Lybrido for Low Libido?

A feature article in last week's New York Times Magazine served as an extended ad for a new book by Daniel Bergner, What Do Women Want? Adventures in the Science of Female Desire. It's filled with post-fashionable pop neuroscience and simplistic neurotransmitter stereotypes that rival those of Naomi Wolf (including her infamous “dopamine is the ultimate feminist chemical in the female brain” quote). The focus of Bergner’s article is on pharmaceutical treatments for the controversial diagnosis of Hypoactive Sexual Desire Disorder (HSDD), particularly the subtly named Lybrido (along with its younger sister, Lybridos).

The heavy-handed branding of Lybrido and Lybridos (both 'working titles') was fascinating to me. While trying to identify the marketing firm behind it, I discovered the trademark was abandoned 6 years ago by Emotional Brain, the Dutch drug company developing them. Finding the active ingredients in Lybrido and Lybridos wasn’t readily apparent from the Emotional Brain site. Nor was it immediately evident from the NYT article, which even used obfuscatory language:

“Female Viagra” is the way drugs like Lybrido and Lybridos tend to be discussed. But this is a misconception.

Actually, this is not a misconception. Both drugs contain a major male sex hormone plus a second ingredient: Lybrido is testosterone + sildenafil (Viagra), while Lybridos is testosterone + buspirone (a serotonin 5-HT_1A receptor partial agonist). The two formulations are in clinical trials for variants of HSDD identified by Emotional Brain researchers and described in a three part series published in the Journal of Sexual Medicine. These pilot studies used the related PDE5 inhibitor, vardenafil (Levitra). PDE5 inhibitors are widely used to treat erectile dysfunction, so claims that Lybrido doesn’t affect physical function in women are disingenuous:

Viagra meddles with the arteries; it causes physical shifts that allow the penis to rise. A female-desire drug would be something else. It would adjust the primal and executive regions of the brain. It would reach into the psyche.

Do Viagra and testosterone replacement therapy reach into the male psyche? Hmm? I don't think so.

HSDD is a diagnosis that can be given to women who have a low (or nonexistent) libido and are distressed about it. Dr. Petra Boynton has written extensively about the problematic aspects of the HSDD diagnosis and the screening tools used to assess it, as well as the medicalization of sex for pharmaceutical marketing purposes. An earlier post provided thorough coverage of issues concerning the safety and effectiveness of the Intrinsa testosterone patch, including its rejection by the FDA.

Nevertheless, plenty of women have voluntarily enrolled in the Lybrido trials. Bergner interviewed some of them to determine the reasons for seeking out an experimental treatment:

Every woman raised a mix of possible reasons. There were the demands of graduate school, the demands of children, the demands of work, medical issues, men who weren’t always as kind or nearly as engaged as they could be. But at bottom there seemed to be one common cause: they had all grown tired of sex with their long-term partners.

Why medicalize boredom within marriage?

…Lori Brotto, a psychologist at the University of British Columbia who has worked clinically with scores of H.S.D.D. patients and who recently led the American Psychiatric Association’s attempt to better delineate the condition in The Diagnostic and Statistical Manual of Mental Disorders. (H.S.D.D. is being reconceived as sexual interest/arousal disorder, S.I.A.D.) “The impact of relationship duration is something that comes up constantly,” she told me about her therapy sessions. “Sometimes I wonder whether it” — H.S.D.D. — “isn’t so much about libido as it is about boredom.”

Basically, to participate in the trials, a woman has to be in a stable, long-term monogamous relationship. How many female patients have tried couples counseling before turning to drugs? Or did they all take their advice from the Daily Mail?

'Women have a responsibility to keep their libidos high for their husbands': Could 'female Viagra' save YOUR marriage?

What efforts have the husbands expended to improve the sexual relationship, what work have they put in to make themselves more desirable to their wives? Are they taking a pill to make them less loutish?

[Lybrido developer Adriaan] Tuiten didn’t openly acknowledge monogamy as the core of the desire problem, but he knew he couldn’t use single subjects who might well find new lovers during the course of the trials. Their results might have to be tossed out because, with or without chemical aids, new lovers bring surges of lust.

Did the clinical trials for Viagra require men to be monogamous?


Dopamine Is Impulse; Serotonin Is Inhibition and Organization

How do the drugs work to restore female desire? Based on very little evidence, they purportedly restore the balance of dopamine and serotonin, despite taking a sledgehammer approach. Here's where Mr. Bergner devolves into dopamine/serotonin stereotypes that are just as bad as those from Naomi Wolf, but more boring. Divorced from the personal, unable to understand the phenomenology of female desire from the inside, Bergner is left with sterile rehashes of rat lust from Ms. Wolf's guru, Dr. James G. Pfaus. He even resorts to the old 'SSRIs simply cure depression by increasing serotonin' saw:

...And then there’s serotonin, dopamine’s foil. It allows the advanced regions of the brain, the domains that lie high and forward, to exert what is termed executive function. Serotonin is a molecule of self-control. It instills calm, stability, coherence (and, too, a sense of well-being, which is why S.S.R.I.'s, by bathing the brain in serotonin, can counter depression). Roughly speaking, dopamine is impulse; serotonin is inhibition and organization. And in sexuality, as in other emotional realms, the two have to work in balance. If dopamine is far too dominant, craving can splinter into attentional chaos. If serotonin overwhelms, the rational can displace the randy.

I guess he hasn't seen the data on the important role of dopamine in executive function in 'the advanced regions of the brain' (e.g., Prefrontal dopamine and behavioral flexibility: shifting from an “inverted-U” toward a family of functions and Dopamine D₂ receptor modulation of human response inhibition and error awareness).

Bergner continues:

To help predict which women will most benefit from which drug, Tuiten has blood drawn from each subject and examines genetic markers related to brain chemistry. Tuiten also asks subjects questions about their comfort with sexual feelings and fantasies. Since our dopamine and serotonin networks are reinforced or attenuated by all we learn, all we think and do, he believes that the answers may provide clues about a given woman’s neurotransmitter systems, which he uses as part of his diagnostic method.

The three part series in the Journal of Sexual Medicine might be worth a future post to describe the methods Tuiten et al. use to guide treatment and decide who gets which drug.


Dr. Helen Fisher, advisor for chemistry.com, developed the concept of four neurotransmitter “archetypes” in her quest for a better, more scientific brand of matchmaking.



Each of these chemistry types is associated with a dominant neurotransmitter or hormone (serotonin, testosterone, dopamine, estrogen). But she knows this is a metaphor and not to be taken literally. "We're a combination of all four systems," Fisher says in a USA Today article.


Neuroplasticity: It's a Girl Thing

Let's conclude with the most puzzling brain-based explanation for HSDD: it's neuroplasticity! I couldn't comprehend the logic of this paragraph, no matter how hard I tried. It's one of those sex-and-relationship-type accounts that's seemingly neuro-related but really devoid of actual neuroscientific content:

This interplay of experience and neural pathways is widely known as neuroplasticity. The brain is ever altering. And it is neuroplasticity that may help explain why hypoactive sexual desire disorder is a mostly female condition, why it seems that women, more than men, lose interest in having sex with their long-term partners. If boys and men tend to take in messages that manhood is defined by sex and power, and those messages encourage them to think about sex often, then those neural networks associated with desire will be regularly activated and will become stronger over time. If women, generally speaking, learn other lessons, that sexual desire and expression are not necessarily positive, and if therefore they don’t think as much about sex, then those same neural networks will be less stimulated and comparatively weak. The more robust the neural pathways of eros, the more prone you are to feel lust at home, even as stimuli dissipate with familiarity and habit.

The book What Do Women Want? Adventures in the Science of Female Desire will be released tomorrow. I doubt that Ecco will be sending me a review copy.


Further Reading:

Media HSDD: "Hyperactive Sexual Disorder Detection"

Underwear Models and Low Libido

Feminist Dopamine, Conscious Vaginas, and the Goddess Array

Of Mice and Women: Animal Models of Desire, Dread, and Despair