Supplements for Female Sexual Dysfunction
Supplements for Female Sexual Dysfunction
By Steven Bratman, MD, and Adriane Fugh-Berman, MD
Loss of libido, painful intercourse, and difficulty achieving orgasm are problems for many women. Possible causes include side effects from drugs (e.g., serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants, antihypertensives, and benzodiazepines), hormonal insufficiency, adrenal insufficiency, and relationship problems. Several dietary supplements, including DHEA, ginkgo, yohimbine, and arginine, have shown promising results in preliminary trials.
DHEA
Levels of DHEA (dehydroepiandrosterone) decline with age and drop precipitately in adrenal failure. Several studies have examined whether supplemental DHEA can increase libido in elderly people and those with adrenal insufficiency.
A randomized, double-blind, placebo-controlled trial assessed DHEA (50 mg/d for 12 months) in 280 individuals (including 140 women) between the ages of 60 and 79 years.1 Subjects were assessed every three months. Women older than 70 years, but not other participants, experienced significantly improved libido (at six and 12 months) and sexual satisfaction (at 12 months). Similar trials that only lasted three months did not find any effect of DHEA, possibly because the trials were not long enough in duration.2,3
A double-blind, placebo-controlled crossover study of 24 women with adrenal failure tested DHEA (50 mg/d) as an adjunct to conventional treatment.4 Each phase lasted four months, with a one-month washout in between. All women had low levels of DHEA at baseline. DHEA improved frequency of sexual thoughts, sexual interest, and sexual satisfaction significantly over placebo (all P < 0.01). Nineteen women reported androgenic skin effects (including acne, greasy skin, and increased body hair); one woman reported hair loss, which ceased when the dose was reduced. Serum aminotransferase concentrations were slightly elevated after one month of DHEA treatment but normalized after that. In women, DHEA can increase androgens, decrease high-density lipoprotein cholesterol,2 and decrease sex hormone-binding globulin.5 Additionally, high levels of DHEA are correlated with increased risk of cardiovascular disease in women.6
Ginkgo biloba
Two open trials of ginkgo extract in antidepressant-induced sexual dysfunction found conflicting results. One trial tested standardized ginkgo extract (60 mg qd to 240 mg bid) for four weeks in 63 patients (33 female) with antidepressant-induced sexual dysfunction; most were on SSRIs.7 Ninety-one percent of women and 76% of men improved by self-report. However, another open one-month trial of ginkgo (300 mg tid) in nine men and 13 women with SSRI-induced sexual dysfunction found that only three women reported partial improvement; none of the men improved.8 Neither of these reports identifies the ginkgo brand or formulation, making these studies difficult to evaluate.
Ginkgo increases blood flow through small vessels, and also inhibits platelet-activating factor. Ginkgo, especially when combined with other anticoagulants, has been linked with bleeding.9
Combination Products
A recent double-blind, placebo-controlled trial evaluated a proprietary combination therapy containing L-arginine; standardized extracts of ginseng (Panax ginseng [30% ginsenosides]), ginkgo (G. biloba [24% flavone glycosides, 6% terpene lactones]) and damiana (Turnera diffusa); vitamins B complex, A, C, and E; and calcium, iron, and zinc (exact amounts were not given).10 Researchers enrolled 77 women between the ages of 22 and 71 years who wanted to improve sexual function; six had previously been treated for sexual dysfunction. After four weeks, 70.6% of women in the treated group reported improvement in sexual desire, compared to 41.9% in the placebo group, a significant difference (P < 0.01). Frequency of intercourse increased in significantly more women (64.7%) in the treated group than the placebo group (26.6%) (P < 0.01). An improved sexual relationship was reported in 61.8% of the treated group vs. 34.9% of the placebo group, a significant difference (P < 0.01).
Arginine, a nitric oxide precursor, is probably the most active ingredient in this formulation. Although generally benign, arginine should not be used in patients with renal insufficiency. Intravenous administration of arginine can cause hyperkalemia in renal failure patients. Orally administered arginine also can increase potassium. A 15-year-old male hemodialysis patient who accidentally ingested 1.5 g L-arginine orally was asymptomatic, but serum potassium rose from 5.4 mmol one hour after ingestion to 6.1 mmol (normal = 3.5-5.5 mmol/L) two hours post-ingestion; two hours later he received sodium polystyene sulfonate, with normalization of potassium levels within 1.5 hours.11
Ginseng and damiana are common components of purported herbal aphrodisiacs. No other clinical trials of damiana were identified. Although no other clinical trials of ginseng for sexual dysfunction in women were identified, one clinical trial in men compared Korean red ginseng (1,800 mg qd) to trazodone (25 mg qhs) or placebo in 90 subjects with erectile dysfunction.12 After three months, ginseng treatment improved libido, rigidity, and tumescence significantly more than trazodone or placebo.
Ginseng has been associated with two cases of postmenopausal vaginal bleeding,13 but large double-blind, placebo-controlled trials of ginseng have found no effects on sex hormones or gonadotropins.14,15
Yohimbine, a drug derived from the bark of the yohimbe tree (Pausinystalia johimbe), is an alpha-2 adrenoceptor antagonist, with weak alpha-1 adrenergic antagonist properties. Yohimbine is available by prescription for the treatment of erectile dysfunction, but yohimbe also is available over the counter in dietary supplements. Studies have only utilized yohimbine, not yohimbe herb.
One small, randomized, double-blind, placebo-controlled crossover study in 23 women with female sexual arousal disorder tested yohimbine (6 mg) alone or in combination with arginine (6 g) against placebo.16 This study was presented at the 26th Annual Meeting of the International Academy of Sex Research in Paris in June, 2000, but has not yet been published. Although the study found that the combination of arginine and yohimbine (but not yohimbine alone) increased vaginal pulse amplitude in response to watching a sexual film, subjective measures of sexual arousal did not change with any treatment.
A small open trial of yohimbine to treat fluoxetine-induced sexual dysfunction found that eight of nine subjects (including two women) improved.17 Without a placebo group, these results cannot be considered reliable.
Yohimbine
Yohimbine is not free of risks. It can cause hypertension, tachycardia, headache, anxiety, diarrhea, palpitations, dizziness, tremor, skin flushing, and increased urinary frequency and can induce manic symptoms in patients with bipolar disorder.18 Combining yohimbe with antidepressants may increase side effects. Yohimbine in doses of 15-20 mg alone may increase blood pressure and induce anxiety, but in combination with tricyclic antidepressants, yohimbine may cause hypertension at substantially lower doses (4 mg tid).18
Conclusion
DHEA, ginkgo, yohimbine, and arginine may have potential in the treatment of female sexual dysfunction; however, larger, longer trials, with delineation of adverse effects, are needed before these supplements should be recommended to patients.
Dr. Bratman is the former medical director of TNP.com.
References
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5. Labrie F, et al. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498-3505.
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7. Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther 1998;24:139-143.
8. Ashton AK, et al. Antidepressant-induced sexual dysfunction in Ginkgo biloba. Am J Psychiatry 2000;157: 836-837.
9. Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355:134-138.
10. Ito TY, et al. A double-blind placebo-controlled study of ArginMax, a nutritional supplement for enhancement of female sexual function. J Sex Marital Ther 2001;27: 541-549.
11. Christianson G, et al. Hyperkalemia following accidental L-arginine ingestion. Abstract presented at the North American Congress of Clinical Toxicology, Sept. 13-18, 2000. Clin Toxicol 2000;38:523.
12. Choi HK, et al. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impotence Res 1995;7: 181-186.
13. Fugh-Berman A, Cott JC. Dietary supplements and natural products as psychotherapeutic agents. Psychosomatic Med 1999;61:712-728.
14. Wiklund IK, et al. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: A double-blind, placebo-controlled trial. Swedish Alternative Medicine Group. Int J Clin Pharmacol Res 1999;19: 89-99.
15. Forgo I, et al. The effect of a standardized ginseng extract on general well-being, reaction time, lung function and gonadal hormones [translated from German]. Med Welt 1981;32:751-756.
16. Meston CM, Worcel M. The effects of L-arginine and yohimbine on sexual arousal in postmenopausal women with female sexual arousal disorder. Presented at the 26th Annual Meeting of the International Academy of Sex Research; Paris, France; June 21-24, 2000.
17. Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53:119-122.
18. De Smet PA, Smeets OS. Potential risks of health food products containing yohimbe extracts. BMJ 1994; 309:958.
Bratman S, Fugh-Berman A. Supplements for female sexual dysfunction. Altern Ther Women's Health 2002;4:25-28.Subscribe Now for Access
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