When your Mojo is a No-Show, Can a Drug Make it Go-Go?

Bremelanotide (Vyleesi), the drug that was recently FDA approved, may end up being used by millions of women that are experiencing the monotony of monogamy as opposed to treating women who have hypoactive sexual desire disorder (HSDD.)  And that may not be a bad thing.

At a recent meeting with my staff at The Northwestern Medicine Center for Sexual Medicine I presented the scientific data that precipitated FDA approval of bremelanotide, an on demand drug indicated for the treatment of HSDD in pre-menopausal women.  I described how bremelanotide needs to be auto-injected in the thigh or abdomen forty-five minutes prior to anticipated sexual activity and works by stimulating the pathway in the brain, which results in the release of dopamine, the neurotransmitter that enhances sexual feelings. Essentially, bremelanotide turns the libido OFF switch to ON.” 

The overwhelming response of my staff comprised of female physicians, advanced practice nurses, and sex therapist was, “Wow, I can’t wait to try it!”

These are not women with HSDD, who by definition are very distressed by a lack of sexual desire, and are highly motivated to do something about it. These are women in loving long-term relationships who enjoy sex but are looking to feel the rush of incredible excitement and heart racing sex typically experienced in a new relationship.  While acknowledging that this drug is not approved for that purpose, we quickly realized that as medical professionals we would have to decide if “wanting to try it” would be a legitimate reason to prescribe it (for someone other than ourselves). 

The treatment of true HSDD is controversial. Some even argue that HSDD is not even a real thing. Those that acknowledge it as a medical disorder disagree if the approach should be pharmacologic, talk therapy or both. 

When flibanserin, the first drug to treat HSDD was released, there was a passionate New York Times op ed written by Emily Nagoski, the author of Come As You Are, asserting that HSDD should never be treated with a pill. I generally agree with her approach, and like many, if not most sexual medicine experts, my feeling is that true HSDD, (loss of libido not explained by painful intercourse, history of trauma, a medical condition, medication or partner issues), is complicated, multifactorial and requires a complete evaluation before determining a treatment course- a treatment course that ideally includes talk therapy with a trained, certified sex therapist.

But, having said that, there is a great deal of credible scientific research which supports the biologic component of HSDD, and in many cases there may be benefit from a little pharmacologic help (in addition to talk therapy) to give those critical neurotransmitters a push in the right direction. An intact libido depends not only on sociocultural, psychological, and interpersonal influences but on intact biology as well.

But, returning to the original issue, what about the woman who does not have HSDD?  What about the typical woman who used to have a terrific libido but has settled into the monotony of monogamy? In nature, the desire to have sex is driven by the need to reproduce. Once that is no longer an option or is biologically undesirable, there are a number of mechanisms in place that decrease libido resulting in the “cycle of sex”. In your twenties, it’s all about sex, all the time. During the baby- making years, it's sex with a purpose. And then, before you know it, the bedroom is a place where all we want to do is get a decent night’s sleep after a long day. Even if you love your partner. Even if he/she is sexy, interesting and wonderful. This is normal. But many women in long-term unions would love to have that “I have to have you RIGHT NOW “ feeling experienced in the early days of a relationship. Is she a candidate for this new drug? Should we, after informed consent that this is an off label use, and disclosure of possible side effects such as nausea, vomiting, flushing and in rare cases a transient rise in blood pressure deny the opportunity to our female patients who do not have HSDD but are looking to restore that new relationship excitement? We were hard pressed to come up with a reason why we would not.

Sildenafil (Viagra) is not recommended for men who do not have erectile dysfunction, and arguably doesn’t even have a benefit. Yet, a guy who desires an enhancer, or maybe just insurance that he will rise to the occasion, will often pop it like Pez in spite of possible side effects such as nasal congestion, muscle pain, nausea, dizziness, heart attack, death, and that infamous erection that doesn't abate for hours…  

Should a woman, once fully informed, also have the opportunity to enhance her sexual experience? Is denial of this drug just one more example of the disparity between the importance of female sexual pleasure versus male sexual pleasure? 

At this point, with no data and no clinical experience prescribing bremelanotide to women without HSDD, I don’t have an academic, evidence-based answer. But as an expert who has treated thousands of women, both with and without HSDD, I think I have a pretty good idea, for better or worse, how this drug is going to be used.

 

 

Everything You Always Wanted to Know About Addyi

by Lauren Streicher, MD

by Lauren Streicher, MD

Now that Flibanserin, or Addyi,  — the new drug to treat low libido, or hypoactive sexual desire disorder (HSDD)  is available,  reporters, patients, my friends, and especially my friends’ husbands have peppered me with questions about this so-called “Viagra for women” .

I have no professional experience with Addyi. I do not work for the drug’s manufacturer, Sprout, or have a financial relationship with them. All of my information is based on the results of clinical trials, which are published in the scientific literature and available on the FDA website.

In response to the 25 most-frequently-asked questions that I get, I’ve been telling people:

1. Who should take Addyi (flibanserin)?

This medication is intended for a woman who loves her partner, but whose libido switch is simply in the off, not on, position. Not every woman who has zero sexual desire wants to do something about it. Women with true hypoactive sexual desire disorder are highly motivated to flip their libido switch back on not only for their own pleasure, but often to save a marriage or relationship sabotaged by the absence of normal sexual relations.

2. What causes low sexual desire in women?

The biological cocktail for an intact libido includes not only hormones, but also neurotransmitters.  Dopamine, norepinephrine and serotonin determine how often people think about, and desire, sex. It’s the balance of those neurotransmitters that creates that “I want sex, I need sex, and I’m thinking about sex” feeling. But this balance also keeps desire under control, so you can stop making love long enough to go do all the other things you must. Women with hypoactive sexual desire disorder do not feel normal sexual desire even if they’re in loving relationships. So essentially, this condition is a biological problem.

3. How do I know if I have hypoactive sexual desire disorder?

It’s perfectly normal to not want to have sex with a partner who smells so bad that you don’t even want to share a room. It’s also normal to not desire sex if it’s excruciatingly painful, you just lost your job, or you haven’t slept in a week. If you’re in one of these situations, you don’t need to take a pill. You need to fix your vagina, fix your work situation, and fix your life.

The Decreased Sexual Desire Screener, a five-question, yes-or-no questionnaire  guides both physicians and patients to, or away from, a diagnosis of HSDD.

4. How common is loss of lust?

Of all sexual problems, loss of lust is by far the most common. Up to 1 in 10 adult women are affected by HSDD.

5. How does the new drug work?

Unlike Viagra (sildenafil), which increases blood flow to a man’s penis, Addyi works on a woman’s brain to balance neurotransmitters and restore normal sexual desire.

6. How many women have taken Addyi?

More than 11,000 women participated in the flibanserin clinical trials. In comparison, 3,000 men were in the clinical trials for Viagra. The FDA only requires that clinical trials to approve a new drug involve 1,000 people.

7. What ages were the women who tried the drug?

The trials included for FDA approval included women who had not yet entered menopause who reported that they’d been in loving relationships for a minimum of 10 years, and who’d had HSDD for at least four years.

8. Were all women in the new drug trials heterosexual?

Yes, but sexual function is sexual function. Whether a woman is heterosexual, homosexual, or self-sexual, the biology of sexual desire is the same. There is no reason to believe the response will be any different no matter who (or what) you have sex with.

9. What about women after menopause? Is flibanserin right for them?

The FDA only considered premenopausal women for approval of the drug. However, postmenopausal women with HSDD were included in the Snowdrop trial,  a study of over 900 women with low sexual desire after menopause the results of which were published in the June 2014 issue of Menopause. And it’s good news: The response to flibanserin was statistically significant compared with a placebo treatment.

Doctors will likely prescribe Addyi for postmenopausal women just as many other drugs proven to be effective are prescribed as off-label. If you are postmenopausal, ask your doctor about the pros and cons of taking Addyi.

10. I heard the FDA initially turned down this new “female Viagra.” That worries me.

It should actually reassure you that the FDA is careful and demands a lot of information before approving a drug. In the United States, it usually takes 12-15 years for a proposed drug to appear in your pharmacy. Only 1 in 5,000 new drugs makes the final cut. Along the way, it’s very common for the FDA to require additional studies.

In the case of Addyi, more than 60 studies were submitted to the FDA. One of the side effects in people who took Addyi in clinical trials was sleepiness. In response, the FDA required a driving test to assure that women taking Addyi at night were not drowsy or impaired the next morning. The result? The women who took Addyi actually drove better than the women who did not!

11. Didn’t Sprout, the drug maker, enlist a PR company and use social media to pressure the FDA?

Even the Score is a campaign founded to raise awareness of the need for gender equity in sexual health.  In addition to Sprout,  24 organizations and non-profits and 60,000 people, support the campaign. But Even the Score isn’t just about one drug: The campaign will continue to address the disparity between research in male and female sexual health. Yes, it was Even the Score that was responsible for the spoof on Viagra commercial.

Remember: For approval, the FDA requires that a drug must both meet an unmet need, and be deemed effective and safe. The FDA approved Addyi because the science is solid, and it demonstrated these criteria. The FDA reviews data, not Tweets.

12. How well does Addyi work?

Women who took flibanserin in clinical trials reported a 53 percent increase in their sexual desire as measured by the Female Sexual Function Index (FSFI). They also reported that their number of satisfying sexual events doubled, and their distress about sexual function decreased by 29 percent.

13. Were the improvements only “modest” for most women?

Modest was the goal. The idea is not to make women hypersexual, but rather to give them normal sexual desire.

Results are an average. They include both people who didn’t respond to the drug, because not everyone is going to benefit from the drug, and “high responders.” The high responders reported six to eight more satisfying sexual events each month, and a return of their sexual desire score to what’s considered normal. That’s meaningful!

14. So how likely is Addyi to work?

There was an average of 53 percent increase in sexual desire overall, but 55 percent of women were high responders and had an even greater response.

15. How soon will it work?

Flibanserin usually starts to show positive effects two to four weeks after a woman begins taking the drug. If you see no difference in two or three months, stop taking Addyi. It’s not going to help you.

16. Why take a pill? What’s wrong with talk therapy?

Sexual problems from interpersonal, psychological, or cultural/social issues are important, and a therapist or change of relationship is often the fix. But brain activity is different in women who have HSDD: No amount of talk therapy is going to correct a biological imbalance. On the other hand, if you hate your partner or you avoid sex because it hurts like hell, a bucket full of Addyi is not going to make a difference, either.

17. Can Addyi make a woman too sexual?

It’s interesting how, on one hand, people are concerned that it doesn’t work well enough, and on the other hand, people are worried that it will turn women into nymphomaniacs. The ideal is to be normal, not hypersexual. Addyi will not cause you to rip off your clothes during a business meeting and seduce your boss any more than an antidepressant will make you euphoric.

18. Does this drug pose a potential “date rape” risk?

No, this is a daily drug that does not start to work for a couple of weeks. Even if your partner sneaks a dose into your morning coffee every day for two weeks, it wouldn’t make you hypersexual or make you do things you did not want to do.

19. Is Addyi a hormone?

No. It’s a new drug that modulates (controls) neurotransmitters like dopamine, norepinephrine, and serotonin that affect women’s desire for sex.

20. I’ve heard about side effects. What are they?

Typically, the most common side effects of a sexual dysfunction drug are cardiovascular problems, visual changes, a drop in blood pressure, or an erection that lasts for more than four hours.

Whoops, that would be Viagra!

Back to Addyi: the most common side effects in the trials included fatigue, nausea, and sleepiness. No serious side effects were reported. The biggest complaint from participants was that when the trial was over, they couldn’t keep taking it. Every drug comes with some risks, though; men have long been able to choose whether to take a drug with known risks to enhance sexual desire.

21. Will Addyi cause weight gain?

No, it did not cause weight gain in the clinical trials.

22. What about interactions between alcohol and flibanserin?

Drinking was allowed in the studies for this new drug, and the women in the clinical trial who identified as “social drinkers” (58 percent of the participants) did not have any significant issues.

The FDA was particularly concerned about binge drinking, so they required an alcohol challenge test to reproduce what heavy drinkers would experience if they were on Addyi. Some of the participants in that study had a drop in blood pressure or passed out.

Interactions with alcohol need to be discussed just as they would with any drug that affects your central nervous system. All centrally-acting drugs (think antihistamines, antidepressants, and hundreds of other drugs) are known to interact with alcohol, and the FDA requires a similar warning for these.

23. I hear that only men were included in the alcohol study. What about women?

The social drinkers in the study were women. However, the “alcohol challenge study” required participants to drink a half-bottle of grain alcohol first thing in the morning. They couldn’t get enough women to agree to the study, so they got permission from the FDA to do the test with men.

24. So does that mean that if I take Addyi, I can never have a glass of wine?

 Remember that 58 percent of women in the clinical trial identified as “social drinkers” and did not have any significant issues. The FDA however is very concerned about a potential alcohol interaction and is requiring physicians to advise their patients to not drink if they take Addyi. Hopefully as more information and experience comes out they will back off on this warning.

25. When and where can I get flibanserin?

 Flibanserin is available now but you must make an appointment with a physician that is a certified prescriber and get it from a pharmacist that has also been certified. Interesting that the FDA does not require doctors and pharmacists to be certified to prescribe and dispense Viagra, anti-depressants, narcotics or hundreds of other drugs that have significantly greater risks and side effects. Some might call that sexist. Just saying.

EDH Aug 2015

Addyi AKA "Female Viagra" Gets FDA Approval!

The FDA approval  of Addyi marks an important day in Herstory. I chatted about it on ABC Nightly  News. My article on Everyday Health is an everything you  want to know guide . Talked to the New York Times about what this will mean for women.  GMA this morning! Lots more to come!

FDA Agrees: Now Is the Time for Women’s Viagra

EveryDayHealth.com June 2,2015

EveryDayHealth.com June 2,2015

“I’m just not interested in sex anymore.”

“I don’t think about sex.”

“I miss feeling sexual.”

Welcome to my office.

Of all the sexual problems my patients report, the loss of libido is by far the most common. The medical term for lack of lust is hypoactive sexual desire disorder, or HSDD: an absence of sexual thoughts, fantasies, or desire for sexual activity that causes distress or interpersonal difficulties. The last part is really important.

Not every woman who has zero libido cares or is motivated to do something about it. But millions of women do care, either because they find this loss of libido personally distressing or disinterest in sex has sabotaged a relationship or marriage.

It is perfectly normal to not want to have sex with a guy who smells like the zoo and with whom you don’t even want to be in the same room with much less share a bed. It is perfectly normal to not want to have sex if it is excruciatingly painful. But the woman with HSDD loves her partner, and things work just fine physically, but her libido switch is simply in the off position.

What Keeps Libido Strong

The biological cocktail for an intact libido includes not only hormones such as estrogen and testosterone, but also neurotransmitters that determine how often women think about, and desire, sex. While many neurotransmitters make a contribution, the essential ones are dopamine, norepinephrine, and serotonin.

Dopamine is all about desire. It’s dopamine that creates that feeling of “I want sex, I need sex, and I can’t stop thinking about sex.” Serotonin is all about keeping desire under control so you can stop making love long enough to go to work and do the laundry.

It’s all about balance — enough dopamine to want sex, and enough serotonin so we don’t want it all the time.

So essentially, HSDD is a biological problem. Currently, there are no FDA-approved medications to help women who have HSDD.

This week, the FDA is taking another look at flibanserin, a promising drug that has been shown in multiple scientific studies to help women with HSDD, but was turned down by the FDA in the past. Experts have been invited to speak at a public forum to explain why flibanserin should — or should not — get the FDA nod of approval. I will be one of the experts in Washington on June 4th to step up to the mic and explain how flibanserin works on the brain to increase dopamine and decrease serotonin levels. I will also emphasize that flibanserin is not for everyone. Flibanserin will not help, and should not be prescribed for,  the woman who has a dysfunctional relationship, painful intercourse, or a hormonal imbalance.

Approval of this drug has become controversial and in many ways has become a political issue rather than a medical issue. Many “experts” claim that HSDD is not real, but is a made-up condition so pharmaceutical companies can sell drugs. Yes, HSDD, like other female sexual problems is real, and I am offended that 26 drugs have been approved for male sexual health and none for women, other than to alleviate vaginal dryness.

5 Myths About HSDD That We Need to Debunk

Here are the facts to balance out the fiction:

Myth 1: HSDD is not a real medical condition.

There are more than 13,000 medical publications about HSDD dating back to 1977. Not to mention that anyone who has spent time in my office knows how real it is.

Myth 2: It is an exaggeration that there are 26 drugs approved for male sexual health.

Actually, there are 41 if you include generic drugs for men. But 26 is the number of unique medications.

Myth 3: Sexual problems are mostly due to interpersonal, psychological, or cultural/social issues.

Yes, all of those things are important, and a therapist or change of relationship is often the fix. But biology is also key. Science has shown that activity in the brain is different in women who have HSDD. It is clear that an imbalance of neurotransmitters is at fault. No amount of talk therapy is going to correct a biological imbalance.

Myth 4: Flibanserin doesn’t work.

Women receiving flibanserin in clinical trials reported a 53 percent increase in sexual desire, as measured by the Female Sexual Function Index (FSFI). Adjusted for placebo response, there was a 37 percent increase. This was a meaningful response for the women in the trial.

Myth 5: Flibanserin has too many side effects to justify giving it to healthy women.

There were more than 11,000 women in the flibanserin clinical trials, and they reported no serious side effects. Some women experienced fatigue, nausea, or sleepiness. In contrast, there were only 3,000 men in the Viagra trials, they had  serious side effects such as cardiovascular problems, visual changes, and a drop in blood pressure. Not to mention, men get to choose if they want to take a risk and take a drug to enhance sexual desire!

Women’s sexual health problems are real and deserving of research and development of new drugs. Flibanserin will not solve every sexual problems, but it will treat low sexual desire in a meaningful way and make a difference for millions of women. So stay tuned. I am optimistic that the FDA will not allow bad politics to trump good science.

UPDATE: Since this post ran, the advisory committee to the FDA panel voted 18 to 6 to recommend that flibanserin be approved. It was an exciting day speaking before the committee, and I was honored to be part of the process in a very small way. Many experts spoke, and to say the discussion was lively would be an understatement.

The FDA still must gave final approval before the drug will be released, and certain conditions must be met to ensure safety. But this a huge victory for women and a clear indication that the FDA appreciates that there is an unmet need.

PHOTO CREDIT: Meriel Jane Waissman/Getty Images

Flibanserin: A Feminist Issue

Everyday Health July, 2015

Everyday Health July, 2015

I get up every morning and am unable to begin my day without it. I have been warned of possible side effects: palpitations, high blood pressure, anxiety, tremors, insomnia, and nausea. I weigh the risks, consider the quality-of-life benefit, and go for it. Every single day.

Aah, that first cup of coffee. It’s good to have a choice.

Then we consider flibanserin.

Feminist Views on Flibanserin

Feminism: the belief that men and women should have equal rights and opportunities (Webster’s Dictionary).

Some so-called feminists are using the discussion about possible FDA approval of flibanserin, also referred to as “female Viagra,” as an opportunity to leverage their views. This drug treats lack of lust, known as hypoactive sexual desire disorder, or HSDD, in women, which is an absence of sexual thoughts, fantasies, or desire for sex that causes distress or interpersonal difficulties.

But many vocal opponents of this new drug have an anti-pharma agenda. They have declared that the risks are so great that the FDA should not approve this drug, which has been shown in clinical trials including 11,000 women to make a meaningful and positive difference in quality-of-life.

A true feminist (who can be male or female) would want to ensure that the bar is no higher for a drug intended for women than it is for a drug for men. A true feminist appreciates that a woman, given good information, is smart enough to decide if she is willing to take a medication that may cause some dizziness, may make her a little sleepy, and has a very small risk of unpredictable fainting. Just as men get to decide if they are willing to take a drug and risk side effects including low blood pressure, visual changes, cardiac arrest, or penile fracture to ensure an erection capable of intercourse.

In my recent NPR interview, the other guest on the show, Leonore Tiefer, PhD, identified herself as a feminist who was only trying to protect women from the evil pharmaceutical company that has medicalized sex to make money. Really?

Why Drugs Get an FDA Green Light

While pharmaceutical companies are profit motivated, it is the job of the FDA to ensure that capitalism and greed do not get in the way of patient safety. The FDA must ensure a drug is beneficial and that the risks do not outweigh the benefits. In the case of flibanserin, the science is solid. Flibanserin is not for everyone, but this new drug will help many women in significant ways.

It’s good to know that the FDA does not give in to public campaigns, as demonstrated last week when the FDA advisory committee voted 18 to 6 to recommend approval of flibanserin. This decision was based on the science about the drug.

I have no financial interests in this drug or the company that owns it, Sprout Pharmaceuticals. But I do have an interest, on behalf of my patients, in sexual-health drugs for women getting the same attention, research, and development as sexual-health drugs for men do.

Why Doctors Work on New Drugs

I am offended on behalf of my esteemed colleagues, who have consulted with Sprout to do research or participate in clinical trials, and have been accused of speaking out on behalf of flibanserin because they have a financial interest. No amount of money could get expert academicians Sheryl Kingsberg, PhD, David Portman, MD, and James Simon, MD — all have spoken about this drug — to say things that are not scientifically true or in the best interests of their patients.

I have consulted (and been compensated for my time and expertise) by other pharmaceutical companies. For every company I consult for, I turn down 20 other companies because the science is not solid enough. I do not preferentially recommend one drug over the other based on a relationship with a company. As an example, in my book Sex Rx, I discuss four options for alleviating vaginal dryness and state that all are equally safe and equally beneficial. I then ask women to make their own decisions based on solid information and personal preference. I am transparent about which companies I consult for, and it is insulting to my colleagues and to me to hear accusations that we give biased information based on compensation for our expertise or research.

I have also heard these critics tell a patient with true HSDD to work on her relationship. This advice is the equivalent of telling my patient with severe vaginal atrophy to schedule a date night, buy new lingerie, and take a bubble bath to decrease the excruciating pain she has every time she attempts intercourse.

For women whose low desire is caused by a relationship issue, talk therapy is the right path. But women with HSDD, where something is happening biologically, deserve access to medical treatment options.

Female Viagra: A New Choice

If flibanserin is approved (and I hope it is), I will identify which patients are appropriate candidates. I will tell many, many women they are not. If someone is an appropriate candidate I will educate her about possible side effects. I will let her know that she should be very careful about drinking alcohol because, while 60 percent of the women in the flibanserin trials self-identified as social drinkers and had no problems, some had side effects. If she chooses to take the drug, I will let her know that not all women respond, and that if she is one of the non-responders, she should discontinue the medication.

Women who are who given good information will make smart choices. It is paternalistic (the attitude or actions of a person, organization, etc., that protects people but does not give them any responsibility or freedom of choice), not feministic, to do otherwise.

And now I am going to finish my cup of coffee.