April 15, 2008
Psychiatric Times.
No. 5
Common Issues in Female Sexual Dysfunction
Bonnie R. Saks, MD
Dr Saks is president of the society for sex therapy and research and clinical professor of psychiatry at the University of South Florida in Tampa. She reports that she is on the Speakers' Bureau of Wyeth, Forest, and Cephalon; and is on the advisory board of Procter and Gamble Pharmaceuticals.
Psychopharmacological and hormonal factors in SD
Hyperactive sexual desire disorder may be an adverse effect of treatment with a serotonin reuptake inhibitor (SRI). Serotonin (5-HT) may decrease dopamine levels, leading to increased levels of prolactin, which in turn can inhibit libido.11 SRIs that stimulate postsynaptic serotonin receptors also affect sexual function. In addition, psychotropic drugs that stimulate the 5-HT2 receptors inhibit orgasm12; and 5-HT1b, 5-HT2, and 5-HT3 stimulation appears to physiologically inhibit libido.13
It has been suggested that dopaminergic drugs may increase libido. One proposed mechanism is that D2 receptors in the pituitary inhibit prolactin production.14 Other clinical studies have shown that l-dopa may also cause an increase in libido by stimulating dopamine receptors.15 Of the serotonin receptor agonists, only those that affect 5-HT1a (eg, buspirone) may slightly enhance libido. The results of a study by Ashton and Rosen16 indicate that bupropion may be an antidote to SRI-induced SD. Agents that deplete serotonin or augment dopamine activity may have prosexual effects, especially in reversing SRI-induced anorgasmia.17 Some SSRIs, such as paroxetine, seem to have stronger inhibitory effects than others.18
It is quite difficult to determine who (other than women who have had both ovaries removed) may be testosterone deficient. It is an even greater conundrum trying to decide to what extent testosterone deficiency inhibits sexual desire in a particular woman. There is a great deal of research and controversy around the use of testosterone in restoring or enhancing sexual desire in women.
As far back as 1950, Greenblatt and colleagues19 reported the results of a double-blind study on methyltestosterone to increase libido in women. Sherwin and Gelfand20 studied women after surgical menopause was induced by removal of both ovaries. They found that women who received estrogen and testosterone had higher sex drive than those who received estrogen alone. When performing hysterectomies, gynecologists no longer routinely remove the ovaries because the ovaries may continue to produce androgen (which helps to preserve sexual interest) well into a woman's later years.21
In the United States, physicians may order, off-label, compounded testosterone cream if they think a patient has a testosterone deficiency. However, overprescribing testoster- one may lead to changes in lipid metabolism, acne, hirsutism and, rarely, liver toxicity.22
It is known that 70% to 80% of testosterone is bound to sex hormone-binding globulin. The remainder is bound primarily to albumin. Only 2% is free and unbound. Even more confounding, the measurement of free testosterone level does not necessarily reflect intracellular level, which is the true biological substrate.23
SSRIs, nitric oxide, and 5-phosphodiesterase inhibitors
SSRIs may also inhibit arousal by inhibiting nitric oxide (NO) synthetase. This leads to reduced ability to relax smooth muscles, thus limiting vasocongestion. Sertraline and fluoxetine inhibit NO synthetase somewhat, but paroxetine inhibits NO synthetase more.
Several case reports suggest that the 5-phosphodiesterase inhibitors (PDE5s) such as sildenafil, tadalafil, and vardenafil may be effective in women,24 especially in restoring orgasm (although it is difficult to know how much may be placebo effect). Study results are difficult to gauge because sexual desire and arousal are multidetermined in women. To compound the complexity of studies in this area, many women are not easily "in touch" with their own arousal. MRI studies have shown that there is a "disconnect" for women—a time lapse—from the occurrence of physical arousal (vasocongestion and vaginal lubrication) to the time when a woman is consciously aware of arousal; and for some women the 2 do not correlate at all.25
Pharmacological treatment strategies
There are several strategies for treating SD. For women with SD induced by an SSRI or nonserotonin reuptake inhibitor, caution must be used to maintain the therapeutic effect of the antidepressant while attempting to reduce SD. This can be accomplished by switching to an antidepressant with fewer adverse sexual effects, reducing the dosage of the SSRI or SRI, or adding another drug to enhance libido (Table). Although some of these treatments are off-label, there are anecdotal successes and theoretical rationale for using these drugs. As always, however, benefit must be balanced against risk.
Conclusion
Although there are pharmacological treatments and other strategies for treating women with SD, many more randomized, controlled clinical studies are needed to elucidate and find the best treatments for various kinds of SD in all stages of a woman's life.
Psychiatrists, along with gynecologists and sex therapists, are in the best position to treat women with sexual difficulties. Understanding a woman's dynamics, her history, her chemistry, and where she is in her life cycle and her relationship(s) is crucial in optimizing treatment. In the meantime, although there is no simple panacea, there are solutions we can offer our patients to minimize sexual difficulties.
• Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294:91-96.
• Heiman JR, Gittelman M, Costabile R, et al. Topical alprostadil (PGE1) for the treatment of female sexual arousal disorder: in-clinic evaluation of safety and efficacy. J Psychosom Obstet Gynecol. 2006;27:31-41.
References
1. Endicott J. The menstrual cycle and mood disorders. J Affect Disord. 1993;29:193-200.
2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54-61.
3. Joffe H, Hall JE, Soares CN, et al. Vasomotor symptoms are associated with depression in perimeno- pausal women seeking primary care. Menopause. 2002;9:392-398.
4. Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry. 2001;58: 529-534.
5. Pearlstein T, Rosen K, Stone AB. Mood disorders and menopause. Endocrinol Metab Clin North Am. 1997;26: 279-294.
6. Basson R. Female sexual response: the role of drugs in the management of sexual dysfunction. Obstet Gynecol. 2001;98:350-353.
7. Grazziotin A, Yee L, Saks, B. Women at their best--sexy sexagenarians--physiology vs. expectations. Symposium at the World Congress of Sexology; April 18, 2007; Sydney, Australia.
8. Whipple B, Perry JD. The G-spot: a modern gynecologic myth. Am J Obstet Gynecol. 2002;187:519.
9. Stahl SM. The psychopharmacology of sex, part 1: neurotransmitters and the 3 phases of the human sexual response. J Clin Psychiatry. 2001;62:80-81.
10. Sabatier N. alpha-Melanocyte-stimulating hormone and oxytocin: a peptide signalling cascade in the hypothalamus. J Neuroendocrinol. 2006;18:703-710.
11. Baldessarini RJ, Marsh E. Fluoxetine and side effects. Arch Gen Psychiatry. 1990;47:191-192.
12. Komisaruk BR, Beyer-Flores C, Whipple B. The Science of Orgasm. Baltimore, Md: Johns Hopkins University Press; 2006.
13. Mendelson SD. Review and reevaluation of the role of serotonin in the modulation of lordosis behavior in the female rat. Neurosci Behav Rev. 1991;16:309-350.
14. Wing YK, Clifford EM, Sheehan BD, et al. Paroxetine treatment and the prolactin response to sumatriptan. Psychopharmacology (Berl). 1996;124:377-379.
15. Barbeau A. l-dopa therapy in Parkinson's disease: a critical review of nine years' experience. Can Med Assoc J. 1969;101:59-68.
16. Ashton AK, Rosen RC. Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry. 1998;59:112-115.
17. Segraves RT. Reversing anorgasmia associated with serotonin uptake inhibitors. JAMA. 1991;266: 2279.
18. Bielski RJ, Bose A, Chang CC. A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder. Ann Clin Psychiatry. 2005;17:65-69.
19. Greenblatt RB, Barfield WE,Garner JF, et al. Evaluation of an estrogen, androgen, estrogen-androgen combination, and a placebo in the treatment of the menopause. J Clin Endocrinol Metab. 1950;10: 1547-1558.
20. Sherwin BB, Gelfand MM. Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. Am J Obstet Gynecol. 1985;151:153-160.
21. Bancroft J, Cawood EH. Androgens and the menopause; a study of 40-60-year-old women. Clin Endocrinol (Oxf). 1996;45:577-587.
22. Mays ET, Christopherson W. Hepatic tumors induced by sex steroids. Semin Liver Dis. 1984;4: 147-157.
23. Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294:91-96.
24. Richardson D, Goldmeier D, Kocsis A. PDE5 inhibitors may help some women with sexual problems. Sexual Relationship Ther. 2005;20:65-69.
25. Polan ML, Desmond JE, Banner LL, et al. Female sexual arousal: a behavioral analysis.Fertil Steril. 2003,80:1480-1487.
26. Saks BR. Mirtazapine: treatment of depression, anxiety, and hyperemesis gravidarum in the pregnant patient: a report of 7 cases. Arch Women Mental Health. 2001;3:165-170.
27. Heiman JR, Gittelman M, Costabile R, et al. Topical alprostadil (PGE1) for the treatment of female sexual arousal disorder: in-clinic evaluation of safety and efficacy. J Psychosom Obstet Gynecol. 2006;27:31-41.
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