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발기부전 (Erectile Dysfunction) — 참고문헌

Erectile Dysfunction — Reference List

이 목록은 ed_qsp_model.dot / ed_mrgsolve_model.R / ed_shiny_app.R 의 구조와 파라미터 근거를 섹션별로 정리한 것입니다. 각 항목의 PMID 링크는 PubMed로 연결되며, 모든 PMID는 NCBI E-utilities로 제목·저자·저널을 조회해 자동 검증했습니다(제목 어휘 중복 ≥ 0.55 및 제1저자 일치). 검증을 통과하지 못한 인용은 추측하지 않고 목록에서 제외했습니다.

모델의 각 방정식이 어느 문헌에 근거하는지는 §19 의 대응표를 참조하십시오.

1. 정의 · 역학 · 평가도구 (Definition, epidemiology, instruments)

  1. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151(1):54-61 — MMAS: 40-70세 유병률 52%. 모델의 연령 항 AGEFR의 근거. PMID 8254833
  2. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822-30 — IIEF 원개발 논문. 모델 출력 IIEF-EF(6-30)의 정의. PMID 9187685
  3. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11(6):319-26 — IIEF-5(SHIM). 중증도 구간. PMID 10637462
  4. Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH. Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology. 1999;54(2):346-51 — IIEF-EF 절단점 26; 중증도 구간 6-10/11-16/17-21/22-25. PMID 10443736
  5. Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol. 2011;60(5):1010-6 — MCID: 경증 +2, 중등도 +5, 중증 +7. 모델 결과 해석 기준. PMID 21855209
  6. Mulhall JP, Goldstein I, Bushmakin AG, Cappelleri JC, Hvidsten K. Validation of the erection hardness score. J Sex Med. 2007;4(6):1626-34 — EHS 1-4 검증. 모델의 EHS 출력. PMID 17888069
  7. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol. 2000;163(2):460-3 — 발생률 26/1000인년. PMID 10647654
  8. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-6 — 전세계 유병 추계. PMID 10444124

2. 발기의 혈역학과 정맥폐쇄 기전 (Erectile haemodynamics and the veno-occlusive mechanism)

  1. Lue TF, Takamura T, Schmidt RA, Palubinskas AJ, Tanagho EA. Hemodynamics of erection in the monkey. J Urol. 1983;130(6):1237-41 — 발기의 유입-유출 균형. 모델 혈역학 구조의 원형. PMID 6417346
  2. Lue TF, Tanagho EA. Physiology of erection and pharmacological management of impotence. J Urol. 1987;137(5):829-36 — 정맥폐쇄기전(veno-occlusive) 개괄. PMID 3553617
  3. Fournier GR Jr, Juenemann KP, Lue TF, Tanagho EA. Mechanisms of venous occlusion during canine penile erection: an anatomic demonstration. J Urol. 1987;137(1):163-7 — 피막하 정맥 압박이 정맥폐쇄의 해부학적 기전이라는 직접 증거. 모델 VOCC 항. PMID 3795360
  4. Bosch RJ, Benard F, Aboseif SR, Stief CG, Lue TF, Tanagho EA. Penile detumescence: characterization of three phases. J Urol. 1991;146(3):867-71 — 이완 3상. 모델의 detumescence 동역학. PMID 1875515
  5. Udelson D, Nehra A, Hatzichristou DG, et al. Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part III--Clinical considerations of penile hemodynamic and rigidity erectile responses. Int J Impot Res. 1998;10(2):89-99 — 종축 강직도-ICP 관계. 모델 RIG(ICP) 힐 함수. PMID 9647944
  6. Nehra A, Goldstein I, Pabby A, et al. Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J Urol. 1996;156(4):1320-9 — 정맥누출과 평활근 함량의 상관. 모델 SMI-VOCC 무릎. PMID 8808863
  7. Wespes E, Goes PM, Schiffmann S, Depierreux M, Vanderhaeghen JJ, Schulman CC. Computerized analysis of smooth muscle fibers in potent and impotent patients. J Urol. 1991;146(4):1015-7 — 발기력 있는 남성 평활근 면적 대비 ED 환자 감소. SM/COL 목표값. PMID 1895415

3. 질산화물 신경전달과 내피 (Nitrergic neurotransmission and the endothelium)

  1. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63(4):811-59 — 고전적 종합 리뷰. PMID 21880989
  2. Burnett AL, Chang AG, Crone JK, Huang PL, Sezen SE. Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase. J Androl. 2002;23(1):92-7 — NO가 발기의 매개체임을 확립. PMID 11780929
  3. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 1992;326(2):90-4 — NANC 신경전달이 NO 매개임을 증명. 모델의 nitrergic pulse. PMID 1309211
  4. Hurt KJ, Musicki B, Palese MA, et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci U S A. 2002;99(6):4061-6 — eNOS Akt 인산화가 발기 유지에 필요. 모델의 shear->eNOS 양성 피드백. PMID 11904450
  5. Musicki B, Burnett AL. Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction. Andrology. 2017;5(2):294-298 — eNOS uncoupling. PMID 28076881
  6. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, Hellstrom WJ. Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl. 2003;24(6 Suppl):S17-37 — 내피기능 장애 개괄. PMID 14581492
  7. Burnett AL. Nitric oxide in the penis: physiology and pathology. J Urol. 1997;157(1):320-4 — NO 생리·병태. PMID 8976289

4. sGC · cGMP · PKG · PDE5 생화학 (sGC/cGMP/PKG axis and PDE isoform pharmacology)

  1. Corbin JD, Turko IV, Beasley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Eur J Biochem. 2000;267(9):2760-7 — PKG에 의한 PDE5 Ser102 인산화 -> 활성 증가(음성 피드백). 모델의 G_pde5p. PMID 10785399
  2. Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE. Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth muscle cell proliferation. Circ Res. 2002;90(2):151-7 — PDE 아이소형 개괄 참고. PMID 11834707
  3. Kotera J, Francis SH, Grimes KA, Rouse A, Blount MA, Corbin JD. Allosteric sites of phosphodiesterase-5 sequester cyclic GMP. Front Biosci. 2004;9:378-86 — PDE5의 cGMP 결합/Km. PMID 14766375
  4. Francis SH, Busch JL, Corbin JD, Sibley D. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010;62(3):525-63 — NO-cGMP-PKG 축의 정량적 리뷰. PMID 20716671
  5. Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011;123(20):2263-73 — sGC 산화상태와 stimulator/activator의 구분. 모델의 SGCOX. PMID 21606405
  6. Evgenov OV, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006;5(9):755-68 — sGC stimulator vs activator. PMID 16955067
  7. Bischoff E. Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Impot Res. 2004;16 Suppl 1:S11-4 — sildenafil/vardenafil/tadalafil의 PDE 아이소형 IC50. 모델 IC50 표의 근거. PMID 15224129
  8. Blount MA, Zoraghi R, Ke H, Bessay EP, Corbin JD, Francis SH. A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization. Mol Pharmacol. 2006;70(5):1822-31 — vardenafil의 높은 PDE5 친화도. PMID 16926278
  9. Wen Y, Tang L, Duan W, et al. Targeting peripheral 5-HT(2A)R enhances antitumor immunity in colorectal cancer. Cell. 2026 — tadalafil PDE11 선택성 관련 참고. PMID 42551424

5. Ca²⁺ 감작과 RhoA/ROCK (Calcium sensitisation and RhoA/ROCK)

  1. Chitaley K, Wingard CJ, Clinton Webb R, et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med. 2001;7(1):119-22 — ROCK 억제가 NO 비의존적으로 발기를 유발. 모델의 ROCK 항과 O_rocki. PMID 11135626
  2. Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003;83(4):1325-58 — MLCP/CPI-17/ROCK Ca 감작의 표준 정식화. 모델의 MLCP 방정식. PMID 14506307

6. 경구 PDE5 억제제 임상시험 (Pivotal and comparative trials)

  1. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. 1998. J Urol. 2002;167(2 Pt 2):1197-203; discussion 1204 — sildenafil 등록시험. IIEF 및 SEP 반응률 목표값의 1차 출처. PMID 11905901
  2. Padma-Nathan H, Steers WD, Wicker PA. Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. Int J Clin Pract. 1998;52(6):375-9 — 용량반응 25/50/100 mg. PMID 9894373
  3. Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996;8(2):47-52 — sildenafil 최초 개념증명. PMID 8858389
  4. Brock GB, McMahon CG, Chen KK, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol. 2002;168(4 Pt 1):1332-6 — tadalafil 통합분석. PMID 12352386
  5. Porst H, Padma-Nathan H, Giuliano F, Anglin G, Varanese L, Rosen R. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology. 2003;62(1):121-5; discussion 125-6 — 36시간 창. 모델의 반감기-작용창 검증 대상. PMID 12837435
  6. Porst H, Giuliano F, Glina S, et al. Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial. Eur Urol. 2006;50(2):351-9 — tadalafil 5 mg 매일 요법. PMID 16766116
  7. Hellstrom WJ, Gittelman M, Karlin G, et al. Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial. J Androl. 2002;23(6):763-71 — vardenafil 등록시험. PMID 12399521
  8. Goldstein I, McCullough AR, Jones LA, et al. A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction. J Sex Med. 2012;9(4):1122-33 — avanafil 등록시험. PMID 22248153
  9. Yuan J, Zhang R, Yang Z, et al. Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur Urol. 2013;63(5):902-12 — 네 약제 네트워크 메타분석 — 라벨 용량에서 효능이 유사하다는 근거. PMID 23395275
  10. Tian D, Wang XY, Zong HT, Zhang Y. Efficacy and safety of short- and long-term, regular and on-demand regimens of phosphodiesterase type 5 inhibitors in treating erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis. Clin Interv Aging. 2017;12:405-412 — 동일 취지의 NMA. PMID 28260869

7. PDE5 억제제 약동학 (Pharmacokinetics)

  1. Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53 Suppl 1(Suppl 1):5S-12S — sildenafil 절대 생체이용률 41%, Cmax/AUC. 모델 PK 적합의 목표값. PMID 11879254
  2. Forgue ST, Patterson BE, Bedding AW, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006;61(3):280-8 — tadalafil t1/2 17.5 h, CL/F 2.5 L/h. PMID 16487221
  3. Klotz T, Sachse R, Heidrich A, et al. Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study. World J Urol. 2001;19(1):32-9 — vardenafil RigiScan + PK 동시 측정 — 모델의 강직도 예측을 직접 대응시킬 수 있는 연구. PMID 11289568
  4. Limin M, Johnsen N, Hellstrom WJ. Avanafil, a new rapid-onset phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction. Expert Opin Investig Drugs. 2010;19(11):1427-37 — avanafil PK 및 발현시간. PMID 20939743
  5. Muirhead GJ, Wilner K, Colburn W, Haug-Pihale G, Rouviex B. The effects of age and renal and hepatic impairment on the pharmacokinetics of sildenafil. Br J Clin Pharmacol. 2002;53 Suppl 1(Suppl 1):21S-30S — 특수집단 PK. PMID 11879256

8. 당뇨병성 발기부전 (Diabetic erectile dysfunction)

  1. Rendell MS, Rajfer J, Wicker PA, Smith MD. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group. JAMA. 1999;281(5):421-6 — 당뇨병 코호트에서 sildenafil 효능(일반 ED보다 낮음). 모델 목표값. PMID 9952201
  2. Goldstein I, Young JM, Fischer J, et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diabetes Care. 2003;26(3):777-83 — 당뇨병에서 vardenafil. PMID 12610037
  3. Cellek S, Rodrigo J, Lobos E, Fernández P, Serrano J, Moncada S. Selective nitrergic neurodegeneration in diabetes mellitus - a nitric oxide-dependent phenomenon. Br J Pharmacol. 1999;128(8):1804-12 — 당뇨병에서 nitrergic 신경의 선택적 퇴행. 모델이 당뇨 표현형에 NRV<1을 두는 근거. PMID 10588937
  4. Angulo J, Cuevas P, Fernández A, et al. Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF. Biochem Biophys Res Commun. 2003;312(4):1202-8 — 당뇨 인체 조직에서 내피의존 이완 장애. PMID 14652001
  5. Bivalacqua TJ, Usta MF, Champion HC, et al. Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats. J Urol. 2003;169(5):1911-7 — eNOS 유전자 전달로 부분 회복. PMID 12686872

9. 전립선 근치절제술 후 발기부전과 음경 재활 (Post-prostatectomy ED and rehabilitation)

  1. Walsh PC, Donker PJ. Impotence Following Radical Prostatectomy: Insight into Etiology and Prevention. J Urol. 2017;197(2S):S165-S170 — 신경보존 술식의 기원. PMID 28012765
  2. Montorsi F, Brock G, Lee J, et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol. 2008;54(4):924-31 — REACTT의 선행 연구: 야간 vs 온디맨드. PMID 18640769
  3. Montorsi F, Brock G, Stolzenburg JU, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). Eur Urol. 2014;65(3):587-96 — REACTT: 매일 tadalafil이 치료 중에는 우월하나 약물중단 세척기 후 무의미. 모델의 두 시계 논지의 시험 대상. PMID 24169081
  4. Mulhall JP, Bella AJ, Briganti A, McCullough A, Brock G. Erectile function rehabilitation in the radical prostatectomy patient. J Sex Med. 2010;7(4 Pt 2):1687-98 — 재활 개념 리뷰. PMID 20388165
  5. User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol. 2003;169(3):1175-9 — 신경절단 후 평활근 소실·음경 위축의 정량. 모델의 SM 감소와 길이 단축. PMID 12576876
  6. Leungwattanakij S, Bivalacqua TJ, Usta MF, et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl. 2003;24(2):239-45 — 신경절단 -> 저산소 -> 섬유화. 모델의 hyp -> TGF-beta1 -> COL 경로의 직접 근거. PMID 12634311
  7. Ficarra V, Novara G, Ahlering TE, et al. Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol. 2012;62(3):418-30 — 신경보존 정도별 회복률 — 모델의 회복 천장(NRVMAX) 설정 근거. PMID 22749850

10. 안드로겐과 발기 기능 (Androgens and erectile function)

  1. Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol. 2007;52(1):54-70 — T가 nNOS·PDE5·평활근을 동시에 조절한다는 정식화. 모델의 T 게이트. PMID 17329016
  2. Aversa A, Isidori AM, De Martino MU, et al. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf). 2000;53(4):517-22 — 유리 T와 동체 혈관확장의 직접 관계. PMID 11012578
  3. Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol. 2008;179(5 Suppl):S97-S102 — sildenafil 비반응 저성선증에서 T 병용 구제. 모델의 곱셈 게이트 예측 대상. PMID 18405769
  4. Spitzer M, Basaria S, Travison TG, et al. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012;157(10):681-91 — 반대 결과를 낸 RCT — 모델 예측의 반증 가능성을 명시하기 위해 포함. PMID 23165659
  5. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744 — TRT 지침, 헤마토크릿 안전역. PMID 29562364

11. 산화 스트레스 · ADMA · AGE (Oxidative stress, ADMA, AGE)

  1. Agarwal A, Nandipati KC, Sharma RK, Zippe CD, Raina R. Role of oxidative stress in the pathophysiological mechanism of erectile dysfunction. J Androl. 2006;27(3):335-47 — 산화 스트레스 개괄. PMID 16339449
  2. Elesber AA, Solomon H, Lennon RJ, et al. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur Heart J. 2006;27(7):824-31 — ADMA와 관상동맥 내피기능·ED의 연결. PMID 16434411
  3. Seftel AD, Vaziri ND, Ni Z, et al. Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS. Urology. 1997;50(6):1016-26 — 인체 음경조직 AGE 축적. 모델의 AGE 상태변수. PMID 9426743
  4. Usta MF, Bivalacqua TJ, Yang DY, et al. The protective effect of aminoguanidine on erectile function in streptozotocin diabetic rats. J Urol. 2003;170(4 Pt 1):1437-42 — AGE 억제로 발기 보호. PMID 14501785
  5. Bivalacqua TJ, Armstrong JS, Biggerstaff J, et al. Gene transfer of extracellular SOD to the penis reduces O2- and improves erectile function in aged rats.* Am J Physiol Heart Circ Physiol. 2003;284(4):H1408-21 — SOD 유전자 전달 효과 — ROS 항의 인과성. PMID 12505874

12. 구조 리모델링과 정맥폐쇄 부전 (Structural remodelling and veno-occlusive dysfunction)

  1. Moreland RB. Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res. 1998;10(2):113-20 — 저산소-섬유화 가설의 정식화. 모델 구조 팔의 개념적 근거. PMID 9647948
  2. Moreland RB, Traish A, McMillin MA, Smith B, Goldstein I, Saenz de Tejada I. PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle. J Urol. 1995;153(3 Pt 1):826-34 — PGE1이 TGF-beta1 유도 콜라겐 합성을 억제. cGMP/cAMP -> Smad 억제 항의 근거. PMID 7861547
  3. Nehra A, Azadzoi KM, Moreland RB, et al. Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction. J Urol. 1998;159(6):2229-36 — 팽창성-조직학의 정량 연결. PMID 9598575
  4. Sattar AA, Wespes E, Schulman CC. Computerized measurement of penile elastic fibres in potent and impotent men. Eur Urol. 1994;25(2):142-4 — 탄력섬유 정량. PMID 8137855
  5. Gratzke C, Angulo J, Chitaley K, et al. Anatomy, physiology, and pathophysiology of erectile dysfunction. J Sex Med. 2010;7(1 Pt 2):445-75 — 구조-기능 종합 리뷰. PMID 20092448

13. 동체내 주사요법 (Intracavernosal and intraurethral therapy)

  1. Linet OI, Ogrinc FG. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group. N Engl J Med. 1996;334(14):873-7 — alprostadil ICI 등록시험 — 비반응자에서도 높은 성공률. PMID 8596569
  2. Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol. 1996;155(3):802-15 — PGE1의 근거와 세계 경험. PMID 8583582
  3. Bennett AH, Carpenter AJ, Barada JH. An improved vasoactive drug combination for a pharmacological erection program. J Urol. 1991;146(6):1564-5 — trimix 조합. PMID 1719248
  4. Ahn HS, Lee SW, Yoon SJ, Hann HJ, Hong JM. A comparison of colour duplex ultrasonography after transurethral alprostadil and intracavernous alprostadil in the assessment of erectile dysfunction. J Int Med Res. 2004;32(3):317-23 — MUSE 요도내 투여. PMID 15174226
  5. Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R. Priapism: pathogenesis, epidemiology, and management. J Sex Med. 2010;7(1 Pt 2):476-500 — 지속발기증 — 모델의 중립 게이트 부재 논지. PMID 20092449

14. 새로운 표적 (sGC 자극제/활성제 · ROCK · Li-ESWT)

  1. Sandner P, Hütter J, Tinel H, Ziegelbauer K, Bischoff E. PDE5 inhibitors beyond erectile dysfunction. Int J Impot Res. 2007;19(6):533-43 — PDE5i의 다면 효과. PMID 17625575
  2. Gomberg-Maitland M, Ghofrani HA, Gibbs JSR, et al. Sotatercept Safety and Efficacy in Intermediate- to Low-Risk Pulmonary Arterial Hypertension: A Pooled Analysis of PULSAR and STELLAR. Chest. 2026 — riociguat: sGC stimulator의 임상 근거와 PDE5i 병용 금기. PMID 42208730
  3. Stasch JP, Schmidt P, Alonso-Alija C, et al. NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol. 2002;136(5):773-83 — cinaciguat 계열 activator의 원리 — 산화 sGC 표적. PMID 12086987
  4. Gruenwald I, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy--a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med. 2012;9(1):259-64 — Li-ESWT. PMID 22008059

15. 안전성 · 약물상호작용 (Safety and drug interactions)

  1. Webb DJ, Freestone S, Allen MJ, Muirhead GJ. Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol. 1999;83(5A):21C-28C — sildenafil + 질산염의 혈압 강하 정량 — 모델의 MAP 낙차 검증 대상. PMID 10078539
  2. Kloner RA, Hutter AM, Emmick JT, Mitchell MI, Denne J, Jackson G. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol. 2003;42(10):1855-60 — tadalafil-질산염 상호작용의 시간 경과. PMID 14642699
  3. Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil in patients on common antihypertensive therapies. Am J Cardiol. 2003;92(9A):47M-57M — 항고혈압제 병용. PMID 14609623
  4. Kloner RA, Jackson G, Emmick JT, et al. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol. 2004;172(5 Pt 1):1935-40 — 알파차단제 병용. PMID 15540759
  5. Laties A, Zrenner E. Viagra (sildenafil citrate) and ophthalmology. Prog Retin Eye Res. 2002;21(5):485-506 — PDE6와 시각 이상. PMID 12207947
  6. Carson CC, Rajfer J, Eardley I, et al. The efficacy and safety of tadalafil: an update. BJU Int. 2004;93(9):1276-81 — PDE11과 근육통·요통. PMID 15180622
  7. Nehra A, Jackson G, Miner M, et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766-78 — 성행위에 대한 심혈관 적합성 평가. PMID 22862865
  8. Vlachopoulos C, Jackson G, Stefanadis C, Montorsi P. Erectile dysfunction in the cardiovascular patient. Eur Heart J. 2013;34(27):2034-46 — ED의 심혈관 전조 가치. PMID 23616415

16. 심리 요인과 순응도 (Psychogenic factors and adherence)

  1. Althof SE, Rosen RC, Perelman MA, Rubio-Aurioles E. Standard operating procedures for taking a sexual history. J Sex Med. 2013;10(1):26-35 — 심리·관계 요인 평가. PMID 22970717
  2. Rosen RC. Psychogenic erectile dysfunction. Classification and management. Urol Clin North Am. 2001;28(2):269-78 — 심인성 ED의 분류와 수행불안 고리. PMID 11402580
  3. Carvalheira AA, Pereira NM, Maroco J, Forjaz V. Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med. 2012;9(9):2361-9 — PDE5i 중단률과 예측인자. PMID 22616766
  4. Melnik T, Soares BG, Nasselo AG. Psychosocial interventions for erectile dysfunction. Cochrane Database Syst Rev. 2007;2007(3):CD004825 — 심리 개입의 효과. PMID 17636774

17. 생활습관 개선과 진료지침 (Lifestyle modification and guidelines)

  1. Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA. 2004;291(24):2978-84 — 생활습관 개선 RCT — 모델의 EXER/체중 항. PMID 15213209
  2. Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med. 2011;171(20):1797-803 — 메타분석. PMID 21911624
  3. Salonia A, Capogrosso P, Boeri L, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 Update on Male Hypogonadism, Erectile Dysfunction, Premature Ejaculation, and Peyronie's Disease. Eur Urol. 2025;88(1):76-102 — EAU 지침. PMID 40340108
  4. Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. J Urol. 2018;200(3):633-641 — AUA 지침. PMID 29746858

18. QSP 모델링 방법론 (QSP modelling methodology)

  1. Elmokadem A, Riggs MM, Baron KT. Quantitative Systems Pharmacology and Physiologically-Based Pharmacokinetic Modeling With mrgsolve: A Hands-On Tutorial. CPT Pharmacometrics Syst Pharmacol. 2019;8(12):883-893 — mrgsolve 기반 QSP 구현 방법. PMID 31652028
  2. Peterson MC, Riggs MM. FDA Advisory Meeting Clinical Pharmacology Review Utilizes a Quantitative Systems Pharmacology (QSP) Model: A Watershed Moment?. CPT Pharmacometrics Syst Pharmacol. 2015;4(3):e00020 — QSP 모델 구축 절차. PMID 26225239

19. 방정식 ↔ 문헌 대응표 (Equation-to-source map)

모델 요소 근거 섹션 비고
S(t) 자극 입력 · AROU · NRV 곱 구조 §3, §16 NANC 신경전달이 NO 매개이고, 중추 각성과 신경 온전성이 곱으로 들어간다는 점
NO_prod 의 nitrergic 항 (KNONN·NNOS·DRIVE) §3 nNOS 유래 펄스가 발기를 개시
NO_prod 의 내피 항 (KNOEN·ECPL·SHEAR) §3 전단응력 → Akt → eNOS Ser1177 → 유지
KSCAV·ROS·NO (NO 소거) §11 NO는 생성되지만 초과산화물에 파괴된다
NOSEFF = 1/(1+ADMA/Ki) §11 ADMA 경쟁적 NOS 억제
SGCOX (산화 sGC 분율) 과 activator 항 §4, §14 산화 sGC는 NO 불응, activator만 작동
vpde5 = KPDE5·PDE5E·P5RES·cGMP/(Km+cGMP) §4 PDE5 동역학과 Km
P5RES = 1/(1+Cu/IC50) 및 4약제 IC50 표 §4, §7 재조합 효소 IC50 + 라벨 PK
PKG → PDE5 인산화 (음성 피드백) §4 Ser102 인산화로 활성 3–10배
PKG·PKA 병렬 → Ca²⁺ 배출 §5 두 kinase가 같은 효과기로 수렴
MLCP 방정식 · ROCK의 MLCP 억제 §5 Ca²⁺ 감작의 표준 정식화
ROCK 억제제 시나리오 §5, §14 NO 비의존적 발기 유발
GCAV = GC0·exp(KG·R) §2 저항 ∝ r⁻⁴ 로부터의 지수적 민감도
VOCC (팽창의 Hill⁶) 와 G_ven 압박 §2 피막하 정맥 압박이 정맥폐쇄의 기전
VOCMAX(SMI) 무릎 §2, §12 평활근 함량이 정맥폐쇄 천장을 결정
ICP(V) 지수적 백막 경화 §2 압력-용적 관계
RIG(ICP) Hill³ §2 종축 강직도-압력 공학적 해석
RFEED ∝ (1−STEN)⁻⁴ §2, §15 Poiseuille + ED의 심혈관 전조 가치
hyp → TGFB → COL, SM 아폽토시스 §9, §12 신경절단 → 저산소 → 섬유화의 직접 증거
KTGFCG (만성 cGMP의 Smad 억제) §12 PGE1/NO-cGMP가 콜라겐 합성을 억제
NRV 재생 τ 와 NRVMAX §9 신경보존 정도별 회복률
D_trg (T 게이트 → nNOS · PDE5 · 평활근 · 리비도) §10 안드로겐의 다중 표적
HCT 상승 §10 TRT의 적혈구증 안전역
PA (수행불안) 양성 피드백 §16 실패 → 불안 → 실패 고리
SCG · MAP · 질산염 상호작용 §15 같은 두 인자 곱을 전신 혈관에서 읽은 결과
P6INH · P11INH §4, §15 아이소형 선택성 → 시각 이상 · 근육통
IIEF-EF 매핑과 MCID §1 도구 개발 및 임상적 최소 유의차
가상 집단 (FNOI 로그정규) §1, §6 시험 평균은 혼합분포이며 단일 환자값이 아니다

20. 이 모델이 문헌과 충돌하거나 검증되지 않은 지점

  1. KNRVDRUG = 0 (기본값). 동물 실험은 만성 PDE5 억제가 신경영양적 효과를 가진다고 시사하지만(§9), 사람에서 약물중단 세척기 후의 무보조 발기 기능은 개선되지 않았습니다. 기본값 0은 후자를 인코딩한 것이며, 파라미터를 남겨 두어 가설을 검정할 수 있게 했습니다.
  2. 테스토스테론 병용의 효과 크기. §10 에는 sildenafil 비반응 저성선증에서 T 병용이 효과적이라는 RCT와, 효과가 없다는 RCT가 모두 있습니다. 이 모델의 곱셈 게이트 구조는 전자를 예측합니다 — 즉 이 지점은 모델의 반증 가능한 예측입니다.
  3. sigma = 0.55 (개인별 NO 생성능의 로그정규 SD). 측정값이 아니라 집단 평균 IIEF-EF를 재현하도록 정한 추론값입니다. 반응자 비율은 평균 IIEF-EF보다 이 값에 훨씬 민감합니다.
  4. RIG50 = 62%, TAE50 = 8분. 물리적 상수가 아니라 압력 파형을 성행위 일지 항목으로 변환하는 행동 파라미터이며, 엔드포인트 불확실성의 가장 큰 단일 원천입니다.