Female sexual dysfunctionBMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7496.E345 (Published 14 April 2005) Cite this as: BMJ 2005;330:E345
- Vivian Lewis, professor, obstetrics/gynecology ()
A common clinical problem
In this issue (p 138), Ray Moynihan argues that female sexual dysfunction is essentially an invention of big pharmaceutical companies. He accuses Procter and Gamble of aggressively marketing awareness of a type of sexual dysfunction—female hypoactive desire disorder—to create a need for its new drug, transdermal testosterone (Intrinsa), which recently failed to gain FDA approval. Moynihan further calls for less influence of marketing on decisions about this condition and its treatment. Clearly, we are well served as physicians and patients by maintaining our objectivity and seeking unbiased sources of health information. But I disagree with Moynihan about the diagnosis of female sexual dysfunction.
The most widely cited prevalence rate of 43% for female sexual dysfunction was actually derived through indirect means.1 Laumann et al applied a statistical technique (latent class analysis) to data from a survey of 1749 women and 1410 men. Far from being a big pharma initiative, this study was funded by the National Institutes of Health (NIH) and the Ford Foundation. The proportion of women who described lack of interest in sex was 27-32%, depending on their age group.1 A large multiethnic NIH-funded study of perimenopausal women, SWAN, found the prevalence of low interest in sex to be approximately 40%.2 Neither of these numbers tells us anything about severity of the problem, however. Approximately 10% of men and 20% of women in the Laumann study had seen a medical professional for help with a sexual problem, which suggests that most people have less severe problems, seemingly unlikely to qualify for a medical diagnosis.1
Soon after publication of the Laumann article, the fourth edition of the Diagnostic and Statistical Manual (DSM-IV) was issued and introduced the condition “female hypoactive sexual desire disorder.” It is defined as persistently low sexual desire resulting in distress or relationship dysfunction, where lack of desire is not due to another condition or circumstance. This definition has been used as a basis for academic dialogue and research as well as practical clinical applications. An international consultation on sexual medicine suggested an expansion and revision of the DSM-IV criteria to incorporate a more biopsychosocial approach to sexuality.3 Their definition of women's sexual desire disorder includes chronicity of low libido and an absence of motivation to attempt sexual arousal (eg, responsive desire). Debate is ongoing and further refinement is likely, but in any case no one disputes that this is a real diagnosis.4
If we accept that the diagnosis of hypoactive desire is a real one, how would a clinician approach such a patient? In the Laumann study, there were clear associations between symptoms of sexual dysfunction and health or lifestyle issues.1 Low sexual desire was more common among those who had experienced significant loss of income and self-described emotional stress. The SWAN study showed an odds ratio of 0.66-0.75 for low sexual desire among women who reported that paying for basics was moderately hard or very hard.2 Clearly, a history of emotional distress, social problems, or partner difficulties increases the risk of sexual dysfunction.
Hormone therapy has been widely studied as a potential treatment for hypoactive sexual desire. Longitudinal studies of midlife women undergoing natural menopause do not show an association between testosterone levels and libido.5 However, women who undergo oophorectomy lose the main source of endogenous androgens, which could theoretically predispose to low sexual desire. In one study, testosterone and estrogen injections significantly increased sexual thoughts and fantasies compared to placebo in a group of oophorectomized women.6 Maximal mean testosterone levels were about twice the normal maximum for postmenopausal women and circulating levels were quite variable. With the transdermal testosterone patch, there is less fluctuation in the concentration of drug.
The first published treatment data in women compared two doses of testosterone and placebo in oophorectomized women taking estrogen replacement. There was a statistically significant increase in the level of sexual responsiveness and less distress surrounding sexual issues for women given the higher dose. Notably, the mean testosterone level for those who received high dose testosterone was 102 ng/dL.7 Consistent with prior trials, statistically significant effects were seen only at supraphysiologic levels of testosterone. Few studies have reported on the use of testosterone in women with intact ovaries, and they also suggest an effect only with higher doses of androgens.8
Short term data suggest few problems with high levels of testosterone in postmenopausal women. We have no long term safety data, but among younger women such high testosterone levels are associated with adverse metabolic consequences (dyslipidemia, insulin resistance).9 The FDA advisory committee voted unanimously that Intrinsa did not have sufficient safety data to recommend approval. Nonetheless, a statistically significant benefit was seen among women treated with the higher doses, although the absolute magnitude was relatively modest.
Could it be that for some women a small objective difference in sexual desire and responsiveness would have a big impact on their relationship? Might there be an intermediate dose of the drug that would be safe and effective? These questions deserve further study to better understand factors that influence sexuality and effective treatments for those who are troubled by unsatisfying relationships. Some of this research is likely to be financed by pharmaceutical companies, but that does not necessarily mean that it won't be quality research.4 As with any disease that receives widespread public attention, physicians must evaluate the quality of the data and then carefully apply the evidence to individual patients.
Education and debate p 138
Competing interests VL served on the FDA advisory committee that recommended against approving Intrinsa. She has received funding from Wyeth Ayerst Research and honoraria from Eli Lilly.