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!

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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.

As you know when you come for your annual gynecologic visit, the receptionist requests that you update your information, sign a confidentiality form, and she checks on your insurance. The nurse then hands you a small plastic cup and asks you to give a urine sample. So there you are in a cramped bathroom trying to aim the stream into what now seems like an impossibly narrow container and thinking: (a) this is humiliating, (b) why is this necessary, I have no problems with my bladder? and possibly (c) I can’t go, so what am I supposed to do now?

A new article in the Journal Obstetrics and Gynecology aptly titled “In the Trenches” emphasizes the importance of checking your urine.

An immediate urine test can be performed with a “dipstick”, a strip of paper that is specially treated to check for white cells (often present if there is an infection) red blood cells or RBC’s (and the rest of this newsletter will deal with this… if blood is present in the urine, the medical term is hematuria), protein (if elevated, a sign of kidney or even systemic disease), glucose (present in urine if blood levels are high), ketones (elevated with kidney problems or dehydration), bilirubin (elevated in liver disease) and pH (acidity).

The journal article dealt specifically with microscopic hematuria in women. “Microscopic” simply means that there is blood (or red blood cells) in urine but the urine doesn’t look bloody to the naked eye or toilet paper…(I realize this is getting a bit gross!) According to the American Urological Association, “significant microscopic hematuria” means there are three or more red blood cells (RBC’s) per high power field (magnified 40 times) on microscopic examination from two to three properly collected urinalysis specimens. To get a proper sample, the first drops of urine should not be included, just the midstream…all the more difficult to get into that cup. If you have your period, recently exercised vigorously, just had sex or vaginal trauma, obviously blood cells in the urine will not count and the test should be repeated another time.

Once a dip stick test is positive for RBC’s …I (or any doctor) will probably send the urine out for a complete urinalysis. The urine is spun down and the sediment is examined for the number of RBC’s, white cells, and/or bacteria. Often we also do a urine culture to rule out infection. (Most women, however, do know when they have a bladder infection…. they have urinary urgency, frequency and burning.)

So why is it so important to detect microscopic hematuria? Before I relate the possible causes and consequences listed in the journal article, I’ll tell the tale of a patient that I saw a few weeks ago. She was menopausal, had no signs of vaginal bleeding or urinary problems, but a routine urine dipstick test was positive for RBC’s. Her urine was sent out for culture (it was negative) and complete urinalysis. The latter confirmed the presence of a significant amount of RBC’s.. I asked her to repeat the test 2 weeks later and once more it showed RBC’s. I then referred her to a urologic specialist for a complete workup.. This ultimately consisted of cystoscopy and a CT scan of her pelvis and kidneys. She was found to have bladder cancer. It was resectable and curable.. This simple urine test probably saved her life.

The two most frequent causes of microscopic hematuria in non-pregnant women (46% of women do have hematuria during their pregnancy) are cystitis (bladder infection) and kidney stones. Additionally, some women seem to shed RBC’s in their urine without any pathology. But the cause that should be ruled out, especially in women over 40, is cancer. Bladder cancer is the 17th most common cancer in women worldwide. In the United States in 2008 there were 17,770 new cases of bladder cancer diagnosed and 4,270 deaths …that means that there were more deaths annually from bladder cancer in women than from cervical cancer! (A personal aside…. many years ago my paternal grandmother died from bladder cancer.)

The risk factors for urologic cancers in women include age over 40, smoking, a history of exposure to chemicals or dyes, a history of gross hematuria (the “gross” here is a medical term and means that urinary blood is visible), analgesic abuse and a history of pelvic radiation. And here is a fact that seems to appear whenever we discuss most cancers: up to 35% of female bladder cancer cases may be attributable to cigarette smoking!

The recommendations put forth in the article state that a complete work up of microscopic hematuria should include an evaluation of the lower urinary tract (the bladder) and upper urinary tract (the ureters and kidneys) in any “high-risk” patient. Once more, you are at risk if you are over 40, have smoked, have had chemical exposure (hair stylists), have a family history of bladder cancer (I guess that’s me) and/or recurrent urologic disease. The work up should include cystoscopy, x-rays with dye and CT scans.

We all know about the need for Pap smears. It turns out that a urine test is just as important. So please don’t bewail that request to pee in a cup.

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.

Let’s discuss several hormonal scenarios: (1) You’ve been on hormones for several years and now think you may try to stop. (2) You have just started having hot flashes and you haven’t quite made up your mind as to whether you will want to take hormones during the menopausal transition. (3) You are not yet menopausal but worry about what you will experience when it inevitably develops.

The defining question for most women (at least in regards to quality of daily life) is: “How long will I experience hot flashes?” One would think that since menopause has been around before and since the written word that we could estimate the average duration of this pesky and sweaty symptom. (Well maybe not, 120 years ago the average life expectancy for women was 47 and most did not outlive their ovaries.)

Hot flashes generally begin when estrogen levels plummet in menopausal or during the premenopausal transitions. The ovaries run out of follicles that are capable of responding to pituitary messages to develop and hence produce estrogen. In the absence of said estrogen, the pituitary works harder (it’s trying to get those damn follicles to work), hence it puts out more and more FSH (follicle stimulating hormone). The pituitary gets its signals from the part of the brain called the hypothalamus which produces GnRH or gonadotropic releasing hormone, the master hormone that instigates FSH production. In the absence of “usual” estrogen production, GnRH and FSH levels soar and there is a veritable hypothalamic storm. This then causes a state of confusion in the central thermostat in the brain which begins to “think” that the body’s core temperature is too hot. In order to correct this, the hypothalamus sends out directives to dilate the small blood vessels in the skin (the flush) and causes water to evaporate from the skin’s surface (as sweat, facial and body perspiration) in order to cool the body down. All of this may lower the core body temperature by as much as half a degree. Often subsequent to a hot flash, a woman may shiver as small muscles contract to re-elevate the core body temperature.

Hot flashes are associated with poor sleep, decreased quality of life, may worsen depressive symptoms and even signal the onset of a major depressive disorder. The flashes may also be a clinical sign for underlying cardio vascular disease as well as a risk factor for poor bone heath. Although “natural”, hot flashes are not great to experience and ultimately may correlate with poor overall health.
What we do know is that the peak incidence of hot flashes occurs approximately 1 year after menopause in 80% of women in the US, but (and this is what is so surprising) the overall duration of hot flushes is unclear.

(Sorry that this intro is so long, but now I’ll get to a recent attempt to answer the “how long will this last” question…) A study published in the May issue of Obstetrics and Gynecology tried to assess the duration of menopausal hot flashes and associated risk factors.

The “flushing and flashing” women that were followed were part of The Penn (Pennsylvania) Ovarian Aging Study of 435 women (half white and half African American) that were monitored for 13 years. Hot flushes (they use this term instead of “flash”) were evaluated at 9 -month and 12-month intervals though in-person interviews. At enrollment, the participants’ ages were 35 to 47 (mean age 42.2) and 91% were still premenopausal. The most common age at onset of moderate-to-severe hot flushes was 45-49(35%); 30% were between 40-44years, 21% were older than age 50and 14% were younger than 40 years. Age at the onset was inversely associated with duration of hot flashes. In other words, the younger the women were, the longer they suffered. This totaled 11.57 years for those whose onset of hot flushes occurred before the age of 40; and decreased with onset at older ages: 11.25 years for those whose flushes started at 40 to 44 years; 8.1 years with onset ages 45-59 and 3.8 years duration with onset at 50 years of age or older.

Other independent predictors of the duration of the flushes were race (African Americans had a longer duration) and body mass (thin women also had a longer duration.) It’s thought that obese women convert hormones produced by their adrenals to estrogen-like hormones in their abundant fat and hence have production of estrogen that “saves them” from many years of flushes. It’s interesting that in this study smoking, alcohol use and number of children the women bore had no association with the duration of their hot flushes. (Although in general, the data has shown that smokers enter the menopause at an earlier age than non smokers, simply because the toxins in cigarettes kill off the follicles in the ovaries….my comment in this article against smoking!).

In the discussion portion of the article, the author’s state that “the median duration of moderate-to-severe hot flushes was 10.2 years, well beyond the duration considered in clinical guidelines. When women who reported mild hot flushes were included, the median duration increased to 11.6 years.”

Before all you women who begin to have menopausal symptoms in your early 50′s freak that these will continue unabated into your 60′s, I have to point out that the majority of the women in this study were younger than 50 when they reported moderate-to-sever hot flushes. (Most were 45 to 49.) Hot flush duration was approximately 8 years for this group compared to less than 4 years when onset occurred at ages 50 years or older.

Bottom line: The earlier you begin to have hot flashes (even if you are still getting your period) the longer you can expect them to continue during menopause. Now that you have this information, discuss therapies with your doctor.

In addition to my usual Friday website article, I felt it was necessary to address the recent JAMA article on estrogen-only therapy (in women who have had a hysterectomy.) The women were followed and results have just been published years after the Women’s Health Initiative (WHI) was stopped. The American Menopause Society (NAMS) said it best and hence I am simply forwarding the message that appeared on their website in response to this article. Once more, their conclusions reinforce the fact that estrogen (without a progestin) did not increase, but actually decreased breast cancer, in follow-up of over 10 years. Premarin (CEE) therapy was found to be beneficial vis a vis heart disease, colorectal cancer and overall, all-cause mortality for women under the age of 70 but appeared to lose its benefits and indeed worsen mortality rates after the age of 70. So here is the data and the NAMS conclusion:

Brief summary of the article: The final results of the Women’s Health Initiative Estrogen-Alone Trial, reflecting a median of 6 years of treatment and an average of 10.7 years of follow-up, are published in this article. The long-term follow-up and post-stopping findings for this trial have not been previously reported. The authors examined health outcomes in 10,739 women with prior hysterectomy, comparing those randomized to receive CEE treatment versus placebo. The median duration of adherence (taking >80% of study pills) to CEE was 3.5 years.

The main outcomes were CHD and invasive breast cancer. In addition, a global index of risks and benefits included CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, hip fracture, and death.

Results: For the overall study population, there was a significantly reduced risk of invasive breast cancer among women randomized to CEE versus placebo over the 10.7 years of follow-up (23% reduction; HR 0.77; 95% CI, 0.62-0.95). Risk reductions were similar in the treatment and post-stopping periods. In the overall study population, there was no significant effect of CEE on CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. However, younger women (ages 50-59 at enrollment) tended to have much more favorable outcomes on CEE than the older women for CHD, heart attack, colorectal cancer, all-cause mortality, and the global index. For heart disease endpoints, risks were 40% to 50% lower with CEE than placebo in women ages 50 to 59 but were higher with CEE than placebo in women ages 70 to 79. For example, for every 10,000 women per year taking CEE, there were 12 fewer heart attacks, 13 fewer deaths, and 18 fewer adverse events for women ages 50 to 59. In contrast, for every 10,000 women per year ages 70 to 79, there were 16 extra heart attacks, 19 extra deaths, and 48 extra adverse events for women taking CEE (P values for interaction by age were statistically significant).

Conclusions: In this randomized trial, conjugated equine estrogens (CEE) use was associated with a decreased risk of invasive breast cancer and much more favorable results for coronary heart disease (CHD), all-cause mortality, and several other outcomes in younger than in older women. Overall, the observed pattern provides more support for the “timing hypothesis.” The findings highlight the differences between estrogen alone and estrogen plus progestin in terms of breast cancer risk and other chronic disease outcomes, as well as important differences by age group. Whether the reduction in breast cancer risk with CEE alone will apply to all women at menopause and to estradiol or other formulations of estrogen, and whether it will persist with longer-term estrogen use, remains unknown.

I’m writing this newsletter while on a flight to New York for a Save the Children board meeting. (And I just had a glass of wine, which seems more potent at 39,000 feet!) So I am tempted (and will indeed succumb) to announce a new initiative by the LA Associates of Save the Children. Two other board members from LA and I have organized a group of women and their daughters in an effort to raise money to build several schools in Africa. The first of these schools will provide primary education in a rural area in Mozambique. A school for over 300 students ages 5 to 13 equipped with desks, books and trained teachers can be built for $140,000. (Not that much considering the $230 million it took to build a high school in LA.) There have been some amazing studies published in the medical journal Lancet that demonstrate the fact that if girls in the developing world are given a primary education, the subsequent child mortality decreases by 50%! That global number currently stands at 8 million children who die every year… half from preventable causes. (It’s a number that I can’t even begin to contemplate as I look at my children and new grandchildren!) Having now “gone public” with our school building effort, if any of my readers or patients want to help, just email me or call the office… Now, onto the medical subject I promised in the title:

There has been an estimated 70% decrease in new use of hormone therapy subsequent to the Women’s Health Initiative reported in 2002. And as we gather more information about the ongoing results of this study, there is a definitive and much publicized concern about the increase in risk over time of breast cancer in women who were on combination Premarin and the synthetic progestin, Provera.  Many physicians now prefer prescribing other forms of estrogen, such as estradiol (especially transdermal, i.e. delivered via skin absorption) and progesterone both similar to what the ovaries produced during our reproductive years. But even then, we are concerned about long-term use. I don’t question the amazing diminishment of symptoms that estrogen therapy renders, especially in the early years of menopause. But at some point, I remind my patients that if they want to continue long-term use, they have to consider whether they are doing so for quality of life (and abeyance of symptoms) or for medical reasons. I have to point out the risks… Well, this time, I also want to point out a study that indicates a risk in stopping hormone therapy.

A recent observational study of postmenopausal women aged 60 or older was conducted using data from 11 Kaiser Permanente medical centers here in Southern California. They assessed the risk of fracture for women who stopped taking hormone therapy compared with those who continued. Between July 2002 and December 2008, hormone therapy use in this population decreased from 85% to 18%. The survey took into account age and race before comparisons were made. Women who did not use hormone therapy in the previous year had a 55% increased risk of hip fracture; moreover, hip fracture increased significantly with 2 or more years of HT cessation.

The study was limited in that the researchers did not have information about previous fractures in this population. But they did compare mean bone mineral density (BMD) and found that it was inversely associated with cumulative years of HT use. (In other words, the longer the women were on HT, the better their bone densities).

There is more information needed before most physicians warn all patients not to stop their HT for fear of fracture.  But this study does give pause for a medical discussion.

Bottom line: If you do stop hormone therapy; you should be followed with appropriate assessment of your bone status. If your risk is deemed high (age over 65, low scores or decreasing scores on a DEXA bone density scans, a significant family history of hip fracture, a personal previous fracture and/or the use of certain medications, especially steroids), then you may need to consider osteoporosis medications such as a bisphosphonates. As usual, I will end with the phrase “discuss this with your doctor.”

What’s your bone density? This query is almost as frequent as: What’s your cholesterol level? (Or it should be if you are postmenopausal.)

I know that I have written about the need to consider risk factors for fractures due to osteoporosis. A quick reminder, these include being female, older age, lack of estrogen in menopause, certain medications, previous fractures, smoking, family history of osteoporosis, and low bone density. All these are put together in the FRAX score which should be calculated before considering treatment with bisphosphonates (such as Fosomax, Actonel, Boniva, Reclast) or other osteoporosis medications. And I’ve also addressed the rare complications that can occur as a result of bisphosphonate therapy; more specifically, jaw bone necrosis and atypical fractures of the femur. (If you want a full description, go to the website and you can look it up in the archived articles.)

But before you read about the potential bad stuff that can occur with bisphosphonate therapy (hey, I can use “stuff” to describe things and events, President Obama does!), I want to report on a study that recently came out in The Journal of Clinical Endocrinologic Metabolism. The authors of the article rightly point out that there is substantial morbidity (illness) and mortality associated with osteoporotic fractures. Between 10% and 20 % of individuals who suffer hip fractures die within 1 year. They analyzed all the placebo-controlled randomized trials of osteoporosis treatment in the literature. They eliminated trials that included women who were on estrogen or SERMS such as Evista (which help maintain bone density) and focused only on those trials that were conducted for more than a year with “approved doses of medication”. Based on these criteria, 8 studies were eligible for analysis.

And here is what they found: There was a greater than 10% reduction in mortality for those individuals who were treated with osteoporosis medications when compared to those on placebo. Surprisingly, the reduction in deaths was neither related to age nor to incidence of hip or other non-vertebral fracture.  Now, even if we consider that treatment for osteoporosis reduces fractures by 5%, and hence an approximate reduction in hip fracture mortality of 2% to 3%, this does not explain the total mortality reduction that was found for osteoporosis therapy in these studies.

Bottom line: There may be more to “just” decreasing fracture rates with osteoporosis treatment. Osteoporosis medications can reduce mortality by over 10%, especially when used to treat older, frailer individuals. So before we shy away from their use because of rare (albeit, scary) side effects, we have to remember that osteoporosis therapy can do more than stave off debilitating fractures… it may help save lives.

It’s nice to occasionally report on a positive finding.

Let me start with the scary and necessary-to-know statistics: Osteoporosis affects 10 to 12 million people in the US and forty million have low bone density (osteopenia). In 2005, over 2 million fractures were diagnosed. One in three Caucasian women over 50 will experience an osteoporotic fracture in her lifetime. (Whites and Asian women tend to have a lower bone mass than women of other ethnicities.) We also “out fracture” men (who have thicker bones) by a factor of 1.6.  And if a woman fractures her hip, she has a 20% chance of dying within a year. Osteoporosis is a very disabling, costly, and yes, mortal disease.

There has been a welcomed increase (both medically and financially) in pharmaceutical therapies that help avoid and/or treat osteoporosis. By now, you have all seen the ads and articles for the various bisphosphonates including oral alendronate (Fosomax), risedronate (Actonel) and ibandronate (Boniva) which can be used daily, weekly or monthly. There are also intravenous bisphosphonates that can be administered every 3 months or just once a year.

Then came the media outcry about potential side effects that these medications could cause….jaw necrosis, perhaps atrial fibrillation and more recently “atypical” fracture of the femoral shaft (long, upper leg bone), especially after long term use. I want to address the latter concern in this article.

Remember, these medications work by binding to the bone, preventing cells called osteoclasts from drilling minute cavities that make the bone porous. Cells called osteoblasts then do “their thing” and fill the cavities up. When stable, the drilling and filling are equal and thus maintain bone structure and strength. However if the drilling outpaces the filling, there is bone loss. This occurs with age (unfortunately after 30), and is accelerated by lack of estrogen (menopause) certain medications, especially steroids, diseases and the “wrong” genes. It is also aided and abetted by lack of proper nutrition.

Just to reiterate, bisphosphonates help stop the drilling and with time those minute cavities that made the bone porous get filled, diminishing the risk of fracture. We now know that these bisphosphonates attach and remain in the bone performing this job for years after being discontinued.

Recent cases have appeared in medical journals in which the femoral bone fractured in a horizontal fashion without prior significant trauma. In most instances, the patients were taking long term bisphosphonates.  How concerned should we be about this newly media reported “atypical” femur fracture?

An article in the May issue of The New England Medical Journal may help allay physician and patient concerns. It concludes that this type of fracture is truly rare. The authors used data from 3 randomized and placebo-controlled, prospective studies involving 14,195 women and 55,000 person years of observation. The risedronate data that they reviewed provided up to 10 years of study. All together, they found a total of 12 fractures in 10 patients that were classified as possible “atypical” femur fractures. (To be accurate, they were called subtrochanteric or diaphyseal fractures). The incidence came out to just 2.3 per 10,000 patient years. The authors also calculated that treating 1,000 women who had osteoporosis for 3 years would prevent about 100 fractures (including 11 hip fractures), a benefit that way exceeded the risk of “atypical” fracture, if indeed it was caused by the bisphosphonates.

So what does this mean? Well according to an editorial that followed the article, “physicians should not rush to judgment and stop prescribing bisphosphonates because of concern about atypical femoral fractures.” They should, however, reevaluate patients who have received long term therapy in the context of contemporary guidelines. (And for these please see my previous website article that discusses the use of FRAX to determine for whom and when to start therapy.)
I now review the FRAX indications for each patient who is at risk for osteoporosis. If she is a candidate for medication I will prescribe it, but carefully follow her with tests to check for bone loss. If she is stable for a number of years (usually 5 years) I suggest stopping the medication or at least taking a drug holiday. The good of the bisphosphonates still outweighs a possible bad, at least for those who need it.

Now, although I usually end my weekly newsletter with just one article, I have to mention another that just came out in JAMA. It also dealt with bone fractures. As we now all know, Vitamin D has become the vitamin “De jour”. The amount of D found in up to 70% of American is inadequate; low levels have been associated with osteoporosis, heart disease and a number of cancers. I ask all my patients about their Vitamin D intake (and exposure, remember you can get it though sun rays) and repeatedly advise them to take at least 1,000 international units (IU’s) daily.  I often check Vitamin D levels with a blood test, especially if there is a history of low bone density. For those whose level is found to be extremely low, I prescribe 50,000 units of Vitamin D-2 a week or every other week for several months, and then recheck their levels. If they have achieved a D level that is sufficiently high, I have them continue with an OTC supplement of up to 2,000 units daily.

Researches in Melbourne, Australia tried to maximize Vit D administration by giving elderly women considered to be at high risk of fracture  a dose of 500,000 IU of Vitamin D orally once a year.  They carried out a double-blind, placebo-controlled trial in 2256 women aged 70 or older. Half were given this very high yearly dose for 3 to 5 years; the others were given a placebo. There was no difference between the 2 groups with regard to calcium intake (indeed it increased for both). But contrary to expectations the group that received the high dose Vitamin D experienced 15% more falls and 26% more fractures than the placebo group. And the increase in falls was most apparent in the 3 months after they were given high dose Vit D! Frankly, the authors couldn’t explain this but went on to suggest that dosing should be more frequent and at lower doses. So far I (and most of my colleagues) will probably stick to advising daily 1,000 units or more of D and if your levels are low that you increase the dose (with a prescription) on a weekly or biweekly schedule. But I doubt we will prescribe that single oral dose once a year. So please continue to use D and calcium on a regular basis for better bones. And if necessary, go ahead and take that bisphosphonate that I or another doctor may have prescribed. The bones you strengthen will be there to stand you in good stead!

A major concern for the majority of women in their late 40′s and early 50′s has been whether and when to start hormone therapy. (Note it used to be called hormone replacement therapy, but the experts now agree that this term suggests that the menopause transition is an endocrine deficiency disorder and not a natural change in our hormonal and reproductive status, so the word “replacement” is out.)  I concur with the current PC terminology, but should point out that 80% of women experience symptoms related to this menopause transition as their estrogen levels plummet. The most common symptoms are hot flashes and night sweats (called vasomotor symptoms or VMS).  Add vaginal dryness, sleep problems (either due to the hormonal transition or to the stresses we face in mid life), mood changes and even a sense of diminished focus and quality of life and it’s clear that for many women, lack of estrogen production in the menopause creates sufficient physiologic and psychological havoc that they want to do something about it. That most effective something has been hormone therapy; estrogen (as pills, patches, creams, sprays. vaginal tablets and rings) and if a uterus is present (i.e. no hysterectomy) some form of progesterone (again as pills, patches, creams, drops or vaginal gels).

Since the Women’s Health Initiative was publicized, women have been encouraged by the FDA and just about every other official agency that reviews the research on hormone therapy, that if they chose to take hormones, they take the smallest effective dose for the shortest duration, preferably no more than 5 years. That “magic|” 5 year mark has been suggested because it’s felt that menopausal symptoms resolve in most women after 5 years. (Much of the “this-won’t last” data comes from women who have chosen not to take HT and have been followed for years to see what happened to their symptoms.)

Many women don’t want to wait for symptoms to resolve, especially if they are not guaranteed a finish date. Indeed some research has shown that 15% of women continue to have symptoms in their 70′s. Twenty five to 50% of women who stopped hormone therapy after the Women’s Health Initiative resumed therapy. Those most likely to do so had severe symptoms before they started HT, were obese, younger at time of menopause, African American, smokers or physically inactive.

When it comes to “it’s time to stop your hormones” advice I generally suggest that quality of life vs. risk be considered: will you feel lousy enough without hormone therapy to counter the possibility of an increase in your risk for breast cancer with long term (probably more than those 5 years) use of HT?  I also explain that estrogen has positive effects on bone mass and in the first years of use is probably heart protective. |But as the years pass and other factors affect our cardiovascular system, estrogen may no longer afford the same cardiovascular protection.

So what is a woman (who has been happy on her hormone therapy) to do? Should she try to “wean off” or just stop after that arbitrary 5 years?  A new article in the Journal Menopause tried to address this in a scientific fashion.  A study was conducted in Sweden in which the researchers recruited women to stop their hormone therapy “cold turkey” or do so gradually by taking it every other day. They wanted 200 women for the study, but when faced with the idea of stopping their hormones, many refused and they could only find 87 volunteers!  At the end of 4 weeks there was no difference in the symptoms of the women who abruptly stopped and those who tapered and then discontinued.  And because vasomotor symptoms came back for many, within 4 months 30% of the participants resumed their hormone therapy and after 1 year that number had risen to 50%!

Now to my clinical experience… I try to lower the dose of HT for most of my patients after they have taken it for 5 years. (This necessitates a discussion of the possible risks associated with long term use). If a patient is amenable, I prescribe a dose that is lower than that which she has taken and suggest she try it for 4 to 6 weeks. Some of my patients can then keep lowering their dose until they successfully stop and have no symptoms. Others state that although their symptoms resumed “they were not that bad” and they try to stop HT for good. But I do have patients (about 30%) who feel pretty awful, either on a lower dose or once they stop. I then suggest that they continue at the very lowest dose that allows them to keep their symptoms under control.  (And in their next visit I will revisit the risks and benefits of long term hormone therapy. Basically we are agreeing to procrastinate.) As long as we have a frank discussion about the pros and cons of long term HT, the final decision should be made on an individual basis.  Unless there is a truly health threatening reason that dictates that she stop, issues regarding her quality of life (and life style) have to be considered.