Female Sexual Dysfunction: Natural and Complementary Treatments

Abstract

Sexual dysfunction, which may affect any part of the sexual response cycle (e.g., libido, arousal, and orgasm), is a highly prevalent condition among women and is associated with significant negative consequences for quality of life. Unfortunately, few effective traditional agents are available to treat this condition, especially in the postmenopausal cohort. It is therefore not surprising that many women seek alternative treatments for relief. The authors review popular alternative treatments for sexual dysfunction, emphasizing randomized, placebo-controlled trials when possible.

A recent survey assessed the effects of sexual dysfunction on quality of life and found that 70% of U.S. women believe that dissatisfaction with their level of sexual desire has interpersonal consequences. These include negative self-perceptions in body image and confidence and a feeling of being less connected to a sexual partner (1). Adequate sexual function is an integral aspect of quality of life, and sexual dysfunction may be so distressing that some patients choose to switch or discontinue effective pharmacological therapies—in particular, antidepressants—because of sexual dysfunction side effects (2).

Sexual dysfunction may affect any part of the sexual response cycle, including libido and desire, arousal, and orgasm. In this review, if not otherwise specified, the term female sexual dysfunction may refer to any or all of the above phases of the sexual response cycle. The most common form of female sexual dysfunction is hypoactive sexual desire disorder, with prevalence rates ranging from 7.2% to 54.8%, depending on age (3).

In the DSM-5, hypoactive sexual desire disorder has been combined with female sexual arousal disorder to create female sexual interest/arousal disorder (FSIAD) (4). The criteria for FSIAD include having no (or a greatly diminished) involvement in or desire for sex, not imagining or thinking about sexual activities, not initiating sex with a spouse or significant other, feeling no enjoyment when participating in sex, and having a complete lack of or significant reduction in sexual interest or sexual arousal. These symptoms must result in distress on the part of the patient and be continuous for six months (4).

Several treatments currently are under investigation for the management of FSIAD, including testosterone, buspirone, bupropion, bremelanotide, and flibanserin. Flibanserin is the only treatment approved by the U.S. Food and Drug Administration (FDA) for FSIAD, although only for the premenopausal population (5). Despite ultimately recommending approval for flibanserin, the FDA advisory panel expressed concerns over both the efficacy of flibanserin and its potential interactions with alcohol.

There currently are no approved treatments for postmenopausal women with sexual dysfunction, a cohort that is especially vulnerable because of declining estrogen levels. Postmenopausal women constitute a largely neglected population in terms of interventions to ameliorate sexual dysfunction. A natural product that is well tolerated and efficacious would convey an advantage over the pharmacologic agents currently used by practitioners attempting to treat sexual dysfunction among women. An increasing number of individuals are choosing to self-medicate with natural over-the-counter treatments, often without informing their physician; this practice can result in adverse drug-drug interactions (6–8). Indeed, reports of adverse interactions with natural agents have been increasing. There is a paucity of data regarding the effectiveness or safety of natural psychotropic agents, be they used alone or in combination with other natural remedies, registered medications, or both.

Despite the risks of over-the-counter polypharmacy, many patients have benefited from taking a natural medication in conjunction with a registered medication or other natural remedies. Clinicians should routinely ask their patients about any natural medication use and should discuss the risks and benefits of polypharmacy with these agents. Using the available information on natural and registered medications, a clinician can develop reasonable strategies for managing patients who desire complementary medicines either to alleviate a particular disorder or to counteract the adverse effects of another medication.

The strategies considered here are largely speculative and do not have extensive evidence-based data to support or reject them. In this particular review, we emphasize those clinical trials that are randomized and placebo-controlled, because placebo response rates in sexual dysfunction trials tend to be quite high. None of the products has data to demonstrate safety for children or women who are pregnant or breastfeeding, and the products therefore should be avoided in these populations.

l-arginine

l-arginine is often found in combination with a variety of other natural remedies used to enhance sexual functioning; for example, ArginMax is a supplement containing a blend of l-arginine, ginseng, ginkgo, damiana, multivitamins, and minerals. In a randomized, controlled trial (RCT), 77 healthy women aged 21 and older who received this supplement demonstrated statistically greater improvements in sexual satisfaction, as compared with placebo (p<.01). Improvements were observed in sexual desire, vaginal dryness, frequency of sexual intercourse and orgasm, and clitoral sensation. The treatment was well tolerated, with no side effects reported (9).

In another follow-up RCT of the same supplement, 108 women, ages 22 to 73 years, with loss of libido (59 premenopausal, 20 perimenopausal, and 29 postmenopausal) received either the supplement or placebo for four weeks. Outcome was measured by the Female Sexual Function Index scales (10). Premenopausal women receiving the supplement demonstrated statistically significant improvement in level of sexual desire (72%), satisfaction with overall sex life (68%), frequency of sexual desire (60%), and frequency of intercourse (56%) compared with the women receiving placebo (p<.05). Among perimenopausal women, significant improvement was reported for frequency of intercourse (86%), satisfaction with sexual relationship (79%), and vaginal dryness (64%; p<.05). Postmenopausal women showed a significant increase in sexual desire (51%) compared with the placebo group (8%; p<.05) (11).

An early study compared the effects of l-arginine combined with yohimbine against the effects of yohimbine alone and placebo on sexual arousal among postmenopausal women with female sexual arousal disorder. The combined treatment demonstrated substantially increased vaginal response to the erotic stimuli compared with placebo, but subjective reports of sexual arousal did not differ among the three groups (12). Recently, Lady Prelox, a commercially marketed product containing 200 mg of l-arginine, was found to improve scores on the FSFI, as compared with placebo, among both pre- and postmenopausal women (13, 14).

l-arginine in these studies seemed safe by itself and in combination with various other sexual-enhancing agents, with the evidence thus far supporting synergistic effects. There remain concerns, however, about the safety of l-arginine, with arguments against its use centering on the increased production of nitric oxide, which may have potentially negative effects, including diarrhea, elevated blood urea nitrogen and serum creatinine levels, flushing, and hypotension,

Ginseng

Ginseng was evaluated in a recent meta-analysis of two randomized, placebo-controlled trials of pre- and postmenopausal women and showed favorable effects on sexual functioning score (15). Two recent studies of Korean red ginseng showed benefit in sexual functioning for menopausal (16) but not premenopausal women (17). FSFI scores did not differ significantly from placebo among premenopausal women (17). However, menopausal women experienced a significant improvement in sexual arousal in the other placebo-controlled trial (16).

Ginkgo

Ginkgo, which may improve blood flow as well as the nitric oxide system, also has long been thought to contain sexual-enhancing properties, and it has been used by itself and in combination with other agents for this indication. To date, however, randomized, placebo-controlled trials of ginkgo for sexual dysfunction have not been particularly encouraging. One trial of ginkgo for antidepressant-induced sexual dysfunction among 37 adults found no significant difference between treatments at weeks 2, 4, and 8 of the study. Both treatment groups, however, showed improvement in some areas of sexual function, which suggests a placebo effect (18).

Another placebo-controlled trial demonstrated that short-term gingko increased short-term physiologic markers of arousal but not subjective improvement in sexual arousal. The study also found that long-term administration of gingko alone did not significantly improve sexual functioning for this group of women with sexual arousal disorder (19). A double-blind trial of ginkgo for antidepressant-induced sexual function among both men and women was also negative (20). A triple-blind (investigator, patient, and statistician) trial of Gingko biloba for antidepressant-induced sexual dysfunction reported some “spectacular individual responses” in both treatment and placebo control groups, but overall there were no statistically significant differences (21).

One of ginkgo’s appeals is that, apart from a risk of hemorrhage among people who take anticoagulants (22), it seems to be safe to combine with most medications, and it has relatively mild common side effects: gastrointestinal disturbances, headache, and general central nervous system activation (e.g., agitation). The full potential of ginkgo in the management of sexual dysfunction requires further investigation.

Maca

Maca (Lepidium meyenii) is a root vegetable (tuber) that grows in the mountains of Peru at altitudes ranging from 11,000 to 14,500 feet. The origins of maca (also called Peruvian ginseng) are not fully understood, but native Peruvians have been known to use maca as a food and for medicinal purposes since before the time of the Incas. The historic uses of maca include nutritional supplementation for life in a harsh environment and enhancement of fertility and sexual potency. Maca’s fertility-enhancing properties were first reported in the literature in 1961, when it was shown that maca administration increased the fertility of rats (23).

Today, maca is growing in popularity, with marketing claims of energizing effects, fertility enhancement, and aphrodisiac qualities. Other uses for maca have included the alleviation of menstrual irregularities and female hormonal imbalances; it has also been proposed to be effective at ameliorating menopausal symptoms, such as hot flashes (24, 25). In the United States and elsewhere, maca is sold in drug stores and health food stores in capsule or powder form. Most commercially available preparations of maca contain about 500 mg of ground tuber in each capsule. Recommended dosages range from 3 to 6 g per day, but there is no consensus on the optimal therapeutic dose of maca.

Although scientists have made great strides in delineating the constituents of maca, debate still exists as to the active ingredients. More than 50 oil components, as well as the secondary metabolites of the tuber, have also been delineated. It is unclear which of the nutrients in maca are responsible for its reputed sex-enhancing properties. Notable candidates include the plant sterols and the isothiocyanates (26). Despite its popularity and supportive anecdotal evidence, very little systematic human research has been carried out on maca as a potential treatment for female sexual dysfunction. Most published human studies have examined the effect of maca on sexual functioning and hormone levels among healthy men.

We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) among females with remitted depression (mean age of 41.5±12.5 years) who also had sexual dysfunction induced by selective serotonergic reuptake inhibitors (SSRIs) or serotonergic and noradrenergic reuptake inhibitors. Remission rates were higher for the maca group than the placebo group, based on attainment of an Arizona Sexual Experience Scale total score of 10 or lower (9.5% for maca vs. 4.8% for placebo), a Massachusetts General Hospital Sexual Functioning Questionnaire score of 12 or lower (30.0% for maca vs. 20.0% for placebo), and a Massachusetts General Hospital Sexual Functioning Questionnaire score of 8 or lower (9.5% for maca vs. 5.0% for placebo). Higher remission rates for sexual functioning in the maca group were associated with postmenopausal status, which suggests that maca root may preferentially alleviate SSRI-induced sexual dysfunction among postmenopausal women (27).

Given the dearth of systematic data to support the use of maca as a sexual enhancer, it is difficult to offer any specific clinical management recommendations at this time. In our opinion, maca is a promising agent for postmenopausal women who have a specific interest in using natural remedies to treat sexual dysfunction. So far, maca has shown no toxicity and no adverse pharmacologic effects. We avoid dosing at night, because maca may disrupt sleep. It is recommended that maca be avoided among women with a history of breast cancer or other hormonal cancers, because certain studies in animals have found that maca can effect female reproductive hormones.

Other Natural Treatments

Dehydroepiandosterone (DHEA) and its sulfate (DHEAS) are precursors to estradiol and androgen in ovaries, and low levels have been associated with decreased female sexual function. A very recent review of published studies on DHEAS found that, overall, it conveyed benefit to peri- and postmenopausal women with sexual dysfunction throughout most of the sexual response cycle (28)

Tribulus terrestris (“Puncturevine”) is considered an energizer and vitalizer in indigenous medicine in Mediterranean areas. It has been used since ancient times, but there are few well-designed trials supporting its efficacy for women. Furthermore, there are some concerns about adverse effects from Tribulus related to its associated increase in DHEA levels. There is at least one case report of gynecomastia developing as a result of its use (29). Another concern is of phototoxic reactions (30). As of now, data are too limited to recommend this compound’s use for sexual dysfunction.

Trifolium pratense (red clover) is a plant rich in phytoestrogens and has both estrogenic effects as well as an affinity for the opiate receptors. Although there are no clinical studies on the use of this plant specifically for the treatment of female sexual dysfunction, it has been shown to have a beneficial effect on vaginal health among postmenopausal women (31). In addition, a meta-analysis supports its use for the treatment of hot flashes (32).

Cimicifuga racemosa (black cohosh) is a perennial herb from North America that has been used widely in the treatment of menopausal symptoms. It is a selective estrogen receptor modulator with both estrogenic and dopaminergic effect. Although some studies have failed to demonstrate any effect on female sexual hormones, including luteinizing hormone, follicular-stimulating hormone, prolactin, estradiol, and sex hormone-binding globulin (33, 34), one study did report a significant reduction in luteinizing-hormone serum levels among women with menopausal symptoms (35). Some studies suggest improvement in vaginal dryness and other domains of sexual functioning among menopausal women (33, 36). There is a lack of data on its chronic use (37).

Vitex agnus-castus (chasteberry fruit) is a dietary supplement with potential effects on opiate systems as well as on a variety of female reproductive hormones. It has been used for the treatment of premenstrual syndrome and has been demonstrated in at least one study to improve vaginal tone and thinning as well as lubrication, resulting in more comfortable intercourse among perimenopausal and menopausal women (38). Given these positive effects, it may improve sexual satisfaction for menopausal women.

Acupuncture in recent studies has shown benefit for traditionally difficult-to-treat aspects of sexual dysfunction. For example, one study of women with antidepressant-induced sexual dysfunction reported a significant improvement in libido and lubrication with acupuncture (39). Another study of premenopausal women with diminished libido found improvement in sexual functioning (40).

Although yoga, an ancient art targeting aspects of both mindfulness and overall physical health, seems to be a logical treatment for sexual dysfunction, there have been relatively few empiric studies documenting its effectiveness among women (41). Recently, however, results from several RCTs of women with comorbid medical conditions, such as metabolic syndrome (42) and multiple sclerosis (43), have supported its use in improving sexual functioning. In at least one study of women between the ages of 22 and 55, yoga seemed to be an effective method of improving all domains of sexual function (44).

Worldwide, natural medications such as Angelica sinensis (dong quai) from China, Ferula hermonis (zallouh) in the Middle East, and Humulus lupulus (hops) in Germany are used to treat sexual functioning, with scant data to support their efficacy (37).

Conclusion

Despite the high prevalence of female sexual dysfunction, there are no FDA-approved agents to treat this condition among postmenopausal woman, and there is only limited choice for others. It is not difficult to understand why many women turn to natural or complementary remedies to relieve their symptoms. Natural remedies may be especially attractive to a population whose sexual dysfunction is a side effect of a required pharmaceutical agent (e.g., antidepressant treatments).

The increasing popularity of these agents seems to have outpaced valid scientific evidence for their effectiveness. There are few well-designed, double-blind, placebo-controlled trials of natural remedies for sexual dysfunction among women. Placebo response rates of 25% to 50% have been reported in clinical trials with sexual-enhancing agents that were ultimately determined to be effective. With the high placebo response rate in treatment of sexual dysfunction, the need for randomized, placebo-controlled studies is of paramount importance. Given the paucity of data on both efficacy and safety, it is often difficult to weigh risks and benefits of using these agents for this condition. To truly weigh the risks and benefits of natural and complementary agents, we need more well-designed, placebo-controlled trials.