This week passed quickly and before I knew it my Friday website was due. As I scanned the various medical journals, I found an interesting article in the Journal of the North American Menopause Society. The long but very comprehensive title of the article is “Calcium/vitamin D supplementation, serum 25-hydroxy vitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial.”

The authors (17 of them in multiple centers in the US) wanted to evaluate whether increased levels of active vitamin D concentrations in the blood, the 25 hydroxy form (25OHD3), became elevated after calcium/Vitamin D supplementation and were associated with improved cholesterol levels in postmenopausal women.

The randomized, placebo-controlled trial included women already in the Women’s Health Initiative Study (WHI) and who had been enrolled in 1993 and 1998. The group they specifically studied included 300 white women, 200 African-American and 100 Hispanic women that were randomly selected from the larger WHI trial. They measured their serum (blood) vitamin D levels before starting the study as well as their lipid levels which included fasting triglycerides (TG), high density lipoprotein cholesterol (HDL- C) and calculated low density lipoprotein cholesterol (LDL- C) levels before and after calcium vitamin/D supplement.

After two years, they compared these blood tests for the women who took 1000 mg of elemental calcium and 400 units of vitamin D (CaD) and those who took a placebo. They found that those who took supplemental CaD significantly increased their vitamin D levels and decreased their LDL- C levels. The women with the higher vitamin D concentrations had more favorable lipid profiles including an increase in their HDL-C (the good cholesterol), lower LDL- C and lower TG.

If you want the numbers… In the study the women on CaD increased their vitamin D levels by 38% compared with those on placebo and those randomized to CaD decreased their LDL- C by 4.46 mg/DL. And if the serum concentrations of vitamin D increased significantly then all three parameters of the lipids improved.

They did add one thing… That many of the women were on hormone therapy and there is the possibility that there is a synergistic relationship between vitamin D and estrogen therapy which could have improved the impact of Vitamin D on lipid levels.

Bottom line: According to this study as well as many others, your vitamin D level is important to your health and improving it with supplements may have a positive impact on your lipid profile and ultimately (and I have to interject “a perhaps” here, since this has not been sufficiently studied) on coronary heart disease. I usually suggest that my patients follow “the one and one” rule. Make sure you get 1000 to 1200 mg of calcium through diet or supplements and take 1000 units of vitamin D.

As physicians who treat women over 40, we’ve always assumed that estrogen is great for our bones. Studies have shown that there is rapid bone loss (as much as 10% in the first three years) after menopause! And even if estrogen is given initially, once it is discontinued, rapid bone loss occurs, again as much as 5 to 6% after one year. But it is not the loss seen on bone mineral density scans that worries us, it’s the increase in fracture rates. In the Million Woman Study in England (Guess how many women participated?), those on estrogen or estrogen and progestin had a 30% reduction in fractures; among those who discontinued their hormones, the fracture rate was similar to that of the untreated population within one year. In a study of a large group in California, the number of women taking estrogen declined from 85% to 18% between 2002 and 2007 as a result of the publication of the initial data from the Women’s Health Initiative (WHI) which scared women and their physicians with evidence that in older women Premarin and Provera increased breast cancer risk. And lo and behold, fracture rates in this population increased by 50%. With all this in mind I was somewhat surprised by a recent article in the journal Menopause published by the North American Menopause Society.

The authors again used the WHI study to look at the impact of hormones as well as calcium and vitamin D on osteoporosis. Several years after starting hormone therapy, half the women in the study who were on Premarin alone or Premarin and Provera were randomized to either a group that took 1200 mg of elemental calcium and 400 units of vitamin D daily or a group that did not. Bone status was then followed for the women on hormones taking no supplements, women taking supplements but no hormones and women in the control group who took neither. A total of 16,089 women participated in this arm of the study.

The researchers looked at the fracture rates and bone density in all of the groups. They found that the effect of hormone therapy on hip fracture was significantly stronger among women who were assigned to also take calcium and vitamin D. In short, calcium and vitamin D supplementation significantly reduced the incidence of hip fractures beyond hormone therapy alone. The beneficial effect of hormone therapy on the bones was evident at a level of 1200 mg of calcium use and continued to increase at even higher doses. Similarly, the benefit of hormone therapy continued to increase at levels higher than 400 units of vitamin D. But the supplements alone were not effective…this study and others that were published based on WHI data have shown no overall significant fracture prevention when calcium and vitamin D supplements were taken alone. The conclusion: although taking calcium and vitamin D may not be statistically effective for fracture prevention but they may have a significant effect when used with hormone therapy. And for hormone therapy to “work” to prevent fracture, these supplements should be added.

In an accompanying editorial, the authors suggest that 1200 mg calcium (by diet and/or supplements) and 600 to 800 units of vitamin D be taken with hormone therapy in order to achieve the hormonal benefit of reduction in risk of osteoporotic fractures.

Bottom line: Hormone therapy alone is not enough for osteoporosis prevention, nor are supplements… But together they are effective. So if you use hormone therapy make sure to add calcium and vitamin D.

Last Friday, I delivered one of the keynote addresses for the annual conference of the Academy of Anti-aging and Regenerative Medicine in Las Vegas. It was a huge conference and I was somewhat overwhelmed by the 3500 medical personnel who attended. The topic of anti-aging is certainly one of major concern to medical practitioners and patients worldwide and indeed there were participants from all over the world. As many of you know, I’m a fairly orthodox physician and want evidence-based medical data upon which to base testing, diagnosis, and therapy. So this was not an easy lecture for me to give. Much of the conference dealt with supplements, novel and “new age” testing and procedures and the use of bio identical, compounded medications. So when I PowerPointed my lecture with 35 slides and titled it “Slow Your Clock Down: on label, off label, gray label” I was aware that the topics and information could be controversial and even confrontational for a vast number of the participants.

I am not going to download the entire presentation but I thought I would detail a few of the slides: I started with our universal goal; health span not life span… That we “optimize the minutes and hours of our internal and external clocks so that we can savor our present and future bodies”. I then went on to delineate the issue of labeling and drug use as follows:

On-label (FDA approved): In order to achieve FDA approval drug companies pay for and perform laboratory and animal tests. They test humans to see if the drug works and whether it is safe and it provides a real health benefit. The data is then sent to the Center for Drug Evaluation and Research. A team then reviews the data and proposes labeling. If the review establishes that a drug’s health benefits out way it’s known risks, the drug is approved for sale.
Off-label: Adding additional indications for an already approved medication requires a supplemental drug application; if it is eventually approved the revenue from it may not offset the expense and effort for obtaining approval. Hence physicians often use FDA approved drugs for non-approved indications.
Gray-label: This indicates a non-FDA approved medication or one that has not yet undergone peer-reviewed studies and is not recognized by evidence-based medicine to treat an illness or perhaps positively impact health span.
I then discussed estrogen therapy, something I’m very comfortable with. First, I described on- label use and the North American Menopause Society (NAMS) recommendation that “current data supports initiation of hormone therapy around the time of menopause to treat menopause related symptoms and to prevent osteoporosis in women at high risk of fracture”. The current on-label systemic estrogen indications are moderate to severe vasomotor symptoms. The off-label estrogen indications are the ones that I often see and treat and they include sleep disturbances, skin changes and skin aging, memory issues, skin sensory issues, joint pain, mood changes and sexuality. I then went on to show several other slides, but the one that I want to emphasis on this website is the fact that the follow-up study of the Women’s Health Initiative (WHI) that included 93,676 women followed for up to 13 years found that neither estrogen therapy nor estrogen progestin therapy affected all-cause mortality.

I thought my next slide might cause some issues at the conference; it was titled “Grey-label: bio-identical hormones”. I presented the following NAMS statement.

Bio-identical hormones may offer patients unsubstantiated claims about safety and effectiveness
The term connotes that they are identical to hormones made in the ovaries, but the same is true of many of the FDA approved prescriptions for hormone therapy
These products may contain dyes, preservatives, contaminants, and vary in dose.
Just to be clear, I did go to discuss the fact that certain progesterones for hormone therapy as well as testosterone are not available as FDA or on-label approved therapies for women and when I feel there is an indication to prescribe them I do. (This made the folks at the meeting happier.)

And despite the fact that specialty vitamin companies were sponsoring many of the booths at the expo at the conference, I did put up a slide that stated that “Vitamins are definitely on the no-label list”. I posed the question: “Are antioxidant supplements associated with higher or lower all cause mortality?” The answer was given with the evidence based trials reported in the JAMA clinical evidence synopsis published September 2013. A review of almost 100 studies showed that beta-carotene, vitamin E and higher doses of vitamin A may be associated with higher all-cause mortality and does not lower mortality rates. And of course the media just covered studies and statements that came out (after the conference) that taking a multivitamin does not increase life span.

I just want to mention one more slide which had to do with exercise… I called it the best label of them all! There is ample evidence that exercise lowers risk of coronary heart disease, stroke, hypertension, type two diabetes, depression, osteoporosis and increases lifespan and health span. The national exercise guidelines state that we should get two hours and 30 minutes of moderate intensity exercise a week, or 75 minutes of vigorous activity (or both), and two sessions of muscle strengthening exercises that work major muscle groups.

This is just a part of my talk at the conference. (I would say brief summary, but once I typed it out it seems pretty long.) I’ve discussed all these topics and the studies that led to my statements in previous website articles but I hey, it’s the end of 2013 and a review a can’t hurt. Oh,and I received some positive comments in the end of my presentation…

We all want to believe in vitamins, especially antioxidants, hoping that they will help us live longer, prevent chronic illness, and like Popeye’s spinach, make us strong.

So when the latest JAMA published a clinical evidence synopsis from the Cochrane review about the power of antioxidants, I was intrigued. Just a reminder, the Cochrane Reviews are systemic reviews of research pertaining to human healthcare and health policy and are internationally recognized as the highest standard in evidence-based healthcare. They take a clinical question, review all the relevant studies and basically give us the bottom line after they have done an exhaustive statistical analysis.

So here is what they found in answer to the clinical question ” Are antioxidant supplements associated with a higher or lower all-cause mortality?”

They reviewed 78 randomized clinical trials which included 296,707 participants whose mean age was 63. And 46% of them were women (I wonder why not 50%, but let’s not go there). Of these, 26 of the studies where of individuals who were healthy and the remaining 54 trials assessed individuals with stable, chronic diseases that included coronary disease, diabetes, Alzheimer’s and age-related eye disease. All the antioxidants were given as oral supplements, either alone or in combination with other vitamins, minerals or other interventions. The mean duration of supplementation was three years. The reviewers then analyzed which of the studies were biased. ( An example of bias would be to ask someone who already has an illness if she or he took the antioxidant in order to prevent the illness.) They concluded that 82% of the participants had a low risk of bias. Obviously, when the low risk trials were analyzed separately from trials with a high risk of bias, the results were considered the most relevant. And here’s the surprising finding: “The antioxidant supplements were associated with a statistically significant higher all-cause mortality. The higher risk of all-cause mortality was observed for beta-carotene and vitamin E, and in some analyses for higher doses of vitamin A. Vitamin C and selenium were associated with neither higher nor lower all-cause mortality”.

I know this is the Fourth of July weekend and many of my patients and readers will be busy with family, barbecues and hopefully celebrating the independence of the fabulous country we live in. (And, of course, there are those wonderful sales!). But if you happen to be glancing at this website, I want to take this opportunity to indulge in a modicum of self-congratulation; a committee opinion from the American College of Obstetricians and Gynecologists was just released and it supports what I’ve been telling my patients for years; that hormone therapy does not increase coronary heart disease risk for healthy women who have recently become menopausal. What also makes this committee opinion novel is that it states that if a woman’s quality of life is diminished by menopausal symptoms past the age of 65, extended therapy may be considered. Let me repeat: The American College of Obstetricians and Gynecologists now recommends against routine discontinuation of systemic estrogen at age 65 for women who need HT to manage their vasomotor symptoms (hot flashes and night sweats).

So that’s the summary. And you can go back to your holiday celebrations. But if you want to read further here are some of the studies and facts that the committee used in its announcement:

Much of the controversy about the impact of hormone therapy (HT) on cardiovascular disease came out of the Women’ Health Initiative (WHI) and the Heart and Estrogen/progestin Study (HERS) which seemed to show an increase in heart attack and stroke in women who took hormone therapy. But more recent studies have cast doubt on some of the methodologies used. Many of the women who were in the those two studies were over the age of 63 when they started hormone therapy and already had underlying coronary heart disease, hence they had an underlying increased risk for developing heart attack and stroke, which perhaps was augmented by hormone therapy. But newer studies indicate that when hormone therapy is started at a younger age, in women aged 50 to 59, the opposite occurs. An important study used CT scans to examine the distribution of calcification (plaque) in the coronary arteries in 1064 women who were in that 50 to 59 year range. Those who took estrogen had calcium scores that were lower than women who took a placebo, moreover, those who stayed on estrogen for more than five years had a significant reduction of 40% in their calcification scores.

The committee also looked at other variables of hormone therapy that could affect cardiovascular disease. They stated that synthetic medroxyprogesterone acetate (Provera) causes constriction of blood vessels whereas natural progesterone causes the vessels to relax and therefore may have a positive effect on blood pressure. In addition, unlike synthetic progestins, natural progesterone causes little or no reduction in high density lipoprotein. (Remember, high density lipoprotein is the good cholesterol and works like a rotor router to protect vessels from plaque formation). The committee doesn’t go so far as to state that ET or HT improve cardiovascular outcomes, they simply state that the evidence is as yet insufficient. But they do say that recent evidence suggests that women in early menopause who are in good cardiovascular health are at low risk of adverse cardiovascular outcomes and should be considered candidates for estrogen therapy or combined estrogen and progesterone therapy for relief of their menopausal symptoms. And women over 65 should talk to their doctor. If their symptoms are persistent, it’s OK to consider continuing their hormone therapy.

My final summation: If you develop symptoms that make you miserable – start hormone therapy in the early years of menopause, there is no increased risk of CHD if you are healthy… and continuation beyond age 65 may be an appropriate option if your quality of life is significantly reduced by these symptoms. We still have to discuss risk- benefits (most specifically breast cancer risk…) There is no free lunch or hormone!

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:

2080 Century Park East,

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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!

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.

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.

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