Systematic Review of l-Arginine for the Treatment of Hypoactive Sexual Desire Disorder and Related Conditions in Women

Nicole E Cieri-Hutcherson, Andrea Jaenecke, Ajeet Bahia, Debra Lucas, Ann Oluloro, Lora Stimmel, Timothy C Hutcherson, Nicole E Cieri-Hutcherson, Andrea Jaenecke, Ajeet Bahia, Debra Lucas, Ann Oluloro, Lora Stimmel, Timothy C Hutcherson

Abstract

This systematic review evaluates the efficacy and safety of l-arginine alone or in combination for the treatment of women with hypoactive sexual desire disorder (HSDD) or related conditions, such as female sexual interest/arousal disorder and female sexual arousal disorder. Medline, Embase, International Pharmaceutical Abstracts, Science Direct, and the Cumulative Index to Nursing and Allied Health Literature were searched using keywords "arginine", "Lady Prelox", "ArginMax", "Stronvivo", "Ristela", "hypoactive sexual desire disorder", "female sexual interest arousal disorder", "female sexual arousal disorder", "sexual dysfunction", "sexual behavior", "dyspareunia", "libido", and permutations thereof. Relevant records were retained if they were primary literature, conducted in women with HSDD or related conditions, and published as full text in English. Five randomized controlled trials and two nonrandomized studies met eligibility criteria. Six of the seven studies reported either an increase in the total mean Female Sexual Function Index score or significant increases in multiple domains therein. One study assessed vaginal pulse amplitude and found a statistically significant increase in a combination treatment group compared to placebo. No significant side effects were reported. Four of seven studies had potential risk-of-bias concerns per Cochrane assessments. This systematic review found that combination products containing l-arginine in the form of ArginMax or Lady Prelox may be considered for the treatment of HSDD and related conditions in women regardless of age.

Keywords: arginine; dietary supplement; hypoactive sexual desire disorder; sexual dysfunction; women’s health.

Conflict of interest statement

There are no conflicts of interest to disclose associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Figures

Figure 1
Figure 1
Screening Process—Inclusion and Exclusion Criteria.

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association; Washington, DC, USA: 2003. Revised; (DSM-4-TR)
    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; Washington, DC, USA: 2013. (DSM-5)
    1. Clayton A.H., Goldstein I., Kim N.N., Althof S.E., Faubion S.S., Faught B.M., Parish S.J., Simon J.A., Vignozzi L., Christiansen K., et al. The International Society for the Study of Women’s Sexual Health Process of Care for Management of Hypoactive Sexual Desire Disorder in Women. Mayo Clin. Proc. 2018;93:467–487. doi: 10.1016/j.mayocp.2017.11.002.
    1. Balon R., Clayton A.H. Further commentary on DSM-5 FSIAD diagnosis. J. Sex. Med. 2015;12:576–577. doi: 10.1111/jsm.12770.
    1. Clayton A.H., Derogatis L.R., Rosen R.C. Intended or Unintended Consequences? The Likely Implications of Raising the Bar for Sexual Dysfunction Diagnosis in the Proposed DSM-V Revisions: 2. For Women with Loss of Subjective Sexual Arousal. J. Sex Med. 2012;9:2. doi: 10.1111/j.1743-6109.2012.02859.x.
    1. Parish S.J., Hahn S.R. Hypoactive Sexual Desire Disorder: A Review of Epidemiology, Biopsychology, Diagnosis, and Treatment. Sex. Med. Rev. 2016;4:103–120. doi: 10.1016/j.sxmr.2015.11.009.
    1. Biddle A.K., West S.L., D’Aloisio A.A., Wheeler S.B., Borisov N.N., Thorp J. Hypoactive Sexual Desire Disorder in Postmenopausal Women: Quality of Life and Health Burden. Value Heal. 2009;12:763–772. doi: 10.1111/j.1524-4733.2008.00483.x.
    1. Foley K., Foley D., Johnson B.H. Healthcare resource utilization and expenditures of women diagnosed with hypoactive sexual desire disorder. J. Med. Econ. 2010;13:583–590. doi: 10.3111/13696998.2010.518114.
    1. Warnock J., Jill K. Female Hypoactive Sexual Desire Disorder: Epidemiology, diagnosis and treatment. CNS Drugs. 2002;16:745–753. doi: 10.2165/00023210-200216110-00003.
    1. Ito T.Y., Trant A.S., Polan M.L. 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. doi: 10.1080/713846828.
    1. Munarriz R., Kim N.N., Goldstein I., Traish A.M. Biology of female sexual function. Urol. Clin. North Am. 2002;29:685–693. doi: 10.1016/S0094-0143(02)00069-1.
    1. Revicki D.A., Margolis M.K., Bush E.N., Derogatis L.R., Hanes V. Content Validity of the Female Sexual Function Index (FSFI) in Pre- and Postmenopausal Women with Hypoactive Sexual Desire Disorder (HSDD) J. Sex. Med. 2011;8:2237–2245. doi: 10.1111/j.1743-6109.2011.02312.x.
    1. Bottari A., Belcaro G., Ledda A., Luzzi R., Cesarone M.R., Dugall M. Lady Prelox® improves sexual function in generally healthy women of reproductive age. Minerva Ginecol. 2013;65:435–444.
    1. Hatch J.P. Vaginal photoplethysmography: Methodological considerations. Arch. Sex. Behav. 1979;8:357–374. doi: 10.1007/BF01541879.
    1. US Food and Drug Administration Approved Risk Evaluation and Mitigation Strategies (REMS): Addyi (filbanserin) [(accessed on 13 January 2021)]; Available online: .
    1. Lodise N.M. Hypoactive Sexual Desire Disorder in Women: Treatment Options beyond Testosterone and Approaches to Communicating with Patients on Sexual Health. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2013;33:411–421. doi: 10.1002/phar.1209.
    1. Schwedhelm E., Maas R., Freese R., Jung D., Lukacs Z., Jambrecina A., Spickler W., Schulze F., Böger R.H. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: Impact on nitric oxide metabolism. Br. J. Clin. Pharmacol. 2008;65:51–59. doi: 10.1111/j.1365-2125.2007.02990.x.
    1. Klotz T., Mathers M., Braun M., Bloch W., Engelmann U. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol. Int. 1999;63:220–223. doi: 10.1159/000030454.
    1. Stanislavov R., Rohdewald P. PACR (Pine Bark Extract, L Arginine, L Citrulline, Rose Hip Extract) Improves Emotional, Physical Health and Sexual Function in Peri-Menopausal Women. J. Women’s Heal. Care. 2014;3 doi: 10.4172/2167-0420.1000195.
    1. Bottari A., Belcaro G., Ledda A., Cesarone M.R., Vinciguerra G., Di Renzo A., Stuard S., Dugall M., Pellegrini L., Errichi S., et al. Lady Prelox® improves sexual function in post-menopausal women. Panminerva Med. 2012;54(Suppl. 1):3–9.
    1. Cesarone M.R., Belcaro G., Scipione C., Scipione V., Dugall M., Hu S., Cotellese R., Feragalli B., Ledda A. Prevention of vaginal dryness in perimenopausal women. Supplementation with Lady Prelox®. Minerva Ginecol. 2020;71:434–441. doi: 10.23736/S0026-4784.19.04466-6.
    1. Kellogg Spad S., Dweck A. 083 The effect of Ristela supplementation on Female Sexual Function in women taking antide-pressants: An open label trial. J. Sex Med. 2020;17:S259–S260. doi: 10.1016/j.jsxm.2020.04.388.
    1. Smetanka A., Stara V., Farsky I., Tonhajzerova I., Ondrejka I. Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction. Physiol. Int. 2019;106:59–69. doi: 10.1556/2060.106.2019.02.
    1. West E., Krychman M. Natural Aphrodisiacs—A Review of Selected Sexual Enhancers. Sex. Med. Rev. 2015;3:279–288. doi: 10.1002/smrj.62.
    1. PRISMA: Transparent Reporting of Systematic Reviews and Meta-Analyses. PRISMA Statement. [(accessed on 11 November 2020)]; Available online:
    1. Zeng X., Zhang Y., Kwong J.S., Zhang C., Li S., Sun F., Niu Y., Du L. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: A systematic review. J. Evidence-Based Med. 2015;8:2–10. doi: 10.1111/jebm.12141.
    1. Sterne J.A., Hernán M.A., Reeves B.C., Savović J., Berkman N.D., Viswanathan M., Henry D., Altman D.G., Ansari M.T., Boutron I., et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi: 10.1136/bmj.i4919.
    1. Sterne J.A.C., Savović J., Page M.J., Elbers R.G., Blencowe N.S., Boutron I., Cates C.J., Cheng H.-Y., Corbett M.S., Eldridge S.M., et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898.
    1. Meston C.M., Worcel M. The effects of yohimbine plus L-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Arch. Sex. Behav. 2002;31:323–332. doi: 10.1023/A:1016220225392.
    1. Ito T.Y., Polan M.L., Whipple B., Trant A.S. The Enhancement of Female Sexual Function with ArginMax, a Nutritional Supplement, Among Women Differing in Menopausal Status. J. Sex Marital. Ther. 2006;32:369–378. doi: 10.1080/00926230600834901.
    1. Nocerino E., Amato M., Izzo A. The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia. 2000;71:S1–S5. doi: 10.1016/S0367-326X(00)00170-2.
    1. Rector T.S., Bank A.J., Mullen K.A., Tschumperlin L.K., Sih R., Pillai K., Kubo S.H. Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral l -Arginine in Patients with Heart Failure. Circulation. 1996;93:2135–2141. doi: 10.1161/01.CIR.93.12.2135.
    1. L-Arginine Supplements Review. . [(accessed on 7 December 2020)];2019 Oct 19; Available online:
    1. Meston C.M., Rellini A.H., Telch M.J. Short- and Long-term Effects of Ginkgo Biloba Extract on Sexual Dysfunction in Women. Arch. Sex. Behav. 2008;37:530–547. doi: 10.1007/s10508-008-9316-2.
    1. Newell C., Anderson L., Phillipson J. Herbal Medicines: A Guide for Health-Care Professionals. The Pharmaceutical Press; London, UK: 1996.
    1. Oh K.-J., Chae M.-J., Lee H.-S., Hong H.-D., Park K. Effects of Korean Red Ginseng on Sexual Arousal in Menopausal Women: Placebo-Controlled, Double-Blind Crossover Clinical Study. J. Sex. Med. 2010;7:1469–1477. doi: 10.1111/j.1743-6109.2009.01700.x.
    1. Wheatley D. Triple-blind, placebo-controlled trial ofGinkgo biloba in sexual dysfunction due to antidepressant drugs. Hum. Psychopharmacol. Clin. Exp. 2004;19:545–548. doi: 10.1002/hup.627.
    1. Moinard C., Nicolis I., Neveux N., Darquy S., Bénazeth S., Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: The Citrudose pharmacokinetic study. Br. J. Nutr. 2007;99:855–862. doi: 10.1017/S0007114507841110.
    1. Andersson U., Berger K., Hogberg A., Landinolsson M., Holm C. Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: A randomized, double-blind, cross-over investigation in obese persons. Eur. J. Clin. Nutr. 2011;66:585–590. doi: 10.1038/ejcn.2011.203.
    1. Rice-Evans C.A., Packer L. Flavonoids in Health and Disease. Marcel Dekker, Inc.; Manhattan, NY, USA: 1998.
    1. Anderson R., Moffatt C.E. Ignorance Is Not Bliss: If We Don’t Understand Hypoactive Sexual Desire Disorder, How Can Flibanserin Treat It? Commentary. J. Sex. Med. 2018;15:273–283. doi: 10.1016/j.jsxm.2018.01.001.
    1. Kingsberg S.A., Althof S., Simon J.A., Bradford A., Bitzer J., Carvalho J., Flynn K.E., Nappi R.E., Reese J.B., Rezaee R.L., et al. Female Sexual Dysfunction—Medical and Psychological Treatments, Committee 14. J. Sex. Med. 2017;14:1463–1491. doi: 10.1016/j.jsxm.2017.05.018.
    1. Lexi-Comp Online . Flibanserin. Lexi-Comp, Inc.; Hudson, OH, USA: Jan 5, 2021.
    1. Clayton A.H. Original Articles: Epidemiology and Neurobiology of Female Sexual Dysfunction. J. Sex. Med. 2007;4:260–268. doi: 10.1111/j.1743-6109.2007.00609.x.
    1. The US National Institutes of Health. . [(accessed on 7 December 2020)]; Available online:

Source: PubMed

3
구독하다