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Podcast Transcript - April 15, 2008

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Welcome to this weeks Annals of Internal Medicine Audio Summary for our April 15, 2008 issue. I’m Michael Berkwits, Deputy Editor at Annals.

We have another captivating issue for this week, with articles on how multiple medical conditions influences the receipt of antihypertensives; the diagnosis and treatment of paroxysmal nocturnal hemoglobinuria; and.the use of antibiotics to prevent hemodialysis catheter-related infections; and the international market as a source of low cost prescription drugs for US patients.

But first, here’s an in-depth summary of this week’s feature article.

Testosterone for Treatment of Decreased Sexual Satisfaction in Premenopausal Women (Time: 00:41)

Our lead and feature article this week is an industry-funded trial evaluating the safety and efficacy of transdermal testosterone for the treatment of decreased sexual satisfaction in premenopausal women. The prevalence of dissatisfaction with sex and of sex without pleasure is estimated to range from 17 to 25% in women of widely varying ages and nationalities. Testosterone might have a role to play in improving the sexual lives of women given that levels and sexual desire appear to decline with age, and past trials have suggested a beneficial effect of the drug.

In this week’s trial, lead author Susan Davis of Monash University and the Alfred Hospital in Melbourne, Australia, and her colleagues, randomized 261 women with low serum testosterone levels and reports of declining sexual satisfaction to receive one of 3 doses of a daily testosterone spray, or placebo. The investigators then assessed changes in the number of the women’s satisfactory sexual events, which the women themselves recorded prospectively in a daily diary, and they followed the women closely for adverse events.

The number of satisfactory sexual events increased in all groups, with a net increase of 0.7 satisfactory events per month at the midrange testosterone dose compared with placebo. That was a difference that was statistically but clearly not clinically significant. The drug was well-tolerated with the main adverse effect being hypertichosis at the site of application.

The authors conclude that the findings “support a testosterone treatment effect,” but they acknowledge that the findings do not support use of the drug, given the lack of a clinically significant change, the absence of a clear dose-response relationship, and the strong placebo effect.

In an accompanying editorial, Dr. Rosemary Basson interprets the findings as strongly suggestive that factors other than testosterone deficiency were causing the womens’ dissatisfaction given that they were capable of having satisfying experiences at baseline and on placebo. She reviews how little we know about the biological determinants of sexual desire and satisfaction in women, and advises a return to first principles in the treatment of low sexual satisfaction in women, namely that a thorough assessment of mental health and relationship issues, and any partner-related issues of sexual dysfunction, is likely to be far more productive and safe than testosterone supplementation or the use of drugs.

Comments from Rosemary Basson, MD (Time: 03:09)

So this was a well-performed and well-reported trial, but I’ve never screened for or evaluated these issues in practice, and they seem not to be brought up that much by women despite their being so prevalent. So I called this week’s editorialist to get a better sense of the standing of testosterone treatment among specialists who treat female sexual dysfunction, and of my responsibilities as an internist caring for women who may have these concerns. Dr. Rosemary Basson is a Clinical Professor of Psychiatry at the University of British Columbia in Vancouver, Canada and she’s the Director of the Sexual Medicine program at Vancouver General Hospital. She graciously agreed to talk to me about how these issue play out in women’s lives, and how they should be approached in practice.

Because the transdermal preparations for men are available, large numbers of women are being given off-label testosterone. It is easy to use those formulations and perhaps give an 8th or 10th of the male dose, which is not unreasonable, if only we could pick out which women truly are short of testosterone activity. Women can’t be recruited on the basis of having low androgen activity by simple blood test, since the blood test just detects serum levels and women are running on intracellular production of testosterone. Testosterone activity can be measured by metabolites, however, it’s not yet being shown that the androgen metabolites correlate with woman’s sexual function, and that study is currently ongoing, but until that is done, we still don’t have a basis for supplementing testosterone.

For clinicians, the big problems are that this is not a short-term therapy. If a woman is distressed about her sexual life, this is an indefinite need. We are very cautious now about estrogen and yet we have long-term systemic testosterone with no published safety data beyond six months and no accruing safety data by the sponsors beyond the time they began the studies which is about 3 years ago.

Drugs in the so-called pipeline are looking at increasing initial desire or spontaneous desire, the kind of desire women have early on in a relationship, desire they remember as a teenager, but the desire that is really not fairly frequent in women in otherwise happy, sexually satisfying ongoing relationships. We know from the SWAN study, the study of women in the States, that the majority of women although they are perfectly satisfied with their sexual response and pleasure, they rarely or never experience that kind of desire. They go ahead and agree to sex or instigate sex because of many benefits. They enjoy the experience once they get into it and get aroused, they feel closer to their partner, they feel more committed, more attractive, find that arguments arise less often, their mood is better, their partner’s moods is better, the list is very long. But it is not all about that initial desire. So some of the drugs in the pipeline are trying to boost that initial desire, which to clinicians seems to be an inappropriate target.

Primary care physicians are the optimal physicians to inquire because they tend to know all aspects to their medical history. They may not be the health provider to continue with any treatment if there is a diagnosis of dysfunction. Many studies show that it is very important for the physician or clinician to initiate the discussion. Also it has been shown that if the doctor has an introductory statement such as “You know, women with diabetes sometimes have sexual difficulties, are you having any?” or “Women who have had pelvic surgery such as yours frequently report changes in their sexual lives. Are you having any difficulties?”, that many more women will be relieved and pleased to be able to have their problems addressed. So that would be a screening question, and then if the visit is really about something else, the clinician can say, “This is legitimate, it needs a full visit, make another appointment.” The primary care physician triages the problem trying to clarify which direction to go either himself or herself or with another colleague: a relationship counselor, a psychologist, or a psychiatrist.

The majority of women who are concerned about low desire, even if they do not currently have a clinical depression, they do show more depressed thoughts, anxious thoughts, have lower self image, lower sexual self image, more lability of their moods than control women, so mental health practitioners who are experiencing sexual difficulties would be an optimal resource for many women who are concerned about their desire.

I think the emphasis should be on looking at the factors that we really do know that correlate with women’s sexual satisfaction and that is the woman’s feelings for her partner of trust and emotional closeness, a willingness and ability to let the partner know the kind of sexual stimuli and sexual context that she needs because this can be changed, there are no risks here, and to seriously look at her mental health and give her the care she needs there.

That was Dr. Rosemary Basson, discussing sexual medicine in primary care, and this week’s article demonstrating a weak effect of testosterone supplementation on women’s sexual satisfaction.

Other Articles in This Week’s Issue (Time: 09:12)

Other articles in this week’s issue include a study of how the number and type of comorbidities influence the management of uncontrolled hypertension in primary care practice, suggesting that the chance a patient will get their treatment intensified goes down with the number of unrelated comorbid conditions a patient has, an important point for assessing the quality of care for patients with hypertension;

We have two reviews, the first a narrative review of the physiology, clinical manifestations, and diagnosis and treatment of paroxysmal nocturnal hemoglobinuria, emphasizing that eculizumab interrupts the complement-mediated intravascular hemolysis which is the hallmark of the disease, but that its effects on survival are unknown; and the second a systematic review of trials evaluating the use of antibiotics for the prevention of hemodialysis catheter-related infections, suggesting that both topical and intraluminal antibiotics reduce bacteremia and the need for catheter removal secondary to complications.

We have a perspective from the United States’ Centers for Disease Control outlining new directions for the treatment, prevention, and control of gonorrhea given rising rates and growing antimicrobial resistance in the US.

We’re publishing a brief perspective on the advantages and disadvantages of obtaining prescription drugs for US patients from international sources, concluding that polcymakers should emphasize far broader use of domestic generic drugs over importing brand-name drugs from other countries, but that importation from countries with active regulatory agencies may be an option if no cheaper generic alternatives are available in the US.

And we have three Clinical Observations in our letters section this week. The first identifies memantine as a probably source of drug-induced hepatitis in a patient with Alzheimer’s disease. The second describes the successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy—you gotta read that one to believe it—and the third describe overanticoagulation of geriatric teaching hospital patients who were receiving warfarin and topical azoles for fungal skin infections.

Well, it’s a short summary for today.

Our theme music is by Brian Poole and Kwesi Marles; the clip you heard earlier was Sophie Tucker with her 1953 recording of Vitamins, Hormones, and Pills off the 2005 Sepia Records release, Sophie Tucker, The Golden Jubilee album.

My e-mail inbox has been empty for weeks, so tell us how we’re doing by writing to podcast{at}annals.org.

Check back in 3 weeks for our regularly scheduled May 6, 2008 issue

I’m Michael Berkwits, and thanks for listening.

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