J Korean Med Assoc.  2016 Feb;59(2):136-143. 10.5124/jkma.2016.59.2.136.

Pharmacologic management of female sexual dysfunction

• Yoon H
• Park K

• KMID: 2153719
• DOI: http://doi.org/10.5124/jkma.2016.59.2.136

Abstract

In female sexual dysfunction (FSD), psychological and contextual factors significantly influence organic components of sexual response and behavior. The hormonal environment also affects FSD. Therefore, a tailored medical approach to each individual's sexual symptom is inevitable. This paper reviews currently available pharmacological treatment of FSD including the most recent advances and future targets in pharmacotherapy. In hormonal therapies for FSD, efficacy of estrogens and androgens on the treatment of vaginal atrophy, low sexual desire, and small subsets of genital arousal disorder, respectively, have been demonstrated. However, we need more data regarding long-term safety. There are two non-hormonal agents approved by the US Food and Drug Administration. Flibanserin has shown marginal benefit over placebo for the treatment of hypoactive sexual desire disorder. Ospemifen has shown beneficial effect on vulvovaginal pain from hormone related atrophy although it requires a longer period data to assess safety in other female genital organs, such as uterus and ovaries. Controversies still remain regarding hormonal therapies for FSD. Besides, some of the developing drugs still require more reliable safety and efficacy data. However, pharmacologic treatment of FSD is a promising field yet to be explored.

Keyword

Female; Sexual dysfunction; Drug therapy

MeSH Terms

Androgens
Arousal
Atrophy
Drug Therapy
Estrogens
Female*
Genitalia, Female
Humans
Ovary
Sexual Dysfunctions, Psychological
United States Food and Drug Administration
Uterus
Androgens
Estrogens

Reference

1. Portman D, Palacios S, Nappi RE, Mueck AO. Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the treatment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial. Maturitas. 2014; 78:91–98.

2. Goldstein SR, Bachmann GA, Koninckx PR, Lin VH, Portman DJ, Ylikorkala O. Ospemifene Study Group. Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy. Climacteric. 2014; 17:173–182.

3. Reviriego C. Flibanserin for female sexual dysfunction. Drugs Today (Barc). 2014; 50:549–556.

4. Derogatis LR, Komer L, Katz M, Moreau M, Kimura T, Garcia M Jr, Wunderlich G, Pyke R. VIOLET Trial Investigators. Treat-ment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the VIOLET Study. J Sex Med. 2012; 9:1074–1085.

5. Jayne C, Simon JA, Taylor LV, Kimura T, Lesko LM. SUN-FLOWER study investigators. Open-label extension study of flibanserin in women with hypoactive sexual desire disorder. J Sex Med. 2012; 9:3180–3188.

6. Yoon H. Management of female sexual dysfunction. Korean Andrology Society. Textbook of andrology. 2nd ed. Seoul: Koonja Publishing;2010. p. 501–510.

7. Segraves RT, Clayton A, Croft H, Wolf A, Warnock J. Bupro-pion sustained release for the treatment of hypoactive sex-ual desire disorder in premenopausal women. J Clin Psycho-pharmacol. 2004; 24:339–342.

8. Segraves RT, Croft H, Kavoussi R, Ascher JA, Batey SR, Foster VJ, Bolden-Watson C, Metz A. Bupropion sustained release (SR) for the treatment of hypoactive sexual desire disorder (HSDD) in nondepressed women. J Sex Marital Ther. 2001; 27:303–316.

9. Davis AR, Castano PM. Oral contraceptive and sexuality. In : Goldstein I, Meston CM, Davis SR, Traish AM, editors. Women's sexual function and dysfunction: study, diagnosis and treatment. New York: Taylor & Francis;2005. p. 290–296.

10. Wierman ME, Nappi RE, Avis N, Davis SR, Labrie F, Rosner W, Shifren JL. Endocrine aspects of women's sexual function. J Sex Med. 2010; 7(1 Pt 2):561–585.

11. Wierman ME. Sex steroid effects at target tissues: mechanisms of action. Adv Physiol Educ. 2007; 31:26–33.

12. Park K, Kim MK, Kim KW, Ahn KY, Lee SE, Ryu SB. Effect of delayed estrogen replacement on clitoral corpus cavernosal blood flow and histologic composition in rabbit. Korean J Urol. 2004; 45:268–273.

13. Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, Sheng L. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol. 2007; 110(2 Pt 1):230–240.

14. Dennerstein L, Dudley E, Burger H. Are changes in sexual functioning during midlife due to aging or menopause? Fertil Steril. 2001; 76:456–460.

15. De Ziegler D, Fanchin R. Progesterone and progestins: appli-cations in gynecology. Steroids. 2000; 65:671–679.

16. Laan E, van Lunsen RH, Everaerd W. The effects of tibolone on vaginal blood flow, sexual desire and arousability in post-menopausal women. Climacteric. 2001; 4:28–41.

17. Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. A prospective longitudinal study of serum testosterone, dehydro-epiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab. 2000; 85:2832–2838.

18. Jun JH, Yoon H. Effect of menopause on the expression of an-drogen receptors in human vagina. Korean J Androl. 2004; 22:24–30.

19. Shifren JL, Avis NE. Surgical menopause: effects on psycholo-gical well-being and sexuality. Menopause. 2007; 14(3 Pt 2):586–591.

20. White WB, Grady D, Giudice LC, Berry SM, Zborowski J, Snabes MC. A cardiovascular safety study of LibiGel (testo-sterone gel) in postmenopausal women with elevated cardio-vascular risk and hypoactive sexual desire disorder. Am Heart J. 2012; 163:27–32.

21. Pfaus J, Giuliano F, Gelez H. Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med. 2007; 4 Suppl 4. 269–279.

22. Safarinejad MR. Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female sub-jects with arousal disorder: a double-blind placebo-controlled, fixed dose, randomized study. J Sex Med. 2008; 5:887–897.

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

24. Nappi RE, Cucinella L. Advances in pharmacotherapy for treat-ing female sexual dysfunction. Expert Opin Pharmacother. 2015; 16:875–887.

25. Wright JJ, O'Connor KM. Female sexual dysfunction. Med Clin North Am. 2015; 99:607–628.

26. Schoen C, Bachmann G. Sildenafil citrate for female sexual arousal disorder: a future possibility? Nat Rev Urol. 2009; 6:216–222.

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

28. Kielbasa LA, Daniel KL. Topical alprostadil treatment of female sexual arousal disorder. Ann Pharmacother. 2006; 40:1369–1376.

29. Van Rooij K, Poels S, Bloemers J, Goldstein I, Gerritsen J, van Ham D, van Mameren F, Chivers M, Everaerd W, Koppeschaar H, Olivier B, Tuiten A. Toward personalized sexual medicine (part 3): testosterone combined with a Serotonin1A receptor agonist increases sexual satisfaction in women with HSDD and FSAD, and dysfunctional activation of sexual inhibitory mechanisms. J Sex Med. 2013; 10:824–837.

30. Van der Made F, Bloemers J, Yassem WE, 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; 6:777–790.