Aug 092011

Horse Hormones vs Bio Identical Hormones
For many years, one of the best-selling drugs in the world was Premarin—a commercially available hormone therapy made with estrogens isolated from the urine of pregnant mares.
Women used Premarin to reduce their menopausal symptoms and decrease their risk of cardiovascular disease. A few years ago, however, the Women’s Health Initiative Study (WHI) questioned the ability of Premarin-like hormone therapy to protect against heart attacks and strokes, and warned that women taking the pills had an increased risk of breast cancer. The news left many women confused. Perhaps Premarin wasn’t the best solution. Meanwhile, what was? After all,

  • the symptoms of menopause were still there,
  • the cardiovascular risks of menopause were still there,
  • the osteoporosis risks of menopause were still there, and
  • the breast cancer risks of menopause were still there.

The Key is to Use the Right Kind of Hormones
As we re-examine the facts, we find that the WHI study didn’t say that using hormones to treat menopausal symptoms and reduce the risk of disease was a bad idea. It did tell us that using Premarin and Provera (a synthetic analogue of progesterone) was not a successful way to do it.
It makes sense. Menopausal symptoms aren’t caused by a lack of horse estrogens or synthetic progesterones. Introducing these foreign hormones into a woman’s body may not help, and further, may actually cause additional problems.
Hot flashes, mood swings, and an increased risk of heart attack and osteoporosis do occur, however, during peri-menopause and menopause—just when the female body is going through hormonal changes. That does tell us there’s a strong hormonal factor involved. Nevertheless, it’s not horse but human estrogen a woman’s body needs; not progesterone chemical analogues, but human bio-identical progesterone.
Many studies have shown the advantages experienced by women who supplement with appropriate bio-identical human hormones like estrogen, progesterone, testosterone, and DHEA. These studies are not well known to the public or mainstream physicians—and they’re not promoted by most pharmaceutical companies—but they do exist, and they’ve shown that using supplemental bio-identical human hormones:

  • lowers cholesterol levels,
  • increases bone density,
  • reduces hot flashes and night sweats,
  • lessens premenstrual-type symptoms, and
  • promotes a feeling of well being.

Physicians using bio-identical hormones in their practices have clinical evidence of the results.
Eating right, exercising, and scheduling regular checkups can go a long way toward helping a woman live a healthy life. From peri-menopause on, however, hormonal balance also becomes a major factor, and finding the right solution can mean the difference between enjoying life and feeling miserable.
If you are interested in trying bio-identical hormones, we encourage you to talk to other women using bio-identical hormone replacement therapy (BHRT), and check with their practitioners as well. Read the books, articles and studies that have led so many women to make this decision.

Haber’s Pharmacy is one of the most trusted and established compounding pharmacies throughout Toronto, offering a wide variety of medical solutions from peri- menopause, BHRT to Bio Identical hormone replacement and much more.

Tagged with:
Mar 072011

From The Globe and Mail
Published Friday, Jan. 21, 2011 6:32PM EST

The woman trying on a tendonitis brace rotates her arm, careful not to knock any merchandise in the tight aisle. The tidy pharmacy is a fraction the size of a typical Shoppers Drug Mart – a chain started by one of the shop’s previous owners from the 1950s.

After a long consult, the pharmacist hands her a slip of paper. It’s not a prescription exactly – pharmacists aren’t allowed to do that. It’s a formula for a tailor-made topical anti-inflammatory that will soon get an official re-write from a doctor.

Owner Marvin Malamed is used to seeing his prescription suggestions come back to him in illegible doctor scrawl. His customers usually end up here at Haber’s Pharmacy on Bathurst Street north of St. Clair Avenue by referral from doctors who consider him a pioneer in the resurgent field of compounding pharmaceuticals.

Whereas most pharmacists will quickly wear out shoes from spinning between their counter and the shelves behind to pick out pre-packaged bottles, compounding pharmacists actually concoct medicines on site for customers who are, for one reason or another, slipping through cracks between the big pharma monoliths.

Dr. Howard Winston sends patients down Bathurst Street to Haber’s from the Centre for Health & Sports Medicine, where he is medical director. A typical script has patients pick up an anti-inflammatory cream into which Mr. Malamed has mixed very effective absorption vehicles. Dr. Winston says it targets localized injuries better than any commercial product he’s come across, with fewer side effects – in particular, no gastrointestinal complications.

“There is some magic happening with this formula, and it’s just not available commercially,” says Dr. Winston.

He’s been sending patients to Haber’s since 1992, when Mr. Malamed started dabbling in compounding.

“He was the only game in town for a number of years,” says Dr. Winston.

But that’s no longer the case.

There are at least a dozen Toronto shops that now do more than the elementary compounding done at typical pharmacies. It is a case of modern-day apothecarists rediscovering a “lost art,” according to David Miller, chief executive officer of the International Academy of Compounding Pharmacists.

Up until the Second World War, most medicines were prepared in local pharmacies according to a prescription slip that read like a recipe (Rx is an abbreviation of the Latin word for recipe). During the 1950s – and spurred on by federal legislation in the United States – the pharmaceutical industry began to supply pharmacies with standardized prepared medicines, instead of just ingredients.

This was, by and large, progress, but in the early 1990s, doctors in long-term-care facilities started demanding more options for seniors with differing metabolic rates and sensitivities to certain medicinal or non-active ingredients. Soon after, Internet-informed consumers began expecting customized doses and formulas to treat stubborn ailments that were not common enough to be addressed by pharmaceutical companies, which often need huge economies of scale to justify bringing a patented drug to market.

According to Mr. Miller, by 2008, compounded pharmaceuticals accounted for $19-billion out of a $300-billion industry in the U.S.

The antique tincture bottles on display along the top of one wall in Haber’s evoke compounding’s gilded age from a century ago, but the glass enclosure at the far end has nothing in common with that old-time physicks. Inside, three pharmaceutical technicians in hair nets and surgical masks work at equipment that includes whirring mixers, polished grinders and a scale so sensitive it has a glass enclosure to block air currents.

Though the equipment adds significantly to the expense and complexity of running the business, Mr. Malamed seems to welcome complications.

“It’s not as straightforward as counting pills, putting them in a bottle and slapping a label on it, but it’s exciting to have to think about how to solve a problem. And rewarding when customers come back and tell you they’re feeling better.”

One such customer is Donna Everatt. The 46-year-old MBA and business strategy researcher suffered for 15 years from a mood disorder caused by a hormonal imbalance. Her own investigations convinced her there had to be a better treatment than what was commercially available. As she explains, natural bio-identical hormone therapies have to be precisely tailored to individuals. She decided she needed the flexible doses and formulas offered by a compounding specialist.

“Marvin consulted with me for three or four hours over several weeks, and eventually suggested formulas for the doctor to prescribe,” says Ms. Everatt.

“It might be dramatic to say the treatment saved my life, but my quality of life was suffering greatly. Marvin is my hero. He’s really on the forefront of an important field.”

Special to The Globe and Mail

© 2011 The Globe and Mail

Jun 082010

With such diverse people in the world that have individual needs and requirements, it is understandable that not everyone responds the same to every type of medication. Many people have specific conditions that prevent them from taking medicine using traditional manufactured pharmaceuticals. Sometimes the type of medicine required by a particular patient is not manufactured by traditional drug companies, or a patient may need to ingest the medicine using a different method than traditionally prescribed. This is when Compound Pharmacists come in to meet the unique individual patient needs.

Compounding pharmacists customize an individual patient’s prescription according to the specific need of the patient. There are a number of circumstances that require consultation with a compounding pharmacist. For instance, a patient will need a compound pharmacist if they are unable to ingest ingredients that are included in traditional medicines such as preservatives, alcohol, dyes, sugar, gluten, lactose, and casein. Patients may also need an alternate route of medicine ingestions such as if a patient has trouble swallowing. Alternate administration routes can include: Transdermal such as a skin patch, nasal spray, liquid form, lozenge, lollipops, creams, and inhalation. If a patient is susceptible to drug side effects or require allergen free medications, using medication prepared by a compounding pharmacist can drastically reduce the potential for side effects and eliminate allergic reactions. A compounding pharmacy can help cancer patients reduce discomfort caused by their medication during treatment.

If a patient requires a specific dosage that is not normally manufactured by a traditional drug manufacturer, a compounding pharmacist can provide the uncommon dosage in order to meet the required strength. Patients who are in need of medications that have been discontinued by pharmaceutical manufacturers can get the medications from a compounding pharmacist. As well, children who will only medications that have a palatable flavor will be able to get a specific drug that has a pleasant tasting flavor from a compounding pharmacist.

Compounded prescriptions are the ideal solutions for a patient that is in need of an alternate route of delivery and an uncommon dosage. Compounding pharmacists are needed in such medical areas as: Bio-identical Hormone Replacement Therapy, Sports Medicine, Wound Therapy, Veterinary practices that include both large and small animals, Chronic Pain Management, Dental Practices, Hospice, Pediatrics, Infertility, Ophthalmic, Dermatology, Neurology, Gastroenterology, and more.

Pharmacy compounding is not just a science of preparing medications, but it is also an art to customizing medications for patients. Compounding is not a new method of providing medications. This type of pharmacy has been around for centuries. However, with increasing more patients requiring alternative forms of drugs and innovations in technology and research, there has be a significant increase in compounding pharmacists. As well, The Food and Drug Administration support the use of compounding, and it is regulated by each State’s Board of Pharmacy.

With the consent of a physician, a compounding pharmacist can modify almost any kind of a medication to make it easier to ingest by the patient and have the exact same effect as traditional manufactured medicine. For many patients, compounding has made the ingestion much easier and less unpleasant. For patients who feel they may require the expertise of compounding pharmacists, it is recommended that they discuss what compounding can do for them with their physician.

Tagged with:
Mar 252010

An excellent and in depth look at the evidence behind bio identical hormones was published by Life Extension Magazine ( in the October 2009 issue. Haber’s Compounding Pharmacy has reprinted this article below. We encourage patients and practitioners alike to give it a read. It asks the increasingly more relevant question with regards to Bio Identical Hormones, namely: Why are they still controversial?

Bioidentical Hormones: Why Are They Still Controversial?

As women enter the menopausal years, they face a difficult decision. Their bodies’ production of estrogen, progesterone, and other hormones needed to maintain youthful vitality rapidly declines.

While individual effects of menopause vary widely, many women suffer because their bodies no longer produce sex hormones at sufficient levels required to optimally sustain critical physiological processes. Depression, irritability, and short-term memory lapses are common menopausal complaints, along with hot flashes, night sweats, insomnia, and weight gain.

Health problems encountered during menopause may adversely affect a woman for the rest of her lifetime in the absence of appropriate hormone replacement. Yet maturing women today are often told by their doctors to limit prolonged use of hormone drugs, only long enough to obtain relief from menopausal symptoms and then no more. Unfortunately, this advice fails to recognize the critical differences between hormone drugs foreign to women’s bodies and hormones identical to those naturally produced by women’s bodies.

The understandable, factual concern espoused by many mainstream doctors is that FDA-approved estrogen-progestin hormone drugs have been shown to increase the risk of cancer and cardiovascular disease. The dilemma facing aging women is that their bodies may still benefit from youthful hormone levels, but many of their doctors say “no.”

There is, in fact, a body of scientific evidence indicating that natural progesterone (as opposed to synthetic progestin drugs) and the natural estriol form of estrogen may help protect against the very diseases caused by unnatural estrogen-progestin drugs that are foreign to the human body.

Mainstream medical practitioners (many of whom prescribed unnatural hormone drugs for decades) and the FDA (which still allows these dangerous unnatural hormones to be sold) are now at the forefront urging aging women to avoid their prolonged use.

Overlooked by mainstream medicine is a plethora of research findings indicating that women may more safely benefit from individualized doses of natural estrogens and progesterone over their lifetime. Almost completely ignored are lifestyle changes (such as assuring optimal vitamin D status and cruciferous vegetable intake) that may prevent and even reverse the kind of damage to cell regulatory genes inflicted by some estrogenic compounds.

In this comprehensive white paper, we present data showing how women may more safely benefit from comprehensive approaches that naturally restore youthful hormone balance, while protecting aging cells against carcinogenic and atherogenic insults.

The Rise and Fall of non-bioidentical Hormone Replacement Therapy

Few topics have attracted as much attention in recent years as hormone replacement therapy (HRT) among postmenopausal women. For decades, physicians were prescribing patented non-bioidentical estrogen and progestin drugs such as Premarin®, Provera®, and Prempro®—to combat the symptoms of menopause. non-bioidentical hormones are not identical in structure or activity to the hormones naturally produced within the body.

Doctors also prescribed non-bioidentical hormones to protect postmenopausal women against osteoporosis and heart disease. The rationale behind heart disease prevention was simple: during their reproductive years, women enjoy lower rates of heart disease than men, supposedly because of the protective effect of estrogen. It seemed only logical to mainstream medicine that by replacing the effect of estrogens lost at menopause with non-bioidentical hormones, women would retain some of their protection against heart disease.

Unfortunately, the logic of non-bioidentical hormone replacement therapy (HRT) turned out to be fatally flawed. In 2002, the results of the Women’s Health Initiative were released early. This landmark study followed more than 16,000 women and assessed the effects of non-bioidentical hormone replacement therapy (HRT), including estrogen-only therapy and therapy that combined non-bioidentical estrogen and progestin. The findings were shocking: the estrogen/progestin arm of the study was terminated early because the non-bioidentical hormone therapy not only failed to protect against heart disease, but was shown to increase the risk of heart attack and breast cancer.1 These alarming findings led a team of researchers to boldly state in the prestigious Journal of the American Medical Association that “…the results indicate that this regimen [non-bioidentical estrogen/progestin] should not be initiated or continued for primary prevention of coronary heart disease.”1

In 2004, the non-bioidentical estrogen-only arm of the study was terminated as well because hormone replacement therapy (HRT) with conjugated equine (horse-derived) estrogen was found to increase the risk of stroke.2 These findings had an immediate impact on the millions of women taking non-bioidentical HRT, of whom up to 50% discontinued their use of non-bioidentical HRT.3

The Bioidentical Hormone Option

Bioidentical hormones have the same exact molecular structure as the hormones produced naturally within the body. The body does not distinguish between supplemental bioidentical hormones and the hormones produced within the body.4 As a result, bio-identical hormones are properly utilized, and are then able to be naturally metabolized and excreted from the body. The use of bioidentical HRT has increased during the last several years as women have sought out a more natural approach to restoring hormonal balance.
Scientific Evidence Suggests Bioidentical Progesterone Does Not Increase the Risk of Breast Cancer

The well-established body of literature demonstrating the harmful effects of non-bioidentical hormones might lead some women to fear taking bio-identical hormones as well. A review of the published scientific literature indicates those fears are misunderstood and unfounded. For example, thirteen studies document that non-bioidentical progestin significantly increases estrogen-stimulated breast cell replication and growth.5-17 In stark contrast; seven studies have shown that bioidentical progesterone does not induce estrogen-stimulated breast cell proliferation.18-24

Numerous studies have demonstrated an increased risk of breast cancer with the use of non-bioidentical progestins.1, 5, 25-48 However, the use of bioidentical progesterone has not been associated with an increased risk of breast cancer. Quite the contrary, research has revealed that bioidentical progesterone decreases the risk of breast cancer. In a study published in the journal Breast Cancer Research and Treatment, 80,000 postmenopausal women using various forms of HRT were followed for more than 8 years. Women who used estrogen in combination with non-bioidentical progestins had a 69% increased risk of breast cancer, compared to women who had never used HRT. However, for women who used bioidentical progesterone in combination with estrogen, the increased risk of breast cancer was completely eliminated with a significant reduction in breast cancer risk compared with non-bioidentical progestin use.49

In another investigation, these same researchers found a 40% increased risk of breast cancer for women who used estrogen with non-bioidentical progestin. Interestingly, in women who used estrogen combined with bioidentical progesterone, there was a promising trend toward a reduced risk of breast cancer, compared to women who had never used HRT.25 In essence, bioidentical progesterone appeared to protect women against the development of breast cancer. These findings confirm work done six years earlier that found a trend toward a reduced risk of breast cancer in 1,150 women using bioidentical progesterone, compared to non-users of progesterone.50

Compelling research offers further insight into natural progesterone’s ability to defend against breast cancer. In a fascinating study, scientists administered estrogen alone, bioidentical progesterone alone, estrogen plus bioidentical progesterone, or placebo to 40 women prior to surgery to remove a breast lump. The hormones were applied topically to the breast for about 12 days before surgery. As expected, when given alone, estrogen caused a 62% increase in breast cell proliferation rates compared to placebo. Conversely, the addition of bioidentical progesterone to estrogen resulted in a significant decrease in the estrogen-induced increase in breast cell proliferation rates. Even more impressive was the finding that the group receiving bioidentical progesterone alone had a 66% lower breast cell proliferation rate compared to the placebo group.18

A growing body of literature has documented a strong connection between a woman’s progesterone levels and her subsequent risk for breast cancer. A trial reported in the International Journal of Cancer in 2004 measured blood levels of progesterone in 5,963 premenopausal women. Incredibly, the analysis of the data revealed that those women with the highest blood levels of progesterone levels who had regular menses experienced an 88% decreased risk of breast cancer.51 These findings corroborate another study in which 1,083 women treated for infertility were followed for upwards of 33 years to determine their subsequent breast cancer risk. Compared to women with normal progesterone levels, those deficient in progesterone had a 540% increased risk of premenopausal breast cancer, and were 10 times as likely to die from any cancer.52

Similarly, researchers at the University of North Carolina School of Public Health measured progesterone levels in pregnant women, who were then followed for upwards of 32 years. The researchers discovered that those women with the highest blood levels of progesterone during pregnancy had a promising trend toward a lower risk of breast cancer, compared to women with the lowest levels of progesterone during pregnancy. When the researchers analyzed the risk of breast cancer in women under age 51, those with the highest progesterone levels had a staggering 70% decreased risk compared to the group with the lowest progesterone levels.53

Findings from two other investigations revealed that survival rates for breast cancer are strongly correlated with the patient’s progesterone levels at the time of surgery.54,55 One study noted that 65% of women with a progesterone level of 4.0 ng/mL or more on the day of their surgical treatment of node-positive cancer were alive 18 years later, while only 35% of women with low progesterone levels on the day of surgery were still living after 18 years. The scientists noted that progesterone lowers the expression of vascular endothelial growth factor, which promotes the increase in new blood vessels (angiogenesis) that is essential for tumor growth. These scientists concluded: “This study has confirmed that a raised level of progesterone at the time of tumor excision is associated with an improvement in prognosis for women with operable breast cancer.”55

Estriol and the Risk of Breast Cancer

When discussing estrogen it is important to note that “estrogen” is an umbrella term for many different estrogens including estriol, estrone, and estradiol. All three of these estrogens are produced in the body and have physiological effects. In the past, estriol was believed to have little physiological significance due to its weak estrogenic activity when compared with estrone and estradiol. Nonetheless, research suggests that estriol’s weakness may confer certain beneficial effects in contrast with more potent estrogens.

The benefits of estriol may, in part, be explained by its mixed pro-estrogenic and anti-estrogenic effects. Scientists investigated the mixture of stimulating and non-stimulating effects produced by estriol on estrogen receptors. When estriol is given together with estradiol, the estradiol-specific stimulation to cells is decreased.66 This little-appreciated scientific fact helps to explain how estriol can reduce pro-carcinogenic effects of more powerful estrogens like estradiol. Experimental studies suggest that estriol has a protective effect against radiation-induced cancer of the breast.67

Estriol and the Risk of Breast Cancer

A greater understanding of estriol’s anti-estrogenic activity becomes apparent when examining the differing effects of the three primary estrogens upon estrogen receptor binding activity. There are two distinct estrogen receptors that estrogen hormones bind on breast cells: estrogen receptor alpha and estrogen receptor beta.68-73 The binding of estrogen hormones to estrogen receptor alpha promotes breast cell proliferation, which can lead to breast cancer development. Conversely, the binding of estrogen hormones to estrogen receptor beta inhibits breast cell proliferation and prevents breast cancer development.74-79

Estrone and estradiol bind to and activate estrogen receptor alpha, thereby explaining the known breast cancer-promoting effects of these two hormones.80,81 Estriol, on the other hand, binds to and activates estrogen receptor beta.80,81 This critical fact helps to explain estriol’s anti-estrogen activity, which led a noted researcher in hormone replacement therapy to state: “This unique property of estriol, in contrast to the selective ER [estrogen receptor] alpha binding by other estrogens, imparts to estriol a potential for breast cancer prevention, while other estrogens [estrone and estradiol], would be expected to promote breast cancer… Because of its differing effects on ER alpha and ER beta, we would expect that estriol would be less likely to induce proliferative [potential cancerous growth] changes in breast tissue and to be associated with a reduced risk of breast cancer.”82

A study published in the International Journal of Cancer in 2004 reported on the use of hormone replacement therapy (HRT) and breast cancer incidence in 31,451 postmenopausal women. The analysis of the data determined that women who used estriol did not have an increased risk of breast cancer, compared to women who never used HRT.83 Additional evidence of estriol’s safety was provided by a study that compared use of HRT in 3,345 women over age 50 with breast cancer to 3,454 women without breast cancer. Those women who used non-bioidentical estrogen had a risk of breast cancer that was double that of women who never used HRT. However, women who used low-dose oral or topical estriol did not have an increased risk of breast cancer, compared to women who never used HRT.33

Intriguing research has uncovered that estriol might confer a protective effect against the development of breast cancer. This was demonstrated in an unpublished 35- to 40-year prospective study of 15,000 women who had pregnancies between 1959 and 1967. The women had samples of their blood frozen for 30 years or more. In 1997, the researchers thawed the blood and measured hormone levels to determine the relationship between estriol levels during pregnancy and subsequent incidence of breast cancer. The researchers found that breast cancer risk was reduced by 58% among women with the highest estriol levels compared to those with the lowest estriol levels.84 This study has important implications, as the findings suggest that having optimal estriol levels can play a pivotal role in the prevention of breast cancer.

Estriol and Uterine Cancer

The increased risk of uterine cancer in users of non-bioidentical estrogen is well-established in the scientific literature.85-87 In contrast, the use of topical lower-potency estriol is not associated with an increased risk of uterine cancer.88 Other studies have demonstrated that the use of intravaginal estriol has low risk. A review of 12 studies determined that the use of intravaginal estriol did not result in endometrial proliferation (abnormal overgrowth of the cells lining the uterus with the potential to become cancerous). The authors of the study concluded that “single daily treatment with intravaginal estriol in the recommended doses in postmenopausal women is safe and without an increased risk of endometrial proliferation or hyperplasia.”89

Although several studies suggest that the oral route of administration of estriol appears relatively safe over the short term (e.g., less than five years), topical application is preferred for long-term use. For example, one study found an increased risk of endometrial atypical hyperplasia and endometrial cancer with oral use of estriol, but not with topically applied estriol over a five-year period. Compared with individuals who did not take estriol, those who took oral estriol for at least five years had a significantly greater risk of uterine cancer.88 Women using topical estriol for at least five years did not have any increased risk.88 As you will read in the “Safety” box, several studies suggest that the use of topical bioidentical progesterone cream may further reduce the risk to the endometrium.90-92

Safety Concerns

Most of the research cited in this article used oral estrogen as the route of administration. For enhanced safety, topical estriol would be a better choice. Several studies have shown that transdermal and transmucosal estrogen confers fewer health risks than oral estrogen.88,93-96 Clinical experience of many doctors over the past 20-30 years suggests that transdermal and transmucosal estrogen is also more effective for some women’s symptoms.97 One reason for this difference is the ‘first-pass effect’—meaning that orally ingested drugs are often first metabolized in the liver, before having any activity in the body. Orally ingested estrogen hormones are among these drugs that are first metabolized in the liver before exerting their effects in the body. Physicians experienced in hormone replacement often observe that women treated with oral estrogens show high levels of estrogen metabolites in 24-hour urine specimens, suggesting that most of the orally ingested hormones are metabolized and then excreted.64,98

In addition, several studies suggest that bioidentical estrogen has fewer health risks when given with low doses of bioidentical progesterone.99,100

Bioidentical Progesterone and Cardiovascular Health

The Women’s Health Initiative, a large randomized clinical trial, demonstrated that the addition of non-bioidentical progestins to non-bioidentical estrogen therapy resulted in a substantial increase in the risk of heart attack and stroke.1,26 Numerous studies, on the other hand, document that bioidentical progesterone has beneficial effects on cardiovascular health. In one trial published in the Journal of the American College of Cardiology, researchers studied postmenopausal women with a history of heart attack or coronary artery disease. The women were given estrogen in combination with either bioidentical progesterone or non-bioidentical progestin. After 10 days of treatment the women underwent exercise treadmill tests. Compared to the non-bioidentical progestin group, the amount of time it took to produce myocardial ischemia (reduced blood flow to the heart) on the exercise treadmill was substantially improved in the bioidentical progesterone group.131

Bioidentical Progesterone and Cardiovascular Health

The risk of a blood clot is a serious concern with the use of unnatural estrogen replacement therapy, especially by the oral route. This risk doesn’t occur when bioidentical progesterone is added to the mix. One investigation compared the risk of blood clots in postmenopausal women taking bioidentical progesterone to the risk in women taking non-bioidentical progestin. The group of women who used non-bioidentical progestin in combination with estrogen had a startling 290% greater risk of blood clots, compared to the group who never used HRT. In a reversal of fortunes, the group receiving bioidentical progesterone in combination with estrogen had a 30% decreased risk of blood clots, compared to women who never used HRT.132

Atherosclerosis (hardening of the arteries) is the leading cause of heart disease. Several studies have determined that non-bioidentical progestin promotes the formation of atherosclerosis.133-135 The story is quite different for bioidentical progesterone, where multiple animal studies have shown that bioidentical progesterone inhibits the process of atherosclerosis.135-137 To illustrate, scientists fed postmenopausal monkeys a diet which is known to cause atherosclerosis for 30 months. The scientists then divided the monkeys into groups that received estrogen alone, estrogen plus non-bioidentical progestin, or a control group that did not receive hormones. The control group developed substantial atherosclerotic plaque. The administration of estrogen resulted in a 72% decrease in atherosclerotic plaque, compared to the control group. Treatment with non-bioidentical progestin yielded disturbing results. The group that received estrogen combined with non-bioidentical progestin had a similar amount of atherosclerotic plaque as the control group, meaning that non-bioidentical progestin completely reversed estrogen’s inhibitory effects on the formation of atherosclerosis.135 In contrast, when the same investigators administered bioidentical progesterone along with estrogen, no such inhibition of estrogen’s cardiovascular benefit was seen.138

Bioidentical Progesterone and HDL

High-density lipoprotein (HDL) functions to remove cholesterol from the arterial wall and thus helps protect against the development of atherosclerosis.139 Low HDL is a proven risk factor that contributes to heart disease. Non-bioidentical progestin is known to cause reductions in HDL levels.140-145 One mechanism by which bioidentical progesterone enhances cardiovascular health is its ability to maintain or even increase HDL levels in women receiving estrogen replacement therapy.141,142,146-148 In one study published in the Journal of the American Medical Association, 875 postmenopausal women were randomized to receive estrogen alone, estrogen combined with non-bioidentical progestin, estrogen combined with bioidentical progesterone, or placebo. The results demonstrated that the group receiving bioidentical progesterone experienced significantly higher HDL levels than the group receiving non-bioidentical progestin.141 These results confirm earlier preliminary data provided by researchers who administered estrogen combined with either non-bioidentical progestin or bioidentical progesterone to postmenopausal women. The use of non-bioidentical progestin resulted in an undesirable 15% decrease in HDL levels, whereas there was no decrease in HDL levels in those patients prescribed bioidentical progesterone.142

Estriol and Cardiovascular Health

Growing evidence suggests that estriol may offer benefits to the cardiovascular system. For instance, Japanese scientists found that a group of menopausal women given 2 mg/day oral estriol for 12 months had a significant decrease in both systolic and diastolic blood pressure.149 Another study compared the use of oral estriol at a dose of 2 mg/day for 10 months in 20 postmenopausal and 29 elderly women. Some of the elderly women had decreases in total cholesterol and triglycerides and an increase in beneficial HDL.150

To examine the effects of estriol on atherosclerosis, researchers conducted an experiment in which female rabbits were fed a high cholesterol diet with or without supplemental estriol. The rabbits had their ovaries removed surgically to mimic menopause. Remarkably, the group receiving estriol had 75% less atherosclerosis than the group fed the high cholesterol diet alone (without estriol).151

Bioidentical Progesterone vs. non-bioidentical Progestin for the Treatment of Menopausal Symptoms

Four head-to-head studies comparing bioidentical progesterone to non-bioidentical progestin reported that women experienced greater satisfaction, improved quality of life, and fewer side effects when they were switched from non-bioidentical progestin to bioidentical progesterone.

In a landmark study, researchers at the Mayo Clinic studied 176 menopausal women receiving hormone replacement therapy. All of these women had previously taken hormone replacement therapy with non-bioidentical progestin, but were switched at a later date to bioidentical progesterone. The findings across the board showed that women had substantially greater improvement in their symptoms when using bioidentical progesterone, compared to non-bioidentical progestin. Sixty-five percent of the women believed that HRT combined with bioidentical progesterone was better than HRT combined with non-bioidentical progestin. The beneficial effects of bioidentical progesterone compared to non-bioidentical progestin included a 30% reduction in sleep problems, a 50% reduction in anxiety, a 60% reduction in depression, a 25% reduction in menstrual bleeding, a 40% reduction in cognitive difficulties, and a 30% improvement in sexual function. Eighty percent of women in the study reported overall satisfaction with the bioidentical progesterone formulation.152 The results of this study provide evidence of the superiority of bioidentical progesterone over non-bioidentical progestin in the treatment of menopausal symptoms.

Further research supports the use of bioidentical progesterone in preference to non-bioidentical progestin. One study of menopausal women receiving HRT found that those receiving non-bioidentical progestin experienced greater vaginal bleeding and breast tenderness than those receiving bioidentical progesterone.153 Two other studies with menopausal women also determined that HRT with non-bioidentical progestin was associated with greater vaginal bleeding compared to those receiving bioidentical progesterone.154,155 Bioidentical progesterone also offers improvements in quality of sleep and cognitive function compared with non-bioidentical forms of the hormone.156,157

Estriol and Menopausal Symptoms

Studies have shown estriol to be effective in the treatment of menopausal symptoms. In one investigation, 52 postmenopausal women were given 2 mg, 4 mg, 6 mg, or 8 mg/day of oral estriol for six months. In all patients, vasomotor symptoms of menopause (such as hot flashes) were decreased. The most improvement was experienced by women taking the highest dose of 8 mg. There were no signs of endometrial hyperplasia confirmed by endometrial biopsy over the six-month treatment period. Mammograms were obtained on six of the patients who had breast hyperplasia at the study’s outset, and no further changes were seen.158

Estriol and Menopausal Symptoms

In another trial, researchers studied the safety of estriol in the treatment of menopausal symptoms. Fifty-three women with either surgically induced or natural menopause were given 2 mg of oral estriol/day for 12 months. Endometrial biopsy and breast ultrasound found normal results in all women. The authors concluded that over a 12-month period, “estriol appeared to be safe and effective in relieving symptoms of menopausal women.”149

A 5-year study demonstrated the successful use of estriol in the treatment of menopausal symptoms. In 71% of the participants, hot flashes and sweating were eliminated completely, while in 21% they were weaker and occurred less frequently. Depressive moods were abolished in 24% of the women and were reduced in severity in another 33%. Reductions in forgetfulness, loss of concentration, irritability, and heart palpitations were also recorded, while the number of women who experienced migraine headaches dropped by two-thirds. Thrombophlebitis occurred in two patients and there were two cases of mammary cancers, which the investigators did not believe were related to the estriol treatment.159

Given the wealth of data demonstrating the superiority of bioidentical HRT over non-bioidentical HRT, a noted researcher in hormone replacement therapy proclaimed that “Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their… animal-derived [non-bioidentical] counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT.”82

Beyond Menopause: Enhancing Health with Bioidentical Hormones

The benefits of bioidentical hormones are by no means limited to the relief of menopausal symptoms. Maturing women can reap long-term health benefits by restoring youthful hormonal balance with the use of bioidentical hormones. The Life Extension Foundation® has written extensively regarding the importance of maintaining optimal hormone balance as we age in order to ensure optimal health.

Estriol Increases Bone Mineral Density

One of the unfortunate consequences of decreased estrogen production in maturing women is the loss of bone density, with the potential to develop osteoporosis. A Japanese study involving 75 postmenopausal women found that after 50 weeks of treatment with 2 mg/day of oral estriol cyclically and 800 mg/day of calcium lactate, women had an increase in bone mineral density with no increased risk of endometrial hyperplasia (uterine tissue overgrowth that may precede cancer).160 In a second study emanating from Japan, researchers treated postmenopausal and elderly women with 2 mg/day of oral estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate alone. Bone mineral density significantly increased in women who received estriol, while the women who did not take estriol experienced a decrease in bone mineral density.150

Estriol Increases Bone Mineral Density

Similar research has confirmed these findings. In this investigation, 25 postmenopausal women were given either 2 mg/day of estriol plus 2 gram/day of calcium lactate, or 2 grams/day of calcium lactate alone for one year. Bone mineral density was significantly reduced in the group that received calcium alone (without estriol). In contrast, the group that received estriol plus calcium experienced a 1.66% increase in bone mineral density after one year. Furthermore, biochemical markers of bone resorption were significantly decreased in the estriol group. “These data indicate that the acceleration of bone turnover usually observed after menopause was prevented by treatment with E3 [estriol],” the authors of this study noted.161

The most dramatic improvements in bone density were reported by scientists in the Journal of Bone and Mineral Metabolism. In this study, 41 women over age 49 with decreased bone density received either 2 mg/day estriol orally with calcium, or calcium alone for 10 months. The group receiving estriol experienced a striking 5% increase in bone density, while the group that did not receive estriol experienced a 3% decrease in bone density.162

Estriol Enhances Sexual and Urinary Health

Postmenopausal women often suffer from urinary incontinence or recurrent urinary tract infections caused in part by hormone deficiencies.

In a prospective, randomized, placebo-controlled study, 88 women were given 2 mg intravaginal estriol suppositories (once daily for two weeks, then twice weekly for six months) or placebo. Of the women in the estriol group, 68% reported improvement in symptoms of incontinence, while only 16% improved in the placebo group.163

In another randomized, double-blind, placebo-controlled trial, women with recurrent urinary tract infections were given either intravaginal estriol cream (containing 0.5 mg estriol, once daily for two weeks, then twice weekly for eight months) or placebo. Incredibly, the incidence of urinary tract infection was reduced by 91% in the estriol group compared with placebo.164

The substantial decrease in estrogen that occurs after menopause can lead to a condition called atrophic vaginitis. The symptoms, which include vaginal dryness, vaginal burning, and painful sex can be quite bothersome for aging women. Fortunately, the use of estriol can offer relief for women suffering from these symptoms. One group of researchers, who prescribed oral estriol to 62 postmenopausal women with vaginal symptoms in a double-blind and placebo-controlled fashion, concluded that “estriol has a remarkably beneficial effect on the vaginal epithelium.”165 Another group of researchers prescribed an estriol cream for women with atrophic vaginitis. After 4 weeks of treatment, the researchers noted that “atrophy of vaginal epithelium and chronic vaginitis stopped or significantly decreased… The subjective complaints relating to the estrogen deficiency (vaginal burning and dryness, itching, dyspareunia [painful sex] and urinary dysfunctions) ceased. Side-effects and complications during the treatment were not found.”166

In a study conducted in Japan, oral estriol (2 mg/day) was administered to 59 postmenopausal women complaining of vaginal itching or discharge. After 14 days of treatment, substantial improvements were noted in the women’s vaginal flora. The authors of the study concluded: “Estriol… has the potential to be highly useful for the treatment of atrophic vaginitis.”167

Estriol Promotes Youthful Skin

One reason that facial skin “shrivels” as we age is that our natural hormone production markedly declines. To make matters worse, blood microcirculation to our skin is reduced as we grow older, thereby depriving our skin of the small amount of natural hormones our body still makes.168 A large number of published scientific studies reveal that estrogen exerts potent anti-aging effects on the skin.169-178 The topical application of natural estrogen can produce dramatic improvements to the skin without systemic absorption concerns.

The deficiency of estrogen that characterizes menopause exacerbates the effects of both normal and environmentally-induced skin aging. According to the findings of a scientific study published in 2007, “Estrogens prevent skin aging. They increase skin thickness and improve skin moisture.”178 Another recent study came to the same conclusion, i.e. “skin aging can be significantly delayed by the administration of estrogen.”170

A critical mechanism by which estrogen maintains a youthful plump appearance is by increasing the synthesis of collagen, which is the skin’s underlying support structure. Collagen atrophy is a major factor in skin aging. There is a strong correlation between skin collagen loss and estrogen deficiency at menopause.169

Skin aging, especially in the face, is associated with a progressive increase in sagging tissues and a reduction in elasticity. In menopausal and postmenopausal women, estrogen administration increases collagen content, dermal thickness and elasticity, while decreasing aging dry skin.169,172

Estriol Promotes Youthful Skin

Estrogens exert significant effects on skin physiology by modulating the effects of key epidermal and dermal cells.170 In fact, the skin is an important estrogen-responsive tissue, and without the growth promoting effects of estrogen, it literally withers away.171 The very thin skin observed in the elderly can be directly correlated to a lack of estrogens needed to generate collagen and maintain skin thickness.171

Topical estrogen application has been shown to be safe and effective in preventing skin aging. In a study published in February 2007, a group of women who were already taking oral estrogen drugs were given a topical 0.01% estrogen cream. After only four months, both dermal and epidermal thickness was enhanced, as were dermal collagen levels. This study showed that topical estrogen application provided rapid and definitive anti-aging effects even in women who had high systemic estrogen blood levels.172 The significance of this study is that it shows how quickly a small amount of estrogen delivered directly into the skin induces profound anti-aging effects.

A six-month study of perimenopausal women was conducted at the University of Vienna in Austria comparing the topical application of estriol and estradiol creams. The doctors found that skin symptoms of aging improved, and that those treated with estriol obtained superior results in decreased wrinkle depth, with no systemic hormonal side effects noted.173

In another study, twenty women with mild crow’s feet, rough-textured skin, and moderate skin tone with some blotching and imperfections applied a topical solution containing estriol with 15 other ingredients on only one side of their faces over a six-week period. All of the subjects reported that their skin texture on the treated side was smoother and that the quality of their skin had improved, while 90% and 80% said that the moisture content and elasticity of their skin had increased, respectively, giving them a healthier and younger-looking appearance. Clinical assessments showed a baseline improvement of 19% increase in elasticity and 9% increase in moisture in the skin after just one week.179

How Bioidentical Estrogen-Progesterone Is Prescribed

Currently, widespread commercial availability of individually tailored bioidentical hormone prescriptions is lacking. As a result, many physicians utilize compounding pharmacies to dispense bioidentical hormone prescriptions for their patients. To obtain the phone number of a compounding pharmacist, call 1-866-864-3027.

Most practitioners use the level of estradiol in women’s blood, along with an assessment of the patient’s clinical symptoms to prescribe the initial dose of bioidentical estrogen. The estradiol blood level must be considered in context to the other hormones such as progesterone. A health care practitioner may also measure levels of estrone and estriol to obtain a more comprehensive assessment of a woman’s estrogen status.

In menopause, a woman typically has an estradiol blood level of 0-19 pg/mL. With the use of bioidentical estrogen topical cream (e.g., compounded estriol and estradiol), the blood estradiol level may go to 100 pg/mL or higher, which indicates to the prescribing doctor that the compounded estrogen formula is being absorbed and has increased the patient’s estradiol level to a more youthful range.

If the patient reports that her menopausal symptoms have resolved, most practitioners would continue the patient on the current program and conduct periodic follow-up.

If, however, the patient is still having symptoms, the bioidentical estrogen topical cream dose can be increased or additional tests ordered such as the total estrogen blood test or a urinary estrogen test to assess other estrogens and their associated metabolites. Based on findings from these tests, a more precise dose of estriol, estradiol, progesterone, and sometimes testosterone can be prescribed. A typical starting dose for bioidentical estrogen topical cream might read as:

Please note that this is a general suggestion for an initial prescription. A physician experienced in bioidentical hormone replacement will tailor the prescription to the person’s individual needs.

Women given estrogen replacement should also be prescribed natural progesterone (in contrast to synthetic progestin drugs like Provera®) in a dose that achieves a youthful balance. Natural progesterone produces many benefits when properly balanced with estrogen. The typical dose for topical progesterone cream may vary between 50-200 mg, depending upon a woman’s unique, individual biochemical needs.

A typical starting dose for over-the-counter (OTC) progesterone cream is one-quarter teaspoon of a 2.5% strength progesterone cream applied to a different part of the body twice each day:

* Premenstrual and perimenopausal women: 1/4 tsp. of a 2.5% progesterone topical cream (approximately 30 mg. natural progesterone) twice daily starting on day 12 of the menstrual cycle continuing up to day 28).
* Menopausal women: 1/4 tsp. twice daily for 21 days followed by 7 days off.

The dose can be adjusted up or down depending on a woman’s symptoms and her response to treatment. If using natural progesterone cream from a pharmacy, a prescription could be written as follows for a postmenopausal woman:

A prescription for a premenopausal woman could also read:

Some physicians will prescribe topical progesterone in a similar way to estrogens, in milligrams per fraction of a cubic centimeter (cc).These dosages are “pressed out” of a syringe onto the skin, and have the dual advantages of more precise dosage adjustment and smaller volume of “crème,” which is less likely to make a mess on clothing.

A blood level target to strive for in aging women might be:

* Estradiol 90-250 pg/mL
* Progesterone 2.0-6.0 ng/mL
* Free testosterone 1.0-2.2 pg/mL

Before a prescription for bioidentical hormones can be written, it is important to have a baseline blood test so the doctor knows what dose of bioidentical estrogens, progesterone, and possibly testosterone may be needed. To order a comprehensive Female Blood Test Panel that includes estradiol, progesterone, and free testosterone, call 1-866-864-3027.

Although this paper focuses on bioidentical estrogen and progesterone, it is important to also address testosterone levels in order to achieve optimal hormonal balance. Although testosterone is thought of as a male hormone, it plays an important role in women’s health as well. Testosterone levels decrease in women as they age. Low testosterone in women can have a negative impact upon sex drive, mood and well-being, bone and muscle mass, and cardiovascular health.180-183 A physician experienced in bioidentical hormone therapy will measure testosterone levels in women, and prescribe bioidentical testosterone if levels are low. Correcting low testosterone in women usually requires a 150 to 300 mcg patch or an individually prescribed testosterone cream.184 Since DHEA (dehydroepiandrosterone) can convert to testosterone in a woman’s body, a woman with low testosterone might be able to increase her testosterone level by taking 15 mg to 25 mg a day of DHEA, which is available as a low cost dietary supplement.185

Too much free testosterone in an aging woman induces abdominal weight gain,186,187 as does a deficiency of estradiol.188-191 Progesterone may be weight-neutral,192 though some complementary practitioners claim it helps facilitate weight loss. Some doctors seek to increase progesterone levels up to 15 ng/mL.

The overall objective is to achieve a more youthful hormone balance to improve the patient’s appearance, state of health, and well-being. The use of estrogen drugs is contraindicated in women with existing estrogen receptor-positive cancer.

Why Skeptics Are Still Concerned About Estriol

Based on what you have read so far, topical estriol appears to be a safe and optimal antidote to correct estrogen deficits. Not everyone agrees, however.

Some doctors are concerned that the long-term use of estriol might increase cancer risk. These doctors seem unaware of the evidence indicating that estriol may reduce breast cancer incidence, or of documented methods to protect against estrogen-induced side effects.

Bioidentical Progesterone vs. non-bioidentical Progestin for the Treatment of Menopausal Symptoms

Unlike cynics who view any form of estrogen as a carcinogen, the Life Extension Foundation® has examined the published studies to ascertain what real risks may exist when supplementing with estriol (and other estrogens).

One concern about all estrogens is that they undergo alterations in the body that can result in these estrogens cascading into either pro-carcinogenic or anti-carcinogenic compounds. The good news is that one can affect whether estrogens increase or decrease cancer risk via their diet and/or supplement intake.

Skeptics view estriol supplementation in a vacuum, as if women will take estriol and do nothing else. You have already read extensive documentation about how natural progesterone significantly protects against estrogen-induced cancers. What you will read next is what all women should do to reduce breast and other cancer risk (whether or not they take supplemental estrogen).

These recommendations are based on large human population studies showing huge reductions in cancer risk and specific protective mechanisms against estrogen’s negative pathways when vitamin D, cruciferous vegetables, soy, D-glucarate, and/or plant lignans are consumed. These cancer rate reductions also occur when red meat, high-fat dairy, and other deleterious foods are reduced or eliminated from the diet.

Anticancer Nutrients That Complement Bioidentical HRT
Critical Importance of Vitamin D

Young women (under age 30) almost never develop breast cancer. As women age, their cell growth-regulatory genes accumulate mutations. As our bodies age, we become less proficient at rapidly repairing (or removing) damage to the cells and tissues of our bodies. When genes that regulate cell division undergo mutation, the result can be uncontrolled cell propagation that results in tumor formation. Aging women experience a dramatic rise in cancer incidence, even as their estrogen levels plummet.

In the presence of changes to genes involved in the growth and proliferation of breast tissue cells, estrogen can promote cancer cell propagation. The good news is that the ingestion of vitamin D, cruciferous vegetables, and other compounds can prevent and help repair gene mutations and thus reduce cancer risk. All women (including those who maintain youthful estrogen levels) should make sure they are ingesting optimal amounts of vitamin D and other compounds that favorably alter gene expression.

How Bioidentical Estrogen-Progesterone Is Prescribed

Vitamin D confers significant protective effects against breast cancer. Laboratory studies have shown that vitamin D suppresses growth of breast cancer by 1) blocking signals that stimulate cancer cell growth, 2) by enhancing signals that inhibit cancer cell growth, and 3) by favorably altering gene regulators of the cell cycle.195-198 This three-pronged effect of vitamin D can prevent mutated cells from becoming malignant and even induce cancer cell death (apoptosis).

Studies have found a strong correlation between blood levels of vitamin D and the risk of breast cancer. A case-control study comparing 1,394 postmenopausal breast cancer patients with 1,365 controls showed that low blood levels of vitamin D were significantly related to breast cancer risk. In fact, women with the highest levels of vitamin D had a nearly 70% reduction in their risk of breast cancer, compared to women with the lowest vitamin D levels.199

Similar research examining the relationship between blood levels of vitamin D and breast cancer risk revealed that women with blood vitamin D levels of approximately 52 ng/mL had a 50% lower risk of breast cancer compared with women who had vitamin D levels below 13 ng/mL.101

In a one report, the effects of administering 1,100 IU a day of vitamin D (with calcium) was evaluated in 1,180 postmenopausal women.127 After only four years, the risk of developing any cancer was 60% lower in the vitamin D (and calcium) group, compared with those who received calcium only. The scientists then performed a more detailed analysis of the data. When excluding cancers diagnosed in the first year of the study, which would have included pre-existing cancers present at the time participants began taking vitamin D, they found an astounding 77% reduction in cancer incidence in the group receiving vitamin D, compared with placebo.

Ensuring vitamin D blood levels over 50 ng/mL is a critical step in reducing cancer risk. Life Extension® is finding that many people require 5,000 IU a day of supplemental vitamin D3 and higher to achieve these optimal blood levels. These doses have been shown to be both effective and safe in human trials.200,201 The heavier one is, the more supplemental vitamin D they often require. (Note that vitamin D status in the body is measured as serum 25-hydroxvitamin D.)

Cruciferous Vegetables Protect Against Tumor-Proliferating Estrogen Metabolites

Scientists have identified compounds in cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, cabbage, kale) that specifically neutralize dangerous breakdown products of estrogen that promote cancer growth.104,202 Cruciferous vegetable compounds also help neutralize the many carcinogens we are inevitably exposed to each day.106-109,203 One of the best-studied cruciferous vegetable compounds is called indole-3-carbinol (I3C). Women seeking to restore youthful hormone balance should make sure to obtain enough I3C from their diet or by taking standardized supplements. The reason for this is that I3C increases levels of a cancer-protective estrogen metabolite (2-hydroxyestrone), while suppressing a dangerous estrogen metabolite (16-alpha-hydroxyestrone) that promotes breast and other cancers.193,194

To emphasize the critical importance of indole-3-carbinol (I3C), please understand that aging women still produce estrogen. All the estrogen in women’s bodies (both endogenously produced and supplemental) can follow two primary metabolic pathways in the body. If estrogen is converted to 16-alpha-hydroxyestrone, then the risk of breast and other cancers is increased. If on the other hand, the estrogen is converted to 2-hydroxyestrone, then the risk for breast and other cancers is decreased.204,205

I3C can readily be obtained by eating lots of cruciferous vegetables and/or taking I3C in dietary supplement form.

To confirm the theory that certain estrogen metabolites can contribute to cancer, researchers analyzed data gathered from over 10,000 Italian women over more than five years. The objective was to determine how dietary and hormonal factors influence breast cancer risk. They found that among premenopausal women, higher levels of 2-hydroxyestrone were associated with protection against breast cancer.204 This same finding has been shown in additional studies of different populations.206,207

The toxic estrogen metabolite 16-alpha-hydroxyestrone acts as a breast tumor promoter.110 By contrast, estrogen metabolized via the 2-hydroxyestrone pathway does not exhibit adverse estrogenic activity in breast tissue.110 Additionally, a form of this less active estrogen metabolite is believed to prevent the formation of blood vessels necessary to feed growing cancers, thus helping to arrest tumor growth.208

Cruciferous vegetable compounds (such as I3C) are effective in shifting estrogen metabolism to the more beneficial pathway, thus reducing levels of toxic 16- alpha-hydroxyestrone and increasing levels of protective 2-hydroxyestrone.110-112,205

This beneficial modulation of estrogen is associated with reduced risk of breast and other cancers, including cervical and head and neck cancers.106,204,205 Cruciferous vegetable compounds thus play an important role in fighting cancer. To illustrate, research conducted at the University of California at Berkeley documented that I3C in combination with the anti-estrogenic chemotherapeutic agent tamoxifen inhibited the growth of human breast cancer cells by an astounding 90%.209

Interestingly, an assay study performed at the National Cancer Institute determined that I3C was superior to 80 other natural substances with regard to anti-cancer potential.210

Soy Slashes Breast Cancer Risk

For the past decade, a controversy has raged over whether people can reduce their risk of cancer by increasing their consumption of soy foods or soy supplements. In response to the debate, a number of studies were initiated in the 1990s to ascertain soy’s effects on human health.

Over the past few years, the results of these studies began to be released. While ignored by the mainstream media, the startling findings indicate that breast (and prostate) cancer risk can be cut in half if people consume more soy.125,211,212

One recent study showed that women who a Western-style style, high in meats and sweets, had nearly twice the risk of developing estrogen receptor-positive breast cancer, compared with women who ate a traditional Asian diet high in soy and vegetables.125 This and other studies provide evidence that compounds found in soy have a breast cancer-preventive effect.

Isoflavones derived from soy have shown great promise in providing natural protection against multiple types of cancer.114-116 Two of the best known soy isoflavones are genistein and daidzein.

Isoflavones exert a number of positive biological effects on the human body, and many practitioners of integrative medicine (and even a small but growing number in mainstream medicine) now believe that consumption of soy and isoflavones can reduce the risk of many chronic diseases, including cancer, heart disease, and osteoporosis.113-116,211-217

Studies conducted in Asia found that breast cancer risk was significantly lower among Asian women who consumed large quantities of isoflavones and other soy products, compared with those who consumed less of these healthful nutrients.115 Because animal studies have shown that a diet high in soy and genistein can protect against breast, colon, and skin tumors, it seemed reasonable to think that soy could also help prevent human cancers and, in particular, breast cancer.218Yet many mainstream medical practitioners remain skeptical that something as simple as soy could have such a profound effect on human health.

Soy isoflavones are correctly classified as selective estrogen receptor modulators.219 Due to their unique molecular structure, soy isoflavones can act as both estrogen receptor agonists and receptor blockers. In fact, elegant biochemical studies have shown that some isoflavones bind to the cancer-protective estrogen beta receptor six to eight-fold more readily than native estrogen.219 With this ability, soy isoflavones are thought by many to confer the beneficial effects of estrogen without its potentially dangerous side effects, especially in hormonally sensitive tissues found in both the breast and endometrium.219

Numerous studies show the potential benefits to women of incorporating soy in their diets to help prevent breast cancer. A landmark case control study of women in Singapore, involving 200 case subjects and 420 control subjects, found that women with the highest consumption of soy-based products had a markedly decreased risk of developing breast cancer.117 Finally, a very large population-based, prospective study of 21,852 Japanese women aged 40-59 found that women with the highest intake of soy isoflavones reduced their risk of breast cancer by up to 54%, compared with women with the lowest intake of soy isoflavones.115

In addition to being a chemopreventive supplement for breast cancer, soy isoflavones are also thought to be effective in warding off other types of cancer that afflict women, including endometrial cancer. A recent case control study reported the effects of soy isoflavones and other phytoestrogens on the risk of developing endometrial cancer.220 The study compared 500 women aged 35-79 who developed endometrial cancer between 1996 and 1999 with 470 age- and ethnicity-matched controls. As in studies examining the effects of isoflavones on breast cancer, this study showed that women with a higher intake of soy isoflavones had a significantly lower risk of developing endometrial cancer. Even more interesting was that the levels of isoflavones needed to provide protection against endometrial cancer were found to be much lower than the amount believed necessary to protect against breast cancer (in fact, they were the amounts that could be obtained from a healthy American-style diet).

Meat Increases Breast Cancer Risk

Studies that look at human populations (epidemiological studies) have consistently shown that what we eat affects our cancer risk. Women who eat more red meat suffer higher breast cancer rates. In one of the better documented studies, postmenopausal women in China who ate a Western-style diet (which included beef, pork, and desserts) were 30% more likely to develop breast cancer than those eating a diet based on vegetables and soy. Even more startling was the finding that in women who developed estrogen receptor-positive breast tumors, those who ate the Western-style diet experienced a 90% increased risk!125 This is in stark contrast to a study that demonstrated a 52% decreased risk of breast cancer in women with the highest intake of vegetables and fruits, compared to the lowest intake.221

However, it’s not known whether meat from “free range” animals (beef, buffalo, wild game, chicken, pigs) also increases breast cancer risk. While even organically raised, grain-fed animals (like commercially raised grain-fed animals) have much more omega-6 (pro-inflammatory) fatty acids than omega-3 (anti-inflammatory) fatty acids, this ratio is reversed in meat from free-range animals, with significantly more omega-3 than omega-6 fatty acids.222 Theoretically, this much more natural ratio should be associated with lower breast (and other) cancer risk, but research still needs to be done on this point.

Fish Oil and Breast Cancer Risk

In addition to fish oil’s well-known cardiovascular benefits, research has revealed that omega-3 rich fish oil might offer protection against breast cancer as well. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two most important components of fish oil. One investigation documented a 49% decreased risk of breast cancer in women with the highest dietary intake of omega-3 fatty acids, compared to those with the lowest intake. Furthermore, women with the highest red blood cell levels of EPA had a remarkable 73% decreased risk of breast cancer, compared to those with the lowest levels.223

A group of researchers in France compared levels of DHA in breast tissue in 241 patients with breast cancer and 88 patients with non-cancerous benign breast disease. They reported that women with the highest levels of DHA in their breast tissue had a 69% decreased risk of breast cancer, compared to women with the lowest levels of DHA in their breast tissue.224

Why Plant Foods Are So Important

The body is bombarded with carcinogens on a daily basis. These cancer-causing agents include pesticides, overcooked food, alcohol, food additives, tobacco, fungal mutagens, and industrial pollutants. While avoiding carcinogens is difficult, it may be possible to mitigate their lethal effects by providing the body with a specific plant extract that facilitates the detoxification and removal of these dangerous substances from the body.

A compound called D-glucarate is found in grapefruit, apples, oranges, broccoli, and Brussels sprouts.225,226 D-Glucarate has been shown to protect against cancer-causing agents by supporting detoxification and removal of dangerous chemicals, and also by protecting against the mutating effects that these carcinogens induce on cellular DNA.227

There are several mechanisms by which the body detoxifies itself. One way of guarding against toxic overload involves a pathway of detoxification in the body whereby carcinogens are combined with water-soluble substances, thus making them more easily removed from the body. This process is called glucuronidation, and D-glucarate has been shown to support this important detoxification mechanism.227

D-Glucarate functions by inhibiting the beta-glucuronidase enzyme, thus protecting the critical “glucuronidation” detoxification mechanism. One example of the importance of glucuronidation can be seen in the risk factors for breast cancer. Excess levels of 16-alpha-hydroxyestrone and beta-glucuronidase enzyme activity are associated with an increased incidence of breast cancer.228 D-Glucarate is thought to decrease estrogen’s effects by favorably affecting estrogen’s metabolism and elimination.

Research studies have shown that D-glucarate inhibits breast tumor incidence.118,119 One study in rats that already had breast cancer showed that oral

D-glucarate administration resulted in a 50% inhibition of beta-glucuronidase, which led to a 30% reduction in mammary tumor growth during the promotion stage and a four-fold reduction in the absolute number of tumors.229 Another report showed a more than 70% decrease in mammary tumor development in rats exposed to carcinogens that were also administered D-glucarate.120 Still another study looked at the effects of D-glucarate on the initiation and promotional stages of mammary cancer. The results showed a reduction of 28% during the initiation stage, while cell replication was reduced by 42% during the promotion stage.121 Inhibition at the initiation stage is a very important part of D-glucarate’s actions, as it reduces the risk that cancer will even start.

Eating lots of the right fruits (grapefruit, apples, cherries) and vegetables (broccoli, Brussels sprouts) supplies the body with D-glucarate, though it is also available in dietary supplements designed to support breast health.

How Lignans Protect the Breast

A number of published studies indicate that dietary lignans may protect against cancer by favorably altering estrogen metabolism, inhibiting angio-genesis, and inducing cancer cells to self destruct.122,123 The greatest support for a role of lignans in cancer prevention has been shown for premenopausal breast cancer.

Researchers in New York assessed breast cancer risk and dietary lignan intake in more than 3,000 women, including about 1,100 patients with confirmed breast cancer and approximately 2,000 cancer-free women who served as controls. The scientists determined that premenopausal women with the highest lignan intake had a 44% reduced risk of developing breast cancer.122

Scientists in Italy suggest a mechanism for the protective effect. Their research indicates that higher blood levels of a phytoestrogen called enterolactone—the primary lignan derived by the body from flaxseed—are associated with a lower risk of breast cancer. Conversely, the researchers noted, “values of serum enterolactone were significantly lower in women who subsequently developed breast cancer,” leading them to conclude that the enterolactone “had a strong protective effect on breast cancer risk.”123

Scientists at the University of Toronto reported that flax lignans can slow down the growth of breast cancer in women. Thirty-two women awaiting surgery for breast cancer were randomized to receive a muffin containing 25 grams of flaxseeds or a muffin that did not contain flaxseed (control group). Analysis of the cancerous tissue after surgery revealed that markers of tumor growth were reduced by 30%-71% in the flaxseed group, while the control group did not experience any reduction in markers of tumor growth. The scientists concluded that “dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.”230

Lignans may also protect against endometrial cancer, a condition associated with prolonged exposure to unopposed estrogens (this means estrogen administered without progesterone). Researchers in California assessed lignan intake and cancer status among nearly 1,000 women in the San Francisco area and determined that women with the highest dietary lignan intake experienced a promising trend toward a lower risk of developing this carcinoma of the uterine lining.220 The relationship between lignans and endometrial cancer risk reduction was slightly stronger among postmenopausal women.

Based on a lot of favorable publicity, health-conscious people are increasingly adding flaxseed to their diet for the purpose of obtaining the beneficial lignans. Highly concentrated lignan extracts are also available in dietary supplements.

Green Tea’s Anti-Cancer Effects

Green tea is rich in plant compounds known as polyphenols. The most active group of green tea polyphenols is the catechins, particularly epigallocatechin gallate (EGCG). Copious evidence supports a role for these compounds in preventing breast cancer. In laboratory studies, green tea polyphenols and EGCG have been shown to suppress the growth and reproduction of human breast cancer cells.231,232 Of even greater interest, these beneficial compounds in green tea delay the appearance of tumors in mouse models of breast cancer and cut down on the total tumor burden (amount of cancer in the body) when human breast cancer cells are injected into laboratory mice.232,233

Why Plant Foods Are So Important

Other exciting benefits of green tea include inhibition of vascular endothelial growth factor (VEGF) production,233,234 which cuts off the blood supply needed for tumor growth; down-regulation of estrogen receptor-alpha function in breast cancer cells;235 reduction of tumor invasiveness;233 and increased apoptosis, or programmed cell death, in cancer cells.236

One experiment showed that EGCG, 50-100 mg/kg/day, added to the drinking water of female mice, inhibited growth of breast cancer. After five weeks of EGCG treatment, the weight of breast tumors was reduced by 68% in mice consuming EGCG daily.237

But green tea’s benefits aren’t restricted to animal or laboratory models. An investigation found a 47% decreased risk of breast cancer in women who drank at least 3 cups per day of green tea, compared to those who did not consume any green tea.238

The medical establishment questions the use of bioidentical hormones out of concern about cancer risks. Earlier in this article, we outlined persuasive data showing the anti-cancer properties of estriol and natural progesterone.

When factoring in the potent anti-cancer effects that occur in response to consuming healthy foods (such as broccoli and soy) and supplements (such as vitamin D and fish oil), while avoiding carcinogenic foods (such as sugar and well-done meat), the argument that maturing women should forever be denied their full complement of natural sex hormones does not stand up to scientific scrutiny.


Dr. Kent Holtorf, MD, a specialist in bioidentical hormone therapy and anti-aging medicine stated:

“A thorough review of the medical literature clearly supports the claim that bioidentical hormones have some distinctly different, often opposite, physiological effects to those of their synthetic [non-bioidentical counterpart] hormones. With respect to the risk for breast cancer, heart disease, heart attack, and stroke, substantial scientific and medical evidence demonstrates that bioidentical hormones are safer and more efficacious forms of HRT than commonly used synthetic versions.”82

Given the preponderance of evidence, maturing women should feel confident that bioidentical hormone replacement, when appropriately prescribed, offers a safer and potentially even more effective alternative to conventional hormone replacement with non-bioidentical hormone drugs to help relieve menopausal symptoms and optimize long-term health. The addition of several proven nutrients to a bioidentical hormone regimen may help optimize estrogen metabolism and reduce cancer risk even further, offering an optimal, balanced approach to health maintenance.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027 or visit

Acknowledgement: The Life Extension Foundation® would like to thank the following diverse group of experts in the scientific disciplines of allopathic medicine, nutrition, biochemistry, and integrative health care for their independent, peer-review of this position paper.

John Boik, PhD
James Cennamo, DO
Mark L. Gordon, MD
Steven Harris, MD
Kent Holtorf, MD
Richard Kratz, MD
Peter Langsjoen, MD
Erika Schwartz, MD
Jonathan Wright, MD


1. JAMA. 2002 Jul 17;288(3):321-33.
2. JAMA. 2004 Apr 14;291(14):1701-12.
3. Ann Intern Med. 2004 Jul 20;141(2):118-25.
5. Climacteric. 2002 Sep;5(3):229-35.
6. J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.
7. Breast Cancer Res Treat. 2001 Aug;68(3):187-98.
8. J Clin Endocrinol Metab. 1999 Dec;84(12):4559-65.
9. Cancer Res. 1992 Dec 1;52(23):6539-46.
10. Mol Cell Endocrinol. 1994 Jun;102(1-2):45-52.
11. Cancer Res. 1990 Dec 15;50(24):7858-62.
12. Biochem Biophys Res Commun. 1987 Jun 15;145(2):706-11.
13. Br J Cancer. 1993 May;67(5):945-52.
14. Breast Cancer Res Treat. 2007 Jan;101(2):125-34.
15. Breast Cancer Res Treat. 1998 Apr;48(3):221-9.
16. Am J Obstet Gynecol. 1996 Jan;174(1 Pt 1):93-100.
17. Cancer Lett. 1986 Feb;30(2):213-8.
18. Fertil Steril. 1995 Apr;63(4):785-91.
19. Fertil Steril. 1998 May;69(5):963-9.
20. Climacteric. 2003 Sep;6(3):221-7.
21. Jpn J Cancer Res. 1985 Aug;76(8):699-704.
22. J Gynecol Obstet Biol Reprod (Paris). 1990;19(3):269-74.
23. J Steroid Biochem Mol Biol. 2000 Jun;73(3-4):171-81.
24. Breast Cancer Res Treat. 1986;8(3):179-88.
25. Int J Cancer. 2005;114:448–54.
26. JAMA. 2003 Jun 25;289(24):3243-53.
27. Cancer Causes Control. 2002 Nov;13(9):847-54.
28. Br J Cancer. 2005 Jun 6;92(11):2049-58.
29. Br J Cancer. 2005 Apr 11;92(7):1293-7.
30. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):593-600.
31. Int J Cancer. 2004 May 1;109(5):721-7.
32. Maturitas. 2004 Sep 24;49(1):44-50.
33. Int J Cancer. 1999 May 5;81(3):339-44.
34. JAMA. 2000 Aug 9;284(6):691-4.
35. J Natl Cancer Inst. 2000 Feb 16;92(4):328-32.
36. Am J Obstet Gynecol. 2004 Apr;190(4):1141-67.
37. Obstet.Gynecol. 2002 Dec;100(6):1148-58.
38. JAMA. 2003 Jun 25;289(24):3254-63.
39. Lancet. 2003 Aug 9;362(9382):419-27.
40. Cancer Causes Control. 2002 Aug;13(6):583-90.
41. Lancet. 1997 Oct 11;350(9084):1047-59.
42. JAMA. 2000 Jan 26;283(4):485-91.
43. Am J Epidemiol. 1998;147:S45.
44. Cancer Causes Control. 1999 Aug;10(4):253-60.
45. JAMA. 2002 Feb 13;287(6):734-41.
46. Steroids. 2000 Oct;65(10-11):659-64.
47. J Clin Endocrinol Metab. 2001 Jan;86(1):16-23.
48. Acta Obstet Gynecol Scand. 2003 Jul;82(7):335-44.
49. Breast Cancer Res Treat. 2008 Jan;107(1):103-11.
50. Cancer Detect Prev. 1999;23(4):290-6.
51. Int J Cancer. 2004 Nov 1;112(2):312-8.
52. Am J Epidemiol. 1981 Aug;114(2):209-17.
53. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):361-8.
54. Eur J Cancer. 1994;30A(4):445-8.
55. Br J Cancer. 1996 Jun;73(12):1552-5.
56. Yakushigaku Zasshi. 2001;36(1):70-5.
57. Fertil Steril. 1999 Sep;72(3):389-97.
58. Exp Clin Psychopharmacol. 2007 Oct;15(5):427-44.
59. Climacteric. 2008 Aug;11(4):273-9.
61. Endocrinology. 2004 Dec;145(12):5745-56.
62. Fertil Steril. 2000 Mar;73(3):516-21.
63. Hum Reprod Update. 1999 Jul-Aug;5(4):365-72.
64. Best Pract Res Clin Obstet Gynaecol. 2008 Apr;22(2):391-405.
65. Menopause. 2005 Mar;12(2):232-7.
66. Mol Endocrinol. 1997 Nov;11(12):1868-78.
67. Cancer. 1989 May 1;63(9):1685-92.
68. Cancer Res. 2004 Jan 1;64(1):423-8.
69. Science. 1997 Sep 5;277(5331):1508-10.
70. Proc Natl Acad Sci USA. 1996 Jun 11;93(12):5925-30.
71. J Steroid Biochem. 1986 Jan;24(1):77-83.
72. Recent Prog Horm Res. 2000;55:163-93.
73. Physiol Rev. 2001 Oct;81(4):1535-65.
74. Oncogene. 2005 Oct 6;24(44):6605-16.
75. Endocr Relat Cancer. 2004 Sep;11(3):537-51.
76. Breast. 2002 Aug;11(4):295-300.
77. Chem Biol. 2001 May;8(5):427-36.
78. Oncogene. 2000 Oct 12;19(43):4970-8.
79. Proc Natl Acad Sci USA. 2000 Jan 4;97(1):337-42.
80. Endocrinology. 2006 Sep;147(9):4132-50.
81. Proc Natl Acad Sci USA. 2002 Jun 25;99(13):8562-7.
82. Postgrad Med. 2009 Jan;121(1):73-85.
83. Int J Cancer. 2004 Oct 20;112(1):130-4.
84. Sitieri PK, Sholtz PI, Cirillo PM, et al. Prospective study of estrogens during pregnancy and the risk of breast cancer. Unpublished study performed in at the Public Health Institute in Oakland, California, and funded by the US Army Medical Research and Material Command under DAMD 17- 99-1-9358.
85. N Engl J Med. 1975 Dec 4;293(23):1167-70.
86. Am J Obstet Gynecol. 1977 Mar 15;127(6):572-80.
87. Am J Epidemiol. 2009 Jul 1;170(1):12-23.
88. Lancet. 1999 May 29;353(9167):1824-8.
89. Eur J Obstet Gynecol Reprod Biol. 1995 Sep;62(1):101-6.
90. Fertil Steril. 2003 Jan;79(1):221-2.
91. Menopause. 2003 Jul;10(4):373-4.
92. Menopause. 2003 Jul-Aug;10(4):374-7.
93. Maturitas. 2005 Oct 16;52(2):111-8.
94. J Am Coll Cardiol. 2003 Apr 16;41(8):1358-63.
95. Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):e164-7.
96. Climacteric. 2003 Mar;6(1):45-52.
97. MedGenMed. 2006;8(3):40.
98. Climacteric. 2004 Dec;7(4):347-56.
99. Fertil Steril. 1993 May;59(5):992-7.
100. Maturitas. 1994 Aug;19(2):103-15.
101. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11.
102. Cancer Res. 2005 Jun 15;65(12):5470-9.
103. Am J Public Health. 2006 Feb;96(2):252-61.
104. J Nutr. 2004 May;134(5):1134-8.
105. Nutr Cancer. 2002;42(1):1-9.
106. Cancer Res. 1999 Aug 15;59(16):3991-7.
107. Cancer Epidemiol Biomarkers Prev. 2000 May;9(5):477-85.
108. Mutat Res. 2007 May;635(2-3):90-104.
109. Cancer Res. 2005 Sep 15;65(18):8548-57.
110. Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):773-9.
111. J Natl Cancer Inst. 1997 May 21;89(10):718-23.
112. J Cell Biochem.Suppl. 1997;28-29:111-6.
113. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):538-45.
114. Am J Clin Nutr. 1999 Sep;70(3 Suppl):439S-50S.
115. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
116. Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):665-8.
117. Lancet. 1991 May 18;337(8751):1197-200.
118. Cancer Lett. 1990 Jan;49(1):51-7.
119. Isr J Med Sci. 1995 Feb;31(2-3):101-5.
120. Carcinogenesis. 1986 Sep;7(9):1463-6.
121. Anticancer Res. 1995 May;15(3):805-10.
122. Int J Cancer. 2004 Sep 1;111(3):440-3.
123. Eur J Cancer. 2004 Jan;40(1):84-9.
124. Br J Cancer. 2007 Apr 10;96(7):1139-46.
125. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1443-8.
126. Simone CB. Cancer and Nutrition. Lawrenceville, NJ: Princeton Institute; 2005.
127. Am J Clin Nutr. 2007 Jun;85(6):1586-91.
128. Nutr Rev. 2008 Oct;66(10 Suppl 2):S116-24.
129. N Engl J Med. 2000 Nov 23;343(21):1566-8.
130. Recent Results Cancer Res. 2003;164:99-110.
131. J Am Coll Cardiol. 2000 Dec;36(7):2154-9.
132. Circulation. 2007 Feb 20;115(7):840-5.
133. Arterioscler Thromb Vasc Biol. 1998 Jul;18(7):1164-71.
134. Circulation. 1996 Nov 1;94(9):2221-7.
135. Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):217-21.
136. Endocrinology. 1997 Aug;138(8):3330-9.
137. Cardiovasc Pathol. 2000 Nov;9(6):317-22.
138. Arteriosclerosis. 1990 Nov;10(6):1051-7.
139. J Intern Med. 2008;263(3):256-73.
140. Maturitas. 1990 Jun;12(2):89-97.
141. JAMA. 1995 Jan 18;273(3):199-208.
142. Eur J Clin Invest. 1983 Dec;13(6):447-53.
143. Fertil Steril. 1981 Feb;35(2):172-9.
144. Clin Pharmacol Ther. 1980 Nov;28(5):602-4.
145. N Engl J Med. 1981 Mar 5;304(10):560-3.
146. Acta Obstet Gynecol Scand Suppl. 1984;127:1-37.
147. Am J Obstet Gynecol. 1985 Mar 15;151(6):746-50.
148. Am J Obstet Gynecol. 1987 Jan;156(1):66-71.
149. Hum Reprod. 2000 May;15(5):1028-36.
150. Nippon Ronen Igakkai Zasshi. 1996 May;33(5):353-9.
151. Life Sci. 2002 May 24;71(1):31-42.
152. J Womens Health Gend Based Med. 2000 May;9(4):381-7.
153. Menopause. 2002 Jul;9(4):253-63.
154. Obstet Gynecol. 1989 Apr;73(4):606-12.
155. Obstet Gynecol. 2002 Nov;100(5 Pt 1):853-63.
156. Menopause. 2001 Jan;8(1):10-6.
157. Clin Ther. 2001 Jul;23(7):1099-115.
158. JAMA. 1978 Apr 21;239(16):1638-41.
159. Horm Metab Res. 1987 Nov;19(11):579-84.
160. J Obstet Gynaecol Res. 1996 Jun;22(3):259-65.
161. Nippon Sanka Fujinka Gakkai Zasshi. 1996 Feb;48(2):83-8.
162. J Bone Miner Metab. 1998; 16:21-6.
163. Menopause. 2004 Jan;11(1):49-56.
164. N Engl J Med. 1993 Sep 9;329(11):753-6.
165. Eur J Obstet Gynecol Reprod Biol. 1993 Sep;51(1):29-33.
166. Orv Hetil. 1995 Feb 12;136(7):343-5.
167. Maturitas. 2001 Sep 28;39(3):253-7.
168. J Cosmet Dermatol. 2006 Mar;5(1):3-8.
169. Menopause Int. 2007 Jun;13(2):60-4.
170. Clin Interv Aging. 2007;2(3):283-97.
171. Exp Dermatol. 2002 Dec;11(6):487-502.
172. Eur J Obstet Gynecol Reprod Biol. 2007 Feb;130(2):202-5.
173. Int J Dermatol. 1996 Sep;35(9):669-74.
174. Br Med J (Clin Res Ed). 1983 Nov 5;287(6402):1337-8.
175. Arch Dermatol. 1997 Mar;133(3):339-42.
176. Altern Med Rev. 1998 Apr;3(2):101-13.
177. Maturitas. 1994 Nov;20(1):25-30.
178. Climacteric. 2007 Aug;10(4):289-97.
179. Essex Testing Clinic, Inc. Data on file.
180. Endocr Metab Immune Disord Drug Targets. 2009 Mar;9(1):29-37.
181. J Sex Med. 2008 Oct;5(10):2282-90.
182. Gynecol Endocrinol. 2009 Jan;25(1):12-20.
183. Rev Med Suisse. 2007 Mar 28;3(104):792-6.
184. N Engl J Med. 2008 Nov 6;359(19):2005-17.
185. Am J Clin Nutr. 2009 May;89(5):1459-67.
186. Metabolism. 2008 Jun;57(6):838-44.
187. J Clin Endocrinol Metab. 1990 Feb;70(2):473-9.
188. Obes Rev. 2004 Nov;5(4):197-216.
189. Maturitas. 2008 May 20;60(1):10-8.
190. Am J Obstet Gynecol. 1998 Jan;178(1 Pt 1):101-7.
191. Acta Diabetol. 2003 Oct;40 Suppl 1:S191-5.
192. Eur J Contracept Reprod Health Care. 2000 Dec;5 Suppl 3:9-16.
193. Cancer Lett. 1997 Mar 19;114(1-2):169-70.
194. J Endocrinol. 1996 Sep;150 SupplS259-65.
195. Cell Cycle. 2008 Apr 1;7(7):917-24.
196. Cancer Prev Res (Phila Pa). 2009 Jun;2(6):598-604.
197. Mol Cancer Ther. 2007 Apr;6(4):1433-9.
198. Cancer Res. 2007 Dec 15;67(24):11840-7.
199. Carcinogenesis. 2008 Jan;29(1):93-9.
200. Am J Clin Nutr. 2008 Jun;87(6):1952-8.
201. Am J Clin Nutr. 2009 Apr;89(4):1132-7.
202. Nutr Cancer. 2004;50(2):161-7.
203. Lancet. 2005 Oct 29;366(9496):1558-60.
204. Epidemiology. 2000 Nov;11(6):635-40.
205. Otolaryngol Head Neck Surg. 2001 Mar;124(3):241-7.
206. Cancer Epidemiol Biomarkers Prev. 1997 Jul;6(7):505-9.
207. Epidemiology. 2006 Jan;17(1):80-8.
208. Steroids. 2003 Jan;68(1):65-72.
209. Cancer Res. 1999 Mar 15;59(6):1244-51.
210. Cancer Res. 1994 Nov 15;54(22):5848-55.
211. Jpn J Cancer Res. 1995 Feb;86(2):146-54.
212. Cancer Causes Control. 1998 Dec;9(6):553-7.
213. JAMA. 2005 Sep 28;294(12):1493-504.
214. Am J Epidemiol. 2007 Oct 15;166(8):924-31.
215. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Apr;27(2):258-61.
216. J Nutr. 2002 Feb;132(2):276-82.
217. Nutr J. 2005;430.
218. J Nutr. 1995 Mar;125(3 Suppl):777S-83S.
219. J Am Coll Nutr. 2001 Oct;20(5 Suppl):354S-62S.
220. J Natl Cancer Inst. 2003 Aug 6;95(15):1158-64.
221. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):81-90.
222. Asia Pac J Clin Nutr. 2006;15(1):21-9.
223. Int J Cancer. 2007 Jul 15;121(2):377-85.
224. Int J Cancer. 2002 Mar 1;98(1):78-83.
226. Biochem Med Metab Biol. 1990 Apr;43(2):83-92.
227. Cancer Detect Prev. 1997;21(2):178-90.
228. Altern Med Rev. 2002 Aug;7(4):336-9.
229. Slaga TJ, Quilici-Timmcke J. D-Glucarate: A Nutrient Against Cancer. Columbus, Ohio: McGraw-Hill; 1999.
230. Clin Cancer Res. 2005 May 15;11(10):3828-35.
231. Cancer Biol Ther. 2007 Dec;6(12):1938-43.
232. Cancer Lett. 2007 Jan 8;245(1-2):232-41.
233. Breast Cancer Res Treat. 2008 Feb;107(3):359-69.
234. J Exp Ther Oncol. 2002 Nov;2(6):350-9.
235. Cancer Detect Prev. 2007;31(6):499-504.
236. Ann NY Acad Sci. 2007 Jan;1095:428-40.
238. Int J Cancer. 2003 Sep 10;106(4):574-9.

Mar 232010

Compounding dental mouthwashes or rinses may offer numerous advantages over commercially available preparations. It is more desirable to compound mouthwashes using pharmaceutical grade bulk powders as a source of active ingredients (antibiotics, anesthetics, etc.) versus the common practice of combining available liquids, due to concerns of palatability, flavour (different products have different flavours, which may not be compatible), limit of alcohol content, and elimination of dyes used to colour liquid preparations which may stain exposed mucosa.

Stability and compatibility are significant issues when drugs are manufactured and must have extended shelf-lives to endure the distribution cycle. When a medication is prepared at the time it is needed to meet the needs of a specific patient, many of these concerns can be eliminated. Compounding allows numerous active ingredients to be incorporated into customized mouthwashes, gels, troches, etc. For example, to treat periodontal disease, antibiotics can be formulated as a mouthwash, or added to an oral adhesive paste or a plasticized gel that will maintain the contact between the tissue and medication for a longer period of time.

Many practitioners are familiar with formulations used to treat stomatitis, such as Kaiser’s, Kraemer’s, Powell’s, Reynold’s, Stanford’s, and T-N-D-D (tetracycline, nystatin, diphenhydramine, and dexamethasone). Customized mouthwashes can be formulated to treat:

Burning Mouth Syndrome: A double-blind, randomized, multicenter parallel group study evaluated the efficacy of topical use of clonazepam. Forty-eight patients (4 men and 44 women, aged 65+/-2.1 years) were included, of whom 41 completed the study. The patients used clonazepam 1 mg or placebo topically (intraorally) for 3 min and then expectorated. This protocol was repeated three times a day for 14 days. The intensity was evaluated by a 11-point numerical scale before the first administration and then after 14 days. Two weeks after the beginning of treatment, the decrease in pain scores was 2.4+/-0.6 and 0.6+/-0.4 in the clonazepam and placebo groups, respectively.
Pain. 2004 Mar;108(1-2):51-7

Chemotherapy or Radiation-induced Mucositis: for prevention of mucositis (i.e., glutamine), to relieve pain (i.e., morphine), to reduce inflammation, or to treat superinfections.

Intraoral Infections: Antibacterial, antifungal, and antiviral preparations.

Aphthous Ulcers: “Rinse #5” (tetracycline, nystatin, triamcinolone, and 2-deoxy-d-glucose) has been used to reduce pain and promote the healing process.

Customized mouthwashes can be compounded to be
alcohol-free to reduce burning of irritated mucosa.
sugar-free to reduce cariogenic potential and for diabetic patients.
flavoured to please each patient.

For more information, or to discuss a particular problem, please contact Canada’s 2005 “Compounding Pharmacist of the Year” Marvin Malamed, B.Sc.Pharm. at Haber’s Pharmacy, 416-656-9800.

Mar 232010

Burning mouth syndrome (BMS, stomatodynia), also referred to as glossopyrosis or glossodynia (when the burning occurs on the tongue only), is a chronic, idiopathic intraoral mucosal pain condition that is not accompanied by clinical lesions or systemic disease. BMS occurs most often among women especially after menopause and is often accompanied by xerostomia (dry mouth) and taste disturbances. The dorsal tongue, palate, lips and gingival tissues, individually or in combination, are the most common sites involved. Bilateral or unilateral oral burning pain has been found to be associated with jaw pain or uncontrollable tightness, taste changes, subjective dry mouth, geographic and fissured tongue, painful teeth, headache, neck and shoulder pain, difficulty speaking, nausea, gagging and swallowing difficulties. BMS has been reported to follow dental treatment, antibiotic usage and a severe upper respiratory infection. Pain is constant, progressively increases over the day, and usually decreases during eating. The lack of pathology to account for the pain can be frustrating. Conditions that have been reported in association with burning mouth syndrome include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes, taste alterations, and changes in salivary function and dry mouth.

Recent studies have pointed to dysfunction of several cranial nerves as a possible cause of burning mouth syndrome. Recently, a neuropathological basis has been proposed; therefore, BMS may be regarded as an oral dysesthesia or painful neuropathy. Therapy for BMS may include the use of centrally acting medications for neuropathic pain, such as low doses of tricyclic antidepressants, benzodiazepines or anticonvulsants such as gabapentin. Topical medications, including clonidine, may be considered for application to local sites.

A combination of oral medications for the management of BMS (clonazepam, gabapentin, baclofen, and lamotrigine) significantly decreased pain in 38 of 45 patients. These results suggest that BMS may be treated with lower doses of a combination of medications rather than higher doses of a single medication, which may help to limit adverse effects such as drowsiness or dizziness.

Clonazepam is a benzodiazepine used either topically or in low doses orally, which appears to have excellent efficacy in the relief of the symptoms related to BMS. It is hypothesised that clonazepam acts locally to disrupt the mechanism(s) underlying stomatodynia. A double-blind, randomized, multicenter parallel group study evaluated the efficacy of topical use of clonazepam. Forty-eight patients (4 men and 44 women, aged 65+/-2.1 years) were included, of whom 41 completed the study. The patients were instructed to suck a tablet of either clonazepam 1 mg or placebo and hold their saliva near the painful sites in the mouth without swallowing for 3 minutes and then to expectorate. This protocol was repeated three times a day for 14 days. The intensity was evaluated by a 11-point numerical scale before the first administration and then after 14 days. Two weeks after the beginning of treatment, the decrease in pain scores was 2.4+/-0.6 and 0.6+/-0.4 in the clonazepam and placebo group, respectively. The formulation for a mouth rinse containing clonazepam 1mg /5ml has been reported, and may be easier to use.

Emerging evidence supports the effectiveness of the antioxidant alpha lipoic acid (ALA, thioctic acid). Alpha lipoic acid is able to increase the levels of intracellular glutathione and eliminate free radicals. A double-blind study compared the use of alpha lipoic acid versus placebo for two months in 60 patients with constant BMS, in whom there was no laboratory evidence of deficiencies in iron, vitamins or thyroid function and no hyperglycemia. Following treatment with alpha lipoic acid 600 mg orally daily, there was a significant symptomatic improvement compared with placebo. This improvement was maintained in over 70% of patients at the 1 year follow-up. Another study showed that patients with BMS who had previously been treated with benzodiazepines responded poorly to therapy with alpha lipoic acid compared with those who had not received benzodiazepines.

For references, more information, or to discuss a particular problem, please contact Canada’s 2005 “Compounding Pharmacist of the Year” Marvin Malamed, B.Sc.Pharm., at Haber’s Pharmacy, 416-656-9800, or visit

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103 Suppl:S39.e1-13
J Eur Acad Dermatol Venereol. 2004 Nov;18(6):676-8
J Oral Pathol Med. 2002 May;31(5):267-9
Adv Otorhinolaryngol. 2006, 63:278–287
Int J Pharm Compounding July/Aug 2005, 9(4):310
Pain 2004 Mar;108(1-2):51-7
Pain Med. 2000 Mar;1(1):97-100

Topical therapies such as a mouth rinse, lozenge, or muco-adhesive paste offer the advantage of direct application to the affected site and a lower incidence of side effects. Contact Haber’s Pharmacy to discuss formulations which will meet the specific needs of each patient.

Oct 272009

Tranexamic acid is an antifibrinolytic agent, which can be applied topically or used as a mouthwash to prevent post-surgical bleeding in anticoagulated patients after oral surgery or extractions, without discontinuation or dose reduction of anticoagulant therapy. The hemostatic effect of tranexamic acid solution (4.8%) used as a mouthwash was compared with a placebo solution in 93 patients on continuous, unchanged, oral anticoagulant treatment undergoing oral surgery. The investigation was a randomized, double-blind, placebo-controlled, multicenter study. Before suturing, the surgically treated region was irrigated with 10 ml of tranexamic acid (46 patients) or placebo solution (47 patients). The patients then used the active or placebo solution as a mouthwash: 10 ml of the solution for 2 minutes four times daily for 7 days. In the placebo group, 10 patients developed bleeding requiring treatment, while none of the patients treated with tranexamic acid solution had bleeding. Tranexamic acid mouthwash was well tolerated.1

A double-blind, placebo-controlled, randomized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery was conducted in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis, a prosthetic cardiac valve, or a vascular prosthesis. Surgery was performed with no change in the level of anticoagulant therapy, and treatment with the anticoagulant agent was continued after surgery. The research concluded that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants.2

A two-day postoperative course of a 4.8% tranexamic acid mouthwash may be equally effective as a 5-day course in controlling hemostasis for post-dental extractions in patients anticoagulated with warfarin.3

Tranexamic acid mouthwash was shown to be as effective and more cost effective than autologous fibrin. This study supports the consensus that dental extractions can be performed without modification of oral anticoagulant treatment.4

Bleeding complications and transfusion requirements after scalings and extractions in patients with hemophilia have also been significantly reduced by local treatment with tranexamic acid.5, 6

1 J Oral Maxillofac Surg 1993 Nov;51(11):1211-6
2 N Engl J Med 1989 Mar 30;320(13):840-3
3 Int J Oral Maxillofac Surg. 2003 Oct;32(5):504-7
4 J Oral Maxillofac Surg. 2003 Dec;61(12):1432-5
5 Br Dent J. 2005 Jan 8;198(1):33-8; discussion 26
6 Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Mar;99(3):270-5

Controlling Hemorrhage in Hemophiliacs After Dental Scaling

A double-blind cross-over randomized control trial at a London (UK) hospital dental practice for patients with inherited bleeding disorders compared the effectiveness of tranexamic acid mouthwash (TAMW) in controlling gingival hemorrhage after dental scaling with that of using factor replacement therapy (FRT) prior to dental scaling in people with hemophilia. The dentists concluded that oral rinsing with TAMW four times daily for up to eight days after dental scaling was as effective as using FRT beforehand in controlling gingival hemorrhage for hemophiliacs.

Br Dent J. 2005 Jan 8;198(1):33-8; discussion 26

Tranexamic acid mouthwash is not commercially available and must be compounded by a compounding pharmacy. When selecting a compounding pharmacy, be certain that the professional staff has received advanced training in current compounding technique We welcome your questions.

For more information, or to discuss a particular problem, please contact Marvin Malamed, B.Sc.Pharm. at Haber’s Compounding Pharmacy, 416-656-9800, or visit

Oct 272009

Complementary Solutions for Dental Problems

Dentists and oral surgeons often encounter problems that do not respond to traditional allopathic therapies, or may require special preparations that are not commercially available. Nutritional deficiencies can affect the integrity of the oral mucosa. Supplementation to replace deficient vitamins, minerals, amino acids, and enzymes, as well as the use of specially-formulated medicated dosage forms can greatly enhance dental care.

Here are just a few examples of dosage forms that can be compounded by prescription to meet the unique needs of dentists and their patients:

- Lip balms for cold sores which contain the natural anti-viral 2-DDG (2-deoxy D-glucose), a glucose derivative which exerts anti-viral activity against herpes simplex and HPV by interfering with the viral replication process. 2-DDG has no known toxicities, and can be incorporated into a variety of topical preparations.
- Electrolyte lozenges to suppress the gag reflex prior to taking an impression or for patients who can not properly perform oral hygiene procedures at home due to a gagging problem1
- Troches or long-acting pilocarpine capsules for dry mouth, which stimulate salivation while avoiding the problems associated with immediate-release pilocarpine products
- Topical muscle relaxants/pain relievers for temporomandibular joint (TMJ) disorder caused by injury or inflammation of the joint. A topical gel containing an anti-inflammatory and a muscle relaxant can be applied over the affected joint to deliver the medication where it is needed and decrease the risk of adverse side effects such as gastrointestinal irritation and drowsiness that occur when medications are administered orally. Iontophoretic delivery of dexamethasone and lidocaine has improved mandibular function in patients who had concurrent temporomandibular joint capsulitis and disc displacement without reduction.
- “Mucosal bandages”, muco-adhesive bases, and oral pastes to cover ulcerated, infected, or tender areas on the oral mucosa, or to maintain medication contact with the oral mucosa

Topical Anesthetics

Novel formulations of topical anesthetics, including intra-oral anesthetics in plasticized gel or an adherent base, may prevent pain associated with laser and soft tissue procedures; phrenectomies; deep scaling, root planing, and curettage; and prior to extraction of primary teeth, and often eliminate the need for injections. The use of topical anesthetics may improve patient recall, because an aversion to injections in patients with recurrent disease or who have dentinal sensitivity may negatively affect their compliance with treatment plans. Vasoconstrictors can be added to preparations to promote local hemostasis, decrease systemic absorption, and prolong the duration of action.

Approximately 1700 pediatric dentists responded to a survey conducted by West Virginia University School of Dentistry, and indicated that most pediatric patients (89%) disliked the taste of topical anesthetics. Compounding pharmacies can customize topical anesthetics in a variety of appealing flavours.

In November 2006, Health Canada issued an advisory regarding an association between the local anesthetic benzocaine and a potentially serious blood condition known as methemoglobinemia (MHb). MHb is an uncommon adverse reaction known to be associated with benzocaine. This condition reduces the ability of red blood cells to deliver oxygen throughout the body, which can lead to bluish discoloration of the skin, nausea and fatigue. It can progress to stupor, coma and death. As of November, 2006, Health Canada had received reports of nine cases of suspected MHb associated with the use of benzocaine. None of the reported cases had a fatal outcome. Almost all reported cases of benzocaine-induced MHb were associated with high-concentration preparations (14 percent to 20 percent benzocaine). Compounding pharmacies can formulate benzocaine-free topical anesthetics, including combinations such as lidocaine and tetracaine or prilocaine.

Topical Medications for Orofacial Neuropathic Pain

The most common neuropathic pain syndromes in the orofacial region include trigeminal neuralgia, traumatic neuropathy; trigeminal neuroma; postherpetic neuralgia; diabetic neuropathy; cancer-related neuropathy; neuropathy induced by AIDS; and chronic-continuous trigeminal nociceptor neuropathy. The pain mechanisms that generate these problems are different for each neuropathy, and treatment protocols need to be structured accordingly. Numerous studies have shown that NMDA-receptor antagonists such as ketamine and gabapentin, may be useful in the treatment of neurogenic pain. Cyclobenzaprine, a muscle relaxant, has been used for peripheral application to relieve muscle trismus and spasm.2

“Miracle Mouthwashes”

Customized oral rinses can be formulated to treat problems such as:

Burning Mouth Syndrome:  Burning mouth syndrome (BMS) is characterized by a burning sensation on the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Burning mouth is reported most often by women, especially after menopause. Typically, patients awaken without pain but note increasing symptoms throughout the day and into the evening. Conditions that have been reported in association with BMS include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes, taste alterations, and changes in salivary function and dry mouth. Recent studies have pointed to dysfunction of several cranial nerves as a possible cause of BMS. Given in low dosages, benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective in treating BMS. The formulation for clonazepam 1mg per 5ml mouthwash was reported in the International Journal of Pharmaceutical Compounding. Topical capsaicin has also been used successfully.3

Gingivitis:  Folate mouthwash appears to have an influence on gingival health through local rather than systemic influence. Use of a mouthwash containing folate 5mg/5ml (twice daily for 4 weeks, rinsing for 1 min before expectorating) reduced gingival inflammation and bleeding in patients with periodontal disease. Folic acid mouthwash and oral tablets both significantly increased folate levels in pregnant women, but only folic acid mouthwash showed a highly significant improvement in gingival health.4 Topical folate has been shown to inhibited gingival hyperplasia to a significantly greater extent than administration of systemic folate or placebo.5

Post-Surgical Bleeding in Anticoagulated Patients:  Tranexamic acid is an antifibrinolytic agent, which can be applied topically or used as a mouthwash to prevent post-surgical bleeding in anticoagulated patients after oral surgery or extractions, without discontinuation or dose reduction of anticoagulant therapy.6, 7

Coenzyme Q10 for Peridontal Therapy

Topical application of Coenzyme Q10 (CoQ10) to the periodontal pocket was evaluated with and without subgingival mechanical debridement. Significant improvements in the modified gingival index, bleeding on probing and peptidase activity derived from periodontopathic bacteria were observed only at sites treated with CoQ10. These results suggest that topical application of CoQ10 improves adult periodontitis not only as a sole treatment but also in combination with traditional nonsurgical periodontal therapy.8

Therapy for Mucositis Caused by Chemotherapy or Radiation

Patients with cancer are at high risk for numerous oral problems. Cytotoxic chemotherapy, radiation to the head and neck, and immunosuppression prior to bone marrow transplantation commonly cause significant inflammation and painful lesions of the oral and esophageal mucosa which lead to difficulty swallowing and can result in a compromised nutritional status. Oral mucositis is the dose-limiting toxicity for patients receiving concurrent chemoradiotherapy regimens for tumors of the head and neck area. Dry mouth secondary to radiation can lead to rampant dental caries. Oral rinses can be formulated to prevention mucositis (i.e., glutamine), relieve pain (i.e., morphine), reduce inflammation, or treat superinfections (bacterial, viral, or fungal).9, 10

Glutamine is a nutrient for rapidly dividing cells. Administration of glutamine suspension after chemotherapy has resulted in significant amelioration of stomatitis and decreased the duration of mouth pain by 4.5 days when compared to placebo. The severity of oral pain may also be reduced significantly when glutamine is provided with chemotherapy. No toxicity has been observed. Oral glutamine appears to be a safe, simple and useful measure to increase the comfort of children and adults at high risk of developing mouth sores as a consequence of chemotherapy.11, 12, 13, 14

Persistent mucosal pain may be helped by topical preparations that provide local protection or anesthesia. For patients with head and neck carcinomas receiving concomitant chemoradiotherapy, morphine mouthwash is a simple and effective treatment to decrease the severity and duration of oral lesions and the duration of functional impairment.15 Also, a three-drug mouthwash containing lidocaine, diphenhydramine and sodium bicarbonate in normal saline has been reported to provide effective symptomatic relief in patients with chemotherapy-induced mucositis.16

Fungal infections of the oral mucosa are common in patients with compromised immune status. Candidiasis usually appears as adherent white plaques but can also present as erythema or angular cheilitis. Amphotericin B and nystatin are potent antifungal agents which are active against most pathogenic fungi like Aspergillus and Candida, and can be formulated as an oral rinse.17 Melaleuca (tea tree oil) rinse has been effective in treating fluconazole-resistant candidiasis in AIDS patients.18

Malignant oral lesions are often associated with anaerobic bacteria that produce a foul odour. The odour can be reduced with a topically applied metronidazole gel.

Relief for Aphthous Ulcers

Aphthous ulcers affect up to 25% of the general population and three month recurrence rates are as high as 50%.19 Aphthous ulcers may be helped with topical corticosteroids prepared as a mouth rinse or paste, or oral rinses containing a combination of medications to combat the various possible causes of these painful oral lesions.

Patients suffering from recurrent aphthous stomatitis (RAS) may have low levels of vitamin B12. A common cause of vitamin B12 deficiency is low intake of meat or other animal products. Administration of vitamin B12 has led to rapid improvement of RAS and complete recovery within several weeks.19

Zinc promotes wound healing and maintains epithelial integrity. Zinc sulfate in doses of up to 660 mg/day produced a significant reduction in frequency of RAS in zinc-deficient patients.20

Licorice can be processed to remove glycyrrhiza, resulting in DGL (deglycyrrhizinated licorice), which does not appear to share the potential metabolic disadvantages (hypertension, hypokalemia, and fluid retention) associated with high doses of licorice. Patients with aphthous ulcers who used DGL mouth wash experienced 50-75% improvement within one day followed by complete healing of the ulcers by third day.21

Application of 5-aminosalicylic acid (5-ASA; mesalamine) 5% cream three times daily for up to 14 days for the treatment of aphthous ulcers shortened healing time and reduced the difficulty in eating. No significant side-effects were reported.22

“Rinse #5″ (tetracycline, nystatin, triamcinolone, and 2-deoxy-D-glucose) has been used to reduce pain and promote the healing process.

Therapy for Osteoporosis

Bisphosphonates (i.e., Fosamax) used to treat osteoporosis and decreased bone density in postmenopausal women have been shown to cause osteonecrosis of the jaw (ONJ; “dead jaw”; slow death of bone tissue that occurs because of poor blood supply). Patients using bisphosphonates intravenously, or who have undergone chemotherapy, have a history of cancer, Paget’s disease or osteoporosis, use steroids while on alendronate, or have a history of major dental work are at an increased risk for ONJ. While osteonecrosis can be managed, it is irreversible. Bio-identical hormone replacement therapy is another option for prevention and treatment of osteoporosis. Compounding pharmacists work together with patients and other health care providers to optimize therapy for each woman.

In summary, dental preparations can be compounded to meet specific patient needs:
-  alcohol-free to reduce burning of irritated mucosa.
- sugar-free to reduce cariogenic potential, decrease risk of fungal and superinfection, and for diabetic patients.
- dye-free to prevent staining of the oral mucosa
- flavoured to improve compliance.

Compounding pharmacies can assist dental professionals by providing customized medications including:
- novel dosage forms such as lozenges, freezer pops, intraoralor topical gels, and muco-adhesive pastes, chewable “gummy treats”, and lollipops which are ideal for children or patients who have difficulty swallowing, or when a medication (such as an antifungal or anesthetic) needs to be held in contact with the oral mucosa.
- combinations of medications such as a mouthwash that contains a topical anesthetic, corticosteroid, antifungal, antibiotic, and/or antiviral.
- topical or transdermal gels for those who can not swallow or to minimize the risk of systemic side effects.
- Recently developed anhydrous bases to deliver medication through lipophilic tissues.

Compounding pharmacists are in a unique position to work with both patient and dentist to customize medications that meet specific patient needs and solve medical problems.

Marvin Malamed, B.Sc.Phm., C.C.N., has owned Haber’s Compounding Pharmacy (Toronto, ON) for over 16 years. He is a national award winning pharmacist (PCCA’s 2005 Canadian Compounding Pharmacist of the Year), a clinical nutritionist, and a founding member of the Ontario Compounding Association. The Professional Compounding Centers of America has described Marvin as “a community leader in the pharmacy compounding profession.” Under his influence, Haber’s Compounding Pharmacy has evolved into a pharmacy with a unique blend of traditional and holistic approaches, always with the focus on solving individual problems. Marvin can be reached by calling 416-656-9800 or by emailing

1 Dent Today. 1991 Dec;10(9):68-71
2 J Am Dent Assoc. 2000 Feb;131(2):184-95
3 Pain. 2004 Mar;108(1-2):51-7
4 J Clin Periodontol  9(3):275-80
5 J Clin Periodontol 14(6):350-6
6 J Oral Maxillofac Surg 1993 Nov;51(11):1211-6
7 Int J Oral Maxillofac Surg. 2003 Oct;32(5):504-7
8 Mol Aspects Med. 1994;15 Suppl:s241-8
9 Cancer. 2002 Nov 15;95(10):2230-6
10 Support Care Cancer. 2000 Jan;8(1):55-8
11 J Pediatr Oncol Nurs. 2007 Jan-Feb;24(1):41-5
12 Bone Marrow Transplant 2005 Oct;36(7):611-6
13 Bone Marrow Transplant 1998 Aug;22(4):339-44
14 Cancer 1998 Oct 1;83(7):1433-9
15 Cancer. 2002 Nov 15;95(10):2230-6.
16 Support Care Cancer. 2000 Jan;8(1):55-8
17 J Pharm Biomed Anal. 2006 May 30 (E-pub ahead of print)
18 HIV Clin Trials. 2002 Sep-Oct;3(5):379-85
19 Can Fam Physician. 2005 Jun;51:844-5
20 South Med J 1977 May; 70(5):559-61
21 J Assoc Physicians India 1989 Oct;37(10):647
22 Br J Dermatol 1992 Feb;126(2):185-8

Aug 282009

As our bodies get older they function less efficiently. Like all sophisticated machines, they eventually suffer the wear and tear of prolonged use. To name a few signs of deterioration: our joints start to hurt, our energy level decreases, our digestion is not as efficient, our thought processes slow down, and our arteries start to narrow. To many, the ‘golden years’ are synonymous with taking medication.

Although some medication is necessary to repair a weakening system, they usually come with a list of side effects. In describing these drugs, terms such as ‘inhibiters’, ‘blockers’, and ‘antagonists’ mean that they will be interfering with something in the body to accomplish the desired effect, and forewarn of a negative. In many cases, this negative can be due to nutrient depletion. Nutrients are vitamins, minerals, amino acids, fatty acids, etc., that are usually obtained from the breakdown of food to supply the biochemical building blocks that the body needs to exist, and their depletion often defines the side effect of the drug.

Western medicine is vigilant in its monitoring of nutrients that can interact negatively with a drug, however, the lack of attentiveness regarding the nutrients that are depleted by a drug is very disconcerting. To illustrate this point, let’s look at Coenzyme Q10 (CoQ10), one of the most important nutrients in the human body.

CoQ10 is a fat-soluble vitamin-like compound that is critical in the production of energy in the mitochondria of every human cell. It is also an important antioxidant and plays a major role in preventing the oxidation of LDL cholesterol and the prevention of atherosclerosis (narrowing of the arteries). Further, it is intimately involved in the production of energy. Consequently, a deficiency of CoQ10 first affects the heart and cardiovascular system because the heart is the most energy-demanding muscle in the human body. Coenzyme Q10 deficiency can cause congestive heart failure, high blood pressure, angina, mitral valve prolapse, stroke, cardiac arrhythmias, cardiomyopathies, lack of energy, gingivitis and generalized weakening of the immune system.

There is an extensive list of pharmaceutical drugs that deplete CoQ10. To name a few: statin drugs (e.g. Lipitor®) used to lower cholesterol, beta blockers (e.g. metoprolol) to lower high blood pressure, thiazide diuretics (e.g. hydrochlorthiazide) to lower high blood pressure, and metformin a common medication used to treat insulin resistance and Type II diabetes.

Aging, by way of lower biochemical production and absorption of critical nutrients such as CoQ10 increase our risk of various cardiac problems, weak immune systems, and lower energy levels. The additional intake of a range of drugs that further deplete our levels of crucial nutrients can increase our risk levels substantially. It must be noted that many of these drugs deplete multiple nutrients important to other functions of the body.

Often, when a change of lifestyle has failed to produce the desired change to one’s chronic illness, it becomes necessary to resort to the use of a drug. For this reason, it is important to pay attention to the nutritional needs not only of that illness but of the nutritional needs made necessary by a particular drug. The failure to address this issue may result in the health problems not being resolved, and may lead to other symptoms later on, which may lead to the prescribing of additional drugs. A health care provider, who is familiar with drug nutrient depletion, can help make your medication more effective and cut down on some of the long term risks.

Marvin Malamed is a national award winning pharmacist, certified clinical nutritionist and President of Haber’s Compounding Pharmacy.  For more information, he can be reached at (416) 656 9800.

Aug 282009

I was recently asked the following question:

My doctor said I have osteopenia and recommended that I take calcium. Is there anything else I can do to prevent my bone density from getting worse?

Yes. There are many things to consider. The same amount of calcium in your diet you ingested when you were young and building a strong skeleton may result in bone degeneration when you are older. However, although calcium is important it can not be isolated as the sole cause.

Paying attention to your nutrition from many aspects is critical. A diet which is rich in minerals and vitamins such as magnesium, boron, silicon, manganese, zinc and copper, vitamin B6, vitamin c, vitamin k among others is important. It may be difficult to get the proper amount of nutrients without supplementing your normal diet with a comprehensive formula for bones.

The proper amount of vitamin D is essential to help absorb the calcium that is ingested in food a/o supplements. Eating enough protein is also vital. Digestive issues should also be considered. As we get older we produce less stomach acid and digestive enzymes. We are therefore less likely to break down our food (and even our supplements) and extract the nutrients.

Whether our diet is alkaline forming or acidic forming is important. An acidic forming diet will help leach calcium from your bones. This is easy to monitor with appropriate ph strips.

Exercise is important throughout life to help maintain bone density and strengthen the soft tissue supporting our skeletons. It is important to incorporate a routine of resistance exercise.

Medical conditions and medications are contributors to osteoporosis as well. Diabetes, Cushing’s syndrome, Hyperparathyroidism, and Rheumatoid Arthritis are some of the conditions that are associated with an increase risk of osteoporosis. Many medications deplete nutrients that are important for maintaining strong bones. It is important to realize what these nutrients are and to supplement accordingly so as not to increase your risk. The overuse of acid blockers for heartburn further decreases the availability of gastric acid, the importance of which has already been mentioned.  

Last but not least, you must look at your hormonal scenario. Estrogen, Progesterone, Testosterone, Dihydroepiandrosterone, and Cortisol balance play a part in maintaining strong bones. The age at which hormonal balance is lost is when the risk of osteoporosis is at its highest.

So often I see people relying on their intake of 1500mg of calcium, while completely ignoring the other issues, only to be pronounced osteoportic two years later. 

Marvin Malamed is a national award winning pharmacist, certified clinical nutritionist and President of Haber’s Compounding Pharmacy.  For more information, he can be reached at (416) 656 9800.