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THE USE OF NATURAL PRODUCTS IN THE TREATMENT OF FEMALE SEXUAL DYSFUNCTION

Alan J Cohen, M.D., Laura E. Stachel, M.D., and Ben Sanders, B.A.

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Gingko biloba
Yohimbine
Panax ginseng
Damiana
Potency Wood
Saw Palmetto
Sarsaparella Root
St John's Wort
Black Cohosh
Chasteberry
Wild Yam
Soybeans

Natural products have become an increasingly popular treatment option for patients who have been dissatisfied with standard Western pharmacotherapy. Physicians are assuming a more collaborative role with patients who may be eager to incorporate herbal extracts, dietary supplements, and other natural products into their therapeutic regimen. Therefore, it would be beneficial for the physician to have a greater understanding of the role these substances may have in treating sexual dysfunction. This article will review information on herbal and plant extracts that can be used for treatment of sexual dysfunction, with focus on antidepressant-induced sexual dysfunction, sexual enhancement, and menopause.

Readers should note that herbs lacking research supporting their efficacy should not be dismissed, and that a distinction should be made between lack of any evidence and lack of efficacy or safety. We mention some herbs here in order to recognize their use by the public, their potential in medicine, and to elicit interest and discussion on the part of practitioners and investigators.

ANTIDEPRESSANT-INDUCED SEXUAL DYSFUNCTION

With depression affecting approximately 24% of women in the United States at some point in their lives,(1) antidepressants have gained greater acceptance by many patients seeking treatment for their mood disorders. Many women, however, find that along with relief of symptoms comes significant impairment in sexual function. Specifically, decreased libido, delayed orgasm, anorgasmia, and even genital sensory impairment are reported in up to 71% of patients using these drugs.(2,3,4)

Several pharmacologic interventions have been utilized to remedy antidepressant-induced sexual dysfunction (ASD). Among the most commonly employed strategies are the reduction of drug dosage, substitution of alternative antidepressants, addition of supplemental agents, and use of "drug holidays." Recent research has demonstrated the efficacy of certain herbal extracts in reversing ASD, confirming prior anecdotal reports describing the benefits of these botanical products in treating sexual dysfunction. The products most investigated are Ginkgo biloba, Yohimbe and Ginseng.

Ginkgo biloba extract

Ginkgo biloba extract (GBE, species Ginkgo biloba) has been used for centuries as part of the ancient Chinese pharmacopoeia in the treatment of respiratory ailments, cognitive impairment, and circulatory disorders. In recent years, Ginkgo has gained great worldwide acceptance for treatment of a number of medical conditions including tinnitus, cognitive decline in dementia, intermittent claudication, asthma, macular degeneration and, most recently, antidepressant induced sexual dysfunction.(5,6,7)

Case reports have confirmed GBE's beneficial effect on ASD.(8,9) An open clinical trial of Ginkgo biloba extract with 63 patients was found to be effective in 84% of patients with ASD.(6) All phases of the sexual response cycle were improved (desire, excitement, orgasm and resolution). Minimal side effects were reported which included gastrointestinal upset, headache, CNS stimulation and easy bruisability. There were no serious adverse events. A double blind placebo-controlled trial of a GBE compound has just been completed and the results are currently under review.

Possible mechanisms of action may include improved circulation and prostaglandin agonist effects, as well as neurotransmitter and nitric oxide second messenger modulation. Although Ginkgo biloba is relatively safe, it also works as a potent inhibitor of platelet activating factor. Therefore, patients taking aspirin, nonsteroidal anti-inflammatory agents, and anti-coagulants, or patients with a coagulopathy should consult a physician and exercise caution when considering adding GBE to their existing regimen. Dose ranges of GBE 50:1 extract are 60 milligram tablets twice a day; this can be advanced to 120 mg twice a day after two weeks.

Yohimbine

Derived from the bark of the yohimbe tree (Pausinystalia yohimbe), Yohimbine's primary action is to increase blood flow to erectile tissue, and is FDA approved for treating male erectile dysfunction. Although several studies have demonstrated some efficacy in men, there are relatively few clinical trials including women. However, Gitlin reports that Yohimbine has been found to diminish ASD in men and women.(10) It can cause increased levels of anxiety and agitation, and the Physician's Desk Reference suggests that patients with psychiatric disorders should not use this product.(11) This opinion has been challenged by Gitlin, as there seems to be little evidence to support the statement.(10) Jacobsen suggests that this contraindication "appears to be based upon concerns of potentially adverse cholinergic and adrenergic interactive effects that may more commonly occur with the tricyclic antidepressants."(12) Except in some cases of noncompliance from its side effects, Yohimbine has been used successfully to treat ASD.(12,13) Side effects may include hypertension, headache, increased heart rate, dizziness, urinary urgency and sweating. Dosages range from 5.4 milligram tablets once to three times daily.

Panax ginseng

The extract of the Chinese root Panax ginseng and the North American Panax quinquefolius contains as its putative active constituents a large group of ginsenosides, four-ring glycosides.(14) Anecdotal reports in the scientific literature suggest that Ginseng can improve sexual dysfunction such as anorgasmia and decreased libido in patients taking antidepressants.(15) Ginsenosides facilitate the release of nitric oxide in endothelial tissue of rabbit corpus cavernosum, a step in the events leading to erection.(16) This property may have promise for women, as the biochemical process of erection is the same in the clitoris. Multiple orgasmic response has also been described with this Chinese herbal.

Ginseng is known to possess phytoestrogen activity. The herb is believed to function as an adaptogen—helping the body adapt to stressful conditions, possibly by augmenting production of the body's own stress hormones (ACTH, Cortisol).

Adverse effects may include hypertension, insomnia, vomiting, headache and epistaxis. Isolated case reports have noted post-menopausal vaginal bleeding and breast nodularity with prolonged usage, suggesting a modest estrogen-like effect. A two-year study of 133 people using ginseng noted a central nervous system stimulant effect.(17) Nervousness and insomnia were noted in 11% of subjects; therefore, ginseng would not be recommended for use in patients with bipolar disorder (manic syndrome) or psychosis. However, this study used doses (15 g/day) on the high end of those recommended, used no placebo, and did not describe the quality or form of the extract used.

The dosage is dependent on the ginsenoside content. With a saponin content of at least 5 mg of ginsenosides with a ratio of Rb1 to Rg1 of 2:1, a typical dose would be to take this 1 to 3 times a day. It is best to begin with a lower dose and to gradually increase this if needed.

SEXUAL ENHANCEMENT

A number of other botanical products are purported to enhance sexual function. Although no data exist on the concurrent use of these products with antidepressants, they are readily available to patients, and may be sold individually or as part of combination preparations. Here is a brief description of some of the commonly used herbal products.

Damiana

Damiana (Turnera diffusa) is reported to be an aphrodisiac, stimulant, mood elevator, and "tonic," and has been in use in the United States since 1874. Despite a paucity of research, it has reported testosterogenic activity, which may account for its traditional use by the Mayan people of Central America for enhancing sexual function in men and women.

Potency Wood

Also known as Muira puama or the Latin Liriosma ovata, potency wood is a shrub that has been used in South American folk medicine for treating decreased libido and erectile dysfunction. We have found mention of a French clinical study in 1990 in which Muira puama extract improved libido in 62% of patients with lack of sexual desire. However, numerous citation database searches on Medline, Biosis, and others have not identified such a study, and few other data seem to be available on this plant.

Saw palmetto

Saw palmetto or the Latin Sabal serrulata has gained increasing acceptance in medical circles for the treatment of prostatic enlargement. It has estrogenic and anabolic constituents as well as other steroidal saponins. It has been used to enhance libido and stimulate breast enlargement. Supportive research, however, is lacking. In treating prostatic enlargement Saw palmetto at least has potential as an alternative to finasteride and its tendencies to decrease libido and sexual performance, as the plant extract scored better in these areas in a French clinical trial.(18)

Sarsaparilla Root

This is also known to possess testosterogenic as well as progesterogenic activity. In Mexico, it has been used as an aphrodisiac.

St. John's Wort

Clinicians have noticed an increase in female patients' use of St. John's Wort hoping to lessen depressive symptoms without use of prescription medications. Patients may be willing to use this as a first-line approach to anxiety and depression, or may consider trying St John's Wort as an alternative to SSRIs if ASD occurs. Of all the herbals on the market in the United States today, the efficacy and safety of St. John's Wort for mild to moderate depression is among the most substantiated by Western science. It should be noted that the mechanism of action is unclear, but St John's Wort may have SSRI or MAOI properties,(19,20) ;and a more recent study indicates a high affinity for alpha receptors, associated with SSRI and MAOI action.(21) As such, it is inadvisable to combine St John's Wort with SSRI s or known MAOIs. There have been no studies examining the risk of sexual dysfunction resulting from St John's Wort.

MENOPAUSE

Menopausal women who present with depression and sexual dysfunction amount to an additional challenge to the treating physician. Levels of estrogen and testosterone decline in menopause, accounting for hot flashes, night sweats, insomnia and sexual dysfunction. Estrogen deprivation has been linked to vaginal dryness, vaginal tissue atrophy and irritation, and decreased libido. Testosterone levels decline by about 30 percent during menopause(22) and this has also been linked to decreased libido.

For the depressed menopausal woman with sexual dysfunction, it would be prudent to investigate whether hormone replacement is being utilized. Both estrogen and testosterone can be administered post-menopausally, with likely improvements in sexual function. For women with an intact uterus, progesterone should be administered concurrently to prevent endometrial neoplasia.

A number of herbal preparations are available for women preferring non-pharmacologic relief of menopausal symptoms. For a more comprehensive resource on the subject, refer to Laucella's book.(23) Women with a personal or strong family history of breast cancer may wish to avoid estrogen-containing preparations, as the risk of breast cancer increases under exposure to unopposed (e.g. by progestogen) estrogen.(24)

Black Cohosh

Black Cohosh (Cimicifuga racemosa) is an herb originally used by Native Americans that has been reported to alleviate menopausal symptoms including hot flashes.

In a large open study involving 131 doctors and 629 female patients, 80% of menopausal women experienced clear improvements in physical and psychological menopausal symptoms within six to eight weeks of use.(25) In a double-blind study, 80 patients given cimicifuga extract showed greater improvements in menopausal symptoms and vaginal lining than either estrogen or placebo.(26) It is reputed to have estrogenic properties inhibiting LH release. Most of these studies use Remifemin® (Schaper, Brümmer, Salzgitter, Germany), a standardized Black Cohosh extract that contains 1 mg of triterpenes calculated as 27-deoxyacteine per tablet. It has been used for decades in Germany, and has been popular in the US and Australia as well. Menopausal dosages range from 40 mg daily to 160 mg a day. Side effects are minimal: mild transient stomach upset is noted infrequently; breast engorgement is noted rarely at maximum doses.

Chasteberry

Chaste tree berries (Vitex agnus castus) has been used to treat reproductive disorders such as premenstrual syndrome. It has been shown in to lower prolactin levels in women, and has been found to be effective in treatment of menopausal discomforts, such as night sweats and hot flashes. Chasteberries historically were used to suppress libido in women of childbearing age; in menopausal women, however, they do not appear to reduce libido.

Wild Yam

The sterole diosgenin, plentiful in a variety of wild yams, can be converted into a progesterone. Available in creams and oils, wild yam preparations contain natural progesterone in varying concentrations, and have won the favor of many women for perimenopausal and postmenopausal symptoms. Lee reports that natural progesterone may improve sexual desire when used in physiologic doses.(27) The preparations available in health food stores are quite variable, however, and it may be unclear how much progesterone is actually being absorbed by these transdermal preparations.

Soy Beans

Recent studies have suggested that dietary supplementation with phytoestrogens (plant estrogens) may be beneficial in the treatment of menopausal symptoms, and dietary supplementation with soy products is being recommended for postmenopausal women. Soy products (Glycine max) containing isoflavones (e.g. genistein) and phytosterols, which have a weak estrogenic effect, are gaining popularity for relief of hot flashes and atrophic vaginitis. Clinical studies have shown phytoestrogens can reduce hot flashes.(28,29) At least one study has shown estrogenic improvements in vaginal cytology.(30) This could diminish the vaginal dryness and atrophy that can affect sexual pleasure in the menopausal years. Phytoestrogen content can be variable within the different soy products available. The whole soy bean itself seems to be the most abundant in phytoestrogen; tofu and soy milk have less phytoestrogens. Some health food stores are selling supplements containing the isoflavone isolates.

CONCLUSION

With the use of natural products becoming increasingly popular, it is important for the physician to be fully informed of all pharmacologically active substances that patients may be using. As alternative medicine becomes increasingly mainstream in the United States, we hope to see more studies evaluating the use of these products for sexual dysfunction and other medical conditions.

REFERENCES

1. Kessler, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994 Jan; 51(1):8-19.

2. Grimes J. B., Labbate L. A., Hines A. H. Sexual dysfunction induced by SSRIs. Presented at the American Psychiatric Association 149th Annual Meeting, New York, May 4-9, 1996. (Abstract 95).

3. Montejo A. L., Llorce G., Izquierdo J. A. Sexual Dysfunction wit SSRIs: a comparative analysis. Presented at the American Psychiatric Association 149th Annual Meeting, New York, May 4-9, 1996. (Abstract 717).

4. Couper-Smartt J. D., Rodham R. A technique for surviving side-effects of tricyclic drugs with reference to reported side effects. J Int Med Res. 1973; 1:473-6.

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7. Cohen A. J. Long term safety and efficacy of ginkgo biloba for antidepressant induced sexual dysfunction. Psychiatry On-Line; 1998: www.priory.com/pharmol/gingko.htm

8. Ellison J. M. and Deluca P. Fluoxetine-induced genital anesthesia relieved by ginkgo biloba extract (letter). J Clin Psychiatry 1998 April; 59(4): 199-200.

9. Cohen, A. J. "Treatment of Antidepressant-induced Sexual Dysfunction with Ginkgo Biloba Extract", Health Watch, Vol. VI, No. 1, 1996.

10. Gitlin, M. Sexual side effects of psychotropic medications. Psychiatric Clinics of North America Annual of Drug Therapy 1997; 4: 61-89.

11. Physicians' Desk Reference, 53rd ed. Medical Economics Company, Inc. Montvale, NJ. 1999.

12. Jacobsen, F. M. Fluoxetine-induced sexual dysfunction and an open trial of Yohimbine. J Clin Psychiatry 1992 Apr; 53(4):119-22. Protocol for yohimbine subjects did not include gradual dose increase; they were given 5.4mg t.i.d.

13. Price, J. and L. J. Grunhaus. Treatment of Clomipramine-induced anorgasmia with Yohimbine: a case report. J Clin Psychiatry 1990 Jan; 51(1):32-3.

14. Gillis C. N. Panax ginseng pharmacology: a NO link? Biochem Pharmacol 1997 Jul; 54(1):1-8.

15. Bartlik, B. Witkins M, Roeloffs, C. Ginseng root lowers orgasmic threshold: Three case reports (in press).

16. Chen X. and Lee TJ-F. Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br J Pharmacol 1995; 115:15-18.

17. Siegel R. K. Ginseng abuse syndrome. JAMA 1979; 241:1614-1615.

18. Carraro, J. C., et al. Comparison of Phytotherapy (Permixon) with Finasteride in the Treatment of Benign Prostate Hyperplasia: A Randomized International Study of 1,098 Patients. Prostate 1996; 29:231-40, discussion 241-2.

19. Suzuki, O., et al. Inhibition of Monoamine Oxidase by Hypericin. Planta Medica 1984; 50:272-74.
20. Perovic, S., et al. Effect on Serotonin Uptake by Postsynaptic Receptors. Arzneimittelforschung, 1995, 45:1145-48.

21. Raffa, R. Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals alpha receptor binding. Life Sciences 1998; 62(16):PL 265-270.

22. Vermeulen, A. The Hormonal Activity of the Postmenopausal Ovary. J Clin Endocrinol Metab 1976; 42:247-253.

23. Laucella L. Hormone Replacement Therapy, Conventional Medicines and Natural Alternatives, Your Guide to Menopausal Health Care Choices. Los Angeles: Lowell House. 1997.

24. Wren, B. G. Hormonal Replacement Therapy and Breast Cancer. Eur Menopause J 1995; 2(4):13-19.

25. Stolze H. An alternative to treat menopausal complaints. Gyne 1982; 3:14 - 16.

26. Stoll W. Phytotherapy influences atrophic vaginal epithelium. Therapeutikon 1987; 1:23-31.

27. Lee, J. What Your doctor May Not Tell You About Menopause. New York: Warner Books. 1996.

28. Albertazzi, P. et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998 Jan; 91(1):6-11.

29. Murkies, A. L. et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995 Apr; 21(3):189-95.

30. Baird, D. D. et al. Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab 1995 May; 80(5):1685-90.

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