(Published May 2005)

Female Lack of Desire

Loss of sexual desire, or hypoactive sexual desire disorder (HSDD), is the most common complaint of women reporting a female sexual disorder. In the National Health and Social Life Survey, approximately 33 percent of women between 18 and 59 years of age reported a loss of desire for at least a few months over the last year.¹ The prevalence increases with age, particularly after age 60, and is linked to age more than menopause status.^2,3

Diagnostic Criteria

The definition of female lack of desire, as most recently described by experts on sexuality gathered by the American Foundation for Urologic Disease and led by Basson, is “absent or diminished feelings of sexual interest or desire, absent sexual thoughts or fantasies, and a lack of responsive desire.”⁴ The reasons for becoming sexually aroused are few and far between or absent, and “the lack of interest is considered to be beyond a normative lessening with life cycle and relationship duration,” and causes distress to the woman. One of the key concepts present in this definition from Basson and colleagues is that spontaneous desire (the biologic drive to have sex) is often missing as a reason for women to engage in sexual activity (hence, the addition of the word “interest”). A lack of desire in a responsive context becomes critical, then, to the diagnosis.

The Massachusetts Women’s Health Study II suggests a number of characteristics of women experiencing decreased sexual desire, including being married, having psychological symptoms, being a current cigarette smoker, and being in perimenopause.⁵

Causal factors in the etiology of desire disorders, which can be assessed during the sexual history, include interpersonal issues (reduced physical attractiveness of the patient or partner, boring sexual routines, situational disturbances, or marital adjustment problems), medical illness (depression, diabetes, hypertension, hypothyroidism, hyperprolactinemia), use of certain medications (such as selective serotonin reuptake inhibitors, antihypertensives, estrogen therapies, and corticosteroids), and a sudden drop in testosterone levels as occurs with surgical menopause.^3,6,7

When diagnosing disorders of desire, it is important to inquire about the duration and nature of low desire for sex. Kingsberg suggests that the following questions be asked:⁶

• How would you describe your loss of desire in your own words?
• How long have you had concern with respect to your desire?
• Is it always a problem, or only at certain times or in certain situations?
• Do you have sexual thoughts, daydreams, or fantasies?
• Has the problem changed over time? If so, how?
• Does anything appear to improve your desire (such as taking a romantic vacation or having sexual relations with a different partner)? Does anything make it worse?
• How is your emotional intimacy with your partner?

Treating Disorders of Desire

There are no drugs specifically indicated for the treatment of any female sexual disorder, including disorders of desire.⁶ A number of therapies are in clinical trials.⁶ Because loss of desire is often related to interpersonal problems rather than biologic factors, relationship, psychological, and situational issues should be evaluated and managed before pharmacotherapy is considered (see Table 10).⁸

Androgens

Testosterone therapies, in transdermal patch, gel, and oral formulations, are in clinical trials and appear to be effective in the treatment of female sexual disorders, specifically low libido, alone or in combination with estrogen/progestin therapy.^9–11 Shifren and colleagues published a placebo-controlled study of transdermal testosterone therapy (150 mcg or 300 mcg per day) in a group of 75 surgically menopausal women between 31 and 56 years of age who were experiencing decreased libido.¹¹ The subjects also received conjugated equine estrogens (0.625–1.25 mg daily) and had been in a stable sexual relationship for 1 year or more. At baseline, testosterone levels were <30 ng/dl and free testosterone was <3.5 pg/ml. Although an “appreciable” placebo response was observed, the 300-mcg dose produced further increases in scores for frequency of sexual activity and pleasure-orgasm (p=0.03 for both comparisons versus placebo) compared with the 150-mcg dose and placebo. The percentage of women who had sexual fantasies, masturbated, or had sexual intercourse at least once a week also increased two to three times over baseline on the higher testosterone dose. No differences were observed between the placebo and testosterone groups in relation to acne, hirsutism, liver function, cholesterol parameters, or hematocrit.

A second randomized, double-blind, multicenter trial of the 300-mcg testosterone patch, delivered twice weekly in 562 surgically menopausal women with a mean age of 49 years, found significant increases in the frequency of satisfying sexual activity and sexual desire score compared with baseline and placebo.¹² The testosterone patch was well-tolerated, and adverse event reports were similar between the drug and placebo groups.

Despite these results, in late 2004 an advisory committee to the Food and Drug Administration voted not to recommend a new drug application for the transdermal testosterone patch, citing the need for data on long-term health risks.¹³ In the interim, testosterone products indicated for men are sometimes prescribed to treat low libido in women.⁶ There is also an oral combination estrogen/testosterone product available for women, which in one trial increased sexual desire significantly over estrogen alone.⁹

A recent review of double-blind randomized controlled trials of postmenopausal testosterone therapy on female sexual functioning found that “certain types of testosterone therapy added to the estrogen-replete woman further improve frequency of sexual activity, satisfaction with that frequency of sexual activity, interest, enjoyment, desire, thoughts and fantasies, arousal, responsiveness, and pleasure.”¹⁴ The extent of improvement in these parameters was unclear, as was the optimal dose, type of preparation, route of administration, and long-term safety. The same review found that “certain types of estrogen therapies are associated with increased frequency of vaginal activity, enjoyment, desire, arousal, fantasies, satisfaction, vaginal lubrication, and feeling physically attractive, and reduced dyspareunia, vaginal dryness, and sexual problems.” The authors noted that the interplay between the two hormones in improving sexual function remains unclear.

Possible risks of testosterone therapy include hirsutism, acne, liver dysfunction, lowering of voice, adverse lipid changes, and potentially the risks of estrogen therapy (because androgens are aromatized to estrogens).^15,16

Dehydroepiandrosterone Supplements

A review study showed that in women with adrenal androgen deficiency syndrome, dehydroepiandrosterone (DHEA) at a dose of 50 mg/day increased levels of DHEA, testosterone, dihyrotestosterone, androstenedione, and androstenediol glucuronide, leading to increased sexual thoughts and fantasies.¹⁷ Some experts are concerned about the quality and potency of DHEA because of the minimal regulation of over-the-counter products.¹⁸

The American College of Obstetricians and Gynecologists has advised caution in prescribing testosterone and DHEA therapies to manage low libido in women because safety and efficacy data are incomplete and the available results lack consistency.¹⁹

Bupropion

A placebo-controlled double-blind trial of 42 patients with a sexual disorder induced by selective serotonin reuptake inhibitors (SSRIs) found extended-release bupropion produced an increase in the desire to engage in sexual activity and in the frequency of engaging in sexual activity compared with placebo.²⁰A trial of bupropion might be appropriate for patients who complain of SSRI-related sexual side effects.

Nutritional Remedies

The efficacy of alternative remedies remains uncertain because there are few data to support their use.²¹ However, a placebo-controlled study of ArginMax™, a nutritional supplement consisting of extracts of ginseng, gingko, and damiana, L-arginine, vitamins, and minerals, was conducted with 77 subjects over the age of 21.²² After 4 weeks, 73.5 percent of the active group reported improved satisfaction with their overall sex life, compared with 37.2 percent of the placebo group. Notable improvements also were observed in sexual desire, reduction of vaginal dryness, frequency of sexual intercourse, orgasm, and clitoral sensation.

References

1. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281:537-544.
2. Anastasiadis AG, Salomon L, Ghafar MA, et al. Female sexual dysfunction: state of the art. Curr Urol Rep 2002;3:484-491.
3. Kingsberg SA. The impact of aging on sexual function in women and their partners. Arch Sex Behav 2002;31(5):431-437.
4. Basson R, Leiblum S, Brotto L, et al. Definitions of women’s sexual dysfunction reconsidered: advocating expansion and revision. J Psychosom Obstet Gynecol 2003;24:221-229.
5. Avis NE, Stellato R, Crawford S, et al. Is there an association between menopause status and sexual functioning? Menopause 2000;7:297-309.
6. Kingsberg S. Just ask! Talking to patients about sexual function. Sexuality, Reproduction & Menopause 2004;2(4):199-203.
7. Whipple B, Brash-McGreer K. Management of female sexual dysfunction. In: Sipski ML, Alexander CJ, eds. Sexual Function in People with Disability and Chronic Illness. A Health Professional’s Guide. Gaithersburg, MD: Aspen Publishers, Inc.; 1997.
8. Walton B, Thorton T. Female sexual dysfunction. Curr Wom Health Rep 2003;3:319-326.
9. Lobo RA, Rosen RC, Yang HM, et al. Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Fertil Steril 2003;79:1341-1352.
10. Sherwin BB. Randomized clinical trials of combined estrogen-androgen preparations: effects on sexual functioning. Fertil Steril 2002;77(suppl 4):S49-S54.
11. Shifren JL, Barunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. New Engl J Med 2000;343(10):682-688.
12. Simon JA, Nachtigal LE, Davis SR, et al. Transdermal testosterone patch improves sexual activity and desire in surgically menopausal women. Obstet Gynecol 2004;103(suppl 4):64S.
13. Staff and wire reports. ‘Female Viagra’ fails to win FDA panel’s approval. USA Today, December 3, 2004.
14. Alexander JL, Kotz K, Dennerstein L, et al. The effects of postmenopausal hormone therapies on female sexual functioning: a review of double-blind, randomized controlled trials. Menopause 2004:11:749-765.
15. Shifren JL. The role of androgens in female sexual dysfunction. Mayo Clin Proc 2004;79(4 suppl):S19-S24.
16. Seagraves RT. Emerging therapies for female sexual dysfunction. Expert Opin Emerg Drugs 2003;8:515-522.
17. Spark RF. Dehydroepiandrosterone: a springboard hormone for female sexuality. Fertil Steril 2002;77(suppl 4):S19-S25.
18. Shifren JL. Therapeutic options for female sexual dysfunction. Menopause Management 2004;13(suppl 1):29-31.
19. American College of Obstetricians and Gynecologists. Androgen replacement no panacea for women’s libido. Press release, October 31, 2000, Washington, DC.
20. Clayton AH, Warnock JK, Kornstein SG, et al. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry 2004;65:62-67.
21. Rowland DL, Tai W. A review of plant-derived and herbal approaches to the treatment of sexual dysfunctions. J Sex Marital Ther 2003;29:185-205.
22. Ito TY, Trant AS, Polan ML. 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.