We all know that Bacchus was a man. Based on gender stereotypes, most of us assume that women are less likely to excessively imbibe alcohol then men. (For the sake of transparency, the Superbowl was playing while I wrote this and all that celebrated testosterone caused me to make that last statement). But not necessarily so… According to a recent CDC report in “Vital Signs,” more than 14 million US women binge drink about three times a month and consume an average of six drinks per binge. This number includes one in eight women and one in five high school girls! The report states that binge drinking is most common in young women, women who are white or Hispanic, and among women with household incomes of $75,000 or more. Oh…and half of all high school girls who drink alcohol report binge drinking.

A woman’s ability to metabolize alcohol differs significantly from that of a man. When we drink alcohol it is absorbed more quickly, deactivated by enzymes less efficiently, and gets to the brain faster. (Well, we always knew that our brains have rapid and superior circulation. ) We generally weigh less than men so we are also less likely to dilute the stuff. As a result, one drink for a women has the impact of two for a man.

The definition of binge drinking for a woman is consumption of four or more alcohol drinks on an occasion. And an occasion is considered to be 2 to 3 hours. Although binge drinking in high school or college can lead to a higher incidence of alcoholism in later life, most binge drinkers are non-alcoholics and not alcohol dependent. The CDC reports that drinking too much (which of course includes binge drinking) results in about 23,000 deaths in women and girls each year and increases the chances of breast cancer, heart disease, sexually-transmitted diseases, unintended pregnancy as well as other health problems. If a woman binge drinks while pregnant, she risks exposing her baby to high levels of alcohol during its development which can lead to miscarriage, low birth weight, sudden infant death syndrome (SIDS), attention deficit/hyperactivity disorder (ADHD), and fetal alcohol syndrome (facial disfigurement and mental deficiencies). This is where I’m supposed to say it’s not safe to drink alcohol any time during pregnancy.

Aside from giving warnings, the CDC and its Guide to Community Preventive Services recommend certain strategies for preventing excessive alcohol consumption.. These include:  

*Increasing alcohol taxes.

*Reducing the number and concentration of stores that sell alcohol in a given area.

*Continuing government controls over alcohol sales.

*Maintaining or reducing the days and hours of alcohol sales.

*Enhanced enforcement of laws prohibiting sales to minors.

*Electronic screening and counseling for excessive alcohol use.

I know some of this sounds excessive and may go against our sense of what the government should and should not do. (There are no blue laws in California, and according to that wonderful series Boardwalk Empire, prohibition doesn’t work!) To help avoid teenage binging, the best plan might be to make sure that our teens can’t get into our liquor closet and of course, maintain zero tolerance for alcohol use before, during and after school parties. And then we should listen to the anti-binge advice ourselves. Remember abstaining from that second and certainly the third drink may lessen our risk for breast cancer, heart disease, stupid behavior, and worse yet, the wrong sexual and reproductive decisions. We just don’t need that extra glass of wine, cocktail or beer to enjoy the game, the dinner or the party. The salute ” Le Chaim” (translated, for those of you who need it) to “To Life” need not be accompanied by 4 drinks…one is healthier and should suffice.

A quick personal note: I am traveling to Mozambique next week with several women to see the school we built through the LA Associates of Save the Children. I will be happy to share pictures and stories upon my return.

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The CDC, most medical journals, and mainstream media have been covering the disastrous infections caused by the contamination of the steroid that was distributed by a compounding pharmacy in New England. Three potentially contaminated lots of this steroid were used by physicians in epidurals, and joint injections in over 14,000 persons. They have, so far, caused stroke, meningitis, bone infections and in some instances death, in over 137 patients.

The initial detection of this serious contamination reads like a detective story. On September 18, 2012 the Tennessee Department of Health was alerted by an observant physician that a patient had a confirmed fungal infection (to be exact, Aspergillus fumigatus) diagnosed 46 days after epidural steroid injection. By September 27, an investigation carried out by the Tennessee Department, in collaboration with the CDC and the North Carolina Department of Health, had identified 8 more cases. All nine patients had received epidural steroid injections with preservative free methyl prednisone acetate solution (MPA) compounded at the New England Compounding in Framingham, Massachusetts. And as of October 10 (when last reported in JAMA) a multistage investigation by the CDC together with local health departments and the FDA have identified 137 cases and 12 deaths associated with this outbreak in 10 states. The invoices from the pharmacy showed that approximately 17,500 vials of MPA were distributed to 75 facilities in 23 states!  By October 6, the vials not already used were recalled. And as of October 10, health departments reported that 90% of patients exposed to the medication from one of the suspected infected lots of MPA had been contacted at least once.

The patients and their doctors have been advised that they should get tested if they develop neurological symptoms such as headache, neck rigidity, fever, nausea, unsteady gait or sensitivity to light…and if so a lumbar puncture should be done to check for the fungal infection. Those patients that had joint injections should notify their physician if they develop increasing pain, redness or swelling, in which case fluid should be aspirated from the affected joint for culture. This all sounds ominous and in fact it is! Right now it’s postulated that the incubation periods for infection range from 4 to 42 days, but the maximum incubation for this infection is not known. Treatment with high dose anti-fungal therapy for months may be necessary.

If anyone doubts the importance of the epidemiological sleuthing carried out by our health departments and the CDC…this should dissuade them. And additionally, there is the issue as to whether products from compounding pharmacies are indeed safe. In an article published on December 6 in The New England Journal of Medicine, the authors summarized the evidence for compounding safety…. First, they explain what these pharmacies do: “Pharmaceutical compounding refers to the combining, mixing, or altering of ingredients of a drug by a licensed pharmacist to produce a drug that is tailored to an individual patient’s medical needs on the basis of a valid prescription from a licensed medical practitioner.” They go on to state that ” there are few reliable data on the prevalence of compounding, but it has been estimated that 0.25% to more than 2% of dispensed  prescriptions in the United States are compounded drugs. Under certain conditions, compounding may serve an important public health benefit by providing access to the needs of individual patients when a commercially available product is unavailable; however, compounded drugs are not approved by the FDA and should not be confused with generic drugs all of which must be approved by the FDA before marketing. Compounded drugs are not reviewed and approved by the FDA; therefore, their safety, efficacy, quality and conformance with federal manufacturing standards have not been established…. The regulatory authority of the FDA over compounding pharmacies is different and more limited than is its authority over pharmaceutical manufacturers.”

Bottom line: Thank you to the FDA and CDC. Even though regulations can be burdensome and costly they are worth it; they protect the purity and sterility of our medications. And if I do prescribe a compounded medication, I tell the patient and request that she fill the prescription in a closely monitored pharmacy.

It’s amazing to realize that it was just 10 years ago that the Women’s Health Initiative results were released with extraordinary media brouhaha, causing as many as 70% of women who were taking menopausal hormone therapy (usually Prempro) to cease and desist…and in many instances flush, flash and lose sleep. But with time, additional studies and empathy, the experts (members of the North American Medical Society, gynecology department heads at major universities, and editors of the American Society for Reproductive Medicine and The Endocrine Society to name just some) now agree on key points regarding the safety and efficacy of hormone therapy in menopause. And since the following is generally what I tell my patients, I am delighted to recap the recommendations just published in several of the major journals.

In a overview, they agree that systemic therapy is an “acceptable” option for relatively young (up to 59 or within 10 years of menopause) and healthy women who are troubled by moderate to severe menopausal symptoms. There is no one therapy fits all, and consideration should be given to a woman’s quality- of- life priorities as well as her risk factors such as age, time since menopause risk of blood clots, heart disease, and stroke and breast cancer. Their consensus then deals with individual issues

Hormone Therapy Risks

Vascular risks Although both estrogen and estrogen with progestogen increase the chance of clots (deep vein thrombosis and pulmonary embolism as well as certain types of strokes) the risk is rare in the 50- to 59- year old age group. Moreover, observational studies have found that transdermal estrogen therapy ( with patches, creams, and sprays) and lowdose oral estrogen therapy have been associated with lower risks of these type of clot caused events.
Breast cancer
An increased risk of breast cancer is seen within 5 years or more of continuous estrogen and progestogen therapy. The risk is not great and risk declines after hormone therapy is discontinued. There is even less risk for women who have had a hysterectomy and don’t need to add progestogen to their estrogen therapy. Use of estrogen alone for a mean of 7 years does not seem to increase risk of breast cancer.
Duration of therapy

This is where everyone sites the same sentence: ” The lowest dose of therapy shouldbe used for the shortest anoint of time to manage menopausal symptoms.” they thenadd that duration should be individualized. I add that if more or longer therapy is neededto achieve quality of life, the patient and her physician should discuss this laststatement. And estrogen therapy alone, allows more flexibility in duration. There arereports of increased risk after 10 or 15 years of use in large observational studies.
Additional information

Evidence is lacking that custom compounded bio identical hormone therapy is safe oreffective. Many medical organizations and societies agree in recommending againsttheir use, particularly given concerns regarding content, purity and labeling. Finally thereis a lack of safety data supporting the use of estrogen or estrogen and progestogentherapy in women who have had breast cancer.

Conclusion

Leading medical societies devoted to the care of menopausal women agree that the decision to initiate hormone therapy should be for the indication of menopause-related symptoms.

Bottom line: there is no question that hormone therapy plays an important role in
managing the symptoms so many women experience during menopause. As usual, we
all recommend that therapy be individualized. So talk to your doctor!

Our new address is:

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I sometimes think that half of the ads I see on TV (when I don’t rush through them with TIVO) show individuals clutching their chest after eating their favorite food or, more visually, chest cavity flames, which are subsequently doused with the right over-the-counter medicine or prescription drug. Having suffered from gastrointestinal reflux disease (GERD) and that sense of heartburn for many years, I am sympathetic. Most of the medications prescribed by physicians (often after suggesting an upper endoscopy to ensure that there are no ulcers or a precancerous condition called Barrett’s esophagitis) are Proton Pump Inhibitors (PPI’s). These reduce the production of acid in the wall of the stomach and assist in the healing of ulcers as well as treat GERD. These medicationss include omeprazole (Prilosec) (Zegerid), lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium), (Zegarid) and dexlansoprazole (Dexilant). Some are by prescription; others are available as generics or even over-the- counter.
 
In the March 14 issue of JAMA, a recent announcement was made by the FDA; that reflux drugs were found to be linked to C difficile-related diarrhea.
 
Clostridium difficile is a bacteria that causes watery diarrhea, abdominal pain and fever, which when it does not resolve, may cause serious intestinal problems and even the need for resection of a portion of the colon. In some cases (rarely, thankfully), the infection can be fatal. C difficile has become more and more common in hospitals, nursing homes and in the general community. It often occurs after the normal flora of the intestine is wiped out by antibiotic therapy. (Even a short course of certain broad spectrum antibiotics can cause this, one of the reasons for our growing reluctance to use antibiotics unless they are absolutely required.) C difficile occurs more frequently in older adults. If a person has had an episode of C. difficile, she is more likely to experience it again, especially with antibiotic treatment. 
 
The FDA reviewed data from 28 observational studies, 23 of which found that PPI users had an elevated risk of C difficile associated diarrhea compared with those who didn’t use these medications. Their risk was 1.4 to 2.75 times greater. As a result of their review, the FDA has officially stated that “the weight of evidence suggests a positive association between the use of PPI’s and C difficile infection and disease”. The labels of these drugs will be updated to reflect this risk.
 
What this means is that if indeed you need a PPI medication, you should use the lowest dose for the shortest duration necessary. And if you do develop diarrhea that doesn’t go away while taking that PPI, see you doctor.

I thought I would start the New Year with a somewhat positive article that came out in the journal published by the North American Menopause Society. The journals’ name is appropriately, “Menopause”. Its cover is bright red…  I am not sure if this is meant to make it stand out or if the color represents hot flashes! I read the journal while trying to catch up on relevant articles during the holidays…these and my recent copies of the New Yorker have kept me mentally occupied. (I know that reading medical literature sounds boring, but actually I like it!)

So here is what caught my eye, and take a deep breath before reading the title; “Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization”.

This was a study of 80,955 postmenopausal women who were 60 years old or older and had filled hormone therapy (HT) prescriptions at least once between January 2002 and June 2002. They were then followed through December 2008. (It takes years to gather the statistics, so most large studies will have concluded a few years before all of the results are actually published.)  The data on whether the women used HT, for how long,  and whether any antiosteoporotic medication was used, as well as the occurrence of hip fractures were collected from an electronic medical record system. The women in the study population were followed through Kaiser Permanente Southern California, which included 11 Southern California medical centers. (Yes they are huge!)  Bone mineral density was assessed with a DEXA scan in 54,209 women at least once  during the study period.

The results demonstrated that  during the 6.5 years of follow-up   (and after accounting for age, race and other medications), the women who discontinued HT were at a 55% greater risk of hip fracture than the women who continued to use HT.  The use of hormone therapy helped prevent fracture as long as it was used. But, within 2 years of stopping HT, hip fracture increased and the risk of fracture rose incrementally the longer the women discontinued this therapy. Every year that the women stopped HT was associated with a lower BMD (The T score which compare BMD to a 30 year old decreased on average – 0.13 a year.)

The authors concluded that “the public health message to women and physicians is that discontinuation of HT is associated with increased hip fracture risk and lower BMD compared to women who continue to take HT.”

There are many reasons to consider hormone therapy at the onset of menopause. For most women it is prescribed to help them deal with severe hot flashes, night sweats, sleep problems, mood changes and for some a feeling of “walking around in a fog”. There are also reasons to consider stopping after several years…. these include risk of breast cancer as well as a potential decrease in cardiovascular benefits.  The pros and cons of continuing HT for decreased risk of bone fracture should now also be considered. Who said this was easy! But it’s a subject that reaches epidemic proportions as approximately 1 million women enter the menopause each year in the United States.

In the year to come I’ll try to keep you up-to-date on the most recent published articles and studies on this and many other topics.

Have a healthy 2012!

The saying that politics makes for strange bedfellows took on a new low when Michelle Bachman came out with her ridiculous statement against HPV vaccination. (In case you didn’t get the pun…HPV infection is most frequently transferred in a bed … or for that matter in any place that allows for sexual contact.)  So I’ll skip the part where we ask why a responsible parent would not want to help diminish the chance that her daughter would get cervical cancer or genital warts. (Yes, their may be parents out there who think that their daughter will not be sexually active with anyone but the man she marries, but what guarantees do they have that the young man she commits to did not have partners before or after he proposed to and married her.) Long-term large studies have shown negligible side effects from HPV vaccination. Sudden “mental retardation” which of course is a truly nonmedical and impolitic term, cannot suddenly occur from a vaccine given to an adolescent girl! (I have given hundreds of shots in my office and at most have seen a few “ouches” at the site of injection.) Okay, I have to stop now and become scientific. Here are the facts I promised in the heading of this week’s newsletter:

There are more than 40 types of human papilloma viruses or HPV’s that infect the general tract; approximately 15 types have been linked with cancers and are classified as carcinogenic or high risk. We now know (or at least the scientists who do the testing know) that 99.7%of cervical cancer specimens, as well as their precancerous predecessors, test positive for at least one of these high risk HPV’s. (Just in case you want to complete your viral numerical knowledge…they are HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 72.) The most common onset of infection occurs in the first years of sexually activity. Thankfully most of the infections in young women and men resolve within 2 years. In a small proportion of women however, HPV infection persists. If this happens, the virus may enter the DNA of cervical cells and cause mutations, which over time can result in precancerous lesions that progress to cancer.  HPV viral infections are extremely contagious. (Put bluntly, a touch of a penis harboring the virus will pass it on.) And there are usually no lesions that signify viral presence. It’s a “down there” scenario akin to that portrayed in the movie Contagion; but with HPV, the consequences of the viral infection occur years later. If a woman has sex with someone, she essentially has a viral contact with everyone he or she has had sex with and everyone those individuals have had sex with… etc., etc.

So it’s not surprising that at least 80% of women will, at some time in their lives, have an HPV infection…most commonly when they are young or when they are exposed to the virus through new or non monogamous partners. In most young women, the virus will clear. In the few in whom infection persists, it takes at least 2 to 3 years for potential progression to a precancerous lesion and more time until it can cause cancer. So adolescents and young adults have a very low risk of developing cervical cancer.

Obviously many young women will initially harbor one of the HPV viruses and as a result may also have some mild changes in a Pap smear screening. If these changes are found and pronounced abnormal, they (and their moms) will go through a lot of unnecessary anxiety over something that usually clears up… and even worse they may go through unwarranted surgical procedures that can scar the cervix and impact their future ability to conceive or have a normal vaginal delivery.

To help avoid unwarranted concern and cut down on unnecessary procedures, the American College of Obstetricians and Gynecologists (ACOG) has released guidelines that should make us all relax with regards to screening. They state that Pap smears should begin no earlier than age 21. And from 21 to 29 women should be screened every 2 years. (But this does not negate the need for annual pelvic exams and, if necessary Chlamydia and other STD testing should be done more frequently.) It’s recommended that by age 30 all women should undergo screening with HPV testing as well as a Pap smear. If both tests are negative and the woman has no new partners, she can then be tested every 3 years. (But again a yearly pelvis exam should be done, and if a woman has a new partner or if she is not sure of the monogamy of her current partner, testing should be more frequent.) All women in high-risk groups (women with HIV, those on immunosuppressive medications, women exposed to DES in utero and women who test positive for high risk HPV or who have been treated for cervical precancerous or cancer) should be screened frequently.

The current vaccines protect against 2 types of high-risk HPV infections that cause 70% of cervical cancers. These vaccines will not cure or get rid of HPV infections that are already present. Hence the best way to help prevent cervical cancer is to vaccinate young women (and ideally young men) before sexual activity occurs. In medical parlance this is when the young person is “sexually naïve”. Because other high-risk HPV’s, which are not covered by the vaccines, can still cause 30% of cervical cancers,  young women who receive the vaccine will still need to begin cervical cancer screening when they reach the age of 21. But when administered at the right time the vaccine will insure that the majority of cervical cancers won’t occur. What’s political about that!

This calls for a 101 on ovarian function: During our reproductive lives, the ovaries provide us with our essential female hormones… estrogen and progesterone which are taken up by receptors in every cell in our body. These hormones are produced through the development of primordial eggs or oocytes within the ovaries. The ovary of the female fetus is endowed with a huge number of oocytes… 6 to 7 million to be sort of exact. But by the time we are born, that number dwindles to “just” 1 million. And by the time we hit puberty, we have a paltry 400,000. Then during our reproductive years, thousands die each month (this is termed “atresia”) while one oocyte becomes a follicle that has the potential for ovulation. This dominant follicle develops for 2 weeks, producing more and more estrogen; it then extrudes an egg that can be fertilized.

Subsequent to ovulation the follicle, now bereft of its egg, is called a corpus luteum. It produces, in addition to estrogen, progesterone and together they create a lush environment in the uterinelining for potential implantation of a fertilized egg (now called a blastocyst).

At what point does all this change? Do regular cycles mean that pregnancy will occur at the “touch” of a sperm (or thousands of them)? It turns out that reproductive menopause can occur years or even a decade before hormonal menopause. There is a national trend to delay childbearing. In my practice in LA, I practically never see women under 35 who are ready to conceive. A common question posed by my patients is “How long can I wait?” or “Is it too late?” So I thought it would be appropriate to share some of the information that was recently published in the “Postgraduate Obstetrics and Gynecology” publication that is sent to me and my colleagues biweekly for continuing education.

A woman’s fertility is definitely dependent on her age. The incidence of infertility in women 20 to 24 years old is 7%; this increases to 15% between ages 30 and 34 and then to 29% in women aged 40 to 44 years.  Not only does the quantity of oocytes dwindle, but so does their quality. The rate of spontaneous miscarriage is 10% before the age of 30; it almost doubles to 18% between ages of 35 and 39 years and then rises to 54% in those older than 45. It’s not the age of the uterus that counts, but that of the eggs. If donor eggs of younger women are used, the pregnancy and miscarriage rates are the same in women younger and older than 40.

IVF success with a woman’s own eggs is dependent on the age of her eggs. (This obviously means her own age, no matter how young she looks!) According to the Society for Assisted Reproductive Technology, women between the ages of 35 and 37 have a 37.3% live birth rate, women between 38 and 40 a 28.2% live birth rate and women between 41 and 42 a 16.7% live birth rate with their own eggs.

There are several ways to assess ovarian reserve and get some reassurance as to whether the oocytes are good enough for a successful pregnancy. (By success we mean a live birth, not whether the child can get into an Ivy League school.) Simply having regular periods is not sufficient evidence.

The first test that most doctors will run is a follicular stimulation hormone (FSH) blood test. FSH is the messenger hormone produced by the pituitary. It “commands” the ovaries’ oocytes to begin the steps towards ovulation. If the estrogen level is low (which is what happens with the onset of the period), the FSH revs up and oocytes’ development takes off. Once a dominant follicle develops and it produces its estrogen, the FSH level goes down (negative feedback). If there are not enough oocytes to pass “go” and the ovary’s reserves are low, the FSH continues to be secreted in a desperate attempt to get those oocytes to do their thing. High levels of FSH in the beginning of the cycle (we usually check around day 2 or 3 after the menstrual cycle has begun) indicate poor ovarian response. And FSH will stay up permanently once the ovaries have run out of oocytes, i.e. throughout menopause. In general, the FSH level should be between 4 and 10 mIU/mL during the early part of an “ovulatory” menstrual cycle. Levels higher than 10 to 15 are considered borderline and those higher than 16 mIU/mL are considered abnormally elevated, indicating poor reserves and predicting diminished success with fertility treatment.

There are other endocrine markers that may show low ovarian reserves. One is called antimullerian hormone or AMH. It is produced by ovarian cells from 36 weeks of gestation until menopause. With menopause it decreases to undetectable levels. AMH is not affected by pregnancy or birth control pills and may be the first ovarian reserve marker that declines. Another endocrine test that can predict potential fertility issues with age is a blood test for inhibin B, a growth factor in the ovary. It rises in the beginning of the cycle and then goes down during the second half. Low levels in the early cycle indicate diminished ovarian reserve.

Finally, ultrasound may help predict the ovaries’ reserve. The number of small “ready to go” follicles can be counted and if there are 10 or less that are seen in a scan, ovarian reserve may be compromised.

If you or a family member question whether you can wait or if it’s too late to try to conceive with your own eggs (especially if you are considering expensive and potentially invasive fertility procedures); screening for ovarian reserve should be done. The easiest test is an FSH level on day 2 of your cycle. It can be done in conjunction with these other tests, but it probably remains the simplest and least expensive method of reserve determination. The question, “How many eggs are left?”, is valid for all women who want to postpone pregnancy.

So a patient comes in to my office (sorry if this sounds like the beginning of one of those bar jokes) and as part of my due diligence I update her chart with her current medications. Upon enquiring as to what she is now taking, I may be given a container of various pills with the statement “I take these once a day”. Or I might get a description of the medication “I now take the pink pills that lower cholesterol; I’m not sure of the name…it’s a small dose; it used to be yellow”. Yes, this sounds ridiculously ambiguous but it’s not her fault. The names, colors and shapes of medications are no longer stable. (And this has nothing to do with their expiration date.) At least 70% of U.S. prescriptions are generic. The good news is that they are a lot less expensive than brand prescription drugs and indeed make up less than 20% of current prescription drug costs in the U.S..

An article about our lack of pill recognition titled “Why Do the Same Drugs Look Different? Pills, Trade Dress, and Public Health” was recently published in The New England Medical Journal. I thought I would share it with you in this week’s newsletter.

The clinical effects of brand and generic medications are supposed to be the same (or according to the authors “interchangeable”) but they often look very different. Whereas a brand medication will always appear identical with each refill, generic medications can vary in size, color and shape depending on the manufacturer supplying the pharmacy. (Need I say the cheapest brands will most likely be the ones that are supplied?) They all have to be approved by the FDA, so cheaper does not mean that quality or concentration of the medication has been compromised. An example that was given in the article (along with pictures) is fluoxetine (brand name Prozac). There are at least 10 generic versions that are pharmacologically equivalent to the original drug yet they vary in their color patterns.

No, this was not done on purpose to confuse the consumer or test the memory of her physician. It turns out that color and shape-shift has its basis in U.S. intellectual-property law. Drug manufacturers have had exclusive ownership of the physical aspects of their products, including their size, shape, color, texture, aroma and flavor. These properties are considered private property under a subset of trade law called “trade dress”.  (I immediately associated this title with words like designer, exclusive and whatever other branding adjectives makes “not-off-the-rack” fashion so unique.) To be fair…. the companies that do research and development of drugs should be compensated for the tremendous costs they assume. Often millions of dollars are spent on trials that have to be abandoned, because the medications that undergo testing are not significantly effective or are found to cause serious side effects in humans.  Without pharmaceutical company development of new drugs that meet the standards that are required for FDA approval, many diseases and conditions would remain untreated and we would all suffer. (Lack of special designer clothes would obviously not have the same effect!)

There were several reasons that pharmaceutical companies were granted broad based legal protections in the mid-20th century.  There was a valid concern that counterfeit drugs would be “palmed -off” to unsuspecting patients (and even their pharmacies) if they had the same appearance and packaging as brand-name drugs. At some point, the Third Circuit Court of Appeals upheld trade-dress protection because near-identical pills would facilitate the practice of “unscrupulous pharmacists” in “substituting less expensive generic drugs for the brand name drugs prescribed without informing their customers and without passing along the benefit of the lower price.” The courts also felt that allowing trade-dress protection served a public health function by preventing the substitution of one drug that was similar but not identical to another.

The 1997 FDA guidelines for expanding direct -to -consumer advertising of prescription drugs also made the images of pills more important to the drug companies. An example is sildenafil (you know it as Viagra, that diamond shaped light blue pill.) We all know about that “little blue pill”…it has become a stand up cultural phenomenon.

But now, that legal protection has begun to unravel. In 2003, there was a legal dispute about Adderall, a medication prescribed for children with attention deficit-hyperactivity disorder. The company that first produced it in 1996 stated that the color, shape and size of various doses helped children adhere to their prescribed regimens. When a generic company (Barr) tried to copy these color schemes the court agreed to let them; after all the original company (Shire) had claimed the importance of the color trade dress.  In the tradition of “if you can’t beat them join them” over the last 5 years, brand-name pharmaceutical companies have begun to license their trade dress to the manufacturers of authorized generics. And (for a price), some generics look the same as the name brand.

The suggestion offered by the authors of the article in NEJM seems to be truly appropriate: “Instituting a more consistent and organized system of pill appearance would increase patient adherence, reduce the complexity of medical regimens, reduce medication error, and encourage the rational use of bioequivalent generic drugs.”  I would also suggest that you bring in your bottle of current drugs so that your doctor or nurse can check the name, dosage and directions for use. None of us should rely on color, shape, aroma or flavor to identify a medication… No matter what it now looks like, it should be taken as directed.

I’ve written several newsletters about potential side effects of bisphosphonates medications used to treat osteopenia and osteoporosis (Fosomax, Boniva, and Actonel….just to remind you of some brand names). This time I want to share some potentially good news about this bone density enhancing class of medications. And I am especially happy to share the report because it comes from a study conducted in Israel. (As many of you know, I have taught and worked there and indeed will be in Tel Aviv when this article appears.)

The Israeli researchers conducted a study entitled The Molecular Epidemiology of Colorectal Cancer. It was supported by the National Cancer Institute and published in the February issue of the American Journal of Clinical Oncology. (I hope I haven’t lost most of my readers by this point…just bear with me. So many of you or your relatives take bisphosphonates so that your skeletons can successfully bear your weight without an osteoporetic fracture)

They found that postmenopausal women who had taken an oral bisphosphonates longer than one year had a 59% reduced risk of colorectal cancer. Like the Scandinavian countries, pharmaceutical records in Israel are extremely well documented. (All the citizens have health insurance and most of their prescription medications are covered…I wish I could say the same for us!) The researchers used computerized pharmacy records and identified almost 2000 women who had colorectal cancer.

They found that in these women, compared to controls who were matched for age, weight, and religion, the use of bisphosphonates longer than 1 year, but not less than 1 year, reduced the risk of colorectal cancer by half, even when they adjusted for other factors that could perhaps lower colorectal cancer risk. (Here is where I list these factors to remind you that they too count in our “war on colorectal cancer”…as does screening. They include vegetable consumption, physical activity, and weight control, use of low-dose aspirin, statins, vitamin D and postmenopausal hormones.)

Ongoing research indicates that oral bisphosphonates may exert a cancer-protective effect (including breast and prostate cancer.)  Clearly this study is not large enough to persuade the FDA to approve any official indication that this class of medication will diminish colorectal cancer. So I’ll end with the phrase that is used in the conclusions of most medical articles: “Further studies are needed”. I felt , however, that a bit of good news about the medications that can lower the huge toll of osteoporotic fractures in women (and men) is welcome.

Several months ago, I wrote about the shingles shot and recommended (or at least the article I cited did) that just about everyone receive it at or after the age of 60. Quite a few of my patients called and told me they had followed up and were vaccinated. Others who were not yet 60 questioned why they should wait. The new news is that the FDA just lowered the age range for the shingles vaccine.

In this week’s JAMA, it was reported that the US Food and Drug Administration (FDA) announced its approval of expanding the age range for the vaccine (marketed as Zostavax) to adults aged 50 to 59 as well as those aged 60 years and older. The Center for Biologics Evaluation and Research (I won’t even bother to give an acronym for that one) stated “The availability of Zostavaz to a younger age group provides an additional opportunity to prevent this often painful and debilitating disease.”

A quick shingles review: (I discussed it fully in a previous newsletter titled “Out, Out, Damn Pox!” posted January 2011.) Shingles is caused by the varicella zoster virus, a herpes virus which triggers chicken pox. (Sorry, I seem to be fixated on herpes viruses lately….I promise to become non-viral next week.) After a bout of chicken pox (which we can assume we have had if we are now 50 or older), the virus remains dormant in certain nerve cells. Then one day, decades later, perhaps due to a combination of factors including age and a weakened immune system, the virus awakens (obviously without need of a sleeping beauty kiss), “climbs up” the nerve root to the skin where it erupts as a cluster of blisters that appear on the part of the body that is enervated but the inflamed nerve. The result is pain that can be excruciating. Though the lesions eventually heal, the pain can remain for months and in some cases, years.

The CDC based its expanded approval on a study carried out in 4 countries on 22,000 participants aged 50 to 59. Half received the vaccine and half received a placebo. After just a year of follow-up, the vaccine reduced the risk of developing shingles by 70% compared with placebo. In the US about 200,000 adults between 50 and 59 develop shingles annually; hence the use of this vaccine could have a significant impact for these not-so-young-any-more baby boomers.

Merck manufactures the vaccine. It’s not cheap. The cost is in the range of $200. You can check with your insurance to see if it’s covered. Many drug stores have it on supply and (like the flu shot) will have a nurse administer it. You can also get it through your physician’s office; just call to make sure it’s in stock.

Bottom line: If you or a family member (or someone you care about) is over 50, a one time (and timely) shingles vaccine is advisable.