Monthly Archives: October 2006

Making Do – Pasta w/ Cannellini & Garlic

Last weekend, I took my daughter and her friend with me to the country to close up our cottage for the winter. It was to be a quick overnight trip, and so I brought few provisions – just some half and half for our coffee- figuring I would use the opportunity to clean out the food cabinets and freezer before shutting the place up till May.

For dinner Saturday night, I actually created my own litle recipe out of what I found in the cabinets and freezer. Served after a first course of thawed mushroom barley soup and with reheated bread, this pasta was actually quite delicious.

It really is true what they say..necessity is the mother of invention.

Penne with Cannellini, Herbs and Garlic

The key to this dish is lots of sliced garlic, cut thin and cooked in olive oil with lots of herbs.

1 lb Penne pasta
1/4 cup olive oil
6 or more garlic cloves, peeled and thinly sliced
1 can cannellini white beans, barely drained and not rinsed
1/4 cup pesto
1 tbsp dried herbs de provence
1 tsp dried oregano
fresh cracked pepper
salt to taste
Parmegiano Reggiano cheese, grated (optional)

Start your salted water boiling for the pasta. In the meantime, heat olive oil in a dutch oven or large saute pan over medium high heat till hot. Add garlic and saute, tossing till it is yellowed and almost browned, but still soft. (The goal is to cook the garlic and flavor the oil, so you may need to turn the heat down so it doesn’t brown too much)

Add in the basil, pepper and spices about half way through to flavor the oil even more.

Add in the beans and cook till heated through, being careful not to stir too much or break up the beans. Just a tiny bit of kosher salt to taste.

Cook the pasta. Drain lightly and carefully toss into the beans. Serve immediately topped with grated parmigiano-reggiano cheese.

Category: Food

Last updated 02/4/13

Are They Selling Drugs or Underwear?

Kevin, MD highlights the most over-the-top pharmaceutical exhibits at a recent medical conference he attended. Head over to his web site for even more hilarious photos, as Big Pharma vies for our attention.

Category: Second Opinions

Last updated 08/3/10

My Blog – You Complete Me

A few of you have asked me why I came back after my little blogging hiatus. I thought about just pointing to the I Love My Blog post, but that wouldn’t explain it, not really. You see…

I tried to live without blogging. Really I did. But it just wasn’t the same.

I missed my blogging friends. The docs, the cooks, and everyone else who reads me and whose blog I read. My little blogging community.

Even more so, I missed who I was when I was blogging. My younger daughter said I was more fun to have around when I had my blog. “Everything you do just seems more interesting.”

And she was right. Blogging adds a new dimension to my daily life. When I am blogging, I look at my world a little differently. I carry my camera everywhere, take photos constantly. I see things I normally would not notice. Everything I do, see, read or experience is a potential post. And that brings my life added dimension, interest and well…joy. My own boring life begins to look like something worth writing (and reading) about, even to me.

In my life, my blog is that added “something”. It ices the cake, fills in the spaces, greases the skids, rounds out the corners. Gives me something to do in the quiet moments, the occasional empty minutes. Of course, it also keeps me up till all hours of the night since those quiet moments seem to generally occur only after everyone else is asleep…

My blog is the only place I get to be completely myself. Most people who know me just know the part they see at work, where I tend to be very busy and serious, beause what I do all day is , well… serious. Here I get to be the whole me.

But most importantly, my blog is the one thing I have in my life that is just for me, just by me. My own voice, my own little view on the world. My Blog. My Mini-Me. It completes me.

And so, that’s why I’m (we’re) back.

Category: Considerations

Last updated 08/3/10

Coffee Guy

This is part 3 of a special TBTAM post series entitled “I Get It On the Streets” . Links to the next post in the series are at the end of each post.
Coffee guy parks his truck across the street from the medical school entrance. I used to stop at his truck every morning for my coffee on the way to the office. It got so that I would get on line, and by the time I reached Coffee Guy’s window, my coffee would be ready, just the way I like it, light with one sugar. This was by no means a unique experience. Any of the other folks standing in line would tell you the same story. How Coffee Guy remembered how we each took our coffee was beyond me.

But here’s what amazes me more. About 5 years ago, my office moved about 7 blocks in the other direction down the Avenue, which here in Manhattan is like living in a different country. I started getting my coffee at the local deli close to my new office. About 8 months after my move, I was heading to the medical school for an early morning meeting, and stopped at coffee guy’s truck for a cuppa’. He took one look at me, smiled and said “Still light with one sugar?”

How does he do it???

Next Up….Vinnie

Category: Considerations

Last updated 03/28/11

Hormone Replacement – Part 4

In Part 1, Part 2 and Part 3 of this series, I’ve said just about everything I know, or you would care to know, I expect, about HRT. But before we leave this topic, I need to say…

A Few Words About Bioidentical Hormones

One concerning impact of the Women’s Health Initiative has been the wholesale marketing of so-called “natural” hormone products to women as the safer alternative to Prempro. These “bioidentical hormones” are manufactured replicas of the same molecules our bodies use. They can be found in the FDA-approved HRT products such as Climara, Vivelle and Prometrium, to name a few.

Many women have the misguided belief that when these same compounds are made in a smaller local compounding pharmacy, they are somehow safer and better than Prempro or the FDA-approved products. There is absolutely no data to support this claim. So, until someone does a placebo-controlled, randomized clinical trial to prove otherwise, estrogen is estrogen, whether it comes from plants, mares urine or the moon.

Don’t get me wrong – I am more than happy to prescribe “natural” hormone replacement. Estrogen is estrogen, after all.

But I will not act as if somehow this stuff is risk-free and safer than it’s synthetic counterpart, or hand it out like candy to every woman who comes into my practice looking for the fountain of youth. I treat it the same way I treat Prempro. That means you can have it if you need it, and as long as you understand the potential risks as we know them today, and the benefits as they have been proven to date. The rest is all hype as far as I am concerned.

And speaking of hype…

The bio-identical hormone crowd have found a new guru in Suzanne Somers, whose books tout the age-defying wonders of bio-identical hormones. Suzanne takes these hormones herself, and sells them as the risk-free answer to the problems of aging, from hot flashes to wrinkles to weight gain to Alzheimers.

Look, I love Suzanne, but she is out of control with this hormone thing and someone has got to rein her in. Here’s a quote from the cover of her latest book “Ageless”:

“The second half of life can be wonderful. I know it because I am living it. This new approach to health gives you back your lean body, shining hair, and thick skin, provided you are eating correctly and exercising in moderation. This new medicine allows your brain to work perfectly and offers the greatest defense against cancer, heart attack, and Alzheimer’s disease. Don’t you want that?”

Somers’ books are the new Feminine Forever, except that they tout bio-identical hormones instead of Premarin. And, just as Femine Forever was a marketing tool of Wyeth, Suzanne is being used as the marketing tool of the anti-aging industry. Her own use of the hormones, as well as her sincerity (and I do believe she is sincere) only make her message that much more appealing.

But we can’t hold Wyeth’s feet to the fire, and then turn around and give Suzanne and her friends a free ride. Unfortunately, this group appears to be operating under the radar of both the FDA and the media, both of whom appear to be ignoring the problem. The media, in fact, is part of the problem, letting Suzy hype her message on every talk show known to man, with nary an opposing viewpoint.

Fortunately, Somer’s book has not influenced mainstream medical practice. But it has convinced a fair number of women to go to their doctors and ask for natural hormones to fulfill some vague notion they have of health, youth and beauty. Perhaps they want look and feel like Suzanne. (This reminds me of the movie Shampoo where the little old lady sits in Warren Beatty’s chair holding up a photo of Princess Diana, saying “I want to look like her.”)

More than a few patients have arrived to their appointment toting Suzie’s book. It can take a lot to get them to be specific about what it is they feel they need hormones to treat, and to understand that natural estrogen is indeed estrogen, with all its risks and benefits. And that we are all going to get old (and look old) someday, estrogen or no estrogen.

But then again, I don’t look like Suzanne, so why should they believe me?
____________________________________

Addendum: Good news – the media seem to be getting the message. Head over to Kevin, MD for the links.

Patient information on bioidentical hormone here.

An excellent review article on bioidentical hormones. (Abstract only – full text for a fee for non-members)

Read the National Women’s Health Network Fact Sheet on Natural Hormones.

Category: Second Opinions

Last updated 06/8/11

Hormone Replacement: Part 3

In part one and part two of this four part series, I reviewed the history and findings of the WHI, the impact of those findings on the medical establishment, and the newer data that have gotten us all muddled up again in our thinking about estrogen.

In the face of all that uncertainty, I have to practice medicine. To that end, I have created my own set of guidelines for prescribing HRT that I would like to share with you now. Feel free to comment, question, criticize or amend these guidelines, or god forbid, to use them yourself.

Please do not ask me if I am “pro-HRT” or “believe in HRT”. Health care is neither politics nor religion, despite that picture up there. It is, however, an uncertain science. Therefore, one must be wary of anyone expressing extremes of opinion about HRT, either for or against its use, and of anyone claiming to have the final word on HRT.

  1. I am willing to prescribe HRT for any of its approved indications (vasomotor symptoms, vaginal dryness, osteoporosis), provided you understand the risks as well as the benefits and know about alternative treatments for these conditions.
  2. I will give you the best data I can find that defines your personal risks and benefits from using HRT. Unfortunately, that data is imperfect, and may change in your lifetime. This will be frustrating for both of us.
  3. I am willing to prescribe HRT for reasons of well-being, mental or physical, provided you are willing to accept the risks and can describe the benefit for me as best as you can.
  4. If you are at increased risk for or have had breast cancer, I am willing to prescribe HRT provided you accept the risks and we have exhausted the non-HRT solutions to your problem, assuming, of course, that it is a problem that HRT can address. (I can count on less than one half of one hand the number of my patients with breast cancer who would fit this rule, but for them, I have it. )
  5. I will not prescribe estrogen without progesterone if you have an intact uterus. If you use anything less than standard progesterone regimens, you must undergo frequent monitoring of the endometrium.
  6. I am unwilling to prescribe estrogen if you are at increased risk for blood clot or stroke. I will do everything I can to find you an alternative that will address your symptoms or condition.
  7. I am not willing to prescribe HRT for cosmetic reasons alone.
  8. I am happy to prescribe bioidentical hormones, but you must assume they have the same risks as Prempro until there is data to prove otherwise.
  9. I consider vaginal estrogen to be safe in almost every woman. (I’ll let you know if I think you are the exception to this rule, and why.) If you feel otherwise, I completely understand.
  10. I will support your decision to use or not use HRT, and will work with you to find the optimal way to manage your menopause, whether it be through lifestyle changes, diet, exercise, hormones and/or medications. It is, after all, your body and your menopause.

Up next: A few words about bioidentical hormones.

Image: I mutilated The Ten Commandments Pressbook Cover. (I just ordered it from Ebay, and can’t wait to get it and see what other images are inside. It is one of my favorite movies of all time.)

Category: Second Opinions

Last updated 04/5/11

Hormone Replacement – Part 2

See Part 1 here.

When we last left the WHI, the results of the estrogen-progesterone arm of the study had just been released. Unexpected results which showed the drug to increase the risks of heart disease, stroke and breast cancer…

The Immediate Reaction

Well, we all know what happened next.

Widespread confusion and not a little panic erupted, helped in no small part by the manner in which the WHI’s findings were released (via press release prior to publication of the paper). The investigators did little in their contact with the media to place their results in perspective or to address how they might relate to women using HRT for treatment of menopausal symptoms. Instead, they fanned the flames of hysteria by making statements to the press like “This is a dangerous drug.” (NY times) That was just irresponsible, in my opinion.

Critical analysis of the paper was lost in the melee. The fact that the WHI was never designed to study the use of HRT for treatment of menopausal symptoms was a fact that received cursory mention at most. Questions of statistical significance and relative risk were rarely mentioned. The WHI was accepted as gospel from day one. I don’t fault the media – most of the reporting I read was intelligent and well meaning. But critical analysis of the data itself was notoriously absent, because no one had time to do it before having to talk to the media.

Overall, about two thirds of women who were taking HRT at the time the WHI results were released stopped their therapy; those who stayed on the drugs tended to be those women who had the worst menopausal symptoms.

Physician reactions were just as strong. Some docs stopped prescribing HRT altogether. One doc I know told her patients, “You can kill yourself if you want to, but I am not going to prescribe the gun'”. One patient of mine was told by her former physician, “I won’t let my wife use it, and I’m not going to prescribe it for you.”

Perhaps they are worried about being sued. Given that there are more lawsuits out there against Wyeth than you can count, I can’t say as I blame them.

Still, it seems to me as if that approach merely exchanges the “one size fits all” approach to estrogen with the “no size fits anyone” approach, and is just more of the medical simple-mindedness that pre-dated the WHI. And when has the practice of medicine ever been simple?

The More Measured Response

In a relatively short time, the medical establishment recovered from the acute shock of the WHI. New guidelines for HRT were formulated by the US Preventive Services Task Force, recommending against the use of hormone replacement for the prevention of chronic conditions in women.

But what to do with all those women on HRT for treatment of menopausal symtoms? The WHI did not address these women, and yet they were the ones using most of the HRT. We were essentially left on own to figure this one out. Professional organizations like the American College of Obstetrics and Gynecology and the North American Menopause Society eventually came out with guidelines that were more detailed and helpful than the “just say no” guidelines of the USPSTF. In 2005, the FDA published HRT guidelines for women considering hormonal therapy.

The new guidelines can be summarized simply as: Talk to your doctor, take the lowest dose needed shortest shortest period of time, make sure you know the risks as well as the benefits, and consider alternative treatment when available.

Lower Doses, Shorter Use
The use of HRT for treatment of menopausal symptoms continues to be supported, but at the lowest effective dose for the shortest period of time necessary. Women are now encouraged to try to wean off of estrogen once it is no longer needed for the symptoms of the menopause transition, which last on average about 18 months. For women who continue to need estrogen past that time, the goal is to find the lowest effective dose.

Are lower doses of estrogen safer in terms of heart disease, blood clots, stroke and cancer? No one knows. We do know, however, that they are likely to be just as effective for prevention of osteoporosis, and are often enough to control symptoms. So why take more if less will do?

Vaginal Estrogen
Vaginal estrogen remains a viable option for the many women whose only real symptom is vaginal dryness. To date, I know of no adverse data associated with vaginal estrogen use, except that if the cream is used, one may occasionally get endometrial stimulation. Some experts still recommend some progesterone to balance that out. Newer vaginal estrogen formulations such as the ring or vaginal tablet appear to be quite safe for the endometrium. For women who are concerned, drawing blood levels can confirm that the absence of significant systemic absorption. Additionally, the endometrium can be sonogramed periodically.

Transdermal Estrogen
Since the WHI, some doctors have begun to preferentially prescribe transdermal estrogen, there being some data that it may impact clotting factors less than oral estrogen. Transdermal patches are a good option for women who want to stay with the so-called “bio-identical” estrogen, 17-beta estradiol. Taken orally, this molecule can have a shorter half life, and I have had more than a few patients need to take either higher doses of more frequent dosing to alleviate their hot flashes. For some women, however, patches can irritate the skin, so they are better off with oral.

Progesterone
Natural progesterone has become de rigeuer, although there are no really good data that it is any safer than Provera was. I do prescribe natural progesterone preferentially, because I find it is generally better tolerated than Provera. But I have no major objections to the so-called synthetic progestins, because natural progesterone can make some women very sleepy, even at low doses. (For most this is an advantage, insomnia being a symptom of menopause.)

Transdermal progesterone, while a very popular health food store item, is very variably absorbed through the skin, and not yet available in any reliable product for endometrial protection. As a result, it is not recommended to “balance” the estrogen part of HRT.

Some women cannot tolerate any progestin, oral, transdermal, natural or synthetic. The Mirena IUD might be an option for these women.

Non-Hormonal Options
For symptomatic women unwilling or unable to take HRT, newer non-hormonal options are being studied and offered off-label for treatment of hot flashes. The SSRI’s fluoxetine, paroxetine, venlafaxine and the anti-seizure medication gabapentin have been shown in small controlled trials to reduce hot flashes by about 65%. Not as good as estrogen, but for some women, enough. No large long term trials of these drugs have as yet been done.

Do you see what is happening? We are beginning to custom tailor the therapy to the patient – her needs, her symptoms, her concerns, her side effects. And her risks. Because, most importantly, doctors have began to weigh the risks and benefits of estrogen a little more carefully, patient by patient.

No more one size fits all. And that’s just better medicine, if you ask me.

The Plot Thickens…

Since 2002, the plot has taken a few twists. The first was the publication of data from the estrogen-only arm of the WHI. In that group, breast cancers were actually fewer in women who took Premarin alone, though not statistically so. (Of course, this data got much less attentionia atention than the combined hormone arm of the study.)

This difference between the data on estrogen-alone and combination HRT has led many to believe the the evil hormone is not estrogen, but progesterone. Or more specifically, medroxyprogesterone acetate, the progestin compound in Prempro. But is the so-called “natural” progesterone safer than Provera? Your guess is as good as mine. Again, no long term data.

The second twist has been an analysis of the younger women in the estogen-only arm of the WHI, those who began the drug in their 50’s, in a manner more typical to the way we gynecologists tend to prescribe it. In this group, there was not an increase in heart disease, but a suggestion of a decrease. This would support the hypothesis of a so-called “window of opportunity”, a period of as yet undefined time after menopause during which HRT, if started, might actually do all the heart-friendly things we all had thought it would do.

Recent findings from the Nurse’s Health Study also support this hypothesis, and suggest that for women who use HRT beginning at menopause, the risks of heart disease are reduced almost a third. A randomized, placebo-controlled trial to investigate this possibility is in the works, but don’t expect an answer anytime soon.

The relatively more favorable data from the estrogen-only arm has led science-saavy women to begin to ask for hormone regimens that use less progesterone. The problem with this approach is the ever-present risk of endometrial cancer from long term use of unopposed estrogen. I have some concerns about this – essentially treading off one low cancer risk (breast) for a higher one (uterine). Quarterly progesterone regimens are associated with higher rates of endometrial hyperplasia, and that has been my experience when my patients have tried these regimens. I have had better success with quarterly progestin regimens when they are combined with less than standard doses of estrogen. I have had one patient go to hysterectomy because she kept developing hyperplasia and was no longer willing to take progesterone of any kind, ever.

So, where are we now?

And so, four years later, we are practically back where we started. Maybe estrogen is good for the heart, as long as you start it early enough. Maybe the breast cancer risk isn’t from estrogen, but from progesterone. Maybe lower doses or transdermal regimens will prove to be safer. Maybe, maybe…

So how does a woman make a decision about HRT given all the unanswered questions? Her hot flashes will not wait for a better study to come along. And how does one practice medicine in this era of uncertainty? It’s not easy, I can tell you. You need to be clear in the face of fuzzy data. You must be internally consistent when externally, all is not. You have to be flexible, but not wishy-washy. It isn’t easy, but it can be done.

Up next…How I do it

Category: Second Opinions

Last updated 06/8/11

Hormone Replacement Therapy – Part 1

I’ve been meaning for some time to pull all my thoughts together about hormone replacement therapy. The opportunity presented itself recently when I was asked to give a talk on the status of HRT four years after the WHI. After giving that talk, I realized that I had a lot more to say, so I am going to just say it all here.

This will be a four part, four day post. The first part is background on HRT use before the WHI, then discusses the WHI and its results. Part two addresses the response in the medical community to the findings of the WHI. Day Three will be TBTAM’s Rules for Prescribing HRT, and Day 4 will address the use of bioidentical hormones. So hop on board, the winds are fair and we’ve got a lot to cover…


Those Were the Days

Those were simpler days, the years prior to the publication of the WHI. “Simple” meaning that, for the most part, we had a “one size fits all” approach to managing menopause. You were a woman, you had menopausal symptoms, you had a heart — you got estrogen. It was that easy.

It seemed simple, but we were not stupid. There was more than a little scientific support for our approach to menopause. Dozens of well done, retrospective and cohort studies had all pointed to the same conclusion – women who took HRT had less heart disease than those who did not.

This conclusion made biologic sense. We knew that the onset of menopause was associated with an increase in the incidence of heart disease in women. Moreover, estrogen raised HDL, the good cholesterol, and lowered LDL, the bad cholesterol. Finally, there was indirect and animal evidence that estrogen caused vasodilation.

Turns out that estrogen also appeared to prevent osteoporosis. It was, and still is, is the most effective treatment for the symptoms of the menopause transition – hot flashes, night sweats, and vaginal dryness. Not to mention its effects on the skin, increasing collagen and decreasing wrinkles.

And the risks? Well, estrogen was known to increase the risk of thromboembolism. In addition, it had been known since the 70’s that it could lead to endometrial cancer, but that risk was alleviated if progesterone was added to the mix. Breast cancer, of course, was a persistent concern, showing up as a potential risk in a number of studies. But the results were inconsistent, even in meta-analyses.

Given that heart disease was the number one killer of women, and that the cardiac benefits seemed to be more consistently apparent than the breast cancer risks, there was a real hope in the medical community that the cardiopreventive properties of estrogen would outweigh the risks.

And yet, looking back at the review articles on estrogen written prior to the WHI studies, all the experts were clear that more evidence was needed before recommending HRT for heart disease prevention on a widespread scale. Almost every paper I read was careful to recommend individualized treatment, weighing the risks and benefits for each woman before prescribing.

As for the world of practicing docs, the primary indication for prescribing HRT in those days was still menopausal symptoms, but we had a much lower threshold for prescribing estrogen than we do now. It didn’t take much in the way of hot flashes for us to prescribe HRT, especially for women we thought might additionally benefit from the cardiac effects of estrogen. For some, a high LDL alone was enough reason to use estrogen. (Remember, we did not have the statins then). And more than a few physicians gave all their menopausal patients estrogen, regardless of symptoms. “My doctor said it was good for me.” is what some of my patients would tell me when I asked them at their first appointment why they were taking estrogen.

Overall, I would say that, prior to the WHI, estrogen was something we felt good about prescribing. We liked it and our patients liked it. It was one of those drugs that had a real and visible effect, which for the overwhelming majority of women was positive. Think about it – relief of hot flashes, insomnia, night sweats and vaginal dryness, prevention of osteoporosis, normalization of lipids, and the possibility of heart disease prevention. That’s one heck of a drug.

Big Pharma, as it turns out, also liked estrogen.


Wyeth and the WHI

Wyeth been the leader in the HRT market for years, spurred on in no small way by the publication in 1996 of “Feminine Forever“, a book which touted the wonders of estrogen in staving off the effects of aging. (The book, as it now turns out, was entirely underwritten by Wyeth. Why am I not surprised?)

Wyeth’s drug was Premarin, a proprietary mixture of conjugated equine estrogens. Equine – that’s a nice way of saying estrogens isolated from horses, specifically from the urine of pregnant mares. (I had read that if you crush the pill , soak it in water, and then sniff, it is clear where it comes from. I did not believe it until I tried it for myself. It’s true.)

I need to say at this point that, having prescribed Premarin extensively in the past and still occasionally now, that it is a very effective estrogen, and despite the smell, I have no real issue with its source. Many women do, however, and so I rarely prescribe it these days since there are numerous alternatives.

For the progesterone component of HRT, Wyeth had Provera, or medroxyprogesterone acetate. (Same stuff as in Depo-Provera, the birth control shot, but at a much lower dose). The two hormones are combined together as Prempro. I did not prescribe Prempro as much as I used Premarin, having moved towards micronized progesterone as soon as it became available, because I found it in general to be better tolerated than Provera.

By 1990, Premarin was one of the most prescribed drugs in the world, and was approved by the FDA not only for the treatment of both hot flashes and vaginal dryness, but also for the prevention of osteoporosis. When studies began to rack up showing that estrogen was also good for women’s hearts, Wyeth asked the FDA to approve Premarin for the prevention of heart disease. Of course, doctors everywhere were already prescribing the drug off-label for that reason. But with a formal FDA indication, Wyeth would be allowed to advertise for the indication, and we all know what Big Pharma advertising does to sales. It was sure to be a slam dunk, and a very profitable one at that, since the prevention market for a drug is absolutely enormous compared to the treatment market.

The problem was that all the data up to this point supporting the cardiac benefits of estrogen were from observational, retrospective or cohort studies. And there were those pesky little problems of breast cancer and blood clots that kept creeping into the study results. The risks appeared relatively small, but they were there nonetheless.

Despite this, the FDA’s advisory committee had actually recommended that Wyeth be given the cardiac indication based on the observational data. But in an unprecendented move, the FDA went against their own advisory commitee’s recommendation and asked for a randomized, placebo-controlled trial. The trial Wyeth would begin was the HERS trail, a study of HRT use in women with pre-existing heart disease, believing, I’m sure, that estrogen’s protective effect would show up quickly in this group at high risk. (It did not, as we found out later.)

At around the same time, feminists at the NIH, FDA and on the Hill were pushing for federal funding for research in Women’s Health. Congress responded by funding the Women’s Health Initiative, a large prospective study of women’s health enrolling over 60,000 women for 15 years. The jewel in the crown of the WHI was a randomized, prospective, placebo-controlled trial of hormone replacement in menopausal women. The study was designed to determine once and for all whether or not estrogen prevented heart disease and treated osteoporosis, and to answer the lurking question about breast cancer risks. Everyone, including the study investigators, expected favorable findings for estrogen in terms of heart disease.

But which estrogen to use? Well, Premarin and Prempro were the most prescribed hormones at that time, so it made sense (although maybe not biologic sense) to use them. And Wyeth? Well, they were more than happy to supply drug for the study. And that’s how Premarin and Prempro became the drugs used in the WHI.

There were two study arms to the WHI – one arm for women with a uterus, who received either Prempro or placebo, and a smaller arm for hysterectomized women, who recieved either Premarin or placebo.

The Bombshell Results

The first sign of trouble came when the HERS study results showed no benefit to HRT use in women with pre-existing heart disease, despite favorable effects on blood lipids. In that study, there was actually an increase in cardiac events in the first year of hormone use, probably due to clotting effects, that disappeared in the subsequent years such that overall, no difference was found in cardiac mortality among users and non-users of HRT.

Then came the results of the WHI, results that came earlier than expected when the Data Safety Monitoring Board decided to stop the study prematurely. Because as we all know now, Prempro did not to prevent heart disease in the WHI. Not only that, it actually appeared to increase that risk, along with that of blood clots and stroke. At least among the women in the Prempro arm of the study, who were on average 10 years post menopausal and 64 years of age at enrollment.

WHI results from the WHI Newsletter

To make things worse, breast cancers were also increased among users of Prempro in the WHI, to the tune of 8 additional cases for every 10,000 women for every year of use. Not a statistically significant increase if you want to get picky. But, since this was a prevention and not a treatment trial, the bar for safety was much higher since subjects were supposedly healthy to begin with. And the Data Safety Monitoring Board was not about to accept an increase in breast cancer if there was no cardiac benefit. Even the benefits in terms of bone and colon cancer were not enough to tip the balance in favor of HRT.

So, they stopped the trial. (The estrogen-only arm was allowed to continue till 2005, when increased stroke risks stopped that study.) Sure makes sense to me.

Whether the whole study design itself made sense in the first place is another story. The study population was deliberately weighted towards older women. Since most cardiac events occurred among older women, benefit would show up earlier in this group. Younger women with menopausal symptoms were specifically excluded from the WHI because it was felt to be unethical to give these women placebo. Of course, this is exactly the opposite of how HRT is prescribed in the real world, and remains the biggest limitation of the WHI in my humble opinion.

Which raises the question – Is an average age of 64 just too late to start estrogen? By that age, arterial plaque is likely to be long-established, and adding in a drug known to increase risk of blood clotting may not be such a great idea. Some experts still believe that if estrogen is given earlier in life, say at the menopause, it may still be preventive for heart disease. Think of it this way – Running is good for you, and can prevent heart disease, but if you are not a runner, have blocked coronaries and try to run a 10K, you might just trigger an MI, which would not be good. It’s an intruiging hypothesis, but at the time of the publication of the WHI, it was just that. An idea.

In 2002, like it or not, the bottom line was that HRT was associated with an increase in the risks of heart disease, stroke and breast cancer. In a disease prevention trial, that just doesn’t hold water, especially when the primary outcome, heart disease, was not prevented anyway.

And that, my dears, is why they stopped the study.

Up next…The Reaction

Category: Second Opinions

Last updated 06/8/11

National Honor Roll Scam – Update

Some months ago, I posted about the National Honor Roll, a stealth marketing scheme disguised as an academic achievement award and scholarship program.

The scheme starts with surveys that our children are asked to complete in the classroom, supposedly for college information. The info then gets shared with the National Honor Roll, the scholarship cover organization, while its partner the Student Marketing Group creates a huge marketing database that they then sell for profit. Read more about it here and here.

If you have any doubt as to the true nature of the National Honor Roll, note this press release below from Nelnet, a publicly-traded student loan finance company:
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For Release: 3/29/2005
Contact: Sheila Odom, 402.458.2329

Nelnet announces acquisitions of Student Marketing Group and National Honor Roll

(LINCOLN, NE) – Nelnet, Inc. (NYSE: NNI) announced today it has acquired Student Marketing Group, Inc. and National Honor Roll, L.L.C.

Student Marketing Group is a full service direct marketing agency providing a wide range of products and services to help businesses cost effectively reach the middle school, high school, college bound high school, college, and young adult marketplace. A division of Student Marketing Group, College Bound Selection Service provides marketing services and college bound student lists to college and university admissions offices nationwide. In addition, Student Marketing Group operates AllScholar.com, a free scholarship search Web site.

National Honor Roll recognizes middle and high school students for exceptional academic success by providing publication in the National Honor Roll Commemorative Edition, as well as scholarships, a College Admissions Notification Service, and notice to local newspapers and elected officials.

“Student Marketing Group and National Honor Roll each bring a strong reputation and a wealth of different experiences building marketing relationships with students and schools,” said Stephen Butterfield, Vice Chairman and Co-Chief Executive Officer of Nelnet. “These acquisitions will further diversify our revenue stream and provide an opportunity to leverage their intellectual capital and wealth of direct marketing expertise in our future operations.”
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Category: Considerations

Last updated 09/9/10

Country Fair, City Fair

Fall Festival
 Forksville, Pa

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6th Avenue
New York, NY
 

 

 

 

 

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Last updated 03/21/12

A Smoke-Free Story

Bar workers in Scotland reported a 33% reduction in respiratory symptoms just 2 short months after smoke-free legislation was enacted in that country, according to a study reported this week in the Journal of the American Medical Association. Objective measures of respiratory tract inflammation and pulmonary function were also significantly improved. (JAMA.2006;296:1742-1748.)

Here in New York City, we passed similar smoke-free legislation in 2003, making ours one of the toughest anti-smoking laws in the United States.

I like to think I had something to do with that…

She was 32 years old, married and head waiter in a swanky hotel bar where smoking was prevalent. So much so that it had become known among the workers there as “The Cigar Bar”. She wanted to get pregnant, but was afraid of exposing her fetus to such large amounts of second hand smoke.

“I need a letter from you to my boss saying that too much second hand smoke is bad for my baby, and that I should be transferred to a different restaurant in the hotel. He doesn’t believe me when I tell him this.”

Of course I wrote the letter. I also gave her a presciption for prenatal vitamins.

“Call me when you’re pregnant”, I said, smiling.

But when I saw her a year later, she still had not left the bar or started her family.

Her boss had agreed to transfer her from the hotel bar to the breakfast cafe. But with the transfer, her income would be cut almost in half ; breakfast cafes just don’t generate the kind of tips that bars do. Without the income, she could not save for the down payment for an apartment big enough to raise a family. So she stayed at the cigar bar, saving as much of her income as she could.

“I figure I need to tough it out there another year, then I can quit and get pregnant,” she explained.

“But you’ll be that much older,” I gently advised. Almost 35.”

“I know’” she said, her eyes filling with tears. “But what else can I do? I really need that income. And if you think I have it bad, it’s even worse for some of the others there.”

Then she told me about her friend, a bus boy in the bar whose asthma had worsened severely since he had begun working there. His co-workers had taken him to the emergency room more than once that spring, gasping for breath, his inhaler useless. He continued to work in the bar because the tips there were too good to turn down, almost every penny of them sent back home to his wife and family in Peru.

She brushed her tears aside, angrily. “What good will he be to his family is he dies?” she said.

“There’s something you can do”, I told her.

I gave her the name and number of a woman I knew who worked with the anti-smoking coalition in New York City. They were actively lobbying for a bill that would ban smoking in restaurants, and seeking individuals to testify at the public hearings scheduled the following month at City Hall.

But my patient refused to take the number. “I don’t want to lose my job. If the management finds out I’m working against them…”

“Look, I can’t tell you what to do. But your story, and your friend’s story, needs to be heard. Just make the call. I’m sure there’s a way to protect your privacy if you really want that.”

I pushed the number gently across the desk.

“Call her.”

As it turns out, she did call that woman. And later that fall, both my patient and that bus boy willingly and openly testified at the City Council Hearings in support of the bill that would ban smoking in NYC restaurants. I heard they were among the most compelling witnesses of the day.

Shortly after that hearing, the New York City Council passed the Smoke Free Air Act of 2002, 47 votes in favor, with 2 abstentions. Mayor Bloomberg signed it into law in March 2003.

And my patient? Well, both she and the bus boy kept their jobs. I hope his asthma is better. Unfortunately she ended up needing in-vitro fertilization, and last I heard, was still trying to get pregnant…
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For information about second-hand smoke in the workplace, and to find out how you can get anti-smoking laws passed in your area, visit The Americans for Non-Smokers’ Rights Website.

For information about tobacco control laws nationwide, see the website of the American Lung Association.

Category: Second Opinions

Last updated 09/9/10