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Topical Compounded Agents

Topical preparations of amitriptyline, baclofen, gabapentin, ketamine and lidocaine, alone or in compounded combinations, have been described for vulvodynia or genital, perineal and rectal pain in clinical guidance and small studies.[8][15][21] In a randomized trial of 399 patients with localized chronic pain, three multi-agent creams did not outperform placebo on average pain at one month.[1][2] Compounded combinations are not FDA-approved; individual commercially manufactured lidocaine products have their own labeling.[3] Genital permeability is a hypothesis for local delivery, but also a potential route for systemic toxicity.[3][4]

For the related comparator classes, see Gabapentinoids, Tricyclic antidepressants, SNRIs, NSAIDs and analgesics, and Local anesthetics.

Why topical in the urogenital tract​

The rationale for multi-agent topical therapy is multimodal peripheral analgesia, blocking several nociceptor mechanisms simultaneously while aiming to limit systemic exposure; absorption depends on ingredients, vehicle, site, barrier integrity and amount applied:[4][5]

TargetAgentPeripheral effect
Voltage-gated Na⁺ channelsLidocaine, amitriptyline (local-anesthetic-like)Blocks action-potential generation at the nociceptor terminal
NMDA receptors on primary afferentsKetamineReduces peripheral sensitization and wind-up
α2δ subunit of voltage-gated Ca²⁺ channelsGabapentinReduces excitatory neurotransmitter release
Peripheral GABA-B receptorsBaclofenModulates nociceptor–immune-cell cross talk
Histamine receptorsAmitriptylineProposed peripheral receptor blockade[5]

Local delivery does not exclude systemic absorption, particularly on mucosa or damaged skin.[30][31][4]

The critical negative trial — Brutcher 2019​

Any discussion of compounded pain creams must be framed against the largest and most rigorous RCT performed to date.[1]

  • Design: three parallel placebo-controlled RCTs at a military treatment facility; n = 399 patients with localized chronic pain classified as neuropathic, nociceptive, or mixed
  • Formulations tested:
    • Neuropathic cream: ketamine plus gabapentin plus clonidine plus lidocaine
    • Nociceptive cream: ketoprofen plus baclofen plus cyclobenzaprine plus lidocaine
    • Mixed cream: ketamine plus gabapentin plus diclofenac plus baclofen plus cyclobenzaprine plus lidocaine
  • Result: no difference versus placebo at 1 month for neuropathic pain (−0.1), nociceptive pain (−0.3), or mixed pain (−0.3)
  • Interpretation: the tested mixtures did not outperform vehicle, and the authors concluded that their higher cost relative to approved products should curtail routine use

A Lancet review questioned the evidence for multi-agent creams.[2]

FDA’s NASEM assessment found limited efficacy evidence and inadequate safety data. An FDA-authored safety review identified 24 systemic adverse-event cases (including 13 from the literature), with agitation, coma, seizures and hypotension; ten involved face or genital application, ten had absorption confirmed by serum, CSF or urine levels, and two adults died. Most were multi-ingredient products (mean about five ingredients).[30][31]

Individual agents — evidence for urogenital use​

Topical lidocaine — indication and comparator matter​

Lidocaine blocks voltage-gated sodium channels on peripheral nociceptors. It has randomized evidence for specific urogenital settings, with both positive and negative findings.[5][6]

  • Zolnoun 2003 (uncontrolled prospective series, n = 61; the authors called for a randomized trial): overnight 5% lidocaine ointment applied to the vestibule for a mean of 7 weeks: 76% of women reported ability to have intercourse (versus 36% before treatment; p = 0.002); intercourse-related pain fell by 39 points on a 100-mm VAS[6]
  • Goetsch 2015 (double-blind RCT, n = 46), summarized in the ACOG breast-cancer-survivor consensus 2021. Among estrogen-deficient breast cancer survivors whose vestibular tenderness abated during lidocaine screening and who attempted intercourse in the blinded month (73% of lidocaine users and 71% of saline users), a 3-minute vestibular application of 4% aqueous lidocaine plus silicone lubricant reduced median intercourse pain by 87.5% to 1.0/10 versus 38% to 5.3/10 with saline plus lubricant (between-group p = 0.01).[7][35]
  • Foster 2010 (133 women): topical 5% lidocaine, oral desipramine and their combination did not significantly outperform placebo for the primary tampon-pain endpoint.[32]
  • Morin 2021 (212 women): multimodal physical therapy was superior to overnight 5% lidocaine for provoked vestibulodynia; intercourse pain differed by 1.8/10 after treatment (95% CI 1.2–2.3), with benefit sustained at six months. Much/very-much improvement was 79% versus 39%.[33]
  • Vestibulodynia UPDATe (NCT03844412): completed, with 209 enrolled; results posted March 19, 2026. The factorial trial compared topical lidocaine/estradiol, oral nortriptyline, both and double placebo. Posted mixed-model comparisons across the four arms did not show significant differences for tampon-test pain (p=0.3630) or SF-MPQ pain change (p=0.9859).[9][34] These are registry results, with paired pain data in 170 participants.[9][34]
  • Intravesical alkalinized lidocaine. An AUA option (Statement 17, Grade B) for IC/BPS, short-term relief only; a small lidocaine–heparin combination trial reported relief through 12 hours.[10][11] Covered separately in Local anesthetics and IC/PBS

Studied formulations include 5% ointment for vestibulodynia and 4% aqueous solution for estrogen-deficient introital pain; ACOG notes that ointments are usually better tolerated than creams.[6][15][35]

Topical gabapentin​

Gabapentin binds the α2δ subunit of voltage-gated calcium channels on peripheral sensory terminals.[5]

  • Boardman 2008 (retrospective, n = 51). Topical gabapentin 2–6% to the vulva for ≥8 weeks: among 35 evaluable women, mean pain score from 7.26 to 2.49 (Δ −4.77; p < 0.001); 51 women were treated; 28/35 evaluable women (80%) achieved ≥50% pain improvement, and discontinuation was reported for 7/50 (14%)[12]
  • Ergisi 2023 narrative synthesis. 4 studies of topical gabapentin for vulvodynia all reported improvement, but all were uncontrolled; the review explicitly called for double-blind RCTs[13]
  • American Academy of Pain Medicine 2025. "limited evidence from single observational studies or case reports suggests that gabapentin 6% might be effective for vulvodynia, burning pain, and itching"[3]

Do not conflate topical with oral. Brown 2018 (double-blind crossover RCT, n = 89) showed oral extended-release gabapentin (1,200–3,000 mg/day) was not superior to placebo on tampon-test pain (adjusted mean 4.0 versus 4.3; p = 0.07).[14]

Studied compounding: gabapentin 2–6% cream.[12]

Topical amitriptyline​

Amitriptyline blocked peripheral sodium channels in preclinical studies; histamine- and serotonin-receptor antagonism are additional proposed topical mechanisms.[5] Systemic exposure cannot be assumed negligible, especially with mucosal application, high concentrations or penetration-enhancing vehicles.[30][31][5][15]

  • ACOG Committee Opinion 673 on persistent vulvar pain (2016) lists topical TCAs compounded into cream among commonly prescribed medications for vulvodynia[15]
  • Ruoss 2021 (single-clinic audit; 376 of 1,054 patients contacted replied, so responder bias is likely). Amitriptyline 0.5% plus oestriol 0.03% in an organogel applied to the vestibule: rated effective by 51–67% across age groups; stinging at application was the main adverse effect[16]
  • Vulvodynia State-of-the-Science review 2023. Amitriptyline cream and amitriptyline-with-baclofen cream showed pre-to-post pain reduction in non-RCT studies; randomized evidence is insufficient[8]

Reported vulvar formulations include amitriptyline 2% cream and amitriptyline 0.5% with oestriol 0.03% in organogel.[8][16] In a prospective uncontrolled series of 150 women with entry dyspareunia treated with 2% amitriptyline cream, 16 (10.7%) stopped early because of local skin irritation.[43]

Topical baclofen​

Baclofen is a GABA-B agonist with a proposed local analgesic action in vulvodynia.[4] The mechanistic argument is explicitly one of modulating nociceptor–immune-cell–epithelial cell cross talk.[4]

  • Keppel Hesselink 2014. Case report of a 33-year-old woman with intractable vulvar and anal pain unresponsive to standard therapy; topical baclofen 5% plus oral palmitoylethanolamide 400 mg three times daily was associated with >50% symptom reduction at 3 months and return of pain-free intercourse[17]
  • AAFP dyspareunia review 2021. "compounded muscle relaxants" listed among vulvodynia options (Level C)[18]

Reported formulations include baclofen 2% with amitriptyline 2% cream and baclofen 5% cream with oral palmitoylethanolamide in a case report.[8][17]

Topical ketamine​

NMDA-receptor antagonist with additional peripheral sodium-channel and opioid-receptor activity at the high local concentrations achievable topically.[19][20]

  • Poterucha 2012 (Mayo Clinic, retrospective, n = 13). Topical amitriptyline-ketamine cream for genital, rectal, or perineal pain: 29 of 1,068 patients received the cream for genital, rectal, or perineal pain, but efficacy was documented for only 13: 1 complete, 6 substantial, 4 some, and 2 no relief (11/13 with any relief; 7/13 with substantial or complete relief); only 1 patient reported occasional irritation. Recorded causes included radiotherapy-induced perineal mucositis, vulvar carcinoma, pruritus ani, pelvic-floor tension myalgia, external hemorrhoids, ulcerative colitis, lichen planus, lichen simplex chronicus, and idiopathic pain.[21]
  • Cochrane 2025. Topical ketamine alone showed no clear evidence of benefit over placebo for chronic non-cancer pain (very low- to low-certainty evidence from 1–2 small trials)[22]
  • AAPM 2025. "small studies of topical ketamine alone did not find statistically significant benefit … smaller non-placebo-controlled trials of ketamine combined with amitriptyline and lidocaine found benefit for peripheral neuropathic pain"[3]
  • Sawynok 2014. Retrospective analyses of topical ketamine combinations show 40–75% response rates; controlled trials show benefit in only some outcomes; optimal dosing unclear[19]

Typical compounding: 2–10% in a cream or gel base; the AAPM panel advises keeping topical ketamine (and amitriptyline) below 10% and monitoring for systemic uptake.[3]

Reported formulations — not standard prescriptions​

Concentrations below are ranges reported in the literature and in compounding practice. Only some are stated in the cited study itself (gabapentin 2–6%, lidocaine 5%, amitriptyline 0.5% with estriol 0.03%, baclofen 5%, lidocaine 5% with estradiol 0.02%); the rest are typical compounding ranges.

FormulationReported concentrationsStudied use (often off-label)Evidence limitsReference
Lidocaine (single-agent)5% cream or ointment; 4% aqueous solution in the survivor trialProvoked vestibulodynia and estrogen-deficient introital pain studied separatelyZolnoun's ointment series was uncontrolled; 5% cream did not beat placebo in Foster, pelvic-floor therapy beat 5% ointment in Morin, and 4% aqueous lidocaine beat saline in Goetsch[6][7][8][32][33][35]
Lidocaine + oestradiolLidocaine 5% + E₂ 0.02% in the published design, E₂ 0.07% in protocol v18; both also print E₂ 0.5 mg/mL, so the dispensed strength is unresolvedVestibulodynia (UPDATe)Completed UPDATe; posted primary pain comparisons not significant[9][42]
Gabapentin (single-agent)2–6%Vulvodynia, vestibular burningRetrospective 51 treated, 35 evaluable; 28 improved ≥50%[12]
Amitriptyline + ketamineAmitriptyline 1–2% + ketamine 0.5%; 3/13 also received lidocaine 2%Genital, rectal, perineal painRetrospective: efficacy documented in 13/29 site-eligible patients; 11/13 had any relief and 7/13 substantial or complete relief[21]
Amitriptyline + oestriolAmitriptyline 0.5% + E₃ 0.03%Vulvodynia, pudendal neuralgiaClinic audit: 376/1,054 contactable patients replied (35.7%)[16]
Amitriptyline + baclofenAmitriptyline 2% + baclofen 2% in the cited studyProvoked vestibulodyniaUncontrolled retrospective pre–post series (n = 38)[8]
Baclofen + PEATopical baclofen 5% plus oral PEA 400 mg three times daily in the 2014 case; a separate report describes baclofen 5% + PEA 1% creamVulvodynia, proctodyniaOne case and a mechanistic report; topical PEA efficacy is unproven[17][4]
Four-agent example from AAPMDiclofenac 2% + gabapentin 5% + amitriptyline 5% + ketamine 5%Localized neuropathic pain generally; genital use not studiedIllustrative formulation[3]

Urologic applications​

Vulvodynia and provoked vestibulodynia — the primary indication​

  • ACOG lists commonly prescribed topical agents and discusses the negative lidocaine trial; first-line efficacy is unproven[15]
  • AAFP 2021 lists compounded gabapentin, compounded muscle relaxants, and amitriptyline among vulvodynia options (SORT C); AAFP 2025 recommends pelvic-floor physical therapy first line for genito-pelvic pain disorders (SORT B).[18][23]
  • Vulvodynia Therapeutic Research Summit 2024 identified neuroinflammation-directed agents (ketotifen fumarate, resiniferatoxin, specialized pro-resolving mediators, luteolin, alpha-lipoic acid) as the highest-priority targets for future research.[24] The traditional compounded agents (amitriptyline, baclofen, gabapentin, ketamine) were not among the top-ranked agents.[24] Of these, ketotifen fumarate is a mast-cell stabilizer under early-stage study for neurogenic vestibular pain, on the rationale that inflammation-induced, mast-cell-derived nerve growth factor is a proposed mechanism in chronic vulvar pain; the supporting data are translational and mechanistic rather than a clinical trial.[37]
  • Review the timing of vestibular pain against hormonal exposures, including combined oral contraceptives, patches or rings, infertility or endometriosis therapies, and oophorectomy, while assessing other causes.[15] In a selected retrospective series of 50 women whose pain began on combined hormonal contraception, pain improved after both contraceptive cessation and topical estradiol/testosterone.[38] A population cohort found no overall association of prior oral-contraceptive use with later vulvodynia, while a 2025 cross-sectional study associated both combined and progestin-only oral contraceptives with self-reported vulvodynia.[39][40] Discuss contraception choices, including progestin-only, long-acting reversible, and nonhormonal methods, and topical hormones individually; none is established here as a standard or safer sequence for vestibulodynia.

Genital, rectal, and perineal pain​

The Mayo Clinic amitriptyline-ketamine series[21] is the most direct evidence; 11/13 reported some relief in a heterogeneous chart series. Selection, placebo effects and concomitant treatment limit interpretation; this does not establish an 85% expected response or reassuring systemic safety.

Chronic pelvic pain (CPP, CP/CPPS)​

No dedicated trials evaluate multi-agent compounded creams for CP/CPPS or female CPP as distinct from vulvodynia. The ACOG CPP Practice Bulletin (2020) recommends trigger-point injections for myofascial CPP.[25] A 2024 review describes pelvic-floor physical therapy and trigger-point injections as mainstays of myofascial pelvic pain care.[26]

Peyronie's disease​

Topical agents used to treat Peyronie plaque or curvature are a distinct literature; the 2026 ICSM consensus generally recommends against topical medical therapy and iontophoresis for PD .[44] The AUA PD guideline lists topical verapamil and topical liposomal rhSOD among unproven "Other Treatments" ; topical magnesium performed like placebo.[27] A systematic review concluded that topical medications did not demonstrate consistent improvement across outcomes.[28] The H-100 gel (nicardipine plus SOD plus emu oil) showed a signal in a small acute-phase pilot RCT.[29] Multi-agent analgesic creams of the type discussed here are not first-line for PD and have no randomized evidence.

Practical use and safety​

Establish the pain diagnosis first. Vulvar dermatoses, infection, GSM, pelvic-floor myalgia and neuropathic pain require different treatment. Multimodal pelvic-floor physical therapy has stronger comparative evidence than routine escalation through compounded creams for provoked vestibulodynia.[15][33]

If an individualized topical trial is selected, document the exact ingredients, concentration, vehicle, measured amount, application site, frequency and stop/reassessment plan with the dispensing pharmacy. A thin layer two or three times daily is not a safe universal instruction for every high-concentration mixture. Local burning may come from the vehicle or active drugs; stopping irritating products can itself help.[15][30]

Systemic toxicity remains possible. Avoid extrapolating intact-skin absorption data to genital mucosa or damaged skin. Review other local anesthetics and CNS-active drugs, prevent accidental child/partner exposure, and counsel about sedation, confusion, neurologic symptoms or cardiovascular symptoms requiring urgent assessment. Do not use high-strength combinations under occlusion without an explicit formulation-specific plan.[31]

Licensed topical products keep their labeled limits. The capsaicin 8% patch (Qutenza) is indicated for postherpetic neuralgia and diabetic peripheral neuropathy of the feet, is applied only to dry, intact skin, and is not to be applied to the face, eyes, mouth, nose or scalp; it is not a vulvar or mucosal option.[36] When an appropriate licensed product can meet the need, consider it before a compounded mixture. Compounded products have not undergone FDA approval for safety, efficacy or quality.[30]

Evidence to carry into counseling​

  • Brutcher 399-person trial: no superiority of the tested compounded mixtures for localized chronic pain; genital applicability remains uncertain.[1]
  • Lidocaine: positive breast-cancer dyspareunia evidence is specific to selected vestibular pain; the vulvodynia placebo trial was negative and a larger comparative trial favored physical therapy.[7][32][33]
  • Gabapentin, amitriptyline, baclofen and ketamine creams: small uncontrolled reports.[8][12][21][31] A 2026 network meta-analysis of 34 vulvodynia RCTs (1,893 participants) found no pharmacologic treatment category superior to placebo for pain immediately after therapy; category pooling provides no formula-specific estimate.[41]
  • UPDATe: recruitment is complete and registry results are available.[34]

See Also​

References​

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2. Cohen SP, Vase L, Hooten WM. "Chronic pain: an update on burden, best practices, and new advances." Lancet. 2021;397(10289):2082–2097. doi:10.1016/S0140-6736(21)00393-7

3. Lawson E, Singla P, Adler J, et al. "Topical analgesics for neuropathic pain: an evidence-informed guide for the practicing clinician." Pain Med. 2026;27(3):279–316. doi:10.1093/pm/pnaf130

4. Keppel Hesselink JM, Kopsky DJ, Sajben N. "New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells." J Pain Res. 2016;9:757–762. doi:10.2147/JPR.S115407

5. Kocot-Kępska M, Zajączkowska R, Mika J, et al. "Topical treatments and their molecular/cellular mechanisms in patients with peripheral neuropathic pain — narrative review." Pharmaceutics. 2021;13(4):450. doi:10.3390/pharmaceutics13040450

6. Zolnoun DA, Hartmann KE, Steege JF. "Overnight 5% lidocaine ointment for treatment of vulvar vestibulitis." Obstet Gynecol. 2003;102(1):84–87. doi:10.1016/s0029-7844(03)00368-5

7. American College of Obstetricians and Gynecologists. "Treatment of urogenital symptoms in individuals with a history of estrogen-dependent breast cancer: clinical consensus." Obstet Gynecol. 2021;138(6):950–960. doi:10.1097/AOG.0000000000004601

8. Schlaeger JM, Glayzer JE, Villegas-Downs M, et al. "Evaluation and treatment of vulvodynia: state of the science." J Midwifery Womens Health. 2023;68(1):9–34. doi:10.1111/jmwh.13456

9. Carey ET, Geller EJ, Rapkin A, et al. "Rationale and design of a multicenter randomized clinical trial of vestibulodynia: understanding pathophysiology and determining appropriate treatments (Vestibulodynia: UPDATe)." Ann Med. 2022;54(1):2885–2897. doi:10.1080/07853890.2022.2132531

10. Clemens JQ, Erickson DR, Varela NP, Lai HH. "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." J Urol. 2022;208(1):34–42. doi:10.1097/JU.0000000000002756

11. Parsons CL, Zupkas P, Proctor J, et al. "Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis." J Sex Med. 2012;9(1):207–212. doi:10.1111/j.1743-6109.2011.02542.x

12. Boardman LA, Cooper AS, Blais LR, Raker CA. "Topical gabapentin in the treatment of localized and generalized vulvodynia." Obstet Gynecol. 2008;112(3):579–585. doi:10.1097/AOG.0b013e3181827c77

13. Ergisi M, Law A, Chaudhari N, et al. "Effectiveness of topical gabapentin in the treatment of vulvodynia: a narrative synthesis." Front Pain Res. 2023;4:1159268. doi:10.3389/fpain.2023.1159268

14. Brown CS, Bachmann GA, Wan J, Foster DC. "Gabapentin for the treatment of vulvodynia: a randomized controlled trial." Obstet Gynecol. 2018;131(6):1000–1007. doi:10.1097/AOG.0000000000002617

15. American College of Obstetricians and Gynecologists. Persistent Vulvar Pain. Committee Opinion 673. 2016. Official guidance.

16. Ruoss CM, Howard EA, Chan K, Stevenson PG, Vancaillie T. "Topical treatment of vulvodynia, dyspareunia and pudendal neuralgia: a single clinic audit of amitriptyline and oestriol in organogel." Aust N Z J Obstet Gynaecol. 2021;61(2):270–274. doi:10.1111/ajo.13292

17. Keppel Hesselink JM, Kopsky DJ, Sajben NL. "Vulvodynia and proctodynia treated with topical baclofen 5% and palmitoylethanolamide." Arch Gynecol Obstet. 2014;290(2):389–393. doi:10.1007/s00404-014-3218-4

18. Hill DA, Taylor CA. "Dyspareunia in women." Am Fam Physician. 2021;103(10):597–604. PMID 33983001

19. Sawynok J. "Topical and peripheral ketamine as an analgesic." Anesth Analg. 2014;119(1):170–178. doi:10.1213/ANE.0000000000000246

20. Kopsky DJ, Keppel Hesselink JM, Bhaskar A, et al. "Analgesic effects of topical ketamine." Minerva Anestesiol. 2015;81(4):440–449. PMID 24847738

21. Poterucha TJ, Murphy SL, Rho RH, et al. "Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal pain and discomfort." Pain Physician. 2012;15(6):485–488. doi:10.36076/ppj.2012/15/485

22. Ferraro MC, Cashin AG, Visser EJ, et al. "Ketamine and other NMDA receptor antagonists for chronic pain." Cochrane Database Syst Rev. 2025;8:CD015373. doi:10.1002/14651858.CD015373.pub2

23. Dalrymple SN, Hoeg L, Thacker H. "Female sexual dysfunction: common questions and answers." Am Fam Physician. 2025;111(5):433–442. PMID 40378324

24. Krapf JM, Yong PJ, Berke MD, et al. "Executive summary of the Vulvodynia Therapeutic Research Summit." Obstet Gynecol. 2026;147(2):266–276. doi:10.1097/AOG.0000000000006118

25. American College of Obstetricians and Gynecologists. "Chronic pelvic pain: ACOG Practice Bulletin, Number 218." Obstet Gynecol. 2020;135(3):e98–e109. doi:10.1097/AOG.0000000000003716

26. Namazi G, Chauhan N, Handler S. "Myofascial pelvic pain: the forgotten player in chronic pelvic pain." Curr Opin Obstet Gynecol. 2024;36(4):273–281. doi:10.1097/GCO.0000000000000966

27. Nehra A, Alterowitz R, Culkin DJ, et al. "Peyronie's disease: AUA guideline." J Urol. 2015;194(3):745–753. doi:10.1016/j.juro.2015.05.098

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32. Foster DC, Kotok MB, Huang LS, et al. Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2010;116:583–593. doi:10.1097/AOG.0b013e3181e9e0ab.

33. Morin M, Dumoulin C, Bergeron S, et al. Multimodal physical therapy versus topical lidocaine for provoked vestibulodynia: a multicenter, randomized trial. Am J Obstet Gynecol. 2021;224:189.e1–189.e12. doi:10.1016/j.ajog.2020.08.038.

34. ClinicalTrials.gov. Vestibulodynia: Understanding Pathophysiology and Determining Appropriate Treatments (UPDATe). NCT03844412. Completed; results posted March 19, 2026. Registry results. Accessed September 12, 2026.

35. Goetsch MF, Lim JY, Caughey AB. "A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial." J Clin Oncol. 2015;33(30):3394–3400. doi:10.1200/JCO.2014.60.7366

36. Averitas Pharma. QUTENZA (capsaicin) topical system: prescribing information (sections 1, 2.1, 5.1). DailyMed set ID 3ffbbcb0-ad93-4f15-bb38-5da76a71c735. DailyMed. Accessed September 24, 2026.

37. Awad-Igbaria Y, Edelman D, Ianshin E, et al. Inflammation-induced mast cell-derived nerve growth factor: a key player in chronic vulvar pain? Brain. 2025;148(1):331–346. doi:10.1093/brain/awae228

38. Burrows LJ, Goldstein AT. "The treatment of vestibulodynia with topical estradiol and testosterone." Sex Med. 2013;1(1):30–33. doi:10.1002/sm2.4

39. Reed BD, Harlow SD, Legocki LJ, et al. "Oral contraceptive use and risk of vulvodynia: a population-based longitudinal study." BJOG. 2013;120(13):1678–1684. doi:10.1111/1471-0528.12407

40. Kiesner J, Bittoni C. "Oral contraceptive use and prevalence of vulvodynia: are genital-specific side effects of OC use early signs of risk?" J Sex Med. 2025;22(9):1629–1639. doi:10.1093/jsxmed/qdaf178

41. Spinillo A, Dominoni M, Tiranini L, et al. "Beyond the placebo effect: a systematic review and a network meta-analysis of treatment strategies for vulvodynia." BMC Womens Health. 2026;26(1):249. doi:10.1186/s12905-026-04469-0

42. Vestibulodynia UPDATe Research Team. Protocol for Vestibulodynia: UPDATe (NCT03844412), version 18. February 21, 2024. ClinicalTrials.gov protocol.

43. Pagano R, Wong S. "Use of amitriptyline cream in the management of entry dyspareunia due to provoked vestibulodynia." J Low Genit Tract Dis. 2012;16(4):394–397. doi:10.1097/LGT.0b013e3182449bd6

44. Chung E, Ziegelmann M, Lin HC, et al. "Management of Peyronie’s disease: recommendations from the Fifth International Consultation on Sexual Medicine (ICSM 2024)." Sex Med Rev. 2026;14(1):qeaf068. doi:10.1093/sxmrev/qeaf068