nuclear translocation, target gene transcription.
    Canonical & non-canonical NF-κB signaling, Qing Guo et al., Sig Transduct Target Ther 9:53 (2024) (CC BY 4.0).

    03 · Inflammation latches on

    NF-κB activation and the cytokine storm

    The redox shift from step 2 directly oxidises the IκB kinase complex (IKKβ). Active IKKβ phosphorylates the inhibitor IκBα, marking it for proteasomal degradation. The released p65/p50 NF-κB heterodimer translocates to the nucleus and transcribes the entire pro-inflammatory program at the plaque: IL-1β, IL-6, TNF-α, COX-2, iNOS, MCP-1, CXCL-8. Neutrophils and monocyte-derived macrophages flood the lesion, both consuming O₂ via their own NADPH oxidase (more ROS) and secreting more TGF-β1 (the next node). This is the self-sustaining loop: ROS activates NF-κB, NF-κB target genes recruit cells that make more ROS. Without intervention, the lesion stops being a one-off injury response and becomes a chronic inflammatory pocket, the biochemical definition of the active phase of Peyronie's.

    What the protocol does at this node

    Multiple compounds intersect NF-κB and its downstream eicosanoid arms:

    • Boswellic acids (Peyflog, 65% titre), inhibit 5-lipoxygenase, blocking the leukotriene side-branch that NF-κB feeds, and suppress IκBα degradation in inflammatory cells.
    • Diclofenac sodium (topical spray, 1–4%), non-selective COX-1/COX-2 inhibition at the plaque; collapses local prostaglandin synthesis without systemic NSAID exposure. Paulis' multimodal-therapy papers specifically include local diclofenac on the overlying skin.
    • Glycyrrhetinic acid (Sclero-Hyal), licorice-derived steroidal anti-inflammatory; blocks 11β-hydroxysteroid dehydrogenase locally, prolonging endogenous cortisol activity at the lesion (cortisone-like effect, no systemic suppression).
    • Cardiospermum halicacabum (Sclero-Hyal), phytosteroidal "cortison-like" effect on cytokine cascade with topical safety profile.
    • Propolis & bilberry flavonoids, direct NF-κB pathway suppression: NF-κB nuclear translocation reduced; iNOS, COX-2, TNF-α expression down (Paulis, 2014 interview citing his earlier mechanistic work).

    Paulis G et al., Inflamm Allergy Drug Targets 2013; Paulis G, Brancato T, Inflamm Allergy Drug Targets 2012;11(1):48–57.

  4. Schematic of TGF-β signaling: ligand binds TβRII/ALK5 receptor complex, R-SMAD (Smad2/3) phosphorylation, complex with Smad4, nuclear translocation, fibrotic gene transcription.
    TGF-β / SMAD signaling, Di Gregorio et al., Front. Cell Dev. Biol. 8:607483 (CC BY 4.0).

    04 · The master switch

    TGF-β1 → ALK5 → SMAD2/3 → fibrotic transcription

    TGF-β1 is the single signalling molecule whose chronic elevation at the tunica albuginea is sufficient, in animal models, to reproduce a Peyronie-like plaque on its own. Released by activated macrophages and platelets, it binds the heterodimeric receptor complex of TβRII and ALK5 (TβRI). The activated receptor phosphorylates the receptor-regulated SMADs (SMAD2 and SMAD3), which complex with the co-SMAD (SMAD4) and translocate to the nucleus. There the trimer drives transcription of the entire fibrotic gene set, COL1A1 and COL3A1 (type-I and type-III collagen), ACTA2 (α-smooth-muscle actin, myofibroblast marker), PAI-1 (suppresses fibrinolysis, locks fibrin into place), TIMP-1 (suppresses collagen-degrading enzymes), and CTGF (autocrine amplifier). This is the keystone node: every downstream fibrotic outcome, myofibroblast differentiation, collagen over-deposition, MMP / TIMP imbalance, flows from here. Paulis 2017 also flags two parallel profibrotic growth factors riding on this same step: PDGF continues to recruit fibroblasts into the lesion, and bFGF (produced by the very fibroblasts and myofibroblasts already present) drives further fibroblast proliferation, stimulates collagen synthesis, induces MMP-1 / MMP-9 and TIMP-1 expression, and amplifies local fibrin deposition, all of which lock the cascade into a self-sustaining state independent of the initial TGF-β1 burst.

    What the protocol does at this node

    TGF-β1 cannot be hit head-on with available oral compounds at safe doses, so the protocol attacks the SMAD pathway laterally and supports the opposing NO/cGMP arm:

    • Silymarin from Silybum marianum (Peyflog, titrated 80%), documented TGF-β1 modulator in liver, lung and renal fibrosis models; suppresses SMAD3 phosphorylation and reduces collagen-I transcription at fibroblast level. Mechanism reviewed at NCBI Bookshelf, Silymarin.
    • Pentoxifylline-class polyphenols, pentoxifylline itself is used by Paulis intralesionally in some patients; orally-available flavonoid analogues in Peyflog (propolis, bilberry, ginkgo) hit the same cAMP / phosphodiesterase arm that down-regulates SMAD signalling.
    • L-citrulline → arginine → eNOS → NO → soluble guanylyl cyclase → cGMP (Alpavir Uno), the NO/cGMP axis directly opposes the profibrotic tone of TGF-β1 in cavernous tissue. Paulis' rationale papers explicitly position this as one of the few endogenous brakes on fibroblast-to-myofibroblast transition.
    • CoQ10 + carnitine, mitochondrial integrity reduces the ROS that cross-activates non-canonical TGF-β / TAK1 signalling; pathway redundancy means oxidative damping helps here too.

    Gonzalez-Cadavid & Rajfer, Nat Clin Pract Urol 2005 (TGF-β as PD keystone) · Di Gregorio et al., Front. Cell Dev. Biol. 8:607483 (canonical / non-canonical TGF-β) · Paulis G et al., Res Rep Urol 2017;9:129–139.

  5. High-resolution fluorescence micrograph of a fibroblast showing the actin cytoskeleton (red), the contractile stress-fibre apparatus that the myofibroblast assembles under TGF-β1.
    Mouse-embryo fibroblast: actin (red), mitochondria (green), DNA (blue). D. Burnette & J. Lippincott-Schwartz, NICHD/NIH (CC BY 2.0).

    05 · The cell transforms

    Fibroblast → myofibroblast (the engine of the plaque)

    Under sustained TGF-β1 signalling, tunical fibroblasts undergo a phenotype switch. They upregulate α-smooth-muscle actin (α-SMA), assemble contractile actomyosin stress fibres (the bright red filaments in the micrograph above are the real thing), couple them to the matrix through supermature focal adhesions, and resist apoptosis through PI3K/Akt-mediated survival signalling. The result, the myofibroblast , is what physically bends the penis. It both builds the disorganised matrix (high-rate collagen secretion) and contracts it (acto-myosin pulling the new collagen taut). In the active phase the plaque is essentially a sheet of these cells coupled to the tunica. When myofibroblasts persist, the plaque calcifies and stiffens. When they apoptose on schedule, wound-healing's normal off-switch, the plaque can soften and remodel.

    What the protocol does at this node

    The myofibroblast is sustained by two inputs: oxidative drive and mechanical tension on the matrix. The protocol attacks both:

    • Hyaluronic acid + sodium hyaluronate (Sclero-Hyal topical), modulates the extracellular-matrix mechanical environment; hyaluronate-rich matrix is softer, transmits less tension to focal adhesions, and pushes myofibroblasts toward apoptosis or de-differentiation.
    • Antioxidant rescue (whole protocol), oxidative stress is one of the inputs that maintain the α-SMA-positive, apoptosis-resistant state. Damping ROS at the source (step 2) lifts the tonic survival signal that keeps myofibroblasts alive past their welcome.
    • Local cortisone-like cover (cardiospermum, glycyrrhetinic acid in Sclero-Hyal), corticosteroid signalling drives myofibroblast apoptosis in cultured tunical fibroblasts; the topical "phyto-corticoid" route avoids the systemic side-effects of oral prednisone.
    • Hypericum perforatum + aloe vera + tocopheryl acetate (Sclero-Hyal), emollient and scar-modulating actions on the overlying skin and tunica; the topical layer is dual-purpose (matrix + cellular).

    Hinz B, J Invest Dermatol 2007 (myofibroblast biology) · Tomasek et al., Nat Rev Mol Cell Biol 2002;3:349 · Paulis 2017 multimodal rationale.

  6. Transmission electron micrograph of densely-packed type-I collagen fibrils showing the characteristic 67 nm banded periodicity, the structural protein over-deposited in Peyronie plaque.
    TEM of type-I collagen fibrils, mammalian connective tissue, Louisa Howard, Dartmouth (Public domain).

    06 · The plaque builds, then unbuilds

    MMP/TIMP imbalance, the clean-up crew is silenced

    Healthy connective tissue is in continuous turnover: matrix metalloproteinases (MMP-1, MMP-2, MMP-9) clip old collagen; their tissue inhibitors (TIMP-1, TIMP-2) modulate that activity. TGF-β1 inverts the balance, MMPs are repressed, TIMPs induced. Type-I and type-III collagen accumulate disorganised (the dense banded fibrils above show what plaque collagen looks like at TEM resolution); lysyl oxidase cross-links the new matrix into a non-remodellable mesh; calcium phosphate seeds on the cross-links, and over years the plaque calcifies. The reversibility window is here. While the matrix is still soft, while lysyl-oxidase cross-linking is incomplete, while calcification has not started, damping the upstream oxidative and TGF-β drive lets the MMP/TIMP balance tip back toward remodelling. Paulis' 2022 case series documented complete radiological disappearance of plaque in three patients on multimodal therapy, with timelines of 18–36 months depending on initial plaque volume. My own 51% reduction over 6 months on the same protocol is consistent with that trajectory.

    What the protocol does at this node

    The whole protocol funnels into this final node. Plaque shrinks because every previous step is being pushed in the direction of resolution:

    • Sustained antioxidant pressure (Peyflog + Alpavita EC, daily, months), keeps the oxidative-stress index suppressed, removes the upstream signal that would otherwise re-activate fibroblasts.
    • Local anti-inflammation (diclofenac + Sclero-Hyal, daily), keeps NF-κB and COX-2 cooled at the plaque so cytokine recruitment of new myofibroblasts stops.
    • NO/cGMP support (Alpavir Uno, daily), restores the endogenous brake on profibrotic signalling.
    • Matrix-modulating topical (Sclero-Hyal hyaluronic acid) , softens the local ECM mechanics that maintain the myofibroblast.
    • Time, Paulis' published timelines show meaningful regression takes months; complete regression takes 18–36 months depending on initial plaque volume. Six months is the window where pain resolves and curvature softens, which matches my own course.

    Paulis G, De Giorgio G, Paulis L, J Med Case Rep 2022;16:359 (complete plaque regression case series) · Paulis et al., Am J Case Rep 2022;23:e936146 (regression of two earlier cases) · Paulis G et al., Andrology 2025 (PMID 40863122) , OSI in 102 PD patients.

04 · Compound detail

Ingredients list

Every ingredient list below is taken from the manufacturer's product page, with per-dose figures as documented from the patient's labels.

Peyflog Farmakos s.r.l. (Italy)

Oral · 2 tablets twice daily on an empty stomach (4 tabs/day total)

Source: farmakos.it/prodotto/peyflog

Per daily dose (4 capsules):

  1. Propolis (10% galangin), 700 mg (70 mg galangin) · flavonoid antioxidant, NF-κB suppression.
  2. Milk thistle Silybum marianum (80% silymarin), 500 mg (400 mg silymarin) · documented TGF-β1 modulator in fibrotic tissue.
  3. Ginkgo biloba folium (6% ginkgoflavonoids), 240 mg (14.4 mg flavonoids) · endothelial / microcirculation support.
  4. Boswellia serrata resin (65% boswellic acids), 200 mg (130 mg boswellic acids) · 5-LOX inhibition.
  5. Bilberry Vaccinium myrtillus (25% anthocyanins), 180 mg (45 mg anthocyanins) · vascular antioxidant; capillary integrity.
  6. Coenzyme Q10, 100 mg · mitochondrial electron-transport-chain support.
  7. Vitamin E (DL-α-tocopherol), 48 mg (~72 IU) · lipid-phase ROS scavenger.
  8. Vitamin C, 50 mg · aqueous-phase ROS scavenger; regenerates vit E.
  9. Superoxide dismutase (11,000 IU/g), 10 mg · direct O₂⁻· dismutation.
  10. L-Acetyl carnitine, 1000 mg (250 mg/capsule × 4) · mitochondrial fatty-acid carrier; ETC and ATP support.

Alpavita EC Alpakos s.r.l.

Oral · 1 capsule once daily, morning, on an empty stomach

Source: alpakos.it/prodotto/alpavita-ec

Per daily dose (1 capsule):

  • Vitamin C (L-ascorbic acid), 130 mg · aqueous-phase antioxidant.
  • Vitamin E (DL-α-tocopherol), 60 mg (~90 IU) · lipid-phase antioxidant.
  • Excipients: microcrystalline cellulose, magnesium fatty-acid salts, animal gelatin.

Adds to the redox baseline contributed by Peyflog. Combined daily intake of the two products: ~108 mg vitamin E and ~180 mg vitamin C.

Alpavir Uno Alpakos s.r.l.

Oral powder · 1 sachet in 250 ml water, morning, empty stomach

Source: alpakos.it/prodotto/alpavir-uno

Per daily dose (1 sachet):

  • L-citrulline DL-malate, 1000 mg · NO precursor; supports endothelial NO/cGMP signalling.
  • Glucosamine sulfate (from crustaceans), 300 mg · connective-tissue substrate.
  • Excipients: isomalt, maltodextrin, potassium hydrogen carbonate, silicon dioxide, sucralose.

Acts on the same NO/cGMP axis as the daily tadalafil, substrate side of the pathway, not the enzyme side. Label warns of laxative effect at high polyol doses.

Sclero-Hyal Alpakos s.r.l.

Topical cream · twice daily on clean skin over the plaque

Source: alpakos.it/prodotto/sclero-hyal

  • Cardiospermum halicacabum, phytosteroidal "cortisone-like" anti-inflammatory.
  • Propolis (depollinated), anti-inflammatory, antimicrobial.
  • Hyaluronic acid + sodium hyaluronate, matrix softening, scar modulation.
  • Hypericum perforatum extract, emollient, scarring support.
  • Aloe vera leaf juice, hydration, anti-inflammatory.
  • Zinc oxide + titanium dioxide, anti-inflammatory, protective.
  • Glycyrrhetinic acid, licorice-derived anti-inflammatory.
  • Tocopherol / tocopheryl acetate, vitamin E.

Diclofenac 4% topical spray

Topical NSAID · once daily over the plaque

Generic NSAID; standard brand examples: Voltaren, Diclac. Paulis' multimodal-therapy publications include local diclofenac as a topical adjunct over the affected tunica.

  • Diclofenac sodium 4%, non-selective COX-1/COX-2 inhibition; local prostaglandin synthesis collapses; eicosanoid drive on the plaque is cut without the systemic GI / renal exposure of oral NSAIDs.

Tadalafil 5 mg PDE5 inhibitor (Cialis)

Oral · 5 mg once daily (low-dose continuous regimen)

Reference monograph: MedlinePlus, tadalafil. Daily low-dose tadalafil for ED has FDA approval; its use in Peyronie's rehabilitation is off-label adjunct supported by mechanistic literature on the NO/cGMP / fibrosis axis.

  • Tadalafil, selective inhibitor of phosphodiesterase 5 (PDE5). PDE5 normally degrades cGMP; blocking it preserves NO/cGMP signalling in cavernous smooth muscle.

Two reasons for daily-dose use here, both downstream of the same pathway: (1) Mechanical, better nocturnal and on-demand erections lower the probability of buckling micro-trauma during the active phase, the microtrauma that ignites step 1 of the cascade. (2) Anti-fibrotic , sustained cGMP elevation has documented anti-fibrotic effects in cavernous tissue and opposes TGF-β1 / SMAD profibrotic tone (step 4). On a daily regimen, blood levels stay above the EC50 round-the-clock, which the on-demand regimen does not achieve.

05 · For clinicians

If a patient walks in with a likely diagnosis

Most men with Peyronie's first present to a urologist. The urologist typically refers them to an andrologist, and the wait for that referral is weeks to months in most national health systems. By the time they see the andrologist, the patient has already lost a substantial portion of the active inflammatory phase, exactly the window in which conservative therapy is most effective. Treatment must begin at the first urologist visit, not after the referral chain finishes. This section is a patient's perspective for the clinician, urologist or andrologist, seeing a likely case for the first time. It is not a guideline.

Imaging, elastosonography is the supreme technique

B-mode ultrasound localises and characterises macroscopic plaque well, but it misses early or partially-fibrotic lesions. Real-time elastography, used together with B-mode US, dramatically extends what can be seen and what can be tracked over time. The Paulis & De Giorgio group has published the strongest case for this in the recent literature:

The clinical implication: in any patient with clinical signs of Peyronie's but a negative or equivocal B-mode US, elastography is not optional. A "no plaque seen" report on B-mode is not the end of the work-up; it is an indication to run elastography before declaring the patient unaffected.

The pharmacologically-induced erection question

The 2025 EAU guidelines on sexual and reproductive health (EAU SRH 2025, Section 8.2.2) list three options for objective assessment of penile curvature in Peyronie's disease, in this stated order: home (self) photography of a natural erection (preferably), a vacuum-assisted erection test, or intracavernous injection of a vasoactive agent. The same section then claims "the ICI method is superior" for inducing a Peyronie-typical erection, and issues a formal recommendation: "Use the intracavernous injection method in the diagnostic work-up of PD to provide an objective assessment of penile curvature with an erection." The recommendation's strength rating is Weak, supported by Level of Evidence 4 (case series / expert opinion, the lowest evidence tier in the EAU grading system) (Salonia et al., Eur Urol 2025).

It is worth checking what the word "superior" rests on in EAU 2025. The three citations attached to it are refs 919, 920, 921: Levine LA et al., Int J Impot Res 2003;15 Suppl 5:S103 (a one-page conference-supplement editorial titled "Establishing a standardized evaluation of the man with Peyronie's disease", i.e. an expert position paper, not a comparative trial); Ozmez A et al., Sex Med 2019;7:311 (a 3-D CT pilot study, on a different imaging question entirely); Hauck EW et al., Eur Urol 2003;43:293 (a 2003 comparison of MRI vs palpation vs ultrasound for plaque imaging, also a different question). Two of the three references do not compare ICI to alternative erection-induction methods at all. The third is a 22-year-old, one-page conference-supplement editorial. There is no head-to-head trial of ICI versus autophotograph or vacuum-erection-test in EAU's evidence base for the "superior" claim. That is also why the accompanying Level of Evidence is 4, the lowest tier in the EAU grading system. The word "superior", on inspection, is doing more work than the citations behind it can support.

Pfizer's own Caverject (alprostadil) labelling is, on this point, considerably less ambiguous than EAU. The Precautions section states verbatim: "The overall incidence of penile fibrosis, including Peyronie's disease, reported in clinical studies with CAVERJECT was 3%. In one self-injection clinical study where duration of use was up to 18 months, the incidence of fibrosis was 7.8%." These figures are for therapeutic ICI; the single-injection diagnostic literature reports lower rates, but is dominated by ED, not Peyronie's, populations and does not segregate the active-phase Peyronie patient as a separate safety class. The Contraindications section, on the same label, is the part that deserves attention here: "CAVERJECT should not be used in patients who have ... cavernosal fibrosis, or Peyronie's disease." Pfizer's own labelling, in other words, contraindicates alprostadil in the very patient group EAU recommends to inject for diagnostic curvature assessment.

And here is the part that makes the contradiction internal, not cross-document. EAU SRH 2025 itself, in the treatment-of-ED section discussing intracavernous-injection therapy with alprostadil, writes the following sentences (verbatim, Section 5.6.7.1, page 51): "Cavernosal fibrosis usually clears within a few months after temporary discontinuation of the injection programme. However, tunical fibrosis suggests early onset of Peyronie's disease and may indicate the need to discontinue intracavernous injections indefinitely." Translation: the same guideline that recommends injecting Peyronie's patients with vasoactive drugs to document their curvature also explicitly states that injection-induced tunical fibrosis means Peyronie's disease has been triggered and ICI must be stopped indefinitely. The recommendation and the safety statement are in the same PDF, 27 pages apart.

Practice patterns suggest the field is, slowly, voting with its feet. Leong, Gaines, Prebay, Ebbott & Chung, Can J Urol 2025 (PMID 41496536) document "low utilization of intracavernosal injection and penile Doppler ultrasound in the evaluation of erectile dysfunction and Peyronie's disease" across contemporary practice. The reasons given track exactly what this section argues: complication concerns, patient acceptance, and the availability of less invasive alternatives.

One last note on the same EAU document, because the asymmetry deserves naming. Section 8.2.3.1 (conservative treatment of PD) opens with the sentence: "The results of the studies on conservative treatment for PD are often contradictory, making it difficult to provide recommendations in everyday, real-life settings." The Guidelines then explicitly decline to recommend pentoxifylline, vitamin E, tamoxifen, procarbazine, potassium para-aminobenzoate, omega-3 fatty acids, or vitamin E + L-carnitine "because of their lack of proven efficacy." A few paragraphs later, under Multimodal treatment, EAU writes: "A long-term study assessing the role of multimodal medical therapy (injectable verapamil associated with antioxidants and local diclofenac) demonstrated that treatment was efficacious to treat PD patients. It concluded that combination therapy reduced pain more effectively than verapamil alone, making this specific combination treatment more effective compared to monotherapy." That cited study is reference [999], Paulis G et al., Inflamm Allergy Drug Targets 2013;12:403: 82 patients, randomised between treated (n=41) and untreated controls (n=41); at 18 months, plaque volume −73.6% in the treatment arm versus +118.7% in controls, curvature improvement in 81.5% versus 8.1%, p < 0.0001. EAU acknowledges the result, then concludes the section with "there does not seem to be a consensus on which drugs to combine or the optimum drug dosage."

First consultation, psychology before pharmacology

How the first conversation goes determines whether the patient enters treatment or enters avoidance. The hardest fact for a clinician to internalise is that this is a sensitive psychological moment that often eclipses the biological one. Three things matter on the first visit:

  • Frame the disease as treatable in the active phase. Most patients arrive having read that surgery is inevitable. Tell them that published case series document complete plaque regression on conservative therapy (Paulis G, De Giorgio G, Paulis L, J Med Case Rep 2022), and that the active inflammatory phase is the window in which that is possible.
  • Tell the patient to keep his sex life. Prescribe daily low-dose tadalafil 5 mg if not contraindicated. Tell him to have normal intercourse, normal masturbation (gentle, not on the plaque, no aggressive squeezing), and normal life. Suppressed nocturnal oxygenation makes the disease worse; reasonable erectile activity helps.
  • Address persistent upstream drivers, but only in a redox-safe way. If anything systemic is keeping the oxidative / inflammatory floor elevated, burnout, post-viral / long-COVID syndromes, chronic stress states, sleep deprivation, persistent metabolic inflammation, that floor will keep refilling the ROS / TGF-β1 reservoir while the protocol is trying to drain it. Treat those drivers, but with interventions that do not collide with the pathways the Peyflog stack is already acting on: avoid duplicate flavonoid loading, avoid additional COX inhibition stacking on top of daily diclofenac, avoid dose-overlapping silymarin or boswellic-acid products. Specific endocrine findings such as hyperprolactinaemia or chronically elevated cortisol may warrant their own targeted intervention, but only in moderate form and only when the individual patient profile clearly demands it. In this patient, prolactin was measured at 29 ng/mL during disease onset (the male upper-limit-of-normal is around 15 ng/mL, so a clear mild hyperprolactinaemia), not re-measured after, but the functional readout was unambiguous: nocturnal erections returned as soon as the chronic psychological stress trigger driving the prolactin elevation was removed. That is the cleanest possible evidence that the hyperprolactinaemia here was stress-driven, not idiopathic, and that removing the upstream driver was sufficient. Fibrinogen during therapy measured ~300 mg/dL, which puts the disease-onset baseline most likely around ~400 mg/dL (the upper end of the normal reference range, where it starts behaving as a meaningful acute-phase reactant). Treatable drivers, not red herrings.

Initiate the multimodal antioxidant protocol immediately

If a patient presents with a likely diagnosis and no contraindications, initiate Paulis' multimodal antioxidant protocol on the same visit. Waiting for biopsy confirmation, or for "natural stabilisation," is waiting through the phase of the disease in which the plaque is most reliably reversible, and Paulis has documented regression even in chronic / partly-calcified plaques, so the loss is not zero even if the patient arrives later. Don't gatekeep the protocol on phase certainty. The protocol composition is documented in his open-access 2017 review and 2022 case series, and currently consists of the components listed in the Compounds section above, namely Peyflog, Alpavita EC, Alpavir Uno, Sclero-Hyal, diclofenac 4% spray and daily low-dose tadalafil 5 mg, in the exact dosing schedule documented there.

If a single component is contraindicated (e.g. crustacean glucosamine in shellfish allergy; salicylate-class flavonoids in aspirin intolerance; topical NSAID in renal-graft / specific anti-coagulant settings; tadalafil under nitrate therapy), do not abandon the whole stack. Substitute a redox-equivalent compound that covers the same node, direct ascorbate / tocopherol top-up for missing flavonoid contribution, oral SOD / glutathione precursors for missing peroxide-clearance, and document the substitution. The point is the network, not any one ingredient.

Pricing and reimbursement. The compounds are sold as nutraceuticals, not prescription drugs, in most jurisdictions. Patients who cannot afford the manufacturer products can buy each active individually (boswellia 65% boswellic acids, silymarin 80%, bilberry 25% anthocyanins, propolis 10% galangin, CoQ10, L-acetyl carnitine, vitamin C, vitamin E, SOD) and reconstruct the stack at lower cost. In Germany / EU, a clinician letter to the patient's Krankenkasse or insurer arguing medical necessity, citing the Paulis case series and the EAU recognition of antioxidants in the conservative armamentarium, is a legitimate and often successful route to partial reimbursement.

Even if the diagnosis is wrong. If the early presentation is actually erectile dysfunction with no plaque developing, this stack is not wasted. The same redox / NO / cGMP support that drives Peyronie's regression also reduces the long-term risk of fibrotic conversion in cavernous tissue under chronic ED. There is no clinical downside to starting it early in a patient with sexual-rigidity loss of unclear cause.

Patient guidance during the active phase

Standing instructions to give the patient on the first visit:

  • Avoid mechanical re-injury. No rough sexual positions that force buckling. No bending the curved penis flat in tight underwear or jeans. Prone (face-down) sleeping in tight underwear can mechanically stress the plaque overnight; in some men switching to looser underwear or to sleeping without can reduce nocturnal stress on the curved tissue.
  • Masturbation is allowed, gentle, no direct manipulation of the plaque area, no aggressive squeezing, no bend-amplifying grip. Total avoidance is not necessary and is psychologically counterproductive.
  • Do not recommend traction, vacuum-erection devices, or repeated manual extension as standalone interventions in the active phase (this is a personal opinion based on the mechanistic rationale, these modalities apply controlled tension to a tissue whose problem is uncontrolled stress-fibre contraction). The published consensus on traction is mixed; my view is that the cellular / molecular route resolves the underlying biology and lets the geometry follow, without piling additional mechanical signalling on a tunica that is already mechanotransduction-compromised.

The same protocol applies post-surgery

If a patient has already had, or is going to have, surgical correction (plication, grafting, prosthesis), the multimodal antioxidant protocol is not redundant. Surgery removes geometry, not pathobiology. The same ROS / NF-κB / TGF-β1 pressure that built the original plaque is still in the tissue and is now also acting on a surgical wound that is, by definition, healing through fibroblast proliferation and matrix deposition. Post-operative scarring and recurrence at the surgical margin are the predictable consequences. A patient placed on the antioxidant protocol post-surgery has reduced fibrotic drive on the wound bed, reduced odds of plaque re-formation at residual disease sites, and reduced odds of contracture in graft tissue. If I were operated on, I would still take the protocol.

Lab work in early-onset cases without a clearly visualisable plaque

The most useful place for laboratory work in Peyronie's is not the confirmatory work-up of an obvious plaque. It is the patient who presents early, loss of nocturnal rigidity, vague induration, occasional pain on erection, no clear lesion on B-mode US, equivocal or absent finding on elastography, and who could be in the active inflammatory phase before any macroscopic plaque has organised. In that context, a small panel of cheap, common markers can shift the picture from "watch and wait" to "start the protocol now, preventatively." The combination becomes suggestive when several of the following move together:

  • Prolactin above the male upper-limit-of-normal (~15 ng/mL). Chronic mild hyperprolactinaemia is increasingly recognised as a fibrotic / vascular co-factor; in this patient prolactin sat at 29 ng/mL at disease onset and tracked closely with chronic psychological stress, with nocturnal erectile activity restoring once the upstream stress driver was removed.
  • 25-OH-vitamin D insufficiency. Vitamin D regulates fibroblast collagen handling and dampens TGF-β1 signalling; deficiency is permissive for fibrotic disorders generally.
  • Mild lymphocyte activation. Not infectious-disease territory, just persistent low-grade activation consistent with a chronic inflammatory background, the NF-κB loop is fed by this even before any plaque is visible.
  • Elevated fibrinogen and/or hs-CRP. Cheap acute-phase reactants that track systemic inflammatory drive and pair with the NF-κB / IL-6 axis driving the lesion. In this patient, fibrinogen measured ~300 mg/dL during therapy, with the disease-onset value most likely closer to ~400 mg/dL, the upper end of the normal range where it starts behaving as a real signal rather than noise.

When a man presents with sub-clinical signs and a coherent set of these markers comes back abnormal, my view is that initiating the multimodal antioxidant protocol becomes a preventative imperative, not a nice-to-have. The window in which conservative therapy can disrupt the cascade before a macroscopic plaque even forms is the most valuable window of all. It costs roughly fifty euros of routine laboratory work to identify it.

A structural argument: the urologist should own the first 80%

Everything above adds up to a conclusion the andrology world has not yet absorbed. Roughly four out of five Peyronie's patients arrive at a urologist first, in the early or active inflammatory phase, with the disease still mechanistically reversible. The current pathway sends almost all of them out the door with a referral, a wait list of weeks to months, and an implicit instruction to do nothing in the meantime. By the time they reach the andrologist who could have started Paulis' protocol, the most treatable phase of the disease has elapsed for no medical reason. The bottleneck is administrative, not biological.

The corrective is a re-allocation of responsibilities:

  • Urologists should own the front 80%. First consultation, B-mode + colour-Doppler + real-time elastosonography performed by the urologist (not deferred to an andrologist months out), baseline endocrine / inflammatory labs on the same visit, and immediate initiation of the multimodal antioxidant protocol when indicated. That is the clinical encounter the literature actually supports. The equipment is not exotic, the protocol is well documented, the substances are nutraceuticals available without specialist prescription, and the decision threshold ("likely Peyronie's, no contraindications") is straightforward. The single capability gap that needs closing is elastosonography fluency, and that is a focused training investment, not a structural barrier.
  • Andrologists should own research and the residual surgical-only cases. Patients who present in established chronic phase with calcified plaque and stable curvature unresponsive to conservative therapy, or whose anatomy genuinely requires plication, grafting or prosthesis, belong in andrology. So does the basic and translational research that refines the protocol, including the elastography methodology, the OSI biomarker work, and the cross-talk with endocrinology that distinguishes Paulis' clinic. That research role is where andrology's depth genuinely adds value.

This is not a softening of the andrologist's importance; it is a rebalancing so that the andrologist's time is spent where it is actually decisive, not consumed by the queue of early-phase patients whose cellular biology a competent urologist could intercept on day one. The practical implication for any urologist reading this: investing in elastosonography training and a clear in-clinic Peyronie's protocol is the single highest-leverage thing your department can do for this patient population. It is also probably the single highest-leverage thing the field as a whole can do to lower the lifetime burden of this disease, because the disease is mechanistically a fibrotic disorder that responds to early redox / anti-inflammatory pressure, and the discipline best positioned by patient flow to deliver that pressure on time is yours, not the specialist they would otherwise wait three months to see.

06 · Peer notes

If you've just been diagnosed, read this

What follows is peer advice from someone who lived it. It is not medical advice. If anything below contradicts your doctor, follow your doctor. The whole point of this page is that you have to do the reading yourself and decide with a qualified clinician.

Don't let it get into your head

The mental damage you can do to yourself is bigger than the disease. I went through it. Anxiety, obsession, scanning yourself a hundred times a day for changes, that loop will hurt you more than the plaque ever will. Step out of it. Live a normal life. Treat the protocol as the work; treat your day as your life. Don't measure the curvature every morning. Don't catastrophise. The disease rewards calm patience much better than it rewards panic.

And the questions are going to come. Will I ever find a partner now? Will I ever have a family? Will my current partner stay? Will I have sex again, or was that it? Will I be the same person in bed afterwards? Do I have to be operated, and what will be left of me if I am? They come at three in the morning. They come in the shower. They come every time you see a couple in the street. Recognise what they actually are: the spiral the diagnosis produces, not the answers it has. The honest answers, on the data this page is built on, are: yes — yes — probably yes — almost certainly yes — very likely yes — and most likely no. Most men on conservative therapy in the active phase do not end up at surgery. Most partners do not leave. Most sex lives recover. Some recover entirely. The catastrophic version of this story is overwhelmingly not the version that plays out, and treating the catastrophic version as the working assumption is itself one of the biggest accelerators of harm. Notice the spiral, name it, and put the question down. The work you can actually do today is take the protocol, sleep, eat, move, talk to someone you trust. Tomorrow's answers will arrive on their own schedule and will mostly be kinder than the version your three-in-the-morning brain is offering you.

You can, and should, keep having sex

If the curve isn't severe enough to make penetration impossible, and pain isn't blocking it, keep your sex life normal. Date normally. Communicate with partners. Have intercourse if you both want to. The disease can heal while you live. It does not require monastic abstinence. Withdrawal from intimacy is one of the biggest hidden costs of this diagnosis, and most of it is self-inflicted.

If penetration isn't possible right now, read this

The previous note assumes the curve still allows penetrative sex. If it doesn't, pain blocks it, the angle blocks it, rigidity blocks it, the following anatomy takes most of the weight off you. Internalise it properly and the temporary loss of penetration stops feeling like a loss of your sex life.

Most women do not orgasm from vaginal penetration alone. The clitoris is far larger than the visible glans, it has internal "legs" called the crura that wrap around the vaginal canal, plus the vestibular bulbs. When a woman feels a "vaginal" or "G-spot" orgasm, the underlying physiology is almost always the internal clitoral structure being stimulated through the vaginal wall. The visible glans clitoris remains by far the most reliable, most innervated trigger. Population studies consistently put the proportion of women who reliably orgasm from intercourse alone at roughly 18–25%.

Penetrative sex, in other words, is mostly fun you want to have. For her it is frequently optional, pleasant if it is good, but not the physiological route to her orgasm. The cultural script that says "real sex equals penetration, everything else is foreplay" is wrong about the biology. Direct clitoral stimulation, fingers, mouth, toy, hand, works for the great majority of women, with or without your penis being part of the picture. While your tunica is healing, lean into that. Communicate, ask what she actually likes, focus on her, and the curvature stops being a sex-life problem and goes back to being only a healing problem.

Your side of the equation is just as flexible. You do not need to be the one penetrating to have an orgasm. Glans stimulation by her hand, oral sex / blowjobs, mutual masturbation, frottage, toys used on you, every one of these is a perfectly normal route to orgasm and ejaculation, and most of them put zero buckling stress on the tunica while it heals. Penetration is one option among several for both partners , not a prerequisite for either of you to come, to have sex, or to feel intimate and satisfied together. The same is true for gay couples, people in transition, and other cases: when receptive or insertive intercourse is temporarily off the table, oral, manual and toy-based routes get you both to the same destination without the mechanical risk to a healing plaque.

And, peer to peer, don't be hard on yourself. Be hard for your partner.

On coffee, timing, and consistency

Coffee is fine. One or two cups a day does not conflict with the protocol; you do not need to give it up. What matters far more than coffee is taking the oral compounds twice daily on an empty stomach, every day, without skipping. Peyflog in particular is prescribed two tablets twice daily on an empty stomach (four tablets total per day), and the rest of the oral stack follows the same morning / evening rhythm. The antioxidant exposure has to be continuous for the cascade on this page to stay suppressed; intermittent dosing is the single most common reason a protocol stalls. Set two fixed times, first thing on waking and last thing before bed are the easiest, leave a 30-minute to 1-hour gap before food, and treat it like brushing your teeth.

On pain, and the NSAID + Tadalafil caution

Topical diclofenac on the plaque is the first move for local pain. If you are tempted to take an oral NSAID on top of it, talk to your doctor first. Daily Tadalafil 5 mg already has a baseline cardiovascular load (it lowers blood pressure); oral NSAIDs add their own (BP, fluid retention, thrombotic risk). Combining the two without supervision is a needless double burden. This is exactly the kind of decision that needs a clinician in the loop. None of this page is a substitute for that conversation.

Healing chances are better when…

…you are younger, leaner, non-diabetic, and don't carry other diseases, metabolic, vascular, autoimmune, that maintain a pro-fibrotic / pro-oxidative baseline. Those comorbidities act as constant upstream triggers: they keep refilling the ROS / TGF-β1 reservoir while you are trying to drain it. Treat them in parallel. Get the basics measured, prolactin, 25-hydroxy vitamin D, fasting glucose / HbA1c, lipid panel, free testosterone. Address what comes back abnormal. The protocol is much more powerful when the baseline isn't actively working against it.

Lifestyle adjustments I would recommend

None of this is groundbreaking, none of it is contested in the literature, and most of it costs nothing. It moves the needle anyway, because every item below either lowers the oxidative / inflammatory floor or removes a constant trickle into the cascade described on this page.

  • Move, but moderately. Steady-state cardio: running, jogging, brisk walking, swimming, cycling at conversational pace. Three to five sessions a week is plenty. Avoid extreme exertion during the active phase, competitive sports, heavy contact sport, maximal-load lifting. Extreme exertion spikes systemic ROS and adds mechanical strain; you do not want either right now. Moderate movement improves endothelial function, lowers fasting glucose, lowers background inflammation, and improves nocturnal erections.
  • Drink water. Properly hydrated tissue handles oxidative load better and supports the renal clearance of metabolites the antioxidant stack is mobilising. Aim for the colour of pale straw in your urine; that is roughly the right amount for you.
  • Cut alcohol back. Alcohol is metabolised through aldehyde intermediates that consume the same antioxidant pool you are trying to refill, and it suppresses nocturnal erections for the following 24–48 hours. Occasional and modest is fine; daily or heavy is not.
  • Stop smoking. Tobacco is a continuous oxidative and vasoconstrictive insult to exactly the cavernous tissue you need functioning. If you smoke, this is the single highest-leverage lifestyle change you can make alongside the protocol.
  • Remove or reframe your psychological stressors. Chronic stress keeps cortisol, sympathetic tone and inflammatory cytokines elevated, all of which feed the same loop. Identify what is actually stressing you. Remove what can be removed. Reframe what cannot, therapy, journalling, an honest conversation with the partner / family member / boss involved. Do the work. It is medically relevant in this disease, not optional.
  • Therapy if you need it. A diagnosis like this dropped on you is genuinely a lot to carry. A few months of cognitive behavioural or psychodynamic therapy is among the most cost-effective interventions you can buy yourself during treatment. Even informal alternatives count: long walks alone with your thoughts, regular reflection, a journal, a trusted friend who will actually listen. Anything that lets the mental load discharge rather than accumulate.
  • Listen to your body. If something, a food, a position, a routine, consistently feels good and coherent, do what feels right for your body, as long as it doesn't conflict with the therapeutic protocol. If something feels off, take it seriously and investigate before dismissing it. The signal-to-noise ratio of your own interoception during this period is unusually high; pay attention to it.

Postscript, if the protocol is working you may feel mildly unwell on some days during the first weeks or months: low energy, dull headaches, vague fatigue, the impression of a low-grade flu without any actual infection and with bloods that come back clean. That is commonly reported on starting a dense antioxidant / anti-inflammatory stack, interpret it as the system rebalancing under genuine intervention, not as the protocol "not agreeing with you." It passes.

Get yourself tested. Properly., and use condoms

This one I am going to be blunt about, because most men reading this will not have done it and the cost of skipping it can be the disease itself. Get tested for bacterial STIs, urethral swab, first-void urine PCR, seminal-fluid culture, and a glans / coronal-sulcus swab if anything looks irritated. Not just the standard quick STI panel: the sub-clinical chronic infections, Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum / parvum, atypical Neisseria, occasional anaerobes from the partner's flora, frequently smoulder for years in men with no urethral discharge, no burning, no obvious symptoms. They are routinely tested for in women during gynaecological care; they are routinely missed in men because no one ever swabs us. A chronically infected urethra or seminal-fluid compartment is exactly the kind of low-grade systemic inflammatory stimulus that keeps the NF-κB / TGF-β1 floor elevated and prevents conservative therapy from getting traction. Test, treat with the right antibiotic if positive, and re-test to confirm clearance. Do this once at the start of the protocol and again if anything stalls.

And, basic knowledge most adult men still ignore, use condoms. With every new partner, until both of you have a clean recent panel and have had a real conversation about it. The guys who skip this are the same guys who end up with the chronic urethritis they don't know they have. None of this is moralising; it is simply mechanism. Bacterial inflammation drives oxidative stress, oxidative stress drives the cascade on this page, and the cascade gives you a curve. Take it seriously from here on, buddy.

On erections during the active phase

Tadalafil 5 mg once daily is a long-term-safe regimen in patients without contraindications, nitrate use, severe hypotension, recent cardiovascular events, severe hepatic / renal impairment. Read the contraindications honestly, take the prescription if you fit. A reasonable erectile life during the active phase actively helps the protocol: nocturnal erections oxygenate cavernous tissue and oppose the fibrotic signal. Avoidance and disuse make things worse, not better.

If you can travel to Rome, go

Paulis is, in my opinion, the first-line treatment for Peyronie's disease worldwide, and that is not casual praise. He is the inventor of the multimodal antioxidant approach to PD: he published the rationale in the early 2010s, refined the protocol across a decade of clinical case series, and has been the perfector of it ever since, iterating dosing, sequencing and individual adjustments through hundreds of treated patients. He is the only andrologist I am aware of who has published case series of complete plaque regression on conservative therapy (J Med Case Rep 2022; Am J Case Rep 2022). Search PubMed yourself, that's not a soft claim, it is checkable. Until other groups replicate his outcomes in print, the rest of the andrology world's surgical-first orthodoxy should be treated with healthy skepticism for anyone still in the active phase.

The reason to actually go, not just buy the compounds online, is that your individual case can only be reliably treated by him, not by his stack alone. Two patients with the same nominal diagnosis differ in plaque morphology, phase, hormonal milieu, comorbidity profile, response trajectory and the upstream drivers keeping the cascade fed. Paulis adjusts the protocol, dose, timing, sequence, additions, substitutions, to that individual signature. That is what makes the difference between a generic regimen and the targeted multimodal therapy his published outcomes are based on. For most patients the stack works as documented and is effectively plug-and-play, but for a meaningful minority, the cases with awkward comorbidities, atypical phase presentation, or upstream drivers that keep refilling the cascade, it is not, and individualisation is exactly what separates a good outcome from a stalled one.

Diagnosis is the other half of it. The protocol is only as good as the imaging it is built on, and proper imaging is itself a specialty, B-mode ultrasound + colour Doppler + real-time elastography of the flaccid penis, performed by an experienced operator with a sufficiently advanced machine, exactly as Paulis' 2022 case series explicitly demands. The ultrasound at his clinic is performed by Giovanni De Giorgio, an expert ultrasound and elastography operator and Paulis' co-author on the 2012, 2022 and 2025 papers; Paulis then does consultation and treatment. Two doctors, both sub-specialised, both publishing in this exact field. That is what a proper diagnosis of Peyronie's looks like, not a single Doppler scan in a urology clinic that sees the disease three times a year.

The visit itself is structured the way every serious specialist clinic works: ultrasound by one doctor, consultation and treatment by another, with first appointments longer than follow-ups. Fees are not posted publicly and you should ask the clinic directly. Done smartly from most EU countries, however, the entire trip, flight, one night in a modest hotel, train or metro to the clinic and the consultation itself, can come in under €500 total. That is in another universe of price-point from a single Xiaflex cycle, an ESWT course, or penile surgery, let alone the lifetime cost of a prosthesis.

And, quite apart from the medicine, Rome is an extraordinary place to be when you are trying to put yourself back together. Walk a city whose stones have been laid down across two and a half thousand years. Sit in piazzas that were built before your country existed, eat properly, the Italian Mediterranean diet is, incidentally, exactly the anti-inflammatory eating pattern this protocol thrives on, drink an espresso looking at the Pantheon, take a slow evening along the Tiber, climb up to the Aventine for sunset. Every day in Rome, even between appointments, lowers your cortisol in a way that no amount of sitting at home and worrying about your curvature ever will. Take the trip as a life experience, not just a medical errand. You will come home with the beginning of healing in your tunica and a real memory of one of the most beautiful cities on earth, that is a much better souvenir than the average diagnosis lets you bring home.

And the obvious joke, because it is too good not to write it down: every andrologist on earth will tell you that all roads lead to surgery. They do not. One of them leads to Rome.

If you cannot get the actual manufacturer products

Peyflog, Alpavita EC, Alpavir Uno and Sclero-Hyal can be ordered online from anywhere; that part is not a travel question. The real constraint is if those specific manufacturer products are genuinely unavailable to you, customs blocks, regulatory limits in your country, the manufacturer pausing distribution, whatever the reason. In that case the protocol can still work, but only if you reproduce it precisely from individual components. Same actives. Same titrations and formulations as the manufacturer products listed above. Same dosing schedule. All of them present together. Remove one, say, skip the topical because you don't like creams, or drop CoQ10 because it's the most expensive line, and you are dismantling a network effect. Each compound covers a node the others don't. As the cellular section of this page shows, the rationale is genuinely synergistic: ROS is damped here, NF-κB suppressed there, TGF-β1 modulated laterally, NO/cGMP sustained from the other side. Take everything, or expect proportionally diminished results.

A word on Paulis, and on Pisa

Most of the andrology world treats Peyronie's as a disease that can only be debrided, sliced, or implant-replaced. Paulis treats it as what it actually is, a chronic inflammatory and fibrotic disorder that obeys the same rules as any other fibrosis, and that responds, like any other fibrosis caught early, to sustained redox + anti-inflammatory pressure plus time. That insight is, in my private opinion, a piece of frontier medicine. He invented the multimodal antioxidant framework for Peyronie's, has spent more than a decade perfecting it across published case series, and remains one of very few clinicians anywhere translating it into a daily protocol that ordinary patients can actually run.

His credentials are worth understanding. Medicine and Surgery, La Sapienza Rome. Specialty in Urology (Rome, 1985). Specialty in Endocrinology, field of Andrology, at the University of Pisa (2002), plus a separate University Masterclass in Andrological Ultrasonography also at Pisa. The University of Pisa is one of Italy's oldest universities (founded 1343) and operates the country's flagship Endocrinology-Andrology specialty programme, the most rigorous integrated training in reproductive endocrinology, sexual medicine and dedicated andrological imaging available in Italy. That is why a Paulis consult is structurally different from any standard urology visit: hormonal axis, tunica biochemistry and high-resolution ultrasound of the plaque are thought about by the same person, in the same room, on the same day. Few clinicians in the world combine all three.

Read his PubMed publication record. Form your own view.

Last thing

If you have just been diagnosed and you are scared: take a breath. The literature is on your side, the protocol is on your side, your own biology is on your side if you treat it well. Be good to yourself. Work toward happiness independently of how the curvature looks tomorrow. That is the only thing actually in your hands, trying everything you can, and being happy regardless of the outcome. Most of the men reading this will get their lives back. Some will not. Either way: live well.