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(Drug information on 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(Drug information on 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(Drug information on 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(Drug information 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(Drug information on fluoxetine) inhibit NO synthetase somewhat, but paroxetine inhibits NO synthetase more.
Several case reports suggest that the 5-phosphodiesterase inhibitors (PDE5s) such as sildenafil(Drug information on sildenafil), tadalafil, and vardenafil(Drug information on 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.
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.
Psychopharmacological and hormonal factors in SD