Treatment of sexual dysfunction in women

Treatment of sexual dysfunction in women

Author
Alan Altman, MD
Section Editor
Robert L Barbieri, MD
Deputy Editor
Kathryn A Martin, MD



Last literature review version 16.2: May 2008 | This topic last updated: June 11, 2007 (More)


INTRODUCTION — A number of nonpharmacologic and pharmacologic therapies are available to treat sexual dysfunction in women. Prior to initiating treatment, however, it is important to emphasize that sexual activity or frequency is not necessarily correlated with sexual satisfaction. Sexual dysfunction only becomes a problem when the patient or her partner finds it to be a problem.

The management of sexual dysfunction in women is reviewed here. The etiology and diagnosis are discussed separately. (See "Etiology and diagnosis of sexual dysfunction in women").

NONPHARMACOLOGIC THERAPY — Treatment of sexual dysfunction can begin with any of a number of nonpharmacologic measures. Blood flow increases during sexual activity; thus, sexual activity begets better sexual function. Masters and Johnson demonstrated this in their early work; sexual activity maintained vaginal pH, pO2, and mucosal health and allowed successful function to continue. The same beneficial effects could be achieved with sexual activity of any kind, partnered or unpartnered, including masturbation or sexual fantasy alone.

A number of other nonpharmacologic interventions also may be helpful.

Communication — Communicating sexual likes and dislikes, in a nonthreatening manner, can reignite novelty and intensify satisfaction. This may be difficult if techniques of communication were never the couple's forte. Sex videos or erotic literature can assist in seeking out new directions. Communication also means giving attention to a partner's presence, discussions, and ideas, which can help validate their importance and self image.

Lifestyle changes — Changes in lifestyle such as smoking cessation, strength training exercises, and aerobic training, can all have positive impacts on sexuality. Strength training, with weights or resistance machines may enhance body image and therefore, indirectly enhance libido.

Vaginal weights — Vaginal weights can be used to strengthen the pelvic floor muscles. In some women with orgasmic disorders, this can improve awareness of sexual response and also potentially correct urine leakage, which might cause a problem during sexual activity [1] .

Vaginal weights are usually available in sets of five weights. The patient inserts the lightest weight and remains upright for 15 minutes, twice a day. With the weight in place, she should feel the urge to hold it in. After a number of days, she will no longer feel the urge to hold in the weight, because an improvement in muscle tone has occurred. She then moves up to the next weight in the progression. Once she no longer feels the urge to hold in the heaviest weight, a significant increase in muscle tone has taken place. Maintenance with the fifth weight should be carried out each month for five to seven consecutive days to preserve muscle tone.

Use of vaginal lubricants — Genitourinary atrophy symptoms, in particular vaginal dryness and dyspareunia, develop in a high percentage of postmenopausal women who are not taking estrogen. Vaginal estroggen is highly effective for treating these symptoms, but water soluble vaginal lubricants are also helpful for continued sexual activity. This topic is reviewed in detail separately. (See "Diagnosis and treatment of vaginal atrophy").

Increased tactile stimulation of partner — Decreased vasocongestion during arousal can create the need for increased manual and/or oral stimulation in the male to help achieve or maintain an erection, and in the female to achieve adequate clitoral, labial, and vaginal response. Just providing an explanation of the need for more stimulation in both partners can have a positive effect, not only on sexual response, but also on the relationship.

Sexual frequency — How frequent is enough? Everyone has a different answer and that answer depends on multiple variables. Surveys are notoriously inaccurate due to their questionable ability to collect honest data. The bottom line has to remain what is comfortable for each individual pair of partners [2] .

PHARMACOLOGIC THERAPY — When education, lifestyle, communication, and behavioral changes do not achieve the desired level of success, pharmacological therapy can be utilized to treat sexual dysfunction in women. Treatment options focus on providing hormonal support and increasing genital blood flow. However, there are few randomized, placebo controlled trials of pharmacologic therapy in postmenopausal women upon which to base recommendations [3] .

Estrogen — Estrogen may positively affect sexual function in a number of ways. Estrogens rapidly restore the superficial cell layer of the vaginal epithelium, reestablish elasticity, restore the balance in vaginal pH, improve mood, and increase vaginal blood flow to enhance lubrication. (See "Postmenopausal hormone therapy: Benefits and risks"). In addition, their positive effect on neuronal growth and nerve transmission could help restore tactile perception and sensation, although treatment with estrogen alone is associated with inconsistent results with respect to sexual desire and arousal.

Short-term studies of estrogen replacement therapy (ERT) have confirmed a benefit in some postmenopausal women with sexual dysfunction:

• In a report of 93 women, 68 percent reported problems with sex, specifically vaginal dryness of at least moderate degree (58 percent); dyspareunia (39 percent); decrease in clitoral sensitivity (36 percent), decrease in orgasmic frequency (29 percent), decrease in orgasm intensity (35 percent), decrease in sexual desire (77 percent), and intercourse once a month or less (50 percent) [4] . Women reported vaginal dryness, pain with penetration, and burning sensation when the serum estradiol concentration dropped below 50 pg/mL. Symptoms decreased markedly when the estradiol concentration was above 50 pg/mL. Overall, oral estrogen therapy resulted in an improvement in clitoral sensitivity. Orgasm rates also improved. The most dramatic response was seen in the women who reported a lack of desire; after three to six months of treatment, 90 percent of these women had an increase in level of desire and increase in sexual activity with ERT.
• In a study of 242 women ages 45 to 65 requiring ERT for climacteric symptoms, women were randomly assigned to blinded treatment with transdermal estrogen or placebo for 12 weeks [5] . Answers to a questionnaire regarding satisfaction with frequency of sexual activity, sexual fantasies, degree of enjoyment, vaginal lubrication, and pain during intercourse were positively influenced by estrogen compared with placebo therapy, while the frequency of orgasm and sexual arousal were not affected.


However, not all studies have demonstrated positive results [6] , possibly because women most likely to respond are those with symptoms of hypoestrogenism. Furthermore, any short term positive effects of oral estrogen may diminish in the long term because of increasing sex hormone binding globulin (SHBG) levels, which lead to reduced estrogen and androgen bioavailability, and consequent decreased desire and activity [7] . The increase in SHBG appeared to be less significant in women who use nonoral delivery systems for ERT, suggesting improved bioavailability of estrogens and androgens [8] . (See "Etiology and diagnosis of sexual dysfunction in women", for a more complete discussion of the effects of SHBG.)

Progestins — Progestational agents down-regulate the estrogen receptor, a desired result in the endometrium, but potentially undesirable in the brain, heart, bone, and genitalia. They generally have an overall negative effect in the CNS with respect to depression and mood, and have been shown to decrease sexual desire and diminish vaginal blood flow [9,10] . Medroxyprogesterone acetate (MPA) is the most potent progestin available, therefore its ability to down-regulate the estrogen receptor and diminish estrogen effects may be particularly intense. Other available options include micronized progesterone (MP) and the 19 nortestosterone derivatives, norethindrone acetate (NA) and norgestimate (NGM). (See "Preparations for postmenopausal hormone therapy"). NA, the more androgenic progestin, has been shown to decrease SHBG and increase bone density.

A number of studies have evaluated the effect of progestins on sexual function:

• The effects of estrogen alone or with MPA on psychological functioning and sexual behavior were evaluated in a study of 48 healthy, naturally menopausal women [9] . The benefits of estrogen were diminished by MPA co-administration [9] .
• A second report comparing the use of estradiol alone or in combination with lynestrenol, a 19-norsteriod, revealed that women who used the combination therapy reported more negative mood symptoms than the estrogen only group [11] .
• In a single-arm, unblinded study, women who were intolerant of a conjugated equine estrogen (CEE)/MPA regimen were switched to CEE plus progesterone and reported better vasomotor, somatic, psychologic, cognitive, and sexual functioning [10] .


Progestins appear to produce a wide range of patient responsiveness and tolerability, suggesting that women who do not tolerate one regimen might be effectively switched to another and experience improvement. When estrogen is given with a progestin, the effect on SHBG depends upon the type of progestin used; 19-nortestosterone derived progestins, such as NA, decrease SHBG levels, a potential benefit while derivatives of C-21 progesterone, such as MPA, do not significantly influence them [12] . Newer studies in progress with more modern combinations of progestins with estrogens and androgens will provide better insight into the progestational effects on sexuality.

Androgens — Androgens play an important role in physiologic aspects of the female sexual response. (See "Etiology and diagnosis of sexual dysfunction in women"). However, the effect of androgen therapy on sexual function in women is controversial. Androgen replacement therapy for women with androgen deficiency (eg, bilateral oophorectomy) must be distinguished from pharmacologic androgen treatment of women with low libido who are not androgen deficient. (See "Androgen production and therapy in women").

Some studies have reported improvements in libido, sexual arousal, and the frequency of sexual fantasies with testosterone therapy in a variety of forms [4,13-15] , while others have been unable to detect a significant benefit from androgen therapy [6,7] . The observation that testosterone therapy may result in improvements in mood and well being [16] is felt by some researchers to be most important; the central sex steroid effect on mood may be what underlies sexual function in both women and men. (See "Androgen production and therapy in women")

Side effects — Potential adverse effects of androgens include a decline in serum high density lipoprotein (HDL) cholesterol with oral preparations, and mild cosmetic side effects such as hirsutism and acne; irreversible virilizing changes are rare. (See "Androgen production and therapy in women", section on Risks and side effects.) Hepatocellular damage is rare at the prescribed doses. The effect of testosterone on breast cancer risk is discussed separately. (See "Postmenopausal hormone therapy and the risk of breast cancer", section on Effect of testosterone).

Preparations — Most early papers demonstrating a benefit of androgens on sexual function utilized injections or pellets. Since that time, compounding pharmacists have formulated testosterone creams, gels, and tablets that can be taken orally or used sublingually, but their production is not uniform, they are not approved by the United States Food and Drug Administration (FDA), and efficacy studies are lacking. Many clinicians have tried creams used for vulvar dystrophies made up with 2 percent testosterone propionate. Others tapered down the potency using micronized testosterone 0.5 percent up to 1 percent, and rarely 2 percent.

Creams were applied first on the inside of the forearms or thighs, while later paraclitoral use became common. Mixed results were common, and the effect of rubbing the cream into the clitoris prior to intercourse may have been nothing more than masturbatory prestimulation. Anecdotally, the creams seemed to work better paraclitorally in patients with sexual arousal disorder than in those with hypoactive sexual desire disorder (HSDD).

A transdermal testosterone preparation has also been studied in clinical trials of postmenopausal women (primarily women who are post-oophorectomy). These trials are discussed in detail elsewhere. (See "Androgen production and therapy in women").

Studies on the use of dehydroepiandrosterone (DHEA), which is available over-the-counter in the United States, have shown an increase in energy level, well-being, sexual satisfaction, and sexual function only in women with primary and secondary adrenal insufficiency [17,18] . There are no receptors for DHEA; side effects occur due to conversion to testosterone and then to estrogens [18] . (See "Dehydroepiandrosterone and its sulfate").

Combination therapy with oral estrogen and methyltestosterone also improved sexual interest/desire in postmenopausal women already taking estrogen who were experiencing hypoactive sexual desire. A double-blind trial randomly assigned such women to four months of therapy with 0.625 mg esterified estrogens alone (n = 111) or with 1.25 mg methyltestosterone (n = 107). Improvements in self-reported sexual desire were seen in the combined therapy group, which correlated with changes in bioavailable testosterone concentrations [19] . However, acne was more common and significant decreases in HDL cholesterol were seen with combined treatment. (See "Androgen production and therapy in women").

Thus, the data that androgen therapy significantly improves sexual functioning are suggestive but not conclusive. Many of the positive studies have been in women who had surgical menopause or who achieved supraphysiologic levels of testosterone with therapy [20] , suggesting that the clinical application may be limited. No guidelines for androgen therapy for female sexual dysfunction are available, and no androgen preparations have been approved for the treatment of sexual desire disorders, although the combination oral estrogen/methyltestosterone preparation described above is approved for management of persistent vasomotor symptoms not relieved by estrogen alone.

Women most likely to benefit from androgen therapy are probably those who have undergone bilateral oophorectomy with hysterectomy.

For any woman considering androgen therapy, the risks and benefits should be discussed prior to initiating treatment. Women with hepatic disease, a history of breast cancer, uncontrolled hyperlipidemia, acne, or hirsutism should not be treated.

Although there are no FDA-approved testosterone products for women presently available in the US, specialists utilize the following products off-label or compounded for women with sexual dysfunction after extensive history and counseling:

• Combination estrogen/methyltestosterone (Estratest or Estratest HS)
• Testim 1 percent testosterone Gel (one to two drops/day)
• Methyltestosterone (1.22 to 2.5 mg/day)
• Micronized oral testosterone (5 mg BID)
• Testosterone injectables/pellets
• Testosterone propionate 2 percent in petroleum applied QOD
• DHEA 50 mg per day

Non-oral estrogen should be administered in conjunction with testosterone therapy to avoid increasing SHBG and to negate any potential negative effects of either on lipoproteins. Baseline free and total testosterone levels, liver function tests, and a lipid profile should be obtained prior to initiating therapy, and women should be current on cervical and breast cancer screening. The lipid profile and liver function tests should be reevaluated along with a clinical evaluation for symptoms in three to four months, and the androgen tapered to the lowest dose possible. Some authors recommend that the serum testosterone concentration remain in the normal range for premenopausal women, but this is not universal. Liver function tests and lipids should be monitored every six months during therapy [1] .

Herbal therapies — The literature on herbal therapies for the treatment of sexual dysfunction in women is sparse. In general, St John's wort, ginseng, dong quai do not appear to be more effective than placebo for sexual dysfunction. Herbal products such as yohimbine have been reported to enhance desire, arousal, and orgasm in women with sexual dysfunction secondary to SSRIs, but results are inconsistent [21,22] .

L-arginine, an amino acid, has been touted as the natural Viagra due to the claimed ability to release nitric oxide, causing increased vasocongestion in the genitalia of both sexes [21,23] . More studies are necessary before conclusions can be drawn regarding any of these products.

Future therapies — A number of products are undergoing research and development for use in women with sexual dysfunction:

Tibolone — Tibolone, currently available in Europe and Australia, has not yet gained FDA approval in the United States. Taken orally, its metabolites have estrogenic, androgenic, and progestational effects. The level of androgenic activity and its potential use for sexual dysfunction is under evaluation. A small placebo controlled trial in postmenopausal women found tibolone increased vaginal lubrication, arousability, and sexual desire, but did not change frequency of sexual intercourse or orgasm compared to placebo [24] . Tibolone is effective for the management of osteoporosis, but may be associated with an increased risk of breast and endometrial cancer. Tibolone is discussed in more detail elsewhere. (See "Overview of the management of osteoporosis in postmenopausal women").

Sildenafil — Preliminary findings on use of sildenafil demonstrated positive effects in the areas of sexual arousal and orgasm in appropriately selected women [25-28] . However, several large scale, placebo controlled studies including about 3000 women with female sexual arousal disorder yielded inconclusive results [29] . For this reason, the manufacturer has decided not to seek regulatory approval to use the drug for female sexual arousal disorder.

Other — Now available in the United States is a clitoral suction device modeled after a pump used before the advent of penile injections and sildenafil to produce and maintain erection in males, uses suction or negative pressure to increase vasocongestion and engorge the clitoris and paraclitoral tissues for enhanced arousal and orgasm [30] .

One placebo-controlled randomized study of daily apomorphine SL administered to premenopausal women suggested this drug may improve sexual desire and function in women with hypoactive sexual desire [31] . Apomorphine SL is not FDA approved for this indication and requires further investigation.

This growing pharmacopoeia should not overshadow the psychosocial, intimacy, and relationship issues that are equally, if not more involved in problems with midlife sexuality.

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Sexual problems in women"). We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics.