S16 From whence comes HSDD? - The Journal of Family Practice

Opportunities for intervention in HSDDTable 1Current options for testosterone therapy in women with HSDDType of therapyCombination of oral esterified estrogensand methyltestosterone*Testosterone products approved forthe treatment of low testosteronedisorders in men (used off-label inwomen)Custom compounded products(eg, buccal therapy with testosteronelozenge)Comments*Manufacturer discontinued supplying product to US market in March 2009.HSDD, hypoactive sexual desire disorder.Table 2• Only for use in postmenopausal women• Available in various formulations (oral, intramuscularinjection, transdermal)• Doses must be adjusted downward for use in women,then titrated according to clinical responseNote: Appropriate doses have not been clearlyestablished for women with low sexual desire.• Requires availability of skilled compoundingpharmacist• Clinician must be knowledgeable andexperienced in this approachHerbal therapies and proposed mechanisms of action in femalesexual dysfunction 33TherapyGinkgo bilobaL-arginineDamiana leafGinsengProposed mechanism of actionIncreases blood flow by inhibiting platelet-activating factorRequired to produce nitric oxide; increases blood flowStimulates sexual desire; may have progestin-like actionPhytoestrogenic activity; increases blood flowdesire, fantasy, orgasm, and overall satisfaction. 26 Currently,no testosterone products are specifically approved bythe US Food and Drug Administration (FDA) for the treatmentof low sexual desire in women. However, some optionsare available, as listed in Table 1. At present, only oraltherapy is FDA approved for use in women (albeit not forthe treatment of sexual dysfunction). Transdermal testosteroneis being evaluated in clinical trials of women withsexual dysfunction. Some practitioners are treating suchwomen with transdermal testosterone products that areapproved by the FDA for various disorders in men; thesetherapies are being prescribed off label in women, withdoses adjusted as needed. Family physicians should familiarizethemselves with the treatments listed in Table 1 so asto evaluate potential advantages in specific patients.The beneficial effects of testosterone therapy haveprompted research into treatments designed specificallyfor HSDD or other forms of female sexual dysfunction(FSD). A wide range of formulations, including injections,implants, and tablets, have been studied, with varying results.27 In recent years, the most active area of developmentin the United States has involved transdermalformulations. A controlled trialof surgically menopausal women withHSDD who were receiving estrogen replacementtherapy found that the additionof a testosterone patch (delivering300 mcg/d) for 24 weeks significantlyincreased the frequency of episodes ofsexually satisfying activity (Figure). 28Furthermore, the testosterone groupexhibited a significant increase in sexualdesire and a significant decreasein distress. The risk of a patient experiencingat least one type of androgen–related adverse effect (eg, acne, alopecia,unwanted hair growth, or voicedeepening) was lower in the testosteronegroup than in the placebo group(12.7% vs 15.8%, respectively). Lipidprofiles were similar in the 2 groups.Other studies likewise documentedsignificant increases in the frequencyof satisfying sexual episodes, as wellas significant increases in desire anddecreases in distress, during 24 weeksof treatment with a testosterone patch(300 mcg) vs placebo in postmenopausalwomen with HSDD who werenot taking estrogen. 29 The overall incidence of androgenicadverse events was higher with the 300 mcg testosteronepatch than with placebo (30.0% vs 23.1%, respectively).Most of this difference was attributable to a significantlyhigher incidence of increased hair growth with testosterone300 mcg/d, compared with placebo (19.9 vs 10.5%, respectively).The frequency and severity of acne, alopecia,and voice deepening were similar between groups, andmost of these events were considered to be mild. However,various studies have produced conflicting data concerningthe safety of exogenous testosterone in women, and thelonger-term effects (including the potential impact on therisk of breast cancer) remain unknown. 27 Large-scale studiesof sufficient duration are needed to shed more light onthese issues.Studies have also documented benefits with transdermaltestosterone creams or gels. In a crossover trial ofpremenopausal women with diminished libido, a ≥50%increase in total sexual self-rating score was reported by46% of women with testosterone cream, compared with19% with placebo, after 12 weeks of treatment with eachstudy drug. 30 A testosterone gel for use in HSDD is currentlyin late stages of clinical development. 31,32Complementary and alternative therapiesSeveral forms of complementary and alternative medicine(CAM) have been used to treat FSD, including symptomsassociated with HSDD. Many herbal derivativesare based on traditional Chinese and Native Americanmedicine. 33 The mechanisms of action of these therapiesare largely unknown, although hypotheses have been advancedto explain their effects (Table 2). 33Only limited data are available concerning the effectivenessand long-term safety of most of these products inHSDD or other forms of FSD. In one of the few publishedreports (a randomized, placebo-controlled, double-blindtrial of women with sexual dysfunction secondary to antidepressanttherapy) improvements were observed withboth ginkgo biloba and placebo, but there were no significantdifferences between treatments. 34 A randomized,double-blind, crossover study of 24 women with sexualarousal disorder found significant improvements frombaseline with yohimbine (with or without L-arginine glutamate),but the effects were not significantly differentfrom those achieved with placebo. 35Other work has produced conflicting results concerningsupplementation with dehydroepiandrosterone(DHEA), which is produced in the adrenal gland and convertedto testosterone. In a 4-month, randomized study ofwomen with adrenal insufficiency, DHEA was associatedwith significant improvements in the frequency of sexualthoughts or fantasies, sexual interest, and sexual satisfaction.36 However, DHEA failed to produce significant improvementsin sexuality measures. 37-39 Commercial DHEAsupplements are sold over the counter.In addition, a variety of nonprescription oral andtopical commercial products are being marketed with theassertion that they can improve female sexual function.These products contain proprietary blends of herbal andother botanical ingredients as well as vitamins and minerals.33 A handful of studies have reported significant increasesin sexual desire and arousal with these treatments. Forinstance, a randomized, double-blind, placebo-controlledtrial found significant improvements in sexual arousal, desire,and pleasure with the use of an herbal topical cream. 40Another controlled study identified improvements in sexualdesire and other measures of sexual function with a nutritionalsupplement that supposedly enhances a woman’ssexual response by increasing blood flow and promotingrelaxation. 41 In the case of most commercial products, how-FigureChanges in 4-week frequency of scoresassociated with transdermal testosteronevs placeboA4 wk mean changefrom baselineBMean change frombaseline (SEM)CMean change from baseline3Total satisfying sexual activity2.521.510.500 4 8 12 16 20 24WeeksSexual desire141210864200 4 8 12 24WeeksPersonal distress0-5-10-15-20-25-300 4 8 12 24WeeksTestosteronePlaceboP≤.05 vs placeboChanges in 4-week frequency of total satisfying sexual activity, sexual desire score,and personal distress with transdermal testosterone vs placebo over 24 weeks.*P≤.05, transdermal testosterone vs placebo.Reprinted with permission from Simon JA, et al. Testosterone patch increases sexualactivity and desire in surgically menopausal women with hypoactive sexual desiredisorder. J Clin Endocrinol Metab. 2005;90:5226-5233.ever, few or no studies have been conducted, and existingdata have been neither peer reviewed nor published, leavingquestions regarding efficacy and safety unanswered. 33Physicians should be aware that an increasing numberof women are using alternative medicines, including productsthat claim to improve sexual response. 33,42 Notably,large-scale surveys have found that approximately 70% ofadults do not disclose the use of CAM to their physicians. 42S28 July 2009 / Vol 58, No 7 / Supplement to The Journal of Family Practice Copyright © 2009 Dowden Health Media and DIME www.jfponline.comSupplement to The Journal of Family Practice / Vol 58, No 7 / July 2009 S29