Are hormones the answer to low libido?

Feb 02, 2013

More than half of postmenopausal women report low sexual desire. Hormonal and nonhormonal treatments vary in efficacy and continued studies are needed.

Up to 43% of women report having sexual dysfunction, with decreased desire being the most common complaint.1 Although the incidence varies among the studies, low sexual desire is reported by more than half of postmenopausal women compared with one-quarter of premenopausal women.2 Hypoactive sexual desire disorder (HSDD) is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a lack of desire that is persistent and leads to personal or interpersonal distress. Sexual dysfunction is multifactorial, including a variety of psychosocial components; however, this discussion will be about treatment options for low libido, focusing primarily on postmenopausal women.

Physiology of libido

The ovaries and adrenal glands produce about 50% of circulating testosterone, whereas the other 50% comes from peripheral conversion of precursor steroids from the ovaries and adrenals. Most circulating testosterone is bound to sex hormone-binding globulin (SHBG) and albumin, which leaves only 1% to 2% as active free testosterone.

Testosterone production is lower in menopause and can lead to decreased libido. In surgically menopausal patients, the ovarian androgen component as well as estrogen production is lost, which can affect sexual function in areas such as libido and vaginal dryness. Administering oral estrogen may be counterproductive because SHBG is increased and will further decrease the available testosterone.

Testosterone

A 2005 position statement from the North American Menopause Society, based on a thorough review of the literature on the use of testosterone therapy in postmenopausal women, concluded that testosterone therapy (preferably administered via transdermal or gel/cream) is an option for postmenopausal women with decreased sexual desire (Table 1).3 At the time of the position statement, testosterone therapy was not recommended without concomitant estrogen therapy, given a lack of evidence.

Since then, results of the APHRODITE study (A Phase 3 Research Study of Female Sexual Dysfunction in Women on Testosterone Patch Without Estrogen), which included 814 postmenopausal women with HSDD, were published and reported that treatment with a patch delivering 300 µg of testosterone per day led to a modest but meaningful improvement in sexual dysfunction without the addition of estrogen replacement.4

Current options for testosterone treatment include a patch, cream, and oral therapies; transdermal methods are preferred because there is no first-pass effect.3 Additionally, unwanted androgen adverse effects and a negative effect on lipids may be reduced with transdermal application, although unwanted hair growth remains an issue.

There is specific dosing for each type of transdermal testosterone product (Table 2). These products are used off-label in women, and the recommended dose and use for men are inappropriate and dosage must be decreased for women. Some products (ie, the Intrinsa patch) are currently not available in the United States. For other products, the specific formulation must be compounded by a specialist pharmacy. Because these products and doses can vary, physicians and patients should talk directly to the pharmacist. These products often are not covered by insurance because they are being used off-label.

Despite studies showing a significant benefit of testosterone therapies in treating low libido and increasing sexual satisfaction, the US Food and Drug Administration (FDA) has not approved such regimens because of concerns about their safety. Some studies have shown a slightly increased risk of breast cancer in women using testosterone therapy.5 Additionally, concerns about its effect on cardiovascular health remain. Positive effects of testosterone treatment can include increased muscle mass, bone retention, and increased overall well-being.

Other androgens

The androgen dehydroepiandrosterone (DHEA; prasterone) has been used in the treatment of sexual dysfunction. Studies have shown no significant improvement, except in women with adrenal insufficiency.6,7  However, it has been shown to be effective when applied intravaginally, because it works in vaginal tissue to treat atrophy through local estrogen and androgen formation.8

In a study of 216 postmenopausal women with severe atrophy, there were significant improvements in arousal/sensation, arousal/lubrication, orgasm, and vaginal dryness after using 1% DHEA over 12 weeks compared with placebo.9 By using DHEA vaginally, systemic adverse effects can be avoided, making this a favorable atrophy treatment option to offer women;10 however, more studies specifically assessing its effect on libido are still needed, and vaginal DHEA is not currently approved by the FDA.

In the past, another androgen (danazol) had been used off-label for treatment of low libido despite its potential androgenic adverse effects. Its use has declined, given the superior options available, although its ability to suppress the endometrium does provide an alternative in the perimenopausal woman with irregular,
anovulatory bleeding.11

Estrogen/Progesterone

Although estrogen may not directly affect libido, estrogen deficiency causes vaginal atrophy and dryness, with associated pain on intercourse that can lead to sexual dysfunction. Estrogen therapy (ET) is commonly accepted as the most effective treatment of moderate to severe vaginal and vulvar atrophy.12,13 Local therapy (oral, patch, vaginal ring) is preferred to systemic because of fewer adverse effects. Local therapy includes vaginal conjugated estrogen and estradiol in the forms of creams or tablets. Both therapies can be managed by the patient at the lowest dose possible while still providing comfort.13 There are various options for local estrogen therapy, with recommended long-term dosing (Table 3); the patient may use the product more frequently when first starting treatment. The addition of progesterone is not indicated if estrogen is only used locally; however, postmenopausal bleeding would warrant evaluation.

Synthetic hormones

Tibolone is a synthetic steroid with metabolites that have androgenic, estrogenic, and progestogenic effects. It decreases SHBG, leading to increased free testosterone and estradiol. In some well-designed trials comparing tibolone to estrogen/progestin therapy, tibolone was similar or superior in the treatment of sexual dysfunction.14,15

However, a recent Cochrane review concluded that tibolone was less effective than hormone replacement therapy but noted that it decreased the incidence of vaginal bleeding.16 There have not been trials directly comparing tibolone to testosterone. Tibolone is commonly used by postmenopausal women in Europe but is not approved or available in the United States because of concerns for risk of breast cancer and stroke.

Nonhormonal options

There are a variety of nonhormonal options available to treat low libido, although they vary in results and adverse effects. Bupropion has been shown to improve sexual function in both premenopausal nondepressed women with HSDD17 and those with selective serotonin reuptake inhibitor (SSRI)-associated sexual dysfunction.18  Flibanserin, which has central effects on serotonin, dopamine, and norephinephrine, has improved sexual function in premenopausal women with HSDD19 but was not approved by the FDA because of concerns about adverse effects. Apomorphine, a dopamine agonist, has shown positive effects on sexual function20 but has numerous adverse effects, limiting its long-term use. Studies with buspirone have shown conflicting outcomes. Phosphodiesterase inhibitors have not been successful in the general population of women; however, they could be helpful in certain subsets, such as those with diabetes and certain neurologic disorders, and to treat SSRI-associated sexual dysfunction.21

Over-the-counter treatments

There are numerous over-the-counter (OTC) treatments for low libido, including topical therapies, that have some clinical data supporting their use. Zestra is a botanical cream that has been shown in trials to significantly increase desire and arousal in women with generalized sexual difficulties.22 ArginMax is a nutritional supplement shown to increase satisfaction with sex life, desire, and frequency of intercourse, and to reduce
vaginal dryness.23

Additionally, there are a plethora of herbal preparations that have marginal information on safety and efficacy. Women should be cautioned about the unknown safety, efficacy, and concentration of active ingredients in these supplements. For example, some with estrogenic components may be associated with the same risks as unopposed estrogen treatment. Patients should feel free to review the use of such products with their physicians. Beyond treatment for low libido, a wide variety of OTC lubricants and moisturizers for vaginal dryness are available at drugstore pharmacies.

Oral contraceptives and libido

Although more postmenopausal women report decreased sexual interest, a significant number of premenopausal women also complain of low libido. Thus, there has been a long debate about the effect of oral contraceptive pills (OCPs) on libido.

Physiologically, OCPs lead to an increase in SHBG and a decrease in ovarian androgen production. In theory, this decrease in free testosterone may lead to a lower libido. There have been numerous studies with varying results.24,25 Schaffir addresses the multifactorial nature of libido and suggests that one must look beyond solely the biologic effects of OCPs.25 For example, a patient may have increased libido on an OCP if she is less worried about an unwanted pregnancy.

In a retrospective study of 124 premenopausal women with sexual health complaints, SHBG levels in the “discontinued user” group did not decrease to the values of “never users.”26 Clearly, prospective studies are needed to determine whether prolonged use of OCPs leads to increased gene expression of SHBG and how this affects long-term libido.

Placebo effect

Beyond the various hormones, drugs, and supplements, just taking a medication may actually help libido. Studies have shown an impressive placebo effect that can approach 40%,27 mandating placebo-controlled studies to evaluate therapies for sexual dysfunction. In a review of data from 16 studies, it was noted that placebo recipients reported significant improvements on 1 or more major sexual dysfunction outcomes compared with baseline.28

Although the responses varied among the studies, the within-group effect sizes were often in the moderate range, thus making a case for the positive effect of the attention and care that accompanies the administration of the placebo.

Summary

Sexual dysfunction, including low libido, is a problem for many women, especially in the postmenopausal years. For women with HSDD, transdermal testosterone can be used with appropriate counseling. Other androgen therapy, including DHEA cream, can be considered. Vaginal estrogen may be used to decrease vaginal dryness and discomfort with intercourse, which can lead to increased sexual satisfaction.

If a woman cannot or does not want to take hormones, she should be careful about using herbal remedies for which the actual dose and absorption of the compounded product are unknown. However, OTC remedies are reasonable options if there are good, published clinical data on efficacy and safety. There are a variety of nonhormonal medications that may be helpful in certain subsets of women.

Continued studies are needed to identify further treatment of low libido. Additionally, sexual dysfunction can be caused by a variety of factors, so although medical treatment is important, counseling and further psychosocial evaluation may also be needed.

References

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