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01-12-2006 | Topic Paper

Potential future options in the pharmacotherapy of female sexual dysfunction

Authors: Stefan Ückert, Margit E. Mayer, Udo Jonas, Christian G. Stief

Published in: World Journal of Urology | Issue 6/2006

Abstract

Female sexual dysfunction (FSD) is considered a common medical problem estimated to affect millions of women in the westernized countries. FSD has been classified into four different categories including sexual arousal disorder (FSAD), sexual desire disorder (HSDD), orgasmic disorder and sexual pain disorder. The focus of this article is the potential role of pharmacological compounds currently under development, in the treatment of sexual arousal and orgasmic disorders in order to enhance the sexual response in adult females. While a number of potential therapeutic options are available to date, not one of the pharmacological treatment regimens has been yet considered the Gold standard in the management of symptoms of FSD. This article reviews the rationale and potential benefits of using distinct drug formulations in the treatment of FSD.

Berman JR, McCarthy MM, Kyprianou N (1998) Effect of estrogen withdrawal on nitric oxide synthase expression and apoptosis in the rat vagina. Urology 51:650–656CrossRefPubMed

Kenemans P, Speroff L, the International Tibolone Consensus Group (2005) Tibolone: clinical recommendations and practical guidelines. A report of the International Tibolone Consensus Group. Maturitas 51:21–28

Sarrel PM (2000) Effects of hormone replacement therapy on sexual psychophysiology and behaviour in postmenopause. J Womens Health Gend Based Med 9(Suppl 1):25–32CrossRef

Rioux JE, Devlin MC, Gelfand MM, Steinberg WM, Hepburn DS (2000) 17beta-estradiol vaginal tablets versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 7:156–161PubMedCrossRef

Nathorst-Bass J, von Schoultz H (1992) Psychological reactions and sexual life after hysterectomy with and without oophorectomy. Gynecol Obstet Invest 34:97–101CrossRef

Davis S, Tran J (2001) Testosterone influences libido and well being in women. Trends Endocrinol Metab 12:33–37CrossRefPubMed

Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, Bachman G, Aguirre OA, Lucas JD, Rodenberg C, Buch A, Watts NB (2005) Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 90:5226–5233CrossRefPubMed

Simon J, Braunstein G, Nachtigall L, Utian W, Katz M, Miller S, Waldbaum A, Bouchard C, Derzko C, Buch A, Rodenberg C, Lucas J, Davis S (2005) Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab 90:5226–5233CrossRefPubMed

Warnock JK, Swanson SG, Borel RW, Zipfel LM, Brennan JJ, for the ESTRATEST Clinical Study Group (2005) Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest. Menopause 12:374–384

10.

Buijsman RC, Hermkens PH, van Rijn RD, Stock HT, Teerhuis NM (2005) Non-steroidal steroid receptor modulators. Curr Med Chem 12:1017–1075CrossRefPubMed

11.

Khosla S (2003) Estrogen, selective estrogen receptor modulators and now mechanism-specific ligands of the estrogen or androgen receptor? Trends Pharmacol Sci 24:261–263CrossRefPubMed

12.

Miller CP (2002) SERMs: evolutionary chemistry, revolutionary biology. Curr Pharm Des 8:2089–2111CrossRefPubMed

13.

Natale V, Albertazzi P, Missiroli N, Pedrini D, Salgarello M (2004) Effects of raloxifene on mood, sleep, libido and cognitive function in postmenopausal healthy women: a pilot study. Maturitas 48:59–63CrossRefPubMed

14.

Becker AJ, Stief CG, Meyer M, Truss MC, Forssmann WG, Jonas U (1998) The effects of the specific phosphodiesterase 4 inhibitor rolipram on the ureteral peristalsis of the rabbit in vitro and in vivo. J Urol 160:920–925CrossRefPubMed

15.

Truss MC, Stief CG, Ückert S, Becker AJ, Wefer J, Schultheiss D, Jonas U (2001) Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside. World J Urol 19:344–350CrossRefPubMed

16.

Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC (2002) Sildenafil influences lower urinary tract symptoms. BJU Int 90:836–839CrossRefPubMed

17.

McMahon CG, McMahon CN, Leow LJ, Winestock CG (2006) Efficacy of type 5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systemic review. BJU Int 98:259–272CrossRefPubMed

18.

Caruso S, Intelisano G, Lupo L, Agnello C (2001) Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, crossover, placebo-controlled study. Br J Obstet Gynaecol 108:623–628CrossRef

19.

Sipski ML, Rosen RC, Alexander CJ, Hamer RM (2002) Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury. Urology 55:812–815CrossRef

20.

Basson R, Brotto LA (2003) Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial. BJOG 110:1014–1024CrossRefPubMed

21.

Berman JR, Berman LA, Toler SM, Gill J, Haughie S, the Sildenafil study Group (2003) Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo-controlled study. J Urol 170:2333–2338

22.

Dasgupta R, Wiseman OJ, Kanabar G, Fowler CJ, Mikol DD (2004) Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis. J Urol 171:1189–1193CrossRefPubMed

23.

Ückert S, Ellinghaus P, Albrecht K, Stief CG, Bischoff E, Jonas U (2004) Expression of messenger RNA (mRNA) encoding for different phosphodiesterase (PDE) isoenzymes in human vaginal tissue. J Sex Med 2 (Suppl 1):29 (abstract)

24.

Guay D, Hamel P, Blouin M, Brideau C, Chan CC, Chauret N, Ducharme Y, Huang Z, Girard M, Jones TR, Laliberte F, Masson P, McAuliffe M, Piechuta H, Silva J, Young RN, Girard Y (2002) Discovery of L-791.943: a potent, selective, non-emetic and orally active phosphodiesterase 4 inhibitor. Bioorg Med Chem Lett 12:1457–1461CrossRefPubMed

25.

Burnett AL, Calvin DC, Silver RI, Peppas DS, Docimo SG (1997) Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. J Urol 158:75–78CrossRefPubMed

26.

Hoyle CH, Stones RW, Robson T, Whitley K, Burnstock G (1996) Innervation of the vasculature and the microvasculature of the human vagina by NOS and neuropeptide-containing nerves. J Anat 188:633–644PubMed

27.

Munarriz R, Kim SW, Kim NN, Traish A, Goldstein I (2003) A review of the physiology and pharmacology of peripheral (vaginal and clitoral) female genital arousal in the animal model. J Urol 170:S40–S45CrossRefPubMed

28.

Pacher P, Mabley JG, Liaudet L, Evgenov OV, Southan GJ, Abdelkarim GE, Szabo C, Salzman AL (2003) Topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), selectively increases vaginal blood flow in anesthetized rats. Int J Impot Res 15:461–464CrossRefPubMed

29.

Porst H (1996) The rationale for prostaglandin E1 in erectile failure: a survey of world-wide experience. J Urol 155:802–815CrossRefPubMed

30.

Goldstein I, Payton TR, Schechter PJ (2001) A double-blind, placebo-controlled, efficacy and safety study of topical gel formulation of 1% alprostadil (Topiglan) for the in-office treatment of erectile dysfunction. Urology 57:301–305CrossRefPubMed

31.

Becher EF, Bechara A, Casabe A (2001) Clitoral hemodynamic changes after a topical application of alprostadil. J Sex Marital Ther 27:405–410PubMed

32.

Bechara A, Bertolino MV, Casabe A, Munarriz R, Goldstein I, Morin A, Secin F, Literat B, Pesaresi M, Fredotovich N (2003) Duplex Doppler ultrasound assessment of clitoral hemodynamics after topical administration of alprostadil in women with arousal and orgasmic disorders. J Sex Marital Ther 29(Suppl 1):1–10PubMed

33.

Padma-Nathan H, Brown C, Fendl J, Salem S, Yeager J, Harninger R (2003) Efficacy and safety of topical alprostadil cream for the treatment of female sexual arousal disorder (FSAD): a double-blind, multicenter, randomized, and placebo-controlled clinical trial. J Sex Marital Ther 29:329–344CrossRefPubMed

34.

Ottesen B (1983) Vasoactive intestinal polypeptide as a neurotransmitter in the female genital tract. Am Obstet Gynecol 147:208–224

35.

Keijzers GB (2001) Aviptadil (Senetek). Curr Opin Investig Drugs 2:545–549PubMed

36.

Ottesen B, Pedersen B, Nielsen J, Dalgaard D, Wagner G, Fahrenkrug J (1987) Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women. Peptides 8:797–800CrossRefPubMed

37.

Gozes I, Reshef A, Salah D, Rubinraut S, Fridkin M (1994) Stearyl-norleucine-vasoactive intestinal peptide (VIP): a novel VIP analog for non-invasive impotence treatment. Endocrinology 134:2121–2125CrossRefPubMed

38.

Kuensch E, Reiners K, Müller-Mattheis V, Strohmeyer T, Ackermann R, Freund HJ (1992) Neurological risk profile in organic erectile dysfunction. J Neurol Neurosurg Psychiatr 55:275–281CrossRef

39.

Goldstein I, Carson C, Rosen R, Islam A (2001) Vasomax for the treatment of male erectile dysfunction. World J Urol 19:51–56CrossRefPubMed

40.

Rosen RC, Phillips NA, Gendrano NC III, Ferguson DM (1999) Oral phentolamine and female sexual arousal disorder: a pilot study. J Sex Marital Ther 25:137–144CrossRefPubMed

41.

Rubio-Aurioles E, Lopez M, Lipezker M, Lara C, Ramirez A, Rampazzo C, Hurtado de Mendoza MT, Lowrey F, Loehr LA, Lammers P (2002) Phentolamine mesylate in postmenopausal women with female sexual arousal disorder: a psychophysiological study. J Sex Marital Ther 28(Suppl 1):205–215CrossRefPubMed

42.

Piletz JE, Segraves KB, Feng YZ, Maguire E, Dunger B, Halaris A (1998) Plasma MHPG response to yohimbine treatment in women with hypoactive sexual desire. J Sex Marital Ther 24:43–54PubMed

43.

Cotzias GC, van Woert MH, Schiffer LM (1967) Aromatic amino acids and modification of parkinsonism. N Engl J Med 276:374–379PubMedCrossRef

44.

Rampin O (2001) Mode of action of a new oral treatment for erectile dysfunction: apomoprhine SL. BJU Int 88(Suppl 3):22–24CrossRefPubMed

45.

Stief CG, Padley RJ, Perdok RJ, Sleep DJ (2002) Cross-study review of the clinical efficacy of Apomorphine SL 2 and 3 mg: pooled data from the three placebo-controlled, fixed-dose crossover studies. Eur Urol 1(No 3, Suppl):12–20

46.

Caruso S, Agnello C, Intelisano G, Farina M, Di Mari L, Cianci A (2004) Placebo-controlled study on the efficacy and safety of daily apomorphine SL intake in premenopausal women affected by hypoactive sexual desire disorder and sexual arousal disorder. Urology 63:955–959CrossRefPubMed

47.

Bechara A, Bertolino MV, Casabe A, Fredotovich N (2004) A double-blind randomized placebo control study comparing the objective and subjective changes in female sexual response using sublingual apomorphine. J Sex Med 1:209–214CrossRefPubMed

48.

Argiolas A, Melis MR, Gessa GL (1988) Yawning and penile erection: central dopamine—oxytocin—adrenocorticotropin connection. Ann NY Acad Sci 525:330–337PubMed

49.

Isidori A, Di Luigi L, Conte D (1984) ACTH 1–17 and sexual behaviour. Ric Clin Lab 14:247–251PubMed

50.

Bretto LA, Gorzalka BB (2000) Melatonin enhances sexual behaviour in the male rat. Physiol Behav 68:483–486CrossRef

51.

Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P (2004) Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci (PNAS) USA 101:10201–10204CrossRef

52.

Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R (2006) An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med 3:628–638CrossRefPubMed

53.

Hedlund P (2004) PT-141 Palatin. Curr Opin Investig Drugs 5:456–462PubMed

54.

Hull KL, Harvey S (2000) Growth hormone: a reproductive endocrine-paracrine regulator. Rev Reprod 5:175–182CrossRefPubMed

55.

Juul A, Andersson AM, Pedersen SA, Jorgensen JO, Christiansen JS, Groome NP, Skakkebaek NE (1998) Effects of growth hormone replacement therapy on IGF-related parameters and on pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled cross-over study. Horm Res 49:269–278CrossRefPubMed

56.

Böger RH, Skamira C, Bode-Böger SM, Brabant EG, von zur Mühlen A, Frölich JC (1996) Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. J Clin Invest 98:2706–2713PubMedCrossRef

57.

Ückert S, Ness BO, Becker AJ, Stief CG, Jonas U (2005) Mechanism of action of human growth hormone (GH) on isolated human penile erectile tissue. J Urol 173 (No 4, Suppl):291 (abstract)

58.

Becker AJ, Ückert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U (2000) Possible role of human growth hormone in penile erection. J Urol 164:2138–2142CrossRefPubMed

59.

Hartmann U, Hannover Medical School, Dept. of Psychiatry, personal communication

60.

Rudman D, Feller AG, Nagraj HS, Gregans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE (1990) Effects of growth hormone in men over 60 years old. N Engl J Med 323:1–6

61.

Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, Grunfeld C (1996) Growth hormone replacement in older men improves body composition but not functional ability. Ann Intern Med 124:708–716PubMed

62.

Smith RG, Sun Y, Betancourt L, Asnicar M (2004) Growth hormone secretagogues: prospects and potential pitfalls. Best Pract Res Clin Endocrinol Metab 18:333–347CrossRefPubMed

63.

Arvat E, Gianotti L, Giordano R, Broglio F, Maccario M, Lanfranco F, Muccioli G, Papotti M, Graziani A, Ghigo E, Deghenghi R (2001) Growth hormone-releasing hormone and growth hormone secretagogue-receptor ligands: focus on reproductive system. Endocrine 14:35–43CrossRefPubMed

64.

Chapman IM, Bach MA, van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO (1996) Stimulation of the growth hormone (GH)—insulin-like growth factor I axis by daily administration of a GH secretagogue (MK 677) in healthy elderly subjects. J Clin Endocrinol Metab 81:4249–4257CrossRefPubMed

65.

Burnett AL, Truss MC (2002) Mediators of the female sexual response: pharmacotherapeutic implications. World J Urol 20:101–105CrossRefPubMed

Title: Potential future options in the pharmacotherapy of female sexual dysfunction
Authors: Stefan Ückert
Margit E. Mayer
Udo Jonas
Christian G. Stief
Publication date: 01-12-2006
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 6/2006
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-006-0121-z

At a glance: The STEP trials

Springer Medicine

Potential future options in the pharmacotherapy of female sexual dysfunction

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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