Chad P. Hubsher, MD
■ Adam Luchey, MD
■ Stanley
Zaslau, MD, MBA, FACS
■ Introduction
■ Treatment of female sexual dysfunction is complicated by the lack of a single causative agent, overlap of different types of dysfunction, and limited proven treatment options.
■ Although sexual therapy and education, such as cognitive behavioral therapy, individual and couple therapy, and physiotherapy, continue to form the basis of treatment, there is limited research to demonstrate the benefit of psychotherapy.
■ Recent developments in the treatment of male erectile dysfunction have led to the investigation of pharmacotherapy for sexual dysfunction in women.
■ This chapter will attempt to describe the various noninvasive interventions to help ameliorate sexual dysfunction in women. However, prior to starting treatment, the patient should be evaluated thoroughly for all medical illnesses and drug history that may produce sexual dysfunction.
■ Psychotherapeutic Interventions
■ Female sexual problems are generally the result of a complex interaction of biological and psychosocial factors.
■ First-line treatment of female sexual dysfunction involves patient education and psychotherapeutic interventions that include:
• Basic counseling
• Cognitive behavioral therapy
• Interventions for the individual woman
• Couple therapy
■ The goal of a psychotherapeutic treatment program is to assist the woman in both understanding her own physiology, feelings, and emotions and in communicating with her partner.
Basic Counseling and Education
■ The initial treatment strategy of psychotherapeutic intervention, basic counseling, starts with the physician’s readiness to give the patient time to talk about her sexuality and sexual problems.
■ According to Annon, who developed a scheme for the behavioral treatment of sexual problems, inviting the patient to talk about her sexuality and entering into a dialogue with her physician may in itself provide a therapeutic effect, helping the patient not to feel so isolated and alone, but rather accepted and understood.1
• As the patient tells her story, it is imperative that the physician engage in active listening. This means allowing her to tell the complete story and then summarizing the story back to her before asking specific questions.
■ Many women have only partial knowledge of the basic facts of anatomy, physiology, and the human sexual response. Providing information about the differences between men and women, dispelling destructive myths concerning male and female sexuality, and educating the patient on the frequency and types of sexual problems women often experience can empower the patient by giving her knowledge and giving her problems a name.
• As described by Bitzer and Brandenburg, some common myths that may be encountered include:
■ A healthy woman always has an orgasm.
■ Sex must lead to orgasm.
■ Masturbation is only for singles.
■ Not having sex leads to health problems.
■ A man always wants sex and can always have it.
■ Passion equals love.
■ Sex must be spontaneous.
■ Menopausal women lose interest in sex.
■ Women want less sex than men.
■ Women always need a lot of foreplay.
■ Pornography is only for men (if at all).2
■ Furthermore, patients should continue to educate themselves about their situation.
• Women should be encouraged to read books or articles about sexual function and understand, for example, that not having orgasms during each sexual encounter does not mean that the experience was a failure and, as discussed by Walton and Thorton, clitoral stimulation may be more likely to lead to orgasm than coital intercourse.2
■ Lifestyle changes are also an important aspect of education, as modification of known risk factors, including hypertension, hyperlipidemia, diabetes, cigarette smoking, or drug or alcohol abuse, is part of the treatment process. A healthy diet, adequate sleep, and exercise will promote physical and sexual well-being.
Cognitive Behavioral Therapy (CBT)
■ In CBT, sexual dysfunction is looked upon as a learned behavior, either via classical conditioning, operant conditioning, or model learning.
■ The result is a behavior sequence characterized by a specific sexual stimuli, response, and contingency.
■ As described by Bitzer and Brandenburg, past experiences, resulting in sexual signals or bodily reactions, may lead to negative or positive emotional consequences that are stored in the amygdala and hippocampus.3
■ CBT attempts to help people become aware of the stimuli, reaction, and consequence of sexual behavior, so that they may learn what enhances or inhibits their own sexual pleasure.
■ Furthermore, patients are encouraged to understand their typical ways of thinking and the associated emotional or physical response, and to use CBT to help alter the resultant reaction.
• For example, according to Bitzer and Brandenburg, the generic thought of lacking interest in sex may be accompanied by feelings of depression and frustration. This, in turn, could provoke reactions of defensiveness or wanting to fight, resulting in inhibition of the physical reactions of pleasure, such as vasodilation.3
• CBT encourages changing the thought to lacking interest in sex intermittently and only in the usual way it is had. In this way, the patient may feel less depressed, which may lead to a better physical response.
■ McCabe analyzed the effectiveness of a CBT program in 54 sexually dysfunctional females and demonstrated that after therapy, respondents experienced:
• Lower levels of sexual dysfunction
• More positive attitudes toward sex
• Perceptions that sex was more enjoyable
• Fewer affected aspects of sexual dysfunction in their relationship
• Lower likelihood of perceiving themselves as a sexual failure4
■ In fact, as discussed by Ghizzani, even when the etiology of female sexual dysfunction is organic, behavioral therapy may help patients change their behavior, overcome anger, sadness, and frustration, and communicate needs, and therefore improve their sexual function.5
Interventions Focusing on the Individual Female
■ Psychotherapeutic interventions that focus on the individual woman attempt to help the patient become aware of her bodily signals and sexuality, while facilitating or inhibiting conditions related to pleasurable feelings.
■ There are two types of therapeutic interventions that focus solely on the woman and have demonstrated some efficacy in improving female sexual dysfunction: pelvic floor and general body awareness exercises.
■ According to Kegel, patients should become aware of the different elements of the pelvic floor, the movements of this part of the body, and the relationship between the pelvic floor muscles and their respiration.6
• Physiotherapists and biofeedback instruments can promote this awareness, and women can learn to train their pelvic floor muscles and use them to increase proprioception of their vagina and vulva.
• Exercises to increase pelvic floor awareness include:
■ Interrupting the flow of urine
■ Core exercises
■ Personal massage
■ Stretching
■ General body awareness exercises, mainly described by LoPiccolo and Lobitz, encourage women to take an active role in their sexuality by exploring and experiencing their body.7
• Each patient is encouraged to investigate her body by:
■ Observing her naked body in a mirror
■ Exploring her genitalia for sensitive areas and areas that can be stimulated
■ Progressively stimulating the genitalia, first by herself and then with a partner.
• These exercises serve to reactivate the personal patterns of excitement, stimulation, and pleasure and help the patient find those postures and movements that lead to sexual excitement.
■ A psychoanalytic, psychodynamic approach to the individual female, as described by Kaplan, views sexual problems as an internal conflict between sexual drive, originating in the id, and the societal norm, originating in the ideal self or superego.8
• This creates a situation in which the bodily expression of the sexual drive, such as excitation and lubrication, is blocked, thus resulting in sexual dysfunction.
• Psychodynamic-oriented therapy helps the patient overcome this internal conflict and encourages acceptance of the various elements of human sexuality, including fantasies and instincts.
Couple Therapy
■ Sexual desire is often directed toward another person and, thus, sexual interaction becomes an issue of communication and exchange.
■ Partners frequently have difficulty listening to each other and accepting the views, feelings, or thoughts of the other person.
■ Partner counseling can teach basic listening skills, as well as the importance of respecting the partner and understanding how to express criticism without hurting the other.
■ The goal is to improve communication and facilitate compromise.
■ Masters and Johnson developed a basic form of couple sex therapy that combines behavioral, cognitive, and psychodynamic therapy.9
• It involves home exercises combined with discussion topics in which the partners are helped to become aware of their thoughts and feelings during intimate interactions (Table 10.1).
• The couple is then instructed to report back to the therapist to discuss any encountered difficulties or resistance to change and learn how to improve their communication.
■ Pharmacological Interventions
■ There are a number of medications available for the treatment of female sexual dysfunction; however, no single therapy has been established as the gold standard.
■ The study of sexual dysfunction in women has lagged behind research into male sexual health, resulting in slow progress in the development of pharmacological therapy for female sexual dysfunction.
■ Nonetheless, estrogens, androgens, dopaminergic agents, nitric oxide donors, prostaglandins, and alpha-melanocyte-stimulating hormones are commonly used to treat female sexual dysfunction, although the results are variable.
AU: If table moved it will fall before table callout
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Table 10.1 Couples Home Exercises and Discussion Topics |
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Exercises to Conduct at Home |
Discussion and Reflection |
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Step 1: Caressing the body excluding the genitals, changing active and passive roles. Two times per week for 45 min. |
What feels good, bad, irritating, or uncomfortable? |
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Step 2: Caressing the body including the genitals, changing active and passive roles. Two times per week for 45 min. |
Exploring without the objective of stimulations, feelings, and communication about the experience. Feeling safe. |
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Step 3: Manual stimulation with changing roles and building up excitation. |
How does it feel to play with stimulation, building it up and letting it subside? |
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Step 4: The man lies back and the woman sits on him, introducing the penis into the vagina. |
The emotional significance of penetration, feeling close, and having the woman in control |
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Step 5: Movement and position experimentation |
Sharing sexual stimulation with body movements and body expression |
Estrogens
■ For many years, estrogens have been the mainstay treatment of sexual dysfunction in women, and are currently the most commonly used medication for the treatment of female sexual dysfunction.
■ Estrogen therapy is available in a variety of forms, including:
• Oral tablets
• Dermal patches
• Vaginal pessaries
• Vaginal estrogen tablets
• Estrogen creams and jellies
■ A meta-analysis conducted by Cardozo and associates revealed a strong correlation between levels of estrogen and sexual function in peri- and postmenopausal women.10
■ Furthermore, irrespective of the route of administration, estrogen significantly improves dyspareunia and vaginal pH.
■ Four randomized placebo-controlled studies by Casson et al., Nathorst-Boos et al., Sherwin, and Dennerstein et al. have all indicated that the improvement of sexual function observed with estrogen replacement in postmenopausal women was primarily based on local vaginal changes, such as relief of vaginal dryness, atrophy, and dyspareunia.11-14
■ Although in postmenopausal women estrogen replacement therapy appears to improve sexual function, one must additionally consider the effects the estrogen has on serum testosterone.
• In plasma, testosterone is largely bound to sex hormone-binding globulin, with only 1-2% of total circulating testosterone being free and biologically active.
• The administration of estrogen replacement therapy increases production of sex hormone-binding globulin, which in turn may result in less available free testosterone and subsequently lead to a decrease in libido, as described by Sherwin.15
• Therefore, it is plausible that postmenopausal women who have failed to correct their sexual dysfunction solely with estrogen replacement therapy may improve their sexual response by also being treated with testosterone. Estrogen replacement therapy is primarily indicated for vaginal dryness and dyspareunia, not decreased libido or frequency of sexual activity.
• However, the systemic effects of estrogen replacement therapy are not observed with local estrogen therapy, such as patches, pessaries, creams, and jellies.
Androgens
■ In clinical practice, testosterone is currently the most commonly used androgen, followed by dehydroepi- androsterone (DHEA) and androstenedione.
■ Although there are no detailed guidelines, many clinicians believe that women with symptoms of low libido
who have a total testosterone level less than 20 ng/dL and a free testosterone level of 0.9 or less may be prescribed testosterone substitution therapy.
■ The prescribed dosages and duration of testosterone treatment vary on a case-by-case basis and, thus, routine monitoring is necessary.
■ Adequacy of treatment is determined by the patient’s self-assessment of improvement in sexual function; however, the side effects of weight gain, clitoromegaly, and increased facial hair should additionally be monitored.
■ In females, the normal range of testosterone varies from 20 to 100 ng/dL.
■ As a woman approaches menopause, she experiences a decline in ovarian function, a decrease in adrenal secretion, and an increase in peripheral androgen metabolism.
• These changes result in a decrease in the levels of circulating androgens, such as DHEA, dehydroepi- androsterone sulfate (DHEA-S), androstenedione, and testosterone.
■ According to Davis, women with testosterone deficiency tend to experience diminished sexual desire and fantasies, a decreased sense of vitality and well-being, and a loss of pubic hair.16
■ A widely accepted indication for testosterone replacement therapy is female androgen deficiency syndrome.
• In this disorder, women present with low libido, decreased motivation, fatigue, and a lack of well-being, but still show normal plasma estrogen levels and free serum testosterone levels in the lower third range.
■ Similarly, hypoactive sexual desire disorder, the most common form of sexual dysfunction in women, may be treated with testosterone therapy, as determined by Laumann and colleagues.17
■ Currently, only one form of testosterone, Estratest, which is a combination of estradiol and methyltestosterone and manufactured by Solvay Pharmaceuticals, has been approved in the United States for women with hypoactive sexual desire disorder.
■ For the treatment to be effective, testosterone levels must be raised to the upper end of the normal range.
■ According to several studies by Modelska and Milian, naturally and surgically menopausal women show greater improvement in psychological symptoms, such as lack of concentration, depression, and fatigue, as well as sexual function, including decreased libido, arousal, and inability to have an orgasm, when taking estrogen replacement therapy plus androgen therapy as compared to estrogen replacement therapy alone.18
■ In women who have never had much sexual desire, or who have not experienced a change in libido, testosterone is probably not the appropriate therapy.
■ However, as described by Burger and Davis, the addition of testosterone may be beneficial in women who have experienced a noticeable decline in desire and sexual function.19
■ Therefore, it is important to properly assess a woman’s sexual behavior and specific complaints of sexual dysfunction prior to deciding therapy regimens.
Oral Testosterone and DHEA
■ Oral testosterone is rapidly metabolized by the liver and therefore has no bioavailability.
■ The oral androgen testosterone undecanoate compounds in a lipid matrix to avoid degradation, but must be administered in substantial amounts two to three times a day to achieve clinical effects. Furthermore, this formulation is only approved for use in Europe and Canada.
■ An orally active testosterone preparation available in the United States, known as methyltestosterone, works by reducing the androgen-binding capacity of sex hormonebinding globulin and, thus, elevates free and non-protein- bound testosterone.20
• This facilitates endogenous and exogenous entry of androgens into the central nervous system and improves sexual function.
• Methyltestosterone has been commonly used for treatment of decreased libido in postmenopausal women when it is combined with estradiol to form Estratest.
• Although methyltestosterone appears to improve decreased libido and ameliorate hypoactive sexual desire disorder, significant concerns, described by Simon, exist regarding possible liver toxicity.21
■ The best way to deliver oral testosterone may be in the form of DHEA replacement.
• In the United States, DHEA is currently available over the counter as a dietary supplement.
• Guay and Jacobson have shown it to have positive effects on libido, and Hackbert and Heiman have shown it to have positive effects on sexual arousal, vaginal pulse amplitude, and vaginal blood flow.22,23
• However, DHEA should be used with caution, as there is not enough research on dosages or duration for specific recommendations to be made.
Transdermal Testosterone
■ Transdermal testosterone can be administered in the form of testosterone patches, creams, or gels and may achieve very high levels of testosterone with fewer side effects than oral testosterone.
■ In a study by Shifren and colleagues, a testosterone patch increased frequency of sexual activity and pleasure/ orgasm in women with bilateral oophorectomy who had impaired sexual function, despite estrogen replacement.24
■ Alternatively, a testosterone cream, often between 1% and 3%, is available by prescription and may be applied to the clitoris and inner labia approximately half an hour before sexual activity to help improve sensation.
• The applied testosterone cream helps to build up thin atrophic genital tissue, but constant use may result in enlargement of the clitoris or increased genital hair growth.
■ Testosterone gels are also available in the United States and have the advantage of providing testosterone in a controlled-delivery format. However, as described by Redmond, these gels should be used with caution, as the relationship of testosterone gel dose to serum testosterone level has yet to be fully investigated.25
■ An alternative method of delivery of testosterone is the subcutaneous administration of testosterone pellets, which are inserted in the abdominal wall every three to six months, often in conjunction with estradiol pellets.
• The subcutaneous implantation of pellets containing testosterone and estradiol has been used in Great Britain and Australia, but is not common in the United States.
• As described by Burger and associates, these hormonal implants provide significant improvement in libido, but may increase total testosterone to supra- physiological levels, causing side effects such as hirsutism and voice changes.26
■ The route of administration, duration, and dosage of testosterone all influence the risk of androgen toxicity in women.
■ It is important to find a balance that will help women with their libido without causing side effects of liver dysfunction or masculinization, including hirsutism, acne, deepening voice, weight gain, and alopecia.
■ Hepatocellular damage is a serious side effect of testosterone replacement and liver function should be monitored whenever testosterone is administered.
Tibolone
■ Tibolone is a synthetic steroid that has tissue-specific estrogenic, prostagenic, and androgenic properties that may improve sexual function, particularly sexual desire and arousal.
■ The effects of tibolone, as described by Kloosterboer, have been attributed to the intrinsic capacity of the A4-isomer, a tissue metabolite of tibolone, which activates the androgen receptor, as well as to the reduction in sex hormone— binding globulin and the resulting increase in bioavailable testosterone.27
■ Recent clinical trials by Egarter and colleagues and Baracat and associates reported beneficial effects of tibo- lone on sexual function in postmenopausal women, due to both an increase in genital blood flow and the central estrogenic/androgenic activity.28,29
■ However, there is a need for future randomized and placebo-controlled trials in order to completely assess the effects of tibolone on sexual function and determine which subtypes of female sexual dysfunction may be effectively treated by tibolone compared to other available therapeutic options.
■ At this time, tibolone has been approved for treatment of female sexual dysfunction only in Europe and Asia.
Sildenafil (Viagra)
■ Sildenafil is an oral phosphodiesterase-5 (PDE-5) inhibitor, the introduction of which has revolutionized the treatment of erectile dysfunction in men. The mechanism of action in the penis is similar to that in the clitoris.
■ PDE-5 inhibitors decrease the catabolism of guanosine monophosphate (cGMP), the second messenger in nitric oxide-mediated relaxation in clitoral and vaginal smooth muscles.
• This results in an accumulation of cGMP in the clitoris.
• Higher cGMP levels cause greater relaxation and dilation of the blood vessels, which may lead to greater and more prolonged clitoral engorgement.
■ However, in 1999, Kaplan and colleagues reported no overall improvement in sexual function in postmenopausal women after sildenafil treatment, even though vaginal lubrication and clitoral sensitivity did increase.30
• Similar results were observed in 2002 by Basson and associates, who conducted a large, randomized, controlled trial of women with female sexual arousal disorders and concluded that sildenafil did not improve sexual function.31
■ Although the effectiveness of sildenafil has yet to be determined in the general population presenting with female sexual dysfunction, several investigators have reported it to increase sexual function in patients taking selective serotonin reuptake inhibitors (SSRIs).
• In fact, Fava and associates and Shaller and colleagues determined that sildenafil improved several aspects of sexual function in women, especially in women whose sexual dysfunction arises from the use of SSRI antide- pressants.32,33 These areas in which improvement was seen include:
■ Vaginal lubrication and clitoral sensitivity
■ Arousal
■ Frequency of sexual fantasies, sexual intercourse, and orgasm
■ Sipski and colleagues have shown success with sildenafil in women with spinal cord injury (SCI). In her study of 19 women with SCI, significant increases in subjective arousal (SA) were observed with both sildenafil and sexual stimulation conditions. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation.34
■ However, at this time, sildenafil is not approved by the U.S. Food and Drug Administration (FDA) for treatment of female sexual dysfunction.
Vardenafil (Levitra) and Tadalafil (Cialis)
■ Vardenafil and tadalafil are PDE-5 inhibitors, similar to sildenafil, that have been approved by the FDA for the treatment of erectile dysfunction in men.
■ However, their role in the treatment of female sexual dysfunction has not been well studied, and the results of clinical studies remain inconclusive.
■ There is some evidence that these medications may show promise, though. Angulo and colleagues conducted a study that showed that vardenafil increases clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs.35
■ At this time, none of the oral PDE-5 inhibitors, sildenafil, vardenafil, or tadalafil, have been approved by the FDA for the treatment of female sexual dysfunction.
Phentolamine and Yohimbine
■ Phentolamine and yohimbine are antagonists of the alpha-adrenergic receptor and in the past have been thought to be beneficial in treating sexual dysfunction in women.
■ They are peripheral nonselective alpha-blockers that act by causing smooth muscle relaxation, resulting in vasodilatation.
■ According to Rosen and colleagues, phentolamine has been shown to increase self-reported lubrication and sexual arousal.36 Furthermore, it may be beneficial in estrogenized postmenopausal women with female sexual arousal disorder, as was determined by Rubio-Aurioles and associates.37
■ Yohimbine, however, failed to show any improvement in placebo-controlled trials, including in patients with female sexual dysfunction induced by SSRIs, as determined by Michelson and colleagues.38
■ Nonetheless, both phentolamine and yohimbine require further clinical evaluation to determine if and how they are effective in treating sexual dysfunction in women.
Other Medications
■ To date, the results of clinical studies of a variety of drugs under evaluation for treatment of female sexual dysfunction have been inconclusive. These drugs include PDE-5 inhibitors (e.g., sildenafil, vardenafil, and tadalafil), peripheral nonselective alpha-blockers (e.g., phentolamine and yohimbine), vasoactive agents (e.g., apomorphine), L-arginine, oxytocin, prostaglandin E1, ginkgo biloba, caffeine, and low doses of psychostimulants.
■ Currently, these medications are being tested in women with sexual dysfunction as single therapy or in combination with each other.
■ Conclusions
■ Sexual dysfunction in women is a multifactorial and complex problem that has only recently begun to be studied.
■ Recent advances in anatomical, physiological, and psychological research have led to increased insight into female sexual function, suggesting that management of female sexual dysfunction should include both psychological and medical evaluation.
■ Treatment of women with sexual problems often starts with sexual therapy and education.
• However, spurred by the recent developments in treatment of male erectile dysfunction, the medical management of female sexual dysfunction is rapidly developing.
■ Currently, hormonal options are the mainstay of treatment, especially in postmenopausal women. Still, there are a number of other medical therapies available that may play a role in future treatment options for women.
■ Further studies are essential for creating effective treatment strategies and obtaining more insight into the phar- macotherapeutic similarities and differences between men and women.
■ References
1. Annon J. The PLISSIT model: a proposed conceptual scheme for the behavioural treatment of sexual problems. J Sex Educ Ther. 1976;2:1-4.
2. Walton B, Thorton T. Female sexual dysfunction. Curr Women’s Health Rep. 2003;3:319-326.
3. Bitzer J, Brandenburg U. Psychotherapeutic intervention for female sexual dysfunction. Maturitas. 2009;63:160-163.
4. McCabe MP. Evaluation of a cognitive behavior therapy program for people with sexual dysfunction. J Sex Marital Ther. 2001;27:259-271.
5. Ghizzani A, Razzi S, Fava A, Sartini A, Picucci K, Petraglia F. Management of sexual dysfunction in women. J Endocrinol Invest. 2003;26:137-138.
6. Kegel AH. Sexual function in the pubococcygeus muscle. West J Surg Obstet Gynecol. 1952;60:521-524.
7. LoPiccolo J, Lobitz WC. The role of masturbation in the treatment of orgasmic dysfunction. Arch Sex Behav. 1972;2:163-171.
8. Kaplan HS. Editorial: Sex is psychosomatic. J Sex Marital Ther. 1975;1:275-276.
9. Johnson VE, Masters WH. A team approach to the rapid diagnosis and treatment of sexual incompatibility. Pac Med Surg. 1964;72:371-375.
10. Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998;92:722-727.
11. Casson PR, Elkind-Hirsch KE, Buster JE, Hornsby PJ, Carson SA, Snabes MC. Effect of postmenopausal estrogen replacement on circulating androgens. Obstet Gynecol. 1997;90:995-998.
12. Nathorst-Boos J, von Schoultz B, Carlstrom K. Elective ovarian removal and estrogen replacement therapy—effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol. 1998;4:283-293.
13. Sherwin BB. The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women. J Clin Endocrinol Metab. 1991;72:336-343.
14. Dennerstein L, Burrows GD, Wood C, Hyman G. Hormones and sexuality: effect of estrogen and progestogen. Obstet Gynecol. 1980;56:316-322.
15. Sherwin B. Use of combined estrogen-androgen preparations in the postmenopause: evidence from clinical studies. Intl J Fertility Womens Med. 1998;43:98-103.
16. Davis S. Testosterone deficiency in women. J Reprod Med. 2001;46:291-296.
17. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999;281:537-544.
18. Modelska K, Milian M. Treatment of female sexual dysfunction in postmenopausal women—what is the evidence? Rev Gynaecol Pract. 2004;4:121-124.
19. Burger H, Davis S. Should women be treated with testosterone? Clin Endocrinol. 1998;49:159-160.
20. Gooren LJ. A ten-year safety study of the oral androgen testosterone undecanoate. J Androl. 1994;15:212-215.
21. Simon JA. Safety of estrogen/androgen regimens. J Reprod Med. 2001;46:281-290.
22. Guay AT, Jacobson J. Decreased free testosterone and de- hydroepiadosterone-sulfate (DHEA-S) levels in women with decreased libido. J Sex Marital Ther. 2002;28:129-142.
23. Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. 2002;11:155-162.
24. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682-688.
25. Redmond GP. Hormones and sexual function. Int J Fertil Womens Med. 1999;44:193-197.
26. Burger H, Hailes J, Nelson J, Menelaus M. Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br Med J. 1987;294:936-937.
27. Kloosterboer HJ. Tibolone: a steroid with tissue- specific mode of action. J Steroid Biochem Mol Biol. 2001;76:231-238.
28. Egarter C, Topcuoglu A, Vogl A, Sator M. Hormone replacement therapy with tibolone: effects on sexual functioning in postmenopausal women. Acta Obstet Gynecol Scan. 2002;81:649-653.
29. Baracat EC, Barbosa IC, Giordano MG, et al. A randomized open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability. Climacteric. 2002;5:60-69.
30. Kaplan SA, Reis RB, Kohn IJ, et al. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology. 1999;53:481-486.
31. Basson R, McInnes R, Smith MD, Hodgson G, Koppiker N. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. J Womens Health Gend Based Med. 2002;11:367-377.
32. Fava M, Rankin MA, Alpert JE, Nierenberg AA, Worthington JJ. An open trial of oral sildenafil in antidepressant-induced sexual dysfunction. Psychother Psychosom. 1998;67:328-331.
33. Shaller JL, Behar D. Sildenafil citrate for SSRI-induced sexual side effects. Am J Psychiatry. 1999;156:156-157.
34. Sipski ML, Rosen RC, Alexander CJ, Hamer RM. Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury. Urology. 2000;55:812-815.
35. Angulo J, Cuevas P, Cuevas B, Bischoff E, Saenz de Tejada I. Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs. Int J Impot Res. 2003;15:137-141.
36. Rosen RC, Phillips NA, Gendrano NC 3rd, Ferguson DM. Oral phentolamine and female sexual arousal disorder: a pilot study. J Sex Marital Ther. 1999;25:137-144.
37. Rubio-Aurioles E, Lopes M, Lipezker M, et al. Phentolamine mesylate in postmenopausal women with female sexual arousal disorder: a study. J Sex Marital Ther 2002;28:205-215.
38. Michelson D, Kociban K, Tamura R, Morrison MF. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake associated female sexual dysfunction: a randomized, placebo controlled trial. J Psychiatr Res. 2002;36:147-152.