Continuing Education Offering: The goal of this article is to educate nurse practitioners about low libido in postmenopausal women. Nurse practitioners may obtain 2 contact hours by reading this article and earning a passing score on the test that follows. For immediate test results, take the quiz online at www.advanceweb.com/np.
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describe method of treating low libido in women.
Directions: Check the box next to the best answer.
There was a time when a diminished sex drive or inadequate sexual performance was a topic for late-night comedy routines or water-cooler gossip. Viagra and its counterparts changed that. A new sexual revolution has emerged, and this time it features baby boomers. Now, in addition to treating the expected cardiac and orthopedic anomalies in middle age and beyond, primary care providers are caught up in the medicalization of sexual satisfaction. Researchers estimate that at least 50% of adult women experience sexual dissatisfaction in the form of decreased desire and arousal.1,2
Classifying Low Libido
Female sexual dysfunction (FSD) is a clinical condition defined as "persistent or recurring reduction of sex drive or aversion to sexual activity, difficulty becoming aroused, inability to reach orgasm, or pain during sexual intercourse."3 According to this definition, FSD encompasses everything from anorgasmia to dyspareunia. This article focuses on postmenopausal women and uses the terms "low libido" and "reduced sex drive" interchangeably.
The International Consensus Development Conference on Female Sexual Dysfunction developed a classification system that includes the components of FSD used by the Food and Drug Administration (FDA) when evaluating the efficacy of drugs (Table 1).4 The same classification list is in the Diagnostic and Statistic Manual of Mental Disorders.5 Using these criteria, low libido would be clinically diagnosed as hypoactive sexual desire disorder (HSDD) or female sexual arousal disorder (FSAD).
The Female Sexual Response
To understand available treatments and related research efforts, knowledge of the female sexual response is necessary. During sexual activity, the brain becomes stimulated through somatic pathways that arise from the skin and travel through the dorsal nerve of the clitoris to the pudendal nerve. The stimulated brain then increases neurologic output to clitoral receptors. This in turn leads to the conversion of L-arginine (stored in clitoral tissue) into nitric oxide. The presence of nitric oxide results in vasodilation of the clitoral erectile tissue, smooth relaxation of the arteriole, and subsequent clitoral-vaginal engorgement. At the same time, similar neurogenic impulses are sent to the vagina, leading to increased lubrication, vaginal wall engorgement and increased vaginal diameter.2
Hormones play an integral role in the female sexual response as well. Adequate estrogen and testosterone must be available for the brain to sense incoming arousal stimuli.6 Research indicates that estrogen preserves the vascular function of female sex organs and affects genital sensation.7 Estrogen receptors are located in the reproductive organs as well as the urethra and bladder neck. The hormone is believed to promote blood flow to these areas and to assist with lubrication and thickening of the vaginal epithelium, characteristics that make intercourse more comfortable.8 In addition, estrogen influences the central nervous system during sexual excitement by mediating the expression of vaginal and clitoral nitric oxide synthase.8
Much less has been determined about the impact of testosterone on female sexual function, but many studies have linked a decrease in testosterone to diminished libido.7-10 Testosterone's specific role in female sexual response is unclear. Some researchers have hypothesized that it is the hormone of sexual desire in women and claim that it has an additional effect on general well-being.8 Pharmaceutical companies are paying particular attention to testosterone, with the hope that a synthetic androgen will provide the same sexual boost for women that it has for men.
Causes of Low Libido
There are multiple and complex reasons why postmenopausal women might be less inclined to engage in or enjoy sexual activity. These can be viewed in the framework of biological, motivational-affective and cognitive domains.6 Assessing patients in this manner allows you to more clearly identify the cause of libido changes, as well as the direction and goal of treatment.
Biological Causes
Whether menopause occurs naturally or surgically, its associated physiologic changes have a significant impact. Age and the presence or lack of intact ovaries distinguishes these patients and helps determine treatment goals.
Biological changes can be divided into physical and hormonal alterations. Physical changes after menopause are most significant in women who have reached menopause naturally.2 About half of these women report some degree of urogenital atrophy, vaginal dryness and dyspareunia.2 Changes in the levator ani muscle and perineal membrane may also lead to painful intercourse or anorgasmia.11 These changes are believed to be the result of aging as well as decreased estrogen production. Younger postmenopausal women typically report fewer symptoms.12
Hormonal changes play a significant role in postmenopausal women as well. A decrease in estrogens — and, more importantly, androgens — can deprive a woman of the ingredients needed to maintain a healthy sex drive. These hormones appear to act on the central and peripheral nervous systems to enhance reaction to sexual stimuli and the quality of sexual responses.11
Ovarian androgen production comprises 50% of the total testosterone level in women. This level drops dramatically after oophorectomy, diminishing the neurobiological aspects of the sexual response. Decreased muscle strength and fatigue have also been linked with decreased androgen levels, further hindering libido.13 The ovary continues secreting androgens after menopause. Therefore, after naturally induced menopause, women experience only a slight, gradual decline in androgen levels and typically experience fewer sexual problems than women who have had oophorectomy.14
Decreased estrogen levels can influence a woman's sexual function as well. Delayed clitoral reaction, decreased vaginal lubrication, diminished circulatory response during sexual stimulation, and reduced contractions during orgasm have all been linked to decreases in circulating estrogen.14 These symptoms can be reversed with hormone replacement therapy, further supporting estrogen's influence on sexual function.3
Motivational Causes
Many factors motivate a woman to engage in sexual activity. Androgen status or biological shifts may be less important than psychosocial factors and health status.15 Stress and poor physical health have been identified as predictors of sexual dysfunction. Some experts suggest that a woman's sexual desire may originate in her response to her partner's interest rather than from a spontaneous sexual reaction.16 For women, sexuality extends far beyond hormones and neurotransmitters.2 Research confirms that arousal is often influenced more by thoughts and emotions than by genital feedback.16
Motivational, affective and cognitive alterations can be rooted in depression, anxiety, stress or relational conflicts that interfere with nervous system pathways involved in arousal.6 Alcohol or drug dependence, outside relationships, personal distress, partner abuse or poor coping skills can influence feelings of sexual desire.16,17 In addition, treatments and procedures such as chemotherapy or mastectomy can influence self-image and interest in sexual contact.
Many patients report complex cognitive and motivational issues that need to be addressed before a healthy sex drive can be achieved. Assessment of these factors is critical to planning treatment and setting reasonable, attainable goals.
Recognizing Low Libido
To ensure that sexual issues are discussed, questions about libido should be a routine part of each well woman visit (Table 2). Answers will lead to further evaluation, including the use of an appropriate assessment tool such as the Female Sexual Function Index (FSFI), the Profile of Female Sexual Function (PFSF), the Sexual Function Questionnaire (SFQ-V1), or an independently developed algorithm.18-21
The FSFI, a brief self-report instrument consisting of 19 items, has been validated as an appropriate screening tool. Nevertheless, it cannot determine the onset or duration of sexual dysfunction or the presence of maintaining or etiologic factors, limiting it to initial collection of data and periodic comparative analysis of treatment efficacy.18
The PFSF is one of the newer instruments specifically designed to assess loss of sexual desire and associated symptoms in postmenopausal women with low libido.20 It is a self-administered, multinational, psychometrically validated instrument that includes the assessment of personal distress as it relates to sexual dysfunction.
Developed primarily for use in clinical trials, the SFQ-V1 has strong validity and reliability in determining the presence of FSD.21 This brief questionnaire contains items that have been judged clinically relevant by an external panel of providers. One achievement unique to this instrument is its specificity. Anxiety, depression and other aspects of life satisfaction were not reflected in scores, suggesting that the SFQ independently reports changes in sexual function.21
In addition to direct questioning, you can encourage patients to initiate discussion about sexuality by providing literature in the waiting room or exam room. Initiate a standard dialogue to help ensure that ashamed, fearful or otherwise hesitant women will not be overlooked because of their reluctance to ask questions or report problems.
Ask about sexual satisfaction when determining differentials for fatigue, depression or anxiety, since these might coexist or be causative stressors in patients with low libido. All postmenopausal women are at high risk for sexual dysfunction and can benefit from regular assessments of sexual satisfaction.
Diagnosing Low Libido
All postmenopausal women should complete a sexual health assessment tool at annual screening appointments. These results establish a baseline and help determine the efficacy of any treatment regimen.2
Once low libido has been identified, an attempt to discover a biological basis for dysfunction might include diagnostic testing. Remember, however, that a decreased androgen level is an expected finding in postmenopausal women. Discovering this may not enhance the plan of care and will certainly add to patient expense. Specific guidelines for the diagnosis of sexual dysfunction have not been developed, but research indicates that no single androgen level is predictive of low libido, making such tests inappropriate.1,10,22
Diagnostic tests can rule out comorbidities, such as thyroid dysfunction, cardiovascular disease and diabetes. Thyroid-stimulating hormone, complete blood count, liver function tests and lipid profile may prove helpful in ruling out an organic etiology, and they are recommended before initiating any therapies.14 The most important part of diagnosis is determining which factors — in addition to the expected hormone deficiencies — are present.
In summary, the diagnosis of low libido is best made based on subjective information. Diagnostic testing is useful only for ruling out a comorbidity that may require attention. Sexual health assessment tools can be helpful in determining the presence of dysfunction and the efficacy of therapy.
Treatment of Low Libido
Treatment choice (Table 3) varies depending on the age of the patient and whether menopause has occurred naturally or as a result of surgery. It is vital that both you and your patient understand that success takes time — and that reevaluation will be necessary.
Prescription Treatments
Some biological causes of low libido can be addressed with hormone replacement.23 Estrogen and its derivatives have been used to treat menopausal symptoms for more than 40 years.23 Estrogen-only hormone therapy (HT) has been the subject of intense research in recent years, and women who have an intact uterus should not take unopposed estrogen therapy due to the risk of endometrial hypertrophy or malignancy.23,24 Instead, they should take only estrogen-progestin combinations.
One aspect of oral estrogen therapy that significantly affects sexual health is its apparent effect on sex hormone-binding globulin (SHBG). Oral estrogens increase SHBG levels, which then decrease the bioavailability of sex steroids such as testosterone.23,25 Postmenopausal patients who report decreased libido and take oral estrogens might benefit from a change in delivery method. Switching to a topical or transdermal method may improve libido symptoms.23 One choice is an estradiol gel (Estrogel), which is recommended for women without an intact uterus.26 To treat low libido, 1.25 g estradiol gel should be applied topically to the arm each day. Estrogen is available orally (Premarin, Estrace), transdermally (Vivelle, Estraderm), topically (Vagifem) or as a vaginally inserted ring (Femring).24
A transdermal methyltestosterone patch, Intrinsa, came close to market approval in 2004 but was rejected by the FDA due to concerns about the long-term safety of topical methyltestosterone.27,28 Several significant studies showed that this 300 mcg/day testosterone patch increased sexual desire and frequency of sexual activity, was well tolerated and presented few side effects.27,28
The North American Menopause Society's (NAMS) position statement about testosterone therapy in postmenopausal women clearly states that transdermal patches and topical gels or creams are preferred over oral products because of first-pass effects.10 This recommendation is for all postmenopausal women. NAMS adds that oral testosterone is generally not well absorbed and does not result in measurable blood levels of the hormone.10 Androgen replacement therapies now in clinical trials include two metered-gel products for transdermal delivery, a 0.5% testosterone gel created by Cellegy (Tostrelle) and another created by BioSante and Antares (LibiGel).29
Solvay Pharmaceuticals is pursuing approval of 1% testosterone gel (Androgel) for the treatment of low libido.29 No oral testosterone medications for women are being investigated in the United States at this time. In Canada, testosterone undecanoate (Andriol), a medication for male androgen deficiency, is often used.10
Available as off-label alternatives in the United States are oral methyltestosterone (Android, Oreton, Testred), transdermal testosterone (Testoderm, Androderm), and topical propionate cream and gel (Androgel). These have FDA indications for men only at this time.24 Administration routes under investigation for women include subcutaneous, intramuscular, sublingual, buccal and transdermal.10
Therapies that combine estrogens and androgens are available by prescription in oral and topical forms. Tablets of 1.25 mg esterified estrogen with 2.5 mg methyltestosterone (Estratest) and 0.625 mg esterified estrogen with 1.25 mg methyltestosterone (Estratest HS) are available. This is the only FDA-approved testosterone product for women and is indicated for moderate to severe vasomotor symptoms associated with menopause. It is often used off label to treat sexual desire disorders.10,23,30 Research shows that adding testosterone to combined esterified estrogen decreases SHBG levels, yielding increased concentrations of bioavailable free testosterone. This has been linked to an increase in female sexual desire.14,30
It is important to inform patients that most androgen replacement therapy has not been approved for use in women. Most of the available data are based on short-term, limited studies.14
Tibolone (Livial), a synthetic steroid developed by Organon that has estrogenic, androgenic and progestagenic properties, has been available in Europe for 20 years and is certainly worth mentioning.3,31 While tibolone itself has no biological activity, its effects represent the activity of its metabolites on various tissues.31 These include an estrogenic effect on bone and vaginal tissue a progestogen effect on endometrial tissue and androgenic effects on the brain and liver.31 This results in improved vaginal blood flow and lubrication, as well as increased sexual desire and arousability.3 Furthermore, tibolone inhibits human breast cell proliferation and stimulates apoptosis.32 Traditional hormone replacement does neither.32 Tibolone does not stimulate the endometrium, eliminating concern about malignancy. Additionally, the substance lowers total cholesterol, plasma triglycerides and lipoproteins.32 Tibilone is now in phase II clinical trials in the United States.29
Few FDA-approved treatments are available for low libido. But the pipeline is crowded with possibilities: melanocortin agonists, alpha-adrenoceptor antagonists, prostaglandins, dopaminergic agents and nitric oxide facilitators.29,33,34
Bremelanotide, an alpha melanocyte-stimulating hormone delivered intranasally, is being investigated by Palatin Technologies for its effect on sexual dysfunction through stimulation of melanocortin receptors in the brain. It is in phase III clinical trials. Bremelanotide focuses on the central nervous system and not the vasculature. It has successfully induced sexual solicitation behaviors in the female rat, leading to increased interest in human investigation.35-37
Phentolamine mesylate (Regitine), an alpha-adrenoceptor antagonist, is being successfully used off label as an injectable treatment for erectile dysfunction in men.33,34 Its manufacturer, Zonagen, has also created a 40-mg oral phentolamine for women. Early research indicates mild improvement in arousal and vaginal lubrication.33,38
Prostaglandins have been used in the treatment of male sexual dysfunction for years, and studies are now investigating their use in women with low libido. This class is perceived to improve libido for women by relaxing the vaginal arterial smooth muscle and increasing vaginal secretions.33,39,40 NexMed is developing a topical alprostadil cream (Femprox) that is in phase II clinical trials and features a permeation applicator to deliver the drug vulvally.14
Bupropion, a dopaminergic agent, has proved fairly successful in treating sexual dysfunction resulting from antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs).41,42 Decreased libido and anorgasmic disorder are both associated with the use of SSRIs. Bupropion is often prescribed off label as an alternative antidepressant. Other dopaminergic agents now in clinical trials include sublingual and intranasal apomorphine, a centrally acting drug used for erectile dysfunction.43,44 It is believed to act on dopamine receptors in the brain that are involved in copulatory behavior. Studies of premenopausal women with low libido are encouraging, and Nastech Pharmaceuticals continues to investigate its possible use for this population.29,34
Sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra) are nitric oxide facilitators and phosphodiesterase inhibitors that can enhance vaginal engorgement during erotic stimulation. However, change in vaginal tone does not consistently result in a subjective sexual arousal.33 Researchers continue to investigate the efficacy and safety of oral sildenafil in women, but results are still fairly inconclusive.45,46 Sildenafil has demonstrated efficacy in the treatment of emergent low libido associated with serotonergic antidepressant use.47
Ongoing, critical investigation is necessary to keep abreast of updated availability and efficacy of all drugs. An excellent way to acquire information about the latest pharmaceutical advances is to visit Center Watch at www.centerwatch.com.
Nonprescription Approaches
Several nonprescription substances have produced promising results in preliminary trials involving women: dehydroepiandrosterone (DHEA), ginkgo biloba, yohimbine and arginine.48,49 Other herbal products are available in combination forms.49
DHEA is an androgenic steroid hormone that, with its sulfate (DHEAS), is the most abundant hormone in the body. DHEA is a precursor in the synthesis of other sex hormones and is produced by the adrenal glands.4,48,49 Circulating DHEA declines with age and suddenly after surgical menopause, and this has been linked to a decline in sexual desire.14,25,48,49 Synthetic DHEA appears to be well tolerated with few reported adverse effects. Its use is not recommended in patients with psychiatric disorders or those with breast or endometrial cancer, due to increased risks.49 A common therapeutic dosage is 25 mg twice daily.
The sexual effects of ginkgo biloba were accidentally discovered when an elderly man with sexual symptoms related to antidepressant use began taking the substance to improve his memory. His sexual function improved significantly, catching the attention of researchers. Ginkgo has since been recommended for the treatment of sexual dysfunction caused by SSRIs, but conflicting research findings and poor study models warrant caution. Postmenopausal women have not been studied.49
Yohimbine is derived from the bark of the yohimbe tree. When combined with arginine, an essential amino acid in animal products, it has produced an increase in measured physical arousal in women.48-50 The yohimbine herb is thought to increase nitric oxide production in women through its alpha-adrenergic blocking effects.48 In the vascular epithelium, arginine is directly converted to nitric acid. This leads to smooth-muscle dilation and increased blood flow.49 Research indicates that this combination increases vaginal response to erotic stimuli, as proven with photoplethysmograph measurements of vaginal pulse amplitude.48,49,51
L-arginine cream is available and widely marketed, as are oral yohimbine and yohimbine-arginine combination products.14 Both compounds carry significant risks and should be carefully evaluated before use.48,49
Berkeley Premium Nutraceuticals markets a supplement called Avlimil for the treatment of hot flashes, night sweats and decreased sexual desire in women.52 This product combines 11 herbal extracts including sage leaf, red raspberry leaf, kudzu root, red clover, bayberry fruit, ginger root and black cohosh root. Many of these substances are phytoestrogens, substances that increase circulating estradiol levels.48 None of the ingredients has been studied for the treatment of low libido.49 Avlimil is said to promote blood flow and muscle relaxation to improve sexual response and restore normal estrogen levels.52 Packaging lists the dose as 756 mg per tablet, but individual herbal components are not quantified.
Drugs that interact adversely with this product include anticoagulants, antiplatelets, diabetes medications, contraceptives, estrogens and antihypertensives, making it a poor choice for many postmenopausal patients.52
Another available herbal supplement, ArginMax by Daily Wellness Company, combines L-arginine with ginseng, ginkgo, damiana, calcium, iron and several vitamins.14 Damiana is an African shrub considered a powerful aphrodisiac via its enhancement of dopamine levels in the brain.48 Preliminary studies of this oral combination demonstrated up to 70% improvement in desire and sexual responsiveness in postmenopausal women.48 Few side effects are linked to this product, with the exception of a noted herpes exacerbation in patients with preexisting oral or genital herpetic infections.48
In addition to oral combination products, several topical treatments are available. The topical massage oil Zestra combines borage seed oil, evening primrose oil, angelica extract, vitamin C, vitamin E and coleus extract.49 The product is designed to enhance female sexual pleasure and arousal when applied to the clitoris, labia and vaginal opening.53 All components of this product are available as dietary supplements in the United States and generally recognized as safe by the FDA.53 The borage and evening primrose oils metabolize to form prostaglandin E, which leads to increased blood flow and nerve conduction in the areas of application. Other ingredients are believed to facilitate the sexual arousal response through various chemical processes, each leading to engorgement of the clitoral and vaginal tissues.53 Safety data on Zestra are limited and should be carefully reviewed with interested patients. A published study determined that Zestra improved desire, arousal, sensations, pleasure and ability to have orgasms. The effects were reported by women with low libido as well as women who had reported no previous sexual difficulty.
Lifestyle Modifications
An effective treatment plan for low libido recognizes and addresses coexisting physical concerns. Biological factors other than hormonal changes, such as fatigue, stress and poor nutritional state, can play a significant role in low libido.12,17 Regular exercise, proper diet and smoking cessation must be part of any plan aimed at restoring sexual satisfaction.
The existence of diseases or disorders must be fully evaluated, since they may influence postmenopausal sexual dysfunction.2,14 Disorders of the neurologic, vascular or endocrine systems can significantly affect libido, as can many medications for common health problems. Neurologic disorders may influence arousal or orgasm by interfering with the neural pathways involved in these responses. Atherosclerosis has been linked to impaired sexual functioning secondary to impaired circulation in the vagina and clitoris.2,14,17,24 Table 4 provides a brief overview of medications and conditions that can result in diminished sexual drive. Proper management of any coexisting conditions may provide significant relief from troubling sexual symptoms.2,14
The Relationship Factor
Certainly the most complex and difficult component of low libido is the human contact involved in sexual intimacy, as well as the relationship (or lack thereof) integral to this contact. This does not pertain to autoerotic activity but does include any partnership regardless of sexual orientation or relationship duration. Women often translate intimacy or relational cues into a desire or lack of desire for sexual activity.2
Interestingly, several studies that have measured vaginal response to erotic stimuli in addition to subjective arousal found that a biologically produced change in sexual organs does not necessarily guarantee a noticeable improvement in subjective sexual desire.16,33 Often, a change in vaginal lubrication or pulse amplitude is not indicative of increased libido. This supports the theory that a woman's interest in sex can be strongly influenced by feelings, beliefs and the relational component of sexual activity with a partner.
In all circumstances, an honest dialogue about relationship status and quality should be a starting point and continuing focus of care. Explain to patients that honesty about their sexual relationships is essential to determining any impact on libido. This is often difficult for women to discuss, especially if their lack of libido has led to relational frustration or anger. Reassure patients that the intent of treatment is to seek the causes of dysfunction, not to place blame. It might be helpful to acknowledge that the problem could be multifactorial, requiring several treatment approaches. This assures the patient that her acknowledgement of relationship problems is not a contraindication to investigation of other therapies.
To clinically address the cognitive and motivational issues that might decrease desire or arousal, become familiar with counselors and psychiatric-mental health NPs in your area. Partnering with a psychiatric-mental health NP, sex therapist or other professional with expertise in this area can provide a truly collaborative plan of care.2
Putting It Into Practice
With a thorough understanding of the physiology of the female sexual response and the changes that occur after menopause, you are now likely to identify more women with low libido. Suggestions for integrating recognition and treatment into daily practice include the following:
Stay informed. Research about low libido is ongoing, and available treatment information is changing constantly. You can become an excellent source for accurate and timely information about all treatment options. When possible, provide copies of these findings, written at the appropriate level, to patients.
Sexual health is an important aspect of the human experience. By keeping an open mind, listening to patients and providing evidence-based treatment options, you can help improve quality of life for postmenopausal patients who experience low libido.
References
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Leila McKinney is a family nurse practitioner who practices in the emergency department at Morton Plant Hospital in Clearwater, Fla. She has a special clinical and personal interest in women's sexual health.