More Testing for Men’s Health

A couple days ago I wrote about the discrepancy between the levels of research into men’s health and into women’s health. As it turns out, there are areas in which we know less about men’s health than about that of women. One of those areas is hormone replacement therapy.

If you were still watching broadcast TV a couple years ago, you couldn’t escape the ads for prescription testosterone therapy. Products were available as pills, as gels, as injections, even as an underarm roll-on. The marketers came up with a condition they called “Low T,” which is just what it sounds like—low blood levels of the hormone testosterone. The ads have pretty much disappeared as prescription testosterone therapy comes under increased scrutiny by the FDA.

The Testosterone Controversy

Testosterone replacement therapy has been around for many years. At one time it was recommended strictly for men who for medical or surgical reasons were unable to manufacture testosterone on their own. The promise of restoring youth was too powerful to resist, though, and doctors began prescribing the therapy to older men who felt their “vitality” slipping away. Low levels of testosterone are associated with loss of skin tone and muscle mass, loss of energy and “drive,” and declining sexual interest. The idea was that restoring levels of testosterone would rejuvenate the patient, making them look and feel like a younger man again.

But a 2002 report from the Institute of Medicine cast doubt on the effectiveness of testosterone therapy—as well as on its safety. More recent clinical trials have reported benefits for certain groups, at least convincing enough that the FDA approved testosterone replacement therapy for a broader population. But concerns still linger about how tightly prescribing should be controlled, and about the overall safety of the therapy.

Ignorance Is Definitely Not Bliss

In 2002 researchers halted a major clinical study because results showed the therapy, hormone replacement therapy for women, increased the risk of heart disease and some cancers. There was a huge outcry at the time. How could it have taken more than 50 years for these risks to become known?

We’re at a similar stage with men’s hormone therapy. Our FDA is getting its act together, although a little late. In March of this year the agency required changes to labeling for all testosterone products to highlight the increased risk of heart attack and stroke in users of the products. And just this week the agency said it is encouraging manufacturers to work together on a large after-market trial to determine the true risks and benefits of testosterone replacement therapy.

I’m not a big fan of the FDA, because I believe they’re generally more responsive to the interests of industry than to those of the American public. I am glad to see that they’re finally “encouraging” such research, even though it should have been done 20 years ago. It’s too bad that the push comes after more than 2,000 lawsuits have been filed by people who believe their use of testosterone replacement therapy caused a heart attack or stroke. We’ll see how those suits turn out; the first one isn’t scheduled to come to trial next year. In the meantime, docs will go on prescribing testosterone for men even without a complete understanding of the risks.


A Quick Note About Carter’s Cancer

We seem to be getting daily updates about the condition of former President Jimmy Carter. The news in this morning’s paper was that his cancer has spread to his brain. And, curiously, that the spots on his brain were found during surgery on his liver. I guess when you’re a Nobel winner you get the super-duper scans.

At any rate, the interesting thing is that he doesn’t have brain cancer. Instead, he has melanoma (a form of skin cancer) in his brain. That’s the way cancer works. When, for example, breast cancer spreads to the liver, the person doesn’t now have liver cancer. Instead, they have breast cancer in both the breast and the liver. The cells spread through the lymphatic and circulatory systems, taking root where they will. Fortunately, a treatment that’s successful against the original cancer has a good chance of success against the metastatic site.

As I mentioned in an earlier post on sun safety, melanoma is the most serious form of skin cancer. President Carter’s melanoma is considered Stage IV, meaning that it has spread to another organ. The statistics are grim: only 15-20% of patients survive another 5 years, and just 10-15% make it for 10 years. His chances are improved by the fact that he’s receiving a novel combination of drugs that has shown promise in melanoma. His chances are diminished because he is, after all, 90 years old. (But don’t forget, his mother, Lillian, lived to age 85. He comes from hardy stock.)

Jimmy Carter is a good man. He’s a wonderful model for life after your “career” is over. I wish him the best.

A Plague of Diseases That Won’t Go Away

I was at least a little alarmed at a report this week that the National Park Service has closed a campground in Yellowstone National Park because of the plague. As you may recall from a class in world history, the plague is spread by insects, usually fleas, and the most common host for these fleas is the nearest available rodent. In this case the culprit appears to be squirrels, so the Park Service is going to spray all the squirrel burrows they can find for fleas.

While the plague may seems like a relic, many diseases that we think of as eradicated are still very much with us. Our CDC puts out a publication called Morbidity and Mortality Weekly Report (MMWR) that tracks 50 or so diseases. Some of them are what you’d expect: flu, tuberculosis, food poisoning, and sexually transmitted diseases. But others seem transported from another place or another time: yellow fever, leprosy (now called Hansen’s disease), and, yes, the plague.

So far this year there have been 2 confirmed cases of plague in the US, after 10 last year. Most cases arise in the mountain West and far West: Nevada, Colorado, California, etc. The last true outbreak of plague in this country was in 1924 in Los Angeles, in which 30 people died. Before that outbreaks had occurred in San Francisco and Oakland that killed more than 100 people.

Making Sense of the Numbers

Here are the MMWR disease tables for the most recent week. When you scan through them, some really interesting (to me, anyway) things pop up. For example:

  • Of the diseases addressed by the MMR and DPT vaccines that create so much controversy, only whooping cough seems to have regained a hold in this country, with more than 19,000 cases last year. In 2014 for mumps the total was under 1,000; for measles 667; and for diphtheria, rubella (German measles), and tetanus combined only 22 cases.
  • Leprosy seems to be holding steady at 80–100 cases a year over the last several years.
  • Tropical diseases are still with us: yellow fever, Q fever, malaria, etc.
  • Only 12 cases of human rabies in 2010 through 2014 combined.
  • Diseases that make the news—think anthrax, ebola, and West Nile virus—come and go. The last confirmed case of anthrax was in 2011, only 6 cases of ebola, and West Nile fell to 414 in 2014 down from nearly 10,000 cases at the peak in 2003.

I don’t think there’s much profound here, but the numbers do help me make sense of what I see in the news.

Sexual Desire in Women

I admit it, I’m a guy. Not quite a bro, but I have been blessed/afflicted with the Y chromosome. So read what’s here with that in mind.

Yesterday’s post was about the approval of the drug flibanserin, aka “Viagra for women.” From my perspective it doesn’t seem like a good idea, and I laid out my reasoning in that post. Today I want to get into what was behind the FDA’s OK of flibanserin, after two failed attempts at approval.

The Politics of Drug Approval

Flibanserin didn’t all of a sudden get any safer. Three events have changed on the political landscape since the drug was first turned down in 2010.

  • Low libido in women has been medicalized—along with so much else—so now they have a condition that needs to be treated: Hypoactive Sexual Desire Disorder.* (This is close to what used to be called “frigidity” in women, with all its pejorative baggage.)
  • The FDA has placed female sexual dysfunction its list of top 20 unmet needs.
  • An advocacy group has formed around the issue. Even the Score is an association of 26 organizations, ranging from the Red Hot Mamas to the National Association of Clinical Nurse Specialists.

Throwing everything in the basket, the environment was ripe for approval.

Research Into Women’s Sexual Health

The viewpoint of Even the Score is that, since there are now more than 20 prescription treatments for low sexual functioning in men, there should be some for women too. The video on the Even the Score website makes the point. The group blames the difference on indifference to women’s interests. Or maybe on actual antipathy to women’s sexual health—both physical and mental.

Here’s where my being a guy comes in. I want my partner (that’s my wife) to be more interested in sexual relations. Just about anything that will do that gets my support. Put 5 guys together in a room, and they’ll tell you the same thing. Unfortunately, put 35 guys in a room, call them an FDA advisory panel (which used to be all male), and the topic of women’s health in general got pushed to the end of the agenda. As a result, research into almost all areas of women’s health lags behind. Fortunately that’s changing, but there’s still a long way to go to catch up.

So I partly agree and partly disagree that the discrepancy is a result of ignoring a women’s issue. It’s true that we’re still wandering in the weeds of pharmacology when it comes to women’s sexual drive, but it’s pretty much the same for men.

Desire Is a Mystery

The simple fact is that we know very about what triggers sexual desire. The search for Love Potion No. 9 has been going on for millennia. But Spanish fly doesn’t work. Powdered rhino horn doesn’t work. Sorry, not even chocolate works. In some older men, higher levels of testosterone can help. But for most of us, the hunt goes on.

We do have a good idea of what kills libido. Depression, stress, and anxiety will all depress your sex drive. Keep in mind that flibanserin was first developed as an antidepressant. My view is that if you can take care of other aspects of your mental and emotional health, your sex drive will take care of itself.

*At least that’s what it was called at the time the New Drug Application was put together for the FDA. Now, with the release of the updated DSM-5 (Diagnostic and Statistical Manual, the medical Bible for mental and emotional health practitioners), HSDD has been split into male and female versions: Male HSDD and Female Sexual Arousal/Interest Disorder.

Drug Disapproval—Flibanserin

The FDA’s approval of “Viagra for women” was all over the news this morning. Sigh. This is just wrong in so many ways. Let’s dive right in.

First, the characterization is completely off. Viagra treats a physical response, while flibanserin (brand name Addyi; and how do you say that?) treats libido, the mental aspect. The makers of Viagra and other meds for erectile dysfunction (ED) have said that if the desire’s not there, their med won’t help. And flibanserin won’t help with a woman’s physical response to sex.

Second, flibanserin is flat-out dangerous. The FDA had already denied approval twice over safety concerns, primarily nausea, dizziness, and headaches. This might not seem like much, but given the level of benefits the adverse effects were enough to kill the application twice. The makers did more studies, as asked. This time around the dangers were even more severe than first thought—but the benefits were no greater. Still, our FDA said “Yes.”

Just Say “No” to Flibanserin

Flibanserin is intended to treat a newly defined condition called Hypoactive Sexual Desire Disorder—in essence, low libido in premenopausal women. How low is “low”? Your guess is as good as mine. The makers of flibanserin define “low” as in the bottom 10% of desire. With more than 75 million women in the US between the ages of 20 and 54, 10% of that number is a nice population of new “patients.”

But what may seem low to one woman may be just fine for another. Measuring any aspect of mental or emotional functioning is a tricky business to begin with. Even in conditions such as depression and anxiety, which have been studied extensively for decades, assessment tools are notoriously imprecise. In physical conditions, part of a doctor’s job is to determine the cause behind your symptoms. Why is your blood pressure so high? What’s causing those headaches? Leaving treatment of a mental or emotional condition to your MD, though, is just asking for the symptom-treatment approach

The makers have said that they’ll require physicians to undergo training before being able to prescribe the drug, and it will be available only through “certified” pharmacists. I’ve taken some of these online training courses: two pages of text then 10 questions at the end, and voila! you’re certified. The seller has also agreed not to conduct any direct-to-consumer promotions for 18 months. Beginning in month 19, though, watch out for ads that could make your mom blush—and maybe your daughter too.

What’s Wrong About Flibanserin

As I said above, the perils of taking this drug are many and great.

  • Flibanserin tends to make you sleepy, so directions will say to take it before bedtime. There were reports in the trials of auto accidents and falls because women were getting sleepy.
  • Flibanserin makes you sleepy because it messes with your brain chemistry. Flibanserin affects receptors for serotonin and dopamine, and was first developed as an antidepressant. When researchers heard about an increase in libido from some participants, the light bulb went on.
  • Flibanserin doesn’t play nice with alcohol. So not nice, in fact, that there’s a “black-box” warning (the most serious kind) in the prescribing instructions, cautioning users not to consume alcohol while taking the drug. Umm… you want to feel like having sex more often, and no alcohol? How realistic is that for most people?
  • Flibanserin doesn’t play nice with contraceptives either. Typical hormonal contraceptives increase the frequency and severity of adverse effects, without improving the benefits. So have more sex but don’t use the Pill (or any other form of hormonal contraceptive).
  • It’s pink. Really? That’s the best marketing device you could come up with?

By the way, I don’t want to come across here as being against women’s sexuality—or even alarmed by it like some Victorian-era patriarch. I’ll go into that aspect of this drug tomorrow.

PS I came across this little tidbit about flibanserin on Friday. Take it in the spirit it’s offered.

Enjoying the Summer Sun

(Be aware that this post is longer than what you’ll usually see here. There’s just lots to say about the topic.)

I’m just back from a vacation in the Caribbean. (That’s why I’ve been away from this blog.) There’s a tree native to the region called the papelillo. It’s also called the “gringo tree,” because the bark turns red and peels off—just like the skin of gringos who come down and get too much sun too fast. And sure enough, I saw plenty of people who had overdone their sunning and were suffering the effects.

Lots of other people had gone overboard the other way, too—after days in the sun they were just as pasty as when they stepped off the plane. While obviously those who had been burned hadn’t done things right, those who didn’t get any color were wrong, too. I’ll talk about why you need sun in another post. In the meantime, here’s why you do need to be sensible about sun exposure.

The big fear of sun exposure is the development of skin cancer. There’s no question that ultraviolet radiation from the sun can cause changes in skin cells. The most common is a non-cancerous form known as actinic keratosis. This is an area of brown or reddish skin that may feel rough. Over time it can turn into the most common form of skin cancer, squamous cell carcinoma. The next most common form is basal cell carcinoma. These two forms make up more than 90 percent of cases of skin cancer. The third kind is melanoma, considered much more serious. The two types of carcinoma, if left untreated, can eventually grow large enough to be disfiguring—and in rare cases can actually be fatal. The real worry is melanoma, though, because this form has a much greater chance of spreading throughout the body and eventually doing you in.

What’s the Real Story on Sun and Skin Cancer?

More than 30 years ago the Australian health authorities developed a public awareness campaign they called “Slip, Slop, Slap”—Slip on a shirt, Slop on sunscreen, and Slap on a hat. At the time the rate of skin cancer there was alarmingly high—nearly three times that in the US—and climbing. Some studies claimed to show a link between the amount of sun exposure and the risk of developing skin cancer, so it seemed to make sense to reduce exposure to the sun.

In spite of this effort, the net effect on skin cancer in Australia has been minimal. While the rate of the carcinomas has dropped significantly, the incidence of the dangerous melanoma has actually risen by about 60 percent since the beginning of the campaign. Supporters of the campaign point to the first fact as proof of success. But they ignore the second fact, that the number of deaths from skin cancer has been rising steadily.

And the story isn’t any better in this country. The rate of skin carcinomas has been falling, while melanoma is the only one among the more common types of cancer whose rate has been rising—nearly tripling between 1972 and 2006.

With the increased attention to sun exposure, and so much use of sunscreen with higher and higher SPF levels, something’s clearly out of whack. Either sunscreen itself is a problem (I’m not going there, at least not today) or the entire premise of “more sun = increased risk” is wrong.

We’re built to deal with sun exposure just fine. People who spend much of their lives outdoors (farmers, construction workers, etc.) have very low rates of skin cancer compared to the general population. And, curiously, when the more dangerous melanoma form of skin cancer does develop in these people, it tends to appear in areas not exposed to the sun, such as the buttocks and the inner side of the upper arms. So be sensible about your sun exposure—an increased number of bad sunburns in your life increases your risk of developing some form of skin cancer—but don’t worry too much about regular time in the sun.

What to Watch For

You probably already know this, but it’s helpful to include the signs to watch for. The useful mnemonic is ABCDE.

  • Asymmetry—Moles are almost always round or nearly so. If you have a spot that’s irregularly shaped, or that has changed shape, get it checked out.
  • Border—Moles typically have a clearly defined border.
  • Color—Moles are almost always brown or black. If you have something that’s a different color, or more than one color, or that has changed color, that’s a bad sign.
  • Diameter—Moles are most often less than ½ inch (that’s about 1 cm) in diameter. If it’s larger than that, or if it’s been growing, it needs to be looked into.
  • Elevation—Moles are flush with the surface of skin. Anything that’s elevated, especially if it has a rough texture, is worth further inspection. (Sometimes you’ll see the E as standing for “Evolving,” but that’s pretty much taken care of under the other headings.)

Where Is a Treatment for Alzheimer’s?

Over the last few days there’s been a burst of news about treatments for Alzheimer’s disease. Unfortunately, the news sounds about the same as everything else we’ve already heard: there’s a potential to slow the progress of the disease, but no real treatment, as in “making things better.”

The brains of people who have Alzheimer’s disease show two characteristic changes. The first is an accumulation of a protein called beta-amyloid on the surface of nerve cells. The second is tangles of a protein called tau inside nerve cells. Either of these disrupts the normal transmission of messages in the brain, leading to the symptoms of memory loss and changes in mood and personality.

Eventually, Alzheimer’s disease often leads to death, typically within 4 to 7 years of the first diagnosis. People with Alzheimer’s can lose the ability to swallow, so they aspirate food and develop pneumonia. Or they lose motor skills and fall. According to the CDC, Alzheimer’s is the sixth leading cause of death in the US. But a study released last year in the journal Neurology showed that Alzheimer’s disease may actually be the third-leading cause of death in this country, after heart disease and cancers. The discrepancy is because Alzheimer’s disease is often not listed on death certificates as a contributing cause.

What’s Making News for Alzheimer’s Disease

The recent news is about 2 “treatments.” The first is deep brain stimulation (DBS). This therapy is pretty much what it sounds like: electrodes are implanted deep in the brain and then charged. The therapy has shown some benefit for movement disorders such as Parkinson’s disease and essential tremor. An early test on 6 people showed that there might be some improvement in cognition, but in the most recent study, of 42 people with mild Alzheimer’s disease, there was no difference between those who received the genuine treatment and those who received sham treatment. (Sham treatment has the same function as placebo treatment—to mimic the real therapy so the patient doesn’t know what they received. “Sham” refers to physical treatments such as surgery or acupuncture.)

The second potential treatment is pharmaceutical. Two drug companies have developed compounds that they had hoped would improve things for people with Alzheimer’s disease. As I said earlier, unfortunately the only benefit is that the therapies slow the advancement of the disease. That’s not to be sneezed at, but it certainly isn’t the breakthrough everyone is hoping for.

The drugs are solanezumab from Eli Lilly and aducanumab from Biogen. Both drugs have been shown to slow the accumulation of beta-amyloid in the brain, and perhaps even clear some of the protein away. Still, there’s no evidence that either solanezumab or aducanumab can reverse the progress of the disease.

Of more than 125 experimental drugs brought to trial since 1998, only 4 have been approved for use in patients with Alzheimer’s disease—and even those 4 don’t really treat the condition. Sadly, with all the effort that’s been put into research into Alzheimer’s disease, there’s been little real progress in dealing with it. I’ll come back to the topic of Alzheimer’s from time to time as news warrants. Given the prevalence of the condition in our society, it’ll likely be sooner rather than later.