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.

By positions I do not mean contortions in a physical sense, although in the gynecologic world the position regarding hormone therapy has created splits and pirouettes among physicians and their menopausal patients. But lo and behold a new position statement by the mavens of menopause, the North American Menopause Society (NAMS to you and me), has been issued and published in the journal “Menopause”. It is 15 pages long and includes a list of 173 references. I’ll spare you the details but try to rephrase the important parts of the article and its summary.

NAMS states that the decision to prescribe hormone therapy (HT) should be made based on a woman’s health, her symptoms, her preferences for quality of life as well as her personal risk factors. (Well, that has certainly not changed from what most of us told our patients in the past.)

They go on to state that once started, continuation is dependent on whether estrogen only or estrogen and a progestin are given. And severity of symptoms should be considered in any decision to terminate hormone therapy. In general they feel it’s “safe” ( the multiple authors use the term “a more favorable benefit-risk profile”) if estrogen therapy without a progestin (ET) is given for 7 years (and perhaps longer depending on the studies cited). But remember we can give estrogen without a progestin only if a woman has had a hysterectomy. If she has not had surgery with removal of her uterus a progestin should be given to prevent endometrial (uterine lining) cancer. In this later instance (i.e. no previous hysterectomy) duration of use of HT (estrogen plus a progestin) should probably be more limited due to the increased risk of breast cancer after 3 to 5 years.

The NAMS statement concluded the estrogen therapy is the most effective treatment of symptoms of vulvae and vaginal atrophy. They advise low-dose, vaginal local estrogen when the only symptom is vaginal atrophy (think dryness and pain with intercourse)…and then state that when this is the only form of estrogen used, there is no need for concomitant progestin.

Women with premature or early menopause who have no contraindications (clots, breast or endometrial cancer) can, and probably should, use HT at least until the median age of natural menopause (age 51). After that time, the same decisions should be made as for women going through natural menopause.

No increase in breast cancer risk was observed in the Women’s Health Initiative with use of estrogen in breast cancer survivors but… they pointed out that there is a lack of good data and one randomized control study found an increase in breast cancer recurrences. So they don’t recommend its use.

Finally they stated that both transdermal estrogen ( patches, creams and sprays) and low dose oral estrogen have been associated with lower risks of deep vein clots and stroke than that found with standard doses or oral estrogen, But they wouldn’t take the final step and commit to this, proclaiming that sufficient randomized studies to endorse this have not as yet been completed.

And finally the NAMS position ends with the statement that there is a “growing body of evidence that HT formulation, route of administration , and timing of therapy produce different results” In other words one size and one type does not fit all.

Starting hormone therapy, the type, route of administration, dose and duration of use remain important issues that all women going through menopause should discuss with their physicians. We now have more studies and guidelines to help you with these hormonal decisions.

Certain songs play over and over again in our minds…One that haunts me was written by Charles Fox and sung by Roberta Flack; “Killing Me Softly with His Song”. I was humming it while reading an article in the journal Menopause. (Please don’t laugh.) The article was a met- analysis  of studies that measured the mean difference in age of natural menopause between smokers and nonsmokers. Menopause occurred 1.12 years earlier in smokers than nonsmokers, and that difference was significant. Hence the heading for my article this week.

Menopause is defined as a permanent cessation of periods for 12 months. And if wis use this 12 month definition, the only way to date menopause is to do so retrospectively. Before our ovaries run out of the follicles that produce the estrogen and progesterone needed to instigate our periods, they “sputter”. The follicles that have not been used up during our teens through our mid forties are the rejects and they simply do not put out (hormonally) as they should. This period of approaching follicular extinction is termed the menopausal transition. On average it begins at age 47 and lasts 4 years. During this transition, even though periods may come and go, symptoms such as hot flashes, sleep disturbances, vaginal dryness and pain with intercourse can occur.

There are more than 3000 chemicals inhaled in cigarette smoke. Many of them are detrimental to the health and well being of the follicles and can contribute to their early demise. The concerns about early menopause do not solely relate to symptoms. Early menopause increases the risk of cardiovascular disease, venus thrombosis (clots) and osteoporosis. Overall it increases the risk of mortality by approximately 2% per year. And to add insult to smoke injury, the combination of earlier loss of estrogen and current smoking further increases a woman’s risk of cardiovascular disease and death!

For this and so many other reasons, quitting smoking is the best thing a smoker can do for her health. Now would putting a picture of ovaries with a big red X over them help to convince women to stop smoking? I’m not sure … But it can’t hurt to add this to all the other warnings.

I know some of you have heard about this on the news or read it in the New York Times, but I feel I would be remiss if I didn’t point out the article in the New England Medical Journal published the end of February. It was titled “Colonoscopic Polypectomy and Long-Term  Prevention of Colorectal-Cancer Deaths”. Just to remind, you colorectal cancer is the third leading cause of cancer deaths in women (after lung cancer and breast cancer). This cancer invariably starts as a type of glandular polyp termed an adenoma. If that “can-develop-into-a-cancer” polyp is removed, the malignancy can be stymied before it gets a chance to take hold (a rather non medical way of phrasing it, but gives us the right image.)  We know that detection of an early-stage cancer, usually by colonoscopy and subsequent surgery can decrease mortality. And it would make sense that removal of something precancerous would do the same. The gastro-intestinal docs are much more likely to find polyps than actual cancer in their routine colonoscopies. Evidence-based-medicine and the medical organizations and physicians who rely on this for recommendations and cost effective decisions would like to be sure that the removal of those polyps significantly prevents colon cancer deaths.

So here is that evidence from Sloan-Kettering Cancer Center, Mount Sinai Hospital in NY, centers in Boston, Minneapolis, Milwaukee, Valley Presbyterian Hospital in Van Nuys and my own Cedars-Sinai Medical Center in Los Angeles. The investigators (and don’t worry I won’t list all their names) followed 2602 patients who had adenomas removed during participation in the study for a median of 15.8 years. Of these patients, I am sad to report, 1246 died… but their deaths were from unrelated causes; only 12 died from colorectal cancer. The estimated expected deaths from colorectal cancer in that general population would have been 25.4. This means that polypectomy during colonoscopy reduced mortality from colorectal cancer by a huge 53%!

I ask every patient over the age of 50 if and when she had her colonoscopy. It remains the best method for the detection of and removal of adenomatous polyps or early cancer. If a suspicious polyp is removed she can’t just rest on her colonic laurels…she has to have follow-up colonoscopies at least three years later.

The current recommendation: If you are free of said polyps you don’t have to repeat a colonoscopy for 10 years provided that you do not have a family history of colon cancer or develop major changes in bowel habits or had previous bowel diseases. (Note, if a relative had colorectal cancer, you should begin colon screening 10 years before the advent of their cancer and if there are several family members with this type of cancer you should consult with your physician about genetic screening.)

Yes the prep for a colonoscopy is not pleasant, but the above shows that detection of precancerous polyps and their removal saves lives. Yuck should not be a synonym for regret.

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