Phosphodiesterase Type 5 inhibitors and female sexual response: Faulty protocols or paradigms?

Journal of Sexual Medicine

Volumn 7, Issue 2 PART 2, 2010, Pages 858-872

  Chivers, Meredith L ^a   Rosen, Raymond C ^b  

^a QUEEN S UNIVERSITY   (Canada)

^b NEW ENGLAND RESEARCH INSTITUTES   (United States)

Author keywords

Female sexual arousal; Female sexual dysfunction; Gender difference; PDE5 Inhibitors for female sexual dysfunction; Sexual concordance; Sildenafil

Indexed keywords

ESTROGEN; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; SEROTONIN UPTAKE INHIBITOR; SILDENAFIL; TESTOSTERONE; VARDENAFIL; CARBOLINE DERIVATIVE; IMIDAZOLE DERIVATIVE; PHOSPHODIESTERASE INHIBITOR; PIPERAZINE DERIVATIVE; PURINE DERIVATIVE; SULFONE; TADALAFIL; TRIAZINE DERIVATIVE;

CLINICAL TRIAL; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; ESTROGEN THERAPY; FEMALE SEXUAL DYSFUNCTION; HORMONE SUBSTITUTION; HUMAN; HYPOACTIVE SEXUAL DESIRE DISORDER; MENOPAUSAL SYNDROME; ORGASM; ORGASM DISORDER; PRIORITY JOURNAL; REVIEW; SEX DIFFERENCE; SEXUAL AROUSAL; SEXUAL AROUSAL DISORDER; SEXUAL FUNCTION; SEXUAL INTERCOURSE; SEXUAL SATISFACTION; UNSPECIFIED SIDE EFFECT; VAGINAL DRYNESS; ANIMAL; CLITORIS; DRUG EFFECTS; FEMALE; PATHOPHYSIOLOGY; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SEXUAL DYSFUNCTIONS, PSYCHOLOGICAL; VAGINA; VASCULARIZATION; WOMEN'S HEALTH;

ANIMALS; CARBOLINES; CLITORIS; FEMALE; HUMANS; IMIDAZOLES; PHOSPHODIESTERASE 5 INHIBITORS; PHOSPHODIESTERASE INHIBITORS; PIPERAZINES; PURINES; SEX FACTORS; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; SEXUAL DYSFUNCTIONS, PSYCHOLOGICAL; SULFONES; TRIAZINES; VAGINA; WOMEN'S HEALTH;

EID: 75649083135     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2009.01599.x     Document Type: Review

References (68)

1. Lue TF. Erectile dysfunction. New Engl J Med 2000, 342:1802-13.
2. Montorsi F, Salonia A, Deho F. Pharmacological management of erectile dysfunction. Br J Urol 2003, 62:121-5.
3. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: A physiologic mediator of penile erection. Science 1992, 257:401-3.
4. 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, noncholingergic neurotransmission. New Engl J Med 1992, 326:90-4.
5. Rosen RC, McKenna KE. PDE-5 Inhibition and Sexual Response: Pharmacological mechanisms and clinical outcomes. Annu Rev Sex Res 2002, 13:36-88.
6. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukoto IM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990, 170:843-50.
7. Pickard RS, Powell PH, Zar MA. The effect of inhibitors of nitric oxide biosynthesis and cyclic CMP formation on nerve evoked relaxation of human cavernosal smooth muscle. Br J Pharmacol 1991, 104:755-9.
8. Lin CS, Lau A, Ru R, Lue TF. Expression of three isoforms of CFMP-binding CGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun 2000, 268:628-35.
9. Rosen RC, Kostis JB. Overview Of Phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol 2003, 92:9-18.
10. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in The United States: Prevalence and predictors. JAMA 1999, 281:537-44.
11. Mercer CH, Fenton KA, Johnson AM, Wellings K, Macdowall W, McManus S, Nanchahal K, Erens B. Sexual function problems and help seeking behaviour in Britain: National Probability Sample Survey. BMJ 2003, 327:426-7.
12. Lindau S, Schumm M, Laumann O, Levinson W, O'Muircheartaigh CA, Waite LJ. A study of sexuality and health among older adults in the United States. New Engl J Med 2007, 357:762-74.
13. West SL, D'Aloisio AA, Agan RP, Kalsbeek WD, Borisov NN, Thorp JM. Prevalence of low sexual desire and hypoactive sexual desire disorder in a nationally representative sample of us women. Arch Intern Med 2008, 168:1441-9.
14. Sipski M, Rosen RC, Alexander C, Hamer R. Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury. Urology 2000, 55:812-5.
15. Berman J, Berman L, Lin H, Flaherty E, Lahey N, Goldstein I, Cantey-Kiser J. Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder. J Sex Marital Ther 2001, 27:411-20.
16. Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: A double-blind, cross-over, placebo-controlled study. Br J Obstet Gynaecol 2001, 108:623-8.
17. DasGupta R, Wiseman OJ, Kanabar G, Fowler CJ, Mikol DD. Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis. J Urol 2004, 171:1189-93.
18. Nurnberg H, Stuart S, Seidman S, Gelenberg AJ, Fava M, Rosen R, Shabsigh R. Depression, antidepressant therapies, and erectile dysfunction: Clinical trials of sildenafil citrate (viagra) in treated and untreated patients with depression. Urology 2002, (2b):58-66. Suppl
19. Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S. Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008, 300:395-404.
20. Basson R, McInnes R, Smith MD, Hodgson G, Koppiker N. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. J Wom Health Gend Base Med 2002, 11:367-77.
21. Nijland E, Davis S, Laan E, Schultz WW. Female sexual satisfaction and pharmaceutical intervention: A critical review of the drug intervention studies in female sexual dysfunction. J Sex Med 2006, 3:763-77.
22. Chivers ML, Seto MC, Laan E, Lalumière ML, Grimbos T. Agreement of genital and subjective measures of sexual arousal: A meta-analysis. Arch Sex Behav in press
23. Rosen RR, Beck JG. Patterns of sexual arousal: psychophysiological processes and clinical applications 1988, New York, The Guliford Press
24. Kaplan SA, Reis RB, Kohn IJ, Ikeguchi EF, Laor E. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology 1999, 53:481-6.
25. Caruso S, Intelisano G, Farina M, Di Mari L, Agnello C. The function of sildenafil on female sexual pathways: A double-blind, cross-over, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2003, 110:201-6.
26. Berman JR, Berman LA, Toler SM, Gill J, Haughie S. Safety And efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: A double-blind, placebo-controlled study. J Urol 2003, 170:2333-8.
27. Basson R, Brotto LA. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: A randomised controlled trial. BJOG 2003, 110:1014-4.
28. Caruso S, Rugolo S, Agnello C, Intelisano G, Di Mari L, Cianci A. Sildenafil improves sexual functioning in premenopausal women with type 1 diabetes who are affected by sexual arousal disorder: A double-blind, crossover, placebo-controlled pilot study. Fertil Steril 2008, 85:1496-1501.
29. Yang C, Cao Y, Guan Y, Heiman JR, Kuffel SW, Peterson BT, Maravilla KR. Influence of PDE5 inhibitor on MRI measurement of clitoral volume response in women with FSAD: A feasibility study of a potential technique for evaluating drug response. Int J Impot R 2008, 20:105-10.
30. Laan E, Van Lunsen RH, Everaerd W, Riley A, Scott E, Boolell M. The enhancement of vaginal vasocongestion by sildenafil in healthy premenopausal women. J Womens Health Gend Based Med 2002, 11:357-65.
31. Van der Made F, Bloemers J, Van Ham D, El Yassem W, Kleiverda G, Everaerd W, Olivier B, Tuiten A. Childhood sexual abuse, selective attention for sexual cues and the effects of testosterone with or without vardenafil on physiological sexual arousal in women with sexual dysfunction: A pilot study. J Sex Med 2009, 6:429-39.
32. van der Made F, Bloemers J, Yassem W, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009, 6:777-90.
33. Traish AM, Kim NN, Munarriz R, Moreland R, Goldstein I. biochemical and physiological mechanisms of female genital sexual arousal. Arch Sex Behav 2002, 31:393-400.
34. D'Amati G, Di Gioia CR, Bologna M, Giordano D, Giorgi M, Dolci S, Jannini EA. Type 5 Phosphodiesterase expression in the human vagina. Urology 2002, 60:191-5.
35. Sher G, Fish JD. Vaginal sildenafil (Viagra): A Preliminary report of a new method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000, 15:806-9.
36. Agha AM, Taha RA. Sildenafil inhibits agonist-evoked rat uterine contractility: Influence of guanylyl cyclase inhibition. Eur J Pharmacol 2001, 428:343-8.
37. Buhimschi CS, Garfield RE, Weiner CP, Buhimschi IA. The Presence and function of phosphodiesterase type 5 in the rat myometrium. Am J Obstet Gyncol 2004, 190:268-74.
38. Downing JW, Ramasubramanian R, Johnson RF, Minzter BH, Paschall RL, Sundell HW, Engelhardt B, Lewis R. Hypothesis: Selective phosphodiesterase-5 inhibition improves outcome in pre-eclampsia. Med Hypotheses 2004, 63:1057-64.
39. Belmonte A, Ticconi C, Dolci S, Giorgi M, Zicari A, Lenzi A, Jannini EA, Piccione E. Regulation of phophodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin. J Soc Gynecol Invest 2005, 12:570-7.
40. Dolci S, Belmonte A, Santone R, Giorgi M, Pellegrini M, Carosa E, Piccione E, Lenzi A, Jannini EA. Subcellular localization and regulation of type-1C and type-5 phosphodiesterases. Biochem Biophys Res Commun 2006, 341:837-46.
41. Vemulapalli S, Kurowski S. Sildenafil Relaxes rabbit clitoral corpus cavernosum. Life Sci 2000, 67:23-9.
42. Musicki B, Liu T, Lagoda G, Bivalacqua TJ, Strong TD, Burnett AL. Endothelial nitric oxide synthase regulation in female genital tract structures. J Sex Med 2009, (3):247-53. Suppl
43. Rosen RC, Weigel M, Gendrano N, Janssen E. Sexual dysfunction, sexual psychophysiology, and psychopharmacology: Laboratory studies in men and women. Psychophysiology of Sex 2007, 381-409. In, ed., Bloomington, Indiana University Press
44. Chivers ML, Reiger G, Latty E. A sex difference in the specificity of sexual arousal. Psychol Sci 2004, 15:736-44.
45. Suschinsky K, Lalumière ML, Chivers ML. Sex differences in patterns of genital arousal: Measurement artifact or true phenomenon? Arch Sex Behav 2009, in press
46. Brotto LA, Basson R, Gorzalka BB. Psychophysiological assessment in premenopausal sexual arousal disorder. J Sex Med 2004, 1:266-77.
47. Meston CM, Heiman JR. Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychi 1998, 55:652-6.
48. Meston CM, Worcel M. The effects of yohimbine plus l-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Arch Sex Behav 2002, 31:323-32.
49. Morokoff PJ, Heiman JR. Effects of erotic stimuli on sexually functional and dysfunctional women: Multiple measures before and after sex therapy. Behav Res Ther 1980, 18:127-37.
50. Chivers ML, Bailey JM. A sex difference in features that elicit genital response. Biol Psychol 2005, 70:115-20.
51. Chivers ML, Seto MC, Blanchard R. Gender and sexual orientation differences in sexual response to the sexual activities versus the gender of actors in sexual films. J Pers Soc Psychol 2007, 93:1108-21.
52. Both S, Everaerd W, Laan E. Modulation of spinal reflexes by aversive and sexually appetitive stimuli. Psychophysiology 2003, 40:174-83.
53. Laan E, Everaerd W. Determinants of female sexual arousal: Psychophysiological theory and data. Annu Rev Sex Res 1995, 6:32-76.
54. Chivers ML. Leading comment: A brief review and discussion of sex differences in the specificity of sexual arousal. Sex Relat Ther 2005, 4:377-90.
55. Gerritsen J, van der Made F, Bloemers J, van Ham D, Kleiverda G, Everaerd W, Olivier B, Levin R, Tuiten A. The clitoral photoplethysmograph: A new way of assessing genital arousal in women. J Sex Med 2009, 6:1678-87.
56. Van Lunsen R, Laan E. Genital vascular responsiveness and sexual feelings in midlife women: Psychophysiologic, brain, and genital imaging studies. Menopause 2004, 11:741-8.
57. Ponseti J, Bosinski HA, Wolff S, Peller M, Jansen O, Mehdorn HM, Büchel C, Siebner HR. A functional endophenotype for sexual orientation in humans. NeuroImage 2006, 33:825-33.
58. Levin RJ, Van Berlo W. Sexual arousal and orgasm in subjects who experience forced or non-consensual sexual stimulation-A review. J Clin Forensic Med 2004, 11:82-8.
59. Stock WE. The Effects of Violent Pornography on The Sexual Responsiveness and Attitudes of Women. 1983, unpublished doctoral dissertation]. Stonybrook, NY: State University of New York
60. Levin RJ. The Mechanisms of human female sexual arousal. Ann Rev Sex Res 1992, 3:1-48.
61. Masters WH, Johnson VE. Human sexual response 1966, Toronto, New York, Bantam Books
62. Kaplan H. The illustrated manual of sex therapy 1975, Oxford, Quadrangle/The New York Times Book
63. Basson R. The female sexual response: A different model. J Sex Marital Ther 2000, 26:51-65.
64. Bancroft J. Human sexuality and its problems 2009, London, Churchill Livingstone Elsevier
65. Foster R, Mears A, Goldmeier D. A literature review and case reports series on the use of phosphodiesterase inhibitors in the treatment of female sexual dysfunction. Int J STD AIDS 2009, 20:152-7.
66. Berman LA, Berman JR. Viagra and beyond: Where sex educators and therapists fit in from a multidisciplinary perspective. J Sex Educ Ther 2000, 25:17-24.
67. Brotto LA, Basson R, Luria MA. Mindfulness-based group psychoeducational intervention targeting sexual arousal disorder in women. J Sex Med 2008, 5:1646-59.
68. Basson R, Leiblum S, Brotto L, Derogatis L, Fourcroy J, Fugl-Meyer K, Graziottin A, Heiman JR, Laan E, Meston C, Schover L, van Lankveld J, Schultz WW. Revised definitions of women's sexual dysfunction. J Sex Med 2004, 1:40-8.