Monday, June 03, 2013

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-HT1A 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, 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

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At June 03, 2013 9:40 AM, Blogger Roger Bigod said...

Duh. It's been well known for 50 years, or more, that androgens increase female libido. The initial clinical observations were based on giving women androgens for medical conditions such as aplastic anemia, with the goal of promoting protein synthesis and cell proliferation. Besides expected changes like hair growth and deepening of voice, there was an increase in libido. Based on this, there were proposals to give a short, low-dose course of testosterone as an adjunct to psychotherapy for women who perceived their libido as sub-optimal.

Women have a natural low level of androgen from the adrenals as a by-product of cortisol synthesis. This produces axillary and pubic hair. The evidence is that lack of androgen receptors produces phenotypic females with no (or scanty) body hair and attractive female figures. Variations in this androgen system may account for differing levels of female libido.

Packaging testosterone with a side-drug (itself a violation of principle) to claim novelty for an ancient therapy is decadent. It's a sign that drug companies can't come up with any real advances and have to depend on snake-oil marketing.

At June 03, 2013 10:54 AM, Blogger Neuroskeptic said...

Great post.

The variant containing buspirone is interesting, given the failure of flibanserin, a 5HT1A agonist (amongst other things) to effectively treat HSDD.

Flibanserin certainly put HSDD on the map, though. It was the original "female Viagra" and, unlike these two, actually had nothing to do with Viagra.

At June 03, 2013 2:46 PM, Blogger The Neurocritic said...

Thanks for your comments. It might be worthwhile to expand on Emotional Brain's strategy for deciding who gets Lybrido (women insensitive to sexual cues) vs. Lybridos (women overly sensitive to sexual cues, but inhibited for various reasons including sexual abuse). Their idea is that the lovely peppermint melt-in-your-mouth testosterone coating is suppose to stimulate sexual arousal, followed by the sustained release portion that either revs up the physical aspects of arousal (Viagra) or reduces inhibition (buspirone, which is supposed to inhibit serotonin acutely via 5-HT1A receptors).

But as we've seen, none of these agents have been particularly effective in isolation, considering that flibanserin's 5-HT1A actions were a flop and the Intrinsa patch was never approved by the FDA. Nonetheless, pink Viagra is still easy to buy online. I think Emotional Brain is counting on the unique timing of its formulations, although time will tell (so to speak) when the clinical trial results are in.

At June 05, 2013 5:50 PM, Anonymous Anonymous said...

I had neutron radiation on my head and neck for ACC, a rare cancer, and it destroyed my healthy sexual desire. I would give anything to get it back so I will try this when it comes on the market.

At June 07, 2013 10:34 AM, Anonymous Anonymous said...

Bremelanotide from Palatin which was mentioned in the article recently completely a 400 patient Phase 2b study that showed great efficacy and safety. They will be moving to P3 this year. It actually acts on the brain and reportedly increases desire and libido. Almost like a true aphrodisiac. It has been shown to work on males as well. The efficacy results look much better than Flibanserin and Libigel as well. The article says bremelanotide has blood pressure issues, however these were addressed in the P2b trials that were just completed.

At June 08, 2013 2:18 PM, Blogger wiley said...

Hmmm. What are the odds that the people running this trial will ask each woman if she is currently taking a drug that reduces libido, and maybe suggest to her that she consider that that might be the reason that her sex drive has declined or disappeared altogether.

Also, are the women being asked if their husband makes an effort to bring her to orgasm?

At November 16, 2013 9:15 AM, Blogger Lucy Kelly is a-comin'! said...

What about women who have a physical reason behind their lack of a sex drive? I'm missing a chunk of my pituitary gland from surgery and I simply don't produce the hormones needed to have a sex drive. Even when I take estrogen, I don't have a sex drive, and now that I'm on Lexapro it's completely dead. Would a drug like this work for me? I WANT to have a sex drive for ME, not for my husband.

At November 16, 2013 10:23 AM, Blogger The Neurocritic said...

Lucy - I do believe one of the drugs could be appropriate in your case, given there's a clear physical cause for your low libido.

At February 24, 2014 11:57 AM, Blogger April said...

Buspar is appropriate for those with SSRI induced sexual dysfunction. It helps to reverse what the serotonin has done to the libido. The viagra part would also help by bringing some blood flow into the equation, I think, just to help get things going, but I don't think that part is necessary. I know because I took buspar for SSRI issues, and at the same time, picked up a bottle of horny goat weed-yes it is called that. The goat weed works like a weak viagra and I found it to be nothing but a distraction and wasn't necessary. The buspar worked miracles and my husband will tell you the same.


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