Sexual Dysfunction in Postmenopausal Women: A Focus on Evaluation and Treatment

After completing this continuing education article, the pharmacist should be able to:

Behavioral Objectives

• Describe the relationship between menopause and a decline in sexual dysfunction, particularly the impact on sexual desire.
• Define hypoactive sexual desire disorder.
• Explain the relationship between androgen concentrations and sexual function in postmenopausal women.
• Identify and compare the various therapeutic options for the management of sexual dysfunction in postmenopausal women.
• Given a patient case, identify an appropriate treatment regimen and its corresponding monitoring plan.

Female sexual dysfunction is a multifaceted problem that includes physiologic, psychological, and emotional components. Sexual dysfunction is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and it is divided into different categories. The primary characteristic of each category is impairment in normal sexual functioning. This may refer to an inability to perform or reach orgasm, painful sexual intercourse, a strong repulsion of sexual intercourse, or an exaggerated sexual response cycle or sexual interest.¹

Sexual dysfunction is further defined as distress and impairment resulting from a disturbance in sexual desire and the emotional and physiologic changes of the sexual response cycle.² Sexual dysfunction is a broad term for various conditions. Hypoactive sexual desire disorder (HSDD) is the most common condition affecting women. HSDD is defined as a lack of desire for sexual activity, including lack or absence of sexual fantasies, that results in personal distress.^2,3

The exact incidence of female sexual dysfunction is unknown.² Community studies wherein women self-report sexual dysfunction, usually via questionnaires, have identified rates of sexual dysfunction ranging from 8% to 50%.⁴ In a probability sample study of sexual behavior in a cohort of almost 2000 American women between the ages of 18 and 59 years, the prevalence of female sexual dysfunction was estimated at 43%.² Low sexual desire was identified as the most common disorder for women, with a prevalence of 22%.² The incidence of HSDD, in particular, has been reported to range from 5% to 46%.⁵

Pathophysiology of Sexual Dysfunction in Perimenopausal Women

Physiologic causes are common in female sexual dysfunction. Many researchers have noted an increase in sexual problems associated with menopause, generally, and surgical menopause in particular.⁶ Women who have undergone surgical menopause, especially with bilateral oophorectomy, may experience decreased levels of sexual desire after the procedure.⁴ Such women commonly report feelings of loss, dissatisfaction, or distress as a result of their diminished libido and, therefore, can be classified as having HSDD.⁴ A prospective study, the Massachusetts Women's Health Study, followed a group of 200 healthy women between the ages of 51 and 61. Premenopausal, perimenopausal, and postmenopausal women were all represented in the study population. When asked whether their sexual arousal was less, the same, or greater than it was at age 40, 45% reported a decline in sexual arousal.⁶

A prospective study of 438 Australian-born women between the ages of 45 and 55 found a significant decline in sexual responsiveness by late perimenopause and an increase in partner problems. Post menopause, further reductions in sexual frequency and interest and increased complaints of vaginal dyspareunia were noted.⁶ These findings were replicated in the Women's Health and Sexuality Survey of American women between the ages of 20 and 70. In this survey, 43% of women reported a decrease in sexual frequency.⁶ Decreased sexual interest was reported by 32% of surgically menopausal women between the ages of 50 and 70 and by 30% of the naturally menopausal women between the ages of 50 and 70 years.⁶

It is hypothesized that this decrease in sexual desire during and after menopause, whether it is surgical or natural, may be associated with lower levels of circulating androgens, perhaps as a result of the loss of ovarian sex steroid production.³ The primary and most well-known androgen is testosterone. Because androgens in women are made by the adrenal glands and the ovaries, low libido is more likely associated with decreased androgen levels in women after oophorectomy.² Androgen levels do decline with aging; therefore, older women have lower levels, compared with younger women.² In addition, whereas low androgen levels may be associated with a decline in sexual function, it is important to note that a clear association between specific androgen levels and satisfactory sexual function has not been identified.² Studies comparing women who have undergone hysterectomy with and without bilateral oophorectomy provide the best available data that low androgen concentrations may be associated with sexual dysfunction.² Women who undergo bilateral oophorectomy experience an approximate 50% reduction in testosterone concentrations.² In a study of women who had undergone hysterectomy, those who had concurrent oophorectomy reported significantly decreased libido and sexual satisfaction postoperatively despite estrogen treatment, compared with women who had their ovaries preserved.²

Diagnosing Sexual Dysfunction

A comprehensive medical and psychosocial history is necessary to diagnose sexual dysfunction (Table 1).⁷ The history includes questioning the patient and the patient's sexual partner. A physical examination may be warranted in certain situations, such as painful spasms of the vagina (vaginismus) and painful intercourse (dyspareunia).⁷ Although laboratory investigations are not needed for the assessment of sexual dysfunction, certain situations may require laboratory testing. When it is suspected that the sexual dysfunction is due to decreased androgen levels, free testosterone and total testosterone levels may be tested.⁷ In order to diagnose HSDD, a thorough differential diagnosis must be conducted, and several causes must first be ruled out. For example, the symptoms the patient is experiencing cannot be due to or caused by substance abuse (medication or drug abuse).¹ It also must be determined that symptoms are not the result of another psychological disorder, such as depression.¹ It is important to note that a patient can only be classified as having HSDD if the symptoms are causing marked distress for the patient and/or distress in the patient's relationships.¹ The symptoms must be negatively affecting the patient's daily functioning to be diagnosed. Further, if the sexual partner of a patient with suspected HSDD feels that this is causing a problem within the relationship, that concern may be sufficient enough for the individual to seek medical attention.¹

A number of medical conditions are known to cause sexual dysfunction (Table 2).⁸ Likewise, and particularly relevant for pharmacists, multiple medications have been associated with sexual dysfunction (Table 3).^9,10 A thorough evaluation must include a review of the patient's medical history and medication profile to identify possible causative or exacerbating factors.

Several questionnaires have been developed to help clinicians assess a patient's sexual dysfunction. The Personal Distress Scale (PDS) is a patient-based questionnaire for the measurement of personal distress over a period of 30 days due to low desire in menopausal women.¹¹ The Profile of Female Sexual Function (PFSF) is a patient-based questionnaire that assesses the loss of sexual desire and associated symptoms in postmenopausal, oophorectomized women experiencing low libido. Table 4 identifies the 7 domains that characterize sexual function in postmenopausal women with HSDD and that are evaluated in the PFSF.⁴ The Sexual Activity Log (SAL) is a patient-based diary that allows menopausal women with HSDD to accurately count and record sexual events, orgasms, and the number of satisfying events.¹² This is very useful for monitoring a patient's response to treatment. The development of such questionnaires is extremely helpful not only to reach a diagnosis of HSDD, but also to reassess the patient after treatment has been initiated.

Therapeutic Options

Estrogen

Reduced sexual arousal and/or orgasm as well as a decline in sexual desire and response may all result from the symptoms of vaginal dryness and vaginal atrophy and their impact on dyspareunia. These symptoms are quite common during and following menopause when estrogen levels decline, and the stimulation of the estrogen receptors located in the female genital tract also decline.

Estrogen replacement can be used to treat these specific symptoms. Estrogen replacement administered via the oral, transdermal, or vaginal routes will treat the symptoms, but the vaginal preparations would be preferred in the absence of other menopausal symptoms such as hot flashes. Oral and transdermal formulations do achieve much higher serum concentrations and are associated with an increased risk of breast cancer and thromboembolic events. Vaginal estrogen preparations (Table 5) include creams, tablets, and rings. They do not generally reach the same serum concentrations as the systemically delivered products and therefore are associated with a more favorable safety profile.

Improvement in the presenting symptoms should be observed within a couple of weeks of therapy initiation. It is important for the clinician to monitor therapy and evaluate whether the improvement in symptoms leads to an improvement in sexual function, notably a positive impact on desire, arousal, orgasm, and overall sexual response that, ultimately, reduces any distress that may have occurred as a result of these.

Androgen Replacement

Although estrogen replacement therapy may be helpful for patients experiencing sexual dysfunction as it relates to dyspareunia resulting from reduced estrogen concentrations in menopausal women, it does not necessarily improve symptoms such as low libido. Estrogen may actually reduce libido as a result of its effects on increasing sex hormone-binding globulin, which, in turn, binds free testosterone. A reduction in the free testosterone may contribute to reduced libido and subsequently HSDD.

Given the available studies to date, the ideal candidate for androgen replacement with a testosterone product would be a postmenopausal woman whose symptoms are not due to estrogen deficiency and whose measured androgen values are in the lowest quartile of normal ranges for premenopausal women.² Therapeutic choices for androgen replacement in women are limited, and it is important to note that none of these products are approved by the Food and Drug Administration (FDA) for the treatment of female sexual dysfunction. Further, the optimal doses of any of these products for managing female sexual dysfunction and HSDD are currently unknown. Table 5 identifies some of the androgen products available and the recommended doses for their use in women.

In attempting to identify the optimal dosing of the testosterone products, it has been noted that the beneficial effects on libido are typically associated with achieving circulating androgen levels that are at or above the upper limit of normal.¹³ The published trials evaluating testosterone products (oral, intramuscular, implants, and transdermal systems) for the treatment of sexual dysfunction in menopausal women are discussed in Table 6. Among these trials, 5 were in surgically menopausal women,^14-18 and 3 were in naturally menopausal women.^19-21

In all of these trials, improvement was noted in one or several of the following: (satisfying) sexual activity, sexual desire, pleasure, and/or orgasm. Significant adverse events included those of the skin: increased sebum production, greasy skin/hair, scalp itching, alopecia, and hirsutism. The lack of long-term safety data represents a shortfall in these studies, which is a contributing factor to the lack of FDA approval of any of these products for female sexual function and HSDD in particular. Specifically, the impact on cholesterol concentrations and cardiovascular disease needs to be evaluated.

Patients receiving androgen replacement for the management of female sexual dysfunction and HSDD should be monitored?eg, sexual activity, frequency, and satisfaction should all be assessed. In addition, the patient should be evaluated as to the presence of adverse events. Free testosterone levels can be measured to ensure that levels are safe.

Role of the Pharmacist

Over the past several years, there has been a large increase in willingness of members of the health care team as well as the general public to discuss sexual dysfunction in men. This is evidenced by the television, magazine, and journal ads for therapeutic options for erectile dysfunction. Sexual dysfunction in females is a bit more difficult to assess, and its presence is much more difficult to diagnose. To this end, evaluation tools have been created and validated, and trials assessing treatments and their effects on factors such as satisfactory sexual desire, intercourse, arousal, and orgasm have recently been performed. Discussion of this topic, however, has yet to be "mainstream."

An important role of the pharmacist is to be aware of and acknowledge the existence of sexual dysfunction among women. Just as society has become more willing to discuss erectile dysfunction in men, so should it be more willing to do so as is related to sexual dysfunction in women. Displaying promotional/ educational materials on female sexual dysfunction in the pharmacy is just one way to start such dialogue. Table 7 lists several strategies that the pharmacist might use to assist the woman experiencing sexual dysfunction.

Pharmacists are well-situated to participate in the evaluation and treatment of female sexual dysfunction. First, pharmacists may be approachable health care providers with whom patients can begin a dialogue about what can be an awkward subject. Pharmacists may then refer the patient to the appropriate clinician for a comprehensive evaluation. Here too pharmacists can play a pivotal role by reviewing the patient's medication profile for drugs that may be causing or exacerbating the condition. Further, pharmacists may help patients to understand the relationship between concomitant disease states (if present) and sexual dysfunction. If identified, pharmacists can participate in the management of comorbidities.

The pharmacist should also ensure that, when a drug treatment option is employed to treat sexual dysfunction in women, it is appropriately monitored. In particular, the presence of androgenic skin effects is quite common in women receiving a testosterone product. Further, negative lipid effects including a reduction in high-density lipoprotein are common with testosterone treatment. As such, it would be important for a fasting lipid panel to be evaluated within 6 to 8 weeks of onset of treatment. When refilling a woman's prescription for a testosterone product, the timing would be ideal for inquiring/suggesting that these evaluations be completed. Whereas the side-effect profile of therapy is fairly well described, sufficient long-term outcomes data to make an evaluation are not available.

A unique role of pharmacy is the compounding of patient-specific formulations that allow for dose titration. Some specialty pharmacies have begun to provide this service in an effort to maximize efficacy of hormonal replacement while minimizing side effects.

Conclusion

An increase in the awareness of female sexual dysfunction has occurred within the medical community over the past 3 years. It is the responsibility of the pharmacist to also become better aware of its existence as well as of the therapeutic options available for its management. To date, these options are limited, and the agents being used for its treatment are products that have been developed for men. In fact, none of the commercially available products are produced specifically for the treatment of female sexual dysfunction. Products developed and approved for this use would serve postmenopausal women, in particular, very well.

Elena M. Umland, PharmD: Barbara H. Korberly Associate Professor of Women's Leadership and Health; Director, Doctor of Pharmacy Program, University of the Sciences in Philadelphia, Pennsylvania; Jill Smethurst, PharmD Candidate: University of the Sciences in Philadelphia.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.

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