Making Womens Health Better

References

Country singer Tammy Wynette sang it best: Sometimes its hard to be a woman. And not just when it comes to being in a relationshipthats a different topic for a different magazine. From their pre-teen years on, women are faced with two major health issues, hormone balance and fertility, that require constant attention, and another, breast cancer, that seemingly develops almost out of nowhere and can have fatal consequences.

Hormone balance is a simple name for a complicated problem. When women start menarche, usually in the early teens, their bodies face constant fluctuations of sexual hormones throughout their lives. Crucial hormones are estrogen, which is responsible for guiding a womans body through pregnancy; progesterone, which works with estrogen on conception and regulates menstruation; luteinizing hormone (LH), which controls follicle release from the ovaries; and androgen, which stimulates growth at puberty then falls off dramatically at menopause.

Premenstrual syndrome (PMS) brings with it myriad symptoms including abdominal bloating, acne, anxiety, backache, cramps and water retention. About 80 percent of women experience some features of PMS, while 10 percent of women have PMS symptoms severe enough to impact their work, relationships or lifestyle in a significant way. Though the exact cause of PMS is not known, hormone imbalance, specifically high levels of estrogen and low levels of progesterone, is thought to be one contributing factor.

A case-control study nested within the prospective Nurses Health Study II cohort found women with the highest intake of vitamin D had almost half the risk of PMS of those in the lowest quintile; high calcium intake produced a 30-percent risk reduction.¹ And a review in Nutrition noted calcium supplementation appears to significantly reduce the physical and emotional symptoms of PMS, and even suggested PMS could be a predictor of osteoporosis induced by low calcium intake.² Calciums functional partner, magnesium, may also support menstrual health. A double blind, placebo-controlled study at the University of Reading, England, found administration of 200 mg/d of magnesium plus 50 mg/d of vitamin B6 significantly reduced anxiety-related PMS symptoms, including mood swings and irritability.³

There are compounds beyond basic macronutrients that may impact PMS. The tea amino acid theanine (as Suntheanine®, from Taiyo, distributed by NutriScience Innovations) was shown in a 2001 Japanese study of 20 women (ages 22 to 49) to alleviate mental and physical symptoms of PMS compared to placebo.⁴ Subjects received two 50 mg/d tablets of Suntheanine or placebo over three menstrual cycles.

Women in their reproductive years not only face pain associated with PMS. Menses can also be highlighted by severe pain and blood loss, known as dysmenorrhea. For this, vitamin E may be of assistance. Researchers in Iran conducted a double blind, placebo-controlled trial involving 278 girls (ages 15 to 17) suffering primary dysmenorrhea.⁵ After two months and four months, girls taking 400 IU/d of vitamin E had lower blood loss and decreased pain severity. The study confirmed the results of an earlier, preliminary study by the same researchers in which 100 girls receiving 500 IU/d of vitamin E had reduced severity of pain over a two-month course of treatment.⁶

Vitex agnus castus, also known as chaste tree, has been shown effective in treating a range of gynecological disorders, including menstrual irregularities, hormone imbalances and cyclic mastalgia, possibly due to the dopaminergenic compounds that influence prolactin levels in the body.⁷

A 2004 study in Obstetrical and Gynecological Survey suggested dysmenorrhea may be caused by a disturbed balance between antiinflammatory, vasodilator eicosanoids derived from omega-3 essential fatty acids (EFAs) and pro-inflammatory, vasoconstrictor eicosanoids derived from omega-6 EFAs.⁸ Increasing the number of omega-3s could thereby reduce the number of disruptive omega-6s, improving conditions for women with menstruation-related problems.

And a small study of women 18 to 35 with prospectively confirmed PMS found treatment with soy protein containing isoflavones during two complete menstrual cycles reduced breast tenderness and headache from baseline after treatment; cramps and swelling were significantly lower compared to milk protein placebo.⁹

Flavonoids also may help women address pain connected with dysmenorrhea and other uterine complaints. A Japanese study, scheduled to be published in The Journal of Reproductive Medicine, investigated 116 women suffering from menstrual pain in a multicenter, randomized, double blind, placebo-controlled study.¹⁰ The first two pre-treatment menstrual cycles were utilized for establishing baseline values for pain and analgesic medication use. Subjects then received French maritime park extract (as Pycnogenol®, from Natural Health Science) or placebo. Treatment with Pycnogenol lowered back pain during menstruation, reflected by a significant reduction in pain medication usage. The number of painful days due to dysmenorrhea decreased from 2.1 days to 1.3, and to 1.3 and 1.2 during the consecutive menstrual cycles, respectively.

Another study compared Pycnogenol to the synthetic peptide Leuprorelin in treating endometriosis, a condition in which endometrial tissue in the uterus grows elsewhere in the body, causing pelvic pain and possible infertility.¹¹ The study, conducted at Kanazawa University School of Medicine, Ishokawa, Japan, sampled 58 women ages 21 to 38 who underwent operations for endometriosis within six months prior to the study. After confirming regular menstruation and ovulation for three months before treatment, patients were examined at four, 12, 24 and 48 weeks after treatment began to check for symptom control (pain, urinary and bowel symptoms, breakthrough bleeding). Patients self-assessed pain levels, and an investigator interviewed and performed a gynecologic examination. Those treated with Pycnogenol saw their pain score lowered by 33 percent during the treatment period. Leuprorelin suppressed menstruation during treatment and, though more effective, caused a dramatic relapse within 24 weeks after obligate discontinuation.

Amenorrhea is the absence of menstruation usually associated with pregnancy or menopause, but which also may occur for other reasons during puberty or later in life. Amenorrhea is a sign, not a disease, and rarely results from a serious condition. The National Institutes of Health (NIH) reports too much iron can be a cause. Too little iron, meanwhile, can lead to iron deficiency anemia. Iron is needed by the body to make hemoglobin, a substance in red blood cells that carries oxygen from the lungs to the cells. Without enough iron, the body produces fewer and smaller red blood cells. As a result, less hemoglobin is available, and the bodys cells do not get enough oxygen. In the United States, iron deficiency is seen most often in children younger than 2 years old and in girls and women who have heavy menstrual periods.

Lack of menstruation is also a symptom of polycystic ovary syndrome (PCOS), the cause of which is unknown. PCOS can also affect fertility, hormonal balance and cardiovascular health. Women with PCOS have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-ch iro-inositol-containing phosphoglycan, a compound that mediates the action of insulin. In a recent study at the Medical College of Virginia, 44 obese women with PCOS received 1,200 mg/d of D-chiro-inositol, a naturally occurring isomer of inositol, or placebo for six to eight weeks to see whether supplementation would replenish stores of the mediator and improve insulin sensitivity.¹² Nineteen of the 22 women in the treatment group ovulated, compared with six of the 22 women given placebo. According to the study, D-chiro-inositol increased insulin activity in patients with PCOS, improving ovulatory function and decreasing serum androgen concentrations, blood pressure and plasma triglyceride concentrations.

Researchers at the State University of New York (SUNY), Stony Brook, analyzed the effects of nutritional supplementation with chromium picolinate (as Chromax®, from Nutrition 21) on six women of reproductive age with PCOS.¹³ After two months of treatment, glucose disposal rate (insulin sensitivity) increased by an average of 35 percent, and baseline insulin levels decreased by 22 percent.

Options also abound to support fertility and healthy pregnancy. A 2004 study in England evaluated a food frequency questionnaire from 11,585 pregnant women and found frequency of intra-uterine growth retardation decreased with consumption of fish, a major source of omega-3 fatty acids.¹⁴ This year, U.S. scientists found a link between low-fat dairy foods and infertility.¹⁵ The March of Dimes, following recommendations from the U.S. Public Health Service, has advised all women of child-bearing age to take 400 mcg/d of folic acid, in addition to eating foods that contain folate. A study by the Lewin Group for the Dietary Supplement Education Alliance (DSEA) found if 10.5 million women supplemented with 400 mcg/d of folic acid during pregnancy, 600 cases of neural tube defects could be avoid annually, yielding a savings of $1.3 billion in lifetime health costs over a five-year period.

Pregnant women are also at risk for iron deficiency anemia. According to NIH, iron requirements of pregnant women are approximately double those of non-pregnant women because of increased blood volume during pregnancy, increased needs of the fetus, and blood loss that occurs during delivery. Iron deficiency anemia of pregnancy is responsible for significant morbidity, such as premature deliveries and giving birth to infants with low birth weight. A 2003 study in Fertility & Sterility found vitamin C significantly reduced infertility caused by luteal phase failure, a condition in which the ovaries dont produce enough progesterone to allow implantation of a fertilized egg.¹⁶ A study in Reproductive Biology & Endocrinology found 1 g/kg body weight of aqueous extract of lyophilized yellow maca (Lepidium meyenii) administered to female mice increased the number of pups per dam at birth.¹⁷

Mastering Menopause

Sexual fertility usually stops when a woman is in her early 50s. As menstruation ceases, declining levels of estrogen and progesterone signal the entry into perimenopause. During this two- to four-year time frame, a womans periods become less regular, and she may experience symptoms such as hot flashes and night sweats. According to the National Institute on Aging, common symptoms of menopause include a change in periods, hot flashes, problems with the vagina and/or bladder, sexual dysfunction, insomnia, mood changes, weight gain, joint pain and memory problems.

For decades, hormone replacement therapy (HRT), now known as menopausal hormonal therapy (MHT), was the main conventional treatment for menopausal symptoms. It was also used to help protect against osteoporosis, the risk of which goes up for both men and women as they age. However, MHT lost a lot of its luster in 2002, after the Womens Health Initiative study found increased risks for serious health problems in participants who had taken a combination of progestin and estrogen for several years.¹⁸ The study ended early but found increased risks for heart disease, breast cancer and stroke.

Fortunately, there are many natural alternatives for womens health, though some may not yet have a strong research base. The National Center for Complementary and Alternative Medicine (NCAAM) has stated evening primrose oil (EPO) does not have any effect on menopausal symptoms. Red clover (Trifolium pratense L.) was cited by researchers at the University of Illinois Chicagos (UIC) NIH Center for Botanical Dietary Supplements Research in a 2006 review as lacking clinical evidence for efficacy, and the safety of its use in women with estrogen-related cancers is unproven.¹⁹

Still, theres always black cohosh (Actaea racemosa, syn. Cimicifuga racemosa). Reviewers from UIC stated black cohosh appears to alleviate menopausal symptoms such as hot flashes, profuse sweating, insomnia and anxiety at a dosage of 40 to 80 mg/d.²⁰ They also noted the extract does not appear to be estrogenic, making it safe for women with estrogen-related cancer concerns. That issue was also addressed by researchers from Northwestern Medical School, Evanston, Ill., whose in vitro work with estrogen-responsive (ER)-expressing breast cancer cells did not find black cohosh had estrogenic activity in those assays.²¹

Clinical trials support the reviewers findings. A 12-week, multicenter, double blind study in Germany involving 304 patients with climacteric complaints found 40 mg/d of black cohosh extract worked to relieve symptoms, particularly hot flushes.²² Similar findings were reported in a Swiss study of 122 menopausal women taking black cohosh for 12 weeks,²³ as well as in an Italian study in 64 menopausal women, in which black cohosh (40 mg/d) was as effective as traditional HRT treatment in reducing climacteric symptoms.²⁴ One of the largest trials involved 2,016 Hungarian women taking black cohosh extract (as Remifemin®); after 12 weeks of intervention, favorable decreases were seen in hot flashes, sweating, insomnia and anxiety.²⁵

Three recent trials have shown black cohosh to be especially effective when paired with St. Johns wort. A prospective, controlled, open-label observational German study of 6,141 women followed for six months to one year showed the fixed combination of black cohosh and St. Johns wort was superior to black cohosh alone in alleviating climacteric mood symptoms.²⁶ Another double blind, randomized, placebo-controlled study followed 301 women with climacteric complaints with psychologic symptoms.²⁷ One group received a placebo, the other ethanolic St. Johns wort extract and isopropanolic black cohosh extract. Menopause-related complaints were measured via the Menopause Rating Scale mean score, while psychological complaints were evaluated by the Hamilton Depression Rating Scale sum score.

The mean menopause score decreased 50 percent in the treatment group compared to 19.6 percent in the placebo group, while the depression-based score decreased 41.8 percent in the treatment group compared to 12.7 percent with placebo.

In Korea, a double blind, placebo-controlled, randomized multi-center study of 89 peri- and post-menopausal women with climacteric symptoms found hot flushes were significantly lower when the treatment group took a proprietary product of St. Johns wort and black cohosh extract (as Gynoplus, from Jin-Yang Pharm).²⁸ However, not all the research is positive. One clinical trial by the Mayo Clinic found black cohosh on its own was ineffective in relieving hot flashes; subjects on placebo had higher satisfaction scores than the treatment group.²⁹

As for red clover, researchers at Vrije Universiteit Medical Centre, Amsterdam, the Netherlands, examined 30 menopausal women who received red clover supplements (as Promensil, 80 mg/d isoflavones) for 12 weeks; intervention significantly reduced hot flushes (44-percent decrease).³⁰ Another study from Ecuador also found intervention with red clover (as Promensil) in menopausal women (n=53) significantly decreased the rate of menopausal symptoms and triglyceride levels.³¹ A study in Vienna, Austria, examined the effect of a red clover extract on hormone levels and endometrium in postmenopausal women.³² They received either two capsules daily of the extract (supplying 80 mg isoflavones/d) or placebo capsules for 90 days; after a seven-day washout, the groups crossed over for another 90-day intervention. Evaluation showed the extract increased plasma testosterone levels and decreased endometrial thickness without affecting estradiol levels, suggesting a role for the product in endometrial hyperplasia.

Kava kava

(Piper methysticum) has long been used to help treat anxiety, a common symptom of menopause. A study at the Institute of Obstetrics and Gynecology, University of Modena (Italy), examined 68 perimenopausal women, half of which took 100 or 200 mg of calcium plus kava a day.³³ After one and three month periods, women in the treatment group saw significant declines (compared to placebo group) in anxiety and depression in three month, and saw an improvement in climacteric symptoms after one and three months.

Another Italian study found pairing HRT with kava extract could be an excellent therapeutic tool for treating women with stabilized menopause.³⁴ Kava use should be discussed with health care providers, as there have been concerns among some regulatory agencies about possible liver toxicity.

The role of soy isoflavones on menopausal complaints has been subject to debate. In a review from Loma Linda University, Calif., researchers noted the estrogen-like effects of isoflavones combined with the reported low frequency of hot flushes in Asian cultures, where soy consumption is more prevalent, has led to increased research into the plausibility of using isoflavone supplements for relief of climacteric complaints.³⁵ The researchers found greater effects of isoflavone supplements in women with more frequent hot flushes. A slew of studiesboth recent and pastsupports the benefits of soy isoflavones for hot flushes and more.

A Swedish study followed 60 healthy postmenopausal women randomly assigned by computer into two groups to receive 60 mg/d isoflavones or placebo for three months.³⁶ Results of this double blind prospective study found women in the treatment group saw hot flashes and night sweats reduced by 57 percent and 43 percent, respectively. A crossover study at Bostons Beth Deaconess Medical Center examined 60 menopausal women who undertook a therapeutic lifestyle changes (TLC) diet alone or a TLC diet of similar energy, fat and protein content in which one-half cup soy nuts divided into three or four portions spaced throughout the day (containing 25 g soy protein and 101 mg aglycone isoflavones) replaced 25 g of non-soy protein.³⁷ At the end of the eight-week diet, compared to the TLC diet alone, the TLC diet plus soy nuts was associated with a 45-percent decrease in hot flashes in women with more than 4.5 hot flashes per day at baseline, and a 41-percent drop in those with fewer or equal to 4.5 hot flashes/d. Soy nut intake was also associated with improved scores on the menopausal symptom quality of life questionnaire, including a trend toward improvement in the sexual score.

Researchers from ADM participated in an analysis of 11 isoflavone studies, which stressed not all isoflavones are created equal.³⁸ In five studies that provided more than 15 mg of genistein, each study reported a significant decrease in hot flash symptoms. In the six remaining studies, all of which featured participants taking less than 15 mg of genistein, all but one study showed no statistically significant decrease in hot flash symptoms. According to the study, The reduction in hot flashes was related to genistein dose, not total isoflavone content of the treatments.

Several proprietary ingredients have also shown menopause-related benefits. In a double blind, randomized, outpatient, multicenter study involving 177 postmenopausal women experiencing five or more hot flushes per day, researchers provided either placebo or soy isoflavone extract providing 50 mg genistein and daidzin per day (as SoySelect®, from Indena).³⁹ While both groups experienced some relief of symptoms, the soy group reported decreases in incidence and severity of hot flushes after only two weeks; differences were statistically significant after six weeks. In addition, the supplement did not stimulate the endometrium. Another study using the SoySelect extract involved 39 postmenopausal women given the extract or placebo alone, and then both treatments combined with conjugated equine estrogen (CEE).⁴⁰ When compared with pretreatment data, at the end of treatment with just the soy extract, there was a significant reduction in the number of hot flushes per week; both placebo- and soy-treated women showed more marked relief when receiving the hormone therapy as well. The researchers suggest the soy treatment could be a safe, efficacious therapy for women not willing or able to take traditional HRT.

Researchers from Samsung Cheil Hospital, Korea, performed a double blind study on a phytochemical formula that includes Shanzhiside methyl ester, Cynanchum wilfordii and Phlomis umbrosa (as EstroG-100, from JLM Marketing); a total of 47 postmenopausal women were included in the study. After three months, there was a significant improvement in hot flashes and vaginal dryness in the EstroG-100 group; after one year, women on the active intervention showed an increase in femoral neck bone mineral density (BMD) and a decrease in serum osteocalcin.

But red clover and soy are not the only source of phytoestrogens studied for their impact on menopausal symptoms. Research from the University of Insubria in Italy defines the optimal dose of phytoestrogen-rich Norway spruce lignans to inhibit symptoms of menopause. In the unpublished study, researchers established the effective median concentration value (EC50) of the compound (as HMRlignan, from Linnea), hydroxymatairesinol and its human metabolite enterolactone in comparison to estradiol. The researchers concluded both hydroxymatairesinol and its metabolite enterolactone are endowed with estrogenic activity, which is likely to be exerted through estrogen receptors and to target the same intracellular mechanisms acted upon by estradiol; they noted the estrogenicity of hydroxymatairesinol and enterolactone is, however, milder than that of estradiol, as indicated by the lower potencies and efficacies of both lignans.

Osteoporosis A Brief, But Relevant Digression

Isoflavones, including soy isoflavones, have also been to shown to have a positive effect on womens bones. A sampling of 24,000 women who participated in the three-year Shanghai Womens Health Study found post-menopausal women who ate the most soy had a 37 percent lower risk of bone fracture compared to women who consumed the smallest amount of soy.⁴¹ A year-long study found 175 postmenopausal women given 80 mg/d of SoyLife® EXTRA, a 10 percent isoflavone extract from soy hypocotyls from Frutarom, had a positive effect on bone mineral content (BMC).⁴² Significant effects were especially prevalent in women with lower BMC at baseline, and occurred at the total hip as well as trochanter and intertrochanter. An increase of 1 mg/d of isoflavones was associated with a yearly increase of 0.018 to 0.028 percent of BMC at these bone sites, according to the study.

Genistein specifically was examined for its bone metabolism effects on 389 osteopenic postmenopausal women.⁴³ These women had a BMD of less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a four-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n=191) or 54 mg/d of genistein (n=198) for 24 months. At studys end, BMD at the anteroposterior lumbar spine had increased in genistein recipients and decreased in placebo recipients. This is not the first time genistein has been acknowledged for its bone benefits. Researchers from the University of Messina, Italy, conducted a one-year, double blind, placebo-controlled study on 90 healthy postmenopausal women; the women received HRT, genistein (54 mg/d) or placebo.⁴⁴ Genistein administration reduced the excretion of pyridinium cross-links (a marker of bone breakdown) at six and 12 months, and increased serum levels of the bone-specific ALP and osteocalcin. At the end of the intervention, HRT and genistein significantly increased BMD in the femur and lumbar spine.

A double blind, randomized, placebo-controlled trial revealed red clover isoflavones may help protect women from the risk of osteoporosis.⁴⁵ Researchers found loss of lumbar spine BMC and BMD was significantly lower in the isoflavone group compared to placebo; bone formation markers were also much higher in the treatment group.

There are numerous nutrients available in the battle against osteoporosis. Theres calcium, of course, since the bones contain 99 percent of the bodys calcium. It may sound obvious, but maintaining proper calcium levels is crucial, so much so that the North American Menopause Society (NAMS) in 2006 updated its position statement on management of osteoporosis in postmenopausal women to note adequate calcium and vitamin D intake is a first-line, nonpharmacologic measure to manage disease risk.⁴⁶Vitamin K also has a storied history of maintaining bone health. It activates certain proteins involved in bone metabolism, and vitamin K deficiencies have been linked to reduced BMD and increased fracture risk.⁴⁷ Vitamin K2 also appears to prevent osteoclastic bone resorption stimulated by magnesium deficiency, thus normalizing bone remodeling.⁴⁸ In vitro, vitamin K2 works as a transcriptional regulator of bone marker genes in osteoblasts and may also assist in collagen accumulation of those bone-building cells. Another critical bone-building mineral is magnesium. Women with lower BMD generally have low magnesium levels,⁴⁹ while higher intake of magnesium by white men and women was found in a cross-sectional study of 2,038 older adults to correlate with higher BMD.⁵⁰

Battling Breast Cancer

The National Cancer Institute (NCI) estimates 12.7 percent of women will be diagnosed with breast cancer at some point in their lives, with women ages 60 through 69 facing the greatest chance of receiving such news. According to the American Cancer Society, the chance of a woman having invasive breast cancer some time during her life is about 1 in 8. Though the numbers have declined, possibly because of improved treatment and earlier detection, the chance of dying from breast cancer is still about 1 in 33.

Researchers from the AFSSA-French Food Safety Agency in Maisons-Alfort noted it may be challenging to isolate the impact of dietary supplements in population cohorts, as they found vitamin/ supplement users were significantly older, leaner and followed a healthier diet, with higher dietary intakes for most micronutrients, fiber and omega-3 fatty acids.⁵¹ As far as dietary consumption, studies have shown higher consumption of calcium and/or dairy products may reduce the risk of developing breast cancer,⁵² as may a higher dietary intake of folate, particularly among women who consume alcohol.⁵³ However, a systematic review in the Journal of the National Cancer Institute found no evidence that higher folate intake was related to lower breast cancer risk.⁵⁴

Resveratrol, found in grape seeds and other plants such as the Chinese botanical Polygonum cuspidatum, has shown some effect against breast cancer, including suppressing mammary carcinogenesis (fewer tumors per subject and longer tumor latency) in rats induced with breast cancer.⁵⁵ A Chinese study reported resveratrol affects the growth of human breast cancer cell lines in a dose-dependent manner, with MCF-7 being the most sensitive.⁵⁶ A 2005 study from the Universidad Central del Caribe in Puerto Rico showed resveratrol decreased the migration of human breast cells, a key to cancer invasion, by altering the cytoskeleton and decreasing adhesion.⁵⁷

Higher dietary intake of carotenoids may also reduce breast cancer risk. A nested, case-control study used plasma from 1,938 women enrolled in the Nurses Health Study, and assessed multivariate risk of breast cancer and carotenoid intake.⁵⁸ Risk of breast cancer was up to 35-percent less for women whose plasma had the highest quintile levels of alpha-carotene, beta-carotene and total carotenoids, compared to those in the lowest quintile.

Researchers from Harvard Medical School and Brigham and Womens Hospital, Boston, found similar results in examining carotenoid intake in relation to breast cancer risk among 90,655 premenopausal women in the Nurses Health Study II cohort.⁵⁹ While there was no general association among carotenoid intake and breast cancer risk, a higher intake of vitamin A and carotenoids did reduce the risk of breast cancer in female smokers. Supporting evidence for the finding comes from in vitro work in which beta-carotene down-regulated a number of MCF-7 breast cancer cells, increasing apoptosis.⁶⁰

Water-soluble antioxidant flavonoids may also play a role in breast health. Italian researchers compared data on overall flavonoid intake and breast cancer incidence in 2,569 patients and 2,588 controls, finding a reduced risk of breast cancer associated with increasing intake of flavones and flavonols.⁶¹ A case-control study of nearly 3,000 women in Long Island, N.Y. (1,434 breast cancer cases and 1,440 controls) found a decrease in breast cancer risk with increased flavonoid intake, with the most pronounced decrease among postmenopausal women.⁶²

One of the major sources of flavonoids in the diet is tea, and researchers have examined the impact of tea consumption on breast cancer risk. A meta-analysis conducted at the University of Minnesota, Minneapolis, included 13 papers looking at breast cancer risk and consumption of black tea, green tea or both.⁶³ Green tea consumption was linked to a lower risk of breast cancer; data on black teas effect was inconclusive. A Canadian meta-analysis on green tea alone concurred with those findings, indicating consumption of five or more cups of green tea per day could prevent breast cancer development and recurrence.⁶⁴ Some of the variance could be related to breast cancer genotype, as researchers from the University of Southern California, Los Angeles, conducted a nested case-control study involving 297 incident breast cancer cases and 665 controls within the Singapore Chinese Health Study.⁶⁵ They found no association between green tea intake and overall breast cancer risk; but, in women with highactivity angiotensin-converting enzyme (ACE) activity, higher green tea consumption significantly reduced risk of breast cancer. However, a study of 1,009 female patients from Southeast Asia (age 20 to 87) with histologically confirmed breast cancer found an association between green tea consumption and a decreased risk of breast cancer.⁶⁶

A recent study from the Cancer Research Laboratory, Methodist Research Institute (Indianapolis), revealed an extract from green tea (GTE) increased the anticancer effect of Ganoderma lucidum extract (GLE) on cell proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of breast cancer cells.⁶⁷ This effect was mediated by the down-regulation of expression of oncogene cmyc in MDA-MB-231 cells. Although individual GTE and GLE independently inhibited adhesion, migration and invasion of MDA-MB-231 cells, a combination of the two demonstrated a synergistic effect, which was mediated by the suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells.

Further research has focused on green teas polyphenol content, particularly epigallocatechin gallate (EGCG), as it impacts breast cancer risk. Researchers from the Uniformed Services University of the Health Sciences, Bethesda, Md., examined the impact of EGCG on tumor regression in vitro and in vivo, using a nude mice model of breast cancer.⁶⁸ EGCG treatment arrested the breast cancer cell cycle in vitro; when nude mice were inoculated with human breast cancer MDA-MB-231 cells, EGCG delayed tumor incidence and reduced tumor burden compared to control animals. In addition, EGCG treatment induced apoptosis and inhibited proliferation of tumor tissue. French researchers further reported EGCG could inhibit the growth of breast cancer cell lines by inducing apoptosis without damaging normal breast epithelial cell function.⁶⁹ Further in vitro work suggests EGCG may also inhibit signaling of hepatocyte growth factor (HGF) and its receptor, Met, to help block invasive cancer growth.⁷⁰

Polyphenol compounds found in pomegranate also appear to have benefits in breast cancer prevention. Researchers from Pusan National University, Korea, found fermented and fresh pomegranate juice both had an anti-proliferative effect on MCF-7 breast cancer cells and also helped inhibit the estrogenic activity of 17-beta-estradiol.⁷¹ In vitro, pomegranate seed oil and fermented juice polyphenols have shown the ability to down-regulate angiogenesis of breast cancer cells and exact anti-proliferative effects on cell growth.⁷² Researchers from UIC evaluated the potential chemo-preventive efficacy of pomegranate seed oil in a mouse model of breast cancer; the oil had an almost 87-percent reduction in number of lesions compared with control.⁷³

Also playing a role in breast cancer is soy, though findings have been somewhat contradictory. A meta-analysis conducted out of Baltimores Johns Hopkins School of Medicine included 18 epidemiologic studies assessed for soy intake and breast cancer risk.⁷⁴ In a pooled analysis, high soy intake was modestly associated with reduced breast cancer risk, with the inverse association somewhat stronger in premenopausal than postmenopausal women. Researchers concluded soy intake could help reduce breast cancer risk, but stated recommending high-dose isoflavone supplements to prevent breast cancer would be premature. Another meta-analysis conducted by researchers from the University of Arkansas for Medical Sciences, Little Rock, found soy protein isolate could protect against breast cancer through multiple mechanisms, including increased mammary gland differentiation, decreased activation of procarcinogens, and regulating genes linked to tumor promotion and/or progression.⁷⁵ Further, a review from Wayne State University, Detroit, noted soy isoflavones, particularly genistein, may induce apoptosis in breast cancer cells and inhibit breast cancer cell growth through its agonistic activity with 17beta-estradiol.⁷⁶ And in vitro work by English researchers determined daidzein was able to disrupt estrogen balance, inhibiting estrogen sulfation.⁷⁷

Animal research has shown promise for soy isoflavones in preventing breast cancer development. In a study from the Wake Forest University School of Medicine, Winston- Salem, N.C., ovariectomized female monkeys were rotated through eight different diets with the human equivalent of 0, 60, 120, or 240 mg/d soy isoflavones with a dose of oral micronized 17beta-estradiol to create a low or high postmenopausal estrogen environment.⁷⁸ The highest isoflavone dose resulted in significantly lower breast proliferation and uterine size in the high-estrogen environment, and all isoflavone doses resulted in lower serum estrone and 17beta-estradiol concentrations in the high-estrogen environment. The researchers concluded soy isoflavones may alter estrogen receptor signaling and induce selective antagonistic effects in the breast in the presence of estrogen.

Human studies have been less conclusive. Data from a cohort of 1,459 breast cancer patients who participated in the Shanghai Breast Cancer Study found no association between soy protein intake and breast cancer survival.⁷⁹ However, German researchers used a population-based case-control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of phytoestrogens and premenopausal breast cancer risk.⁸⁰ In their analysis, the researchers determined higher intakes of genistein and daidzein were protective against ER-positive tumors, while increased levels of the plant lignan matairesinol and mammalian lignans reduced overall breast cancer risk. 

The role of lignans as protective phytoestrogens has gained momentum in the research community. A German study measuring enterolactone and genistein concentrations in samples of 220 premenopausal cases and 237 age-matched controls found breast cancer risk decreased with increasing plasma enterolactone concentrations, while there was no significant association between plasma genistein concentration and premenopausal breast cancer risk.⁸¹ A French study relied on a self-administered diet history questionnaire among some 58,000 postmenopausal women to examine the risk of postmenopausal invasive breast cancer and dietary intake of four plant lignans (pinoresinol, lariciresinol, secoisolariciresinol and matairesinol) and estimated enterolignans (enterodiol and enterolactone).⁸² During 383,425 person-years of follow-up (median follow-up, 7.7 years), 1,469 cases of breast cancer were diagnosed. Compared with women in the lowest intake quartiles, those in the highest quartile of total lignan intake (>1,395 mcg/d) had a reduced risk of breast cancer. A Swedish study of ovariectomized mice revealed flaxseed, enterodiol and enterolactone counteracted estradiol-induced growth and angiogenesis in solid tumors.⁸³ In breast cancer, estradiol (E-2) increased vascular endothelial growth factor, a stimulator of angiogenesis, which is key in cancer progression. The mice were treated with continuous release of E2. MCF-7 tumors were established and mice were fed with basal diet or 10 percent flaxseed, and two groups that were fed basal diet received daily injections with enterodiol or enterolactone (15 mg/kg body weight). Researchers from the Roswell Park Cancer Institute, Buffalo, N.Y., examined breast cancer risk and dietary lignan intake in a population-based casecontrol study of 1,122 women with breast cancer and 2,036 controls as part of the Western New York Exposures and Breast Cancer (WEB) Study.⁸⁴ While no association was seen between lignan intake and postmenopausal breast cancer, premenopausal women in the highest quartile of lignan intake had a 34-percent reduction in breast cancer risk compared to the lowest intake group.

Sulforaphane, an isothiocyanate derived from the hydrolosis of glucoraphanin, has been gaining the attention of researchers. It may have particularly strong activity by inducing phase II detoxification enzymes,⁸⁵ and inhibiting chemically-induced mammary tumors in rodents, possibly through mitotic cell cycle arrest.⁸⁶ Researchers at Johns Hopkins University observed a single 150 mumol oral dose of sulforaphane in the rat mammary gland altered gene expression in cell culture. They also observed a three-fold increase in H-quinone oxidoreductase and four-fold elevated immunostaining of heme oxygenase (HO-1), an enzyme with antioxidative properties, in rat mammary epithelium.⁸⁷ A related pilot study had eight healthy women undergoing reduction mammoplasty take a single dose of broccoli sprout preparation with 200 mumol of sulforaphane. Researchers also found sulforaphane metabolites were readily measurable in human breast tissue enriched for epithelial cells. After observing the effects of sulforaphane on several human breast cancer cell lines, another study at John Hopkins University found sulforaphane treatment inhibited cell growth, induced a G(2)-M cell cycle block, increased expression of cyclin B1 [a breast tumor antigen], and induced oligonucleosomal DNA fragmentation in four human breast cancer cell lines.⁸⁸

EFAs have a role to play in breast cancer prevention as well. Potential mechanisms of action for omega-3 EFAs against breast cancer include modulation of inflammation, decreased angiogenesis, increasing susceptibility for apoptosis and influence on estrogen signaling.⁸⁹ The omega-3s in alpha lipoicacid suppressed the overexpression of HER2 oncogene at the transcriptional level, which, in turn, interacted synergistically with antioncogenetrastuzumab-based immunotherapy.⁹⁰ Further, a case control study examining E F A consumption and the composition of breast adipose tissue showed a higher intake of omega-6s was connected to greater risk of breast cancer, while omega-3s had a protective effect.⁹¹ In vitro trials have shown eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can decrease cell proliferation and induce apoptotic death in human breast cancer cells, possibly by decreasing ER signal transduction,⁹² and increasing neutral sphingomyelinase (N-SMYase) activity in tumors, thus inhibiting breast cancer cell growth.⁹³

For ingredient suppliers and supplement manufacturers, the amount of new researchcoupled with a solid foundation of past revelationsshows natural alternatives can make it easier for a woman to handle the punches thrown out by a lifetime of hormonal changes.

And with conventional medicine losing its luster, more women are ready to stand behind natural products. 

Pete Croatto is a New Jersey-based freelance writer who has been covering the natural products industry since 2003. He is also a professional book and movie reviewer.

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44. Morabito N et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: A randomized double blind placebo-controlled study. J Bone Min Res. 17(10):1904-12, 2002. www.jbmr-online.org 

45. Atkinson C et al. The effects of phytoestrogen isoflavones on bone density in women; a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 79(2)326-33. 2004.

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47. Adams J, Pepping J. Vitamin K in the treatment and prevention of osteoporosis and arterial calcification. Am J Health Syst Pharm. 62(15):1574-81, 2005. www.ajhp.org 

48. Amizuka N, Li M, Maeda T. The interplay of magnesium and vitamin K2 on bone mineralization. Clin Calcium. 15(7):57-61, 2005.

49. Saito N et al. Bone mineral density, serum albumin and serum magnesium. J Am Coll Nutr. 23(6):701S-3S, 2004. www.jacn.org 

50. Ryder KM et al. Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc. 53(11):1875-80, 2005.

51. Amizuka N, Li M, Maeda T. [The interplay of magnesium and vitamin K2 on bone mineralization.] Clin Calcium. 15(7):57-61, 2005.

52. Ichikawa T et al. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 281(25):16927-34, 2006 www.jbc.org 

53. Martini LA et al. Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism. Osteoporos Int. 17(6):929-35, 2006. www.link.springer.de/link/service/journals/00198

54. Lewis SJ et al. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst. 98:1607-1622, 2006.

55. Whitsett T et al. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. J Carcinog. 2006 May 15;5:15

56. Li Y et al. Resveratrol-induced cell inhibition of growth and apoptosis in MCF7 human breast cancer cells are associated with modulation of phosphorylated Akt and caspase-9. Appl Biochem Biotechnol. 2006 Dec;135(3):181-92.

57. Azios NG, Dharmawardhane SF. Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells. Neoplasia. 2005 Feb;7(2):128-40.

58. Tamimi RM et al. Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol. 161(2):153-60, 2005. http://aje.oupjournals.org

59. Cho E et al. Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 12(8):713-20, 2003. http://cebp.aacrjournals.org 

60. Li Z et al. [Effect of beta-carotene on gene expression of breast cancer cells.] Ai Zheng. 22(4):380-4, 2003.

61. Bosetti C et al. Flavonoids and breast cancer risk in Italy. Cancer Epidemiol Biomarkers Prev. 14(4):805-8, 2005. http://cebp.aacrjournals.org 

62. Fink BN et al. Dietary flavonoid intake and breast cancer risk among women on Long Island. Am J Epidemiol. 2007 Mar 1;165(5):514-23. Epub 2006 Dec 

63. Sun CL et al. Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies. Carcinogenesis. 27(7):1310-5, 2006. http://carcin.oupjournals.org 

64. Seely D et al. The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis. Integr Cancer Ther. 4(2):144-55, 2005.

65. Yuan JM et al. Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore. Carcinogenesis. 26(8):1389-94, 2005. http://carcin.oupjournals.org 

66. Zhang M et al. Green tea and the prevention of breast cancer: a case-control study in Southeast China. Carcinogenesis. 2007 May;28(5):1074-8. Epub 2006 Dec 20.

67. Thyagarajan A et al. Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells. Int J Oncol. 2007 Apr;30(4):963-9.

68. Thangapazham RL et al. Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett. Epub March 3, 2006. www.elsevier.com/locate/canlet 

69. Vergote D et al. (-)-Epigallocatechin (GC) of green tea induces apoptosis of human breast cancer cells but not of their normal counterparts. Breast Cancer Res Treat. 76(3):195-201, 2002. www.springerlink.com/link.asp?id=102860 

70. Bigelow RL, Cardelli JA. The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene. 25(13):1922-30, 2006.

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72. Toi M et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis. 6(2):121-8, 2003.

73. Mehta R, Lansky EP. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev. 13(4):345-8, 2004.

74. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst. 98(7):459-71, 2006. http://jncicancerspectrum.oupjournals.org 

75. Badger TM et al. Soy protein isolate and protection against cancer. J Am Coll Nutr. 24, 2:146S-49S, 2005. www.jacn.org 

76. Sarkar FH et al. The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy. Mini Rev Med Chem. 6(4):401-7, 2006.

77. Harris RM et al. Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment. J Clin Endocrinol Metab. 89(4):1779-87, 2004. http://jcem.endojournals.org 

78. Wood CE et al. Dietary soy isoflavones inhibit estrogen effects in the postmenopausal breast. Cancer Res. 66(2):1241-9, 2006. http://cancerres.aacrjournals.org 

79. Boyapati SM et al. Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 92(1):11-7, 2005. www.springerlink.com/link.asp?id=102860 

80. Linseisen J et al. Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 110(2):284-90, 2004. www.3.interscience.wiley.com 

81. Piller R et al. Plasma enterolactone and genistein and the risk of premenopausal breast cancer. Eur J Cancer Prev. 2006 Jun;15(3):225-32.

82. Touillaud MS. Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst. 2007 Mar 21;99(6):475-86.

83. Bergman Jungestrum M. Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo. Clin Cancer Res. 2007 Feb 1;13(3):1061-7.

84. McCann SE et al. Dietary lignan intakes and risk of pre- and postmenopausal breast cancer. Int J Cancer. 111(3):440-3, 2004. www.3.interscience.wiley.com   

85. Wang W et al. Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J Agric Food Chem. 53(5):1417-21, 2005. http://pubs.acs.org/journals/jafcau 

86. Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr. 134(9):2229-36, 2004. http://jn.nutrition.org 

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90. Menendez JA et al. HER2 (erbB-2)-targeted effects of the omega-3 polyunsaturated fatty acid, alpha-linolenic acid (ALA; 18:3n-3), in breast cancer cells: the fat features of the Mediterranean diet as an anti-HER2 cocktail. Clin Transl Oncol. 2006 Nov;8(11):812-20.

91. Bagga D et al. Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer. Nutr Cancer. 42(2):180-5, 2002. www.erlbaum.com/Journals/journals/NC/nc.htm 

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93. Wu M et al. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer. 117(3):340-8, 2005.www.3.interscience.wiley.com

Addressing Urogenital Health

Womens physical makeup is one reason specific urogenital conditions, such as candidiasis or urinary tract infections (UTIs), are much more prevalent in females. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one woman in five will develop a UTI in her lifetime, and the recurrence rate is relatively high. Infection of the urinary tract occurs when microorganisms, often Escherichia coli (E. coli), cling to the opening of the urethra and begin to multiply. And while standard medical treatment of a UTI is a course of antibiotics, certain nutrients can help shorten the infection time and prevent recurrence.

Perhaps the best known botanical for treatment and prevention of UTIs is cranberry. A review from Keighley Health Centre, West Yorkshire, England, noted cranberries may help prevent and treat UTIs in several ways, including increasing acidity of urine and preventing adhesion of E. coli to uroepithelial cells in the bladder.¹ And a Cochrane Database review assessed the effectiveness of cranberry juice and other products in preventing UTIs, and concluded, from the seven trials that met inclusion criteria, that there is some evidence that cranberry juice may decrease the number UTIs in women, though more research on dosages and administration method is needed.²

The efficacy of cranberry is likely in its ability to prevent the adhesion of bacteria in the urinary tract. In vitro research conducted at the Naval Research Laboratory, Washington, found cranberry juice reduced nonspecific adhesion of bacteria,³ while a study at the Worcester Polytechnic Institute, Mass., found even pH-neutralized cranberry juice was able to affect bacterial surface adhesion behavior.⁴

Clinical trials have shown a benefit to cranberry intake. A study at the University of Oulu, Finland, involved 150 women with UTIs who received 50 ml of cranberry juice concentrate daily for six months, a probiotic drink or a placebo intervention.⁵ After six months, there was a 20-percent reduction in absolute risk in the cranberry group compared to the placebo and probiotic intervention. Similar findings were reported by French researchers, who found a dose-dependent decrease in bacterial adherence of different E. coli uropathogenic strains in 20 adults consuming cranberry juice.⁶ Another clinical trial looked at the effectiveness and cost impact of concentrated cranberry tablets (as Cran-Max®, from Proprietary Nutritionals), cranberry juice or placebo as a prophylaxis against UTIs in 150 sexually active women.⁷ Both cranberry juice and tablets significantly reduced the number of patients experiencing at least one UTI/year compared to placebo and also decreased the number of antibiotic treatments; however, the cost of the tablets was less than half of the juice treatment, providing a cost-effective preventive.

Another common urinary issue in women is incontinence, including overactive bladder and stress incontinence. One questionnaire that included women between the ages of 20 to 80 years, reported an overall prevalence for urinary incontinence of 53.2 percent; even in younger women (between 20 to 49 years of age) had a the prevalence was 47 percent.⁸ While primary medical therapy revolves around strengthening the pelvic floor, there are some nutrients that may assist in urinary function. Horsetail (Equisetum arvense) may have application for urinary incontinence and enuresis (involuntary discharge of urine). It was used by Native American tribes as a urinary aid, and was approved by the German Commission E for bacterial infections and inflammation of the lower urinary tract.

A new combination of horsetail with the Ayurvedic botanical Crateva nurvala (as UroLogic, from BioLogic Health Solutions) was studied in a placebo-controlled study of patients (n=73) with overactive bladder and urinary incontinence.⁹ The researchers reported 85 percent of patients who received the combination formula had an improvement in frequency and/or leakage at the end of two months; in addition, 67 percent of the active group had a reduction in daily urinary frequency. Women on active treatment also reported a significant improvement in quality of life.

Another serious urogenital issue is infection of the vagina, commonly seen as vaginosis, when pathogenic bacteria cause infection, or candidiasis, the growth of the fungus Candida albicans. Such infections commonly occur during pregnancy and in connection with hormonal fluctuations (such as during menstruation), as well as with the use of HRT or birth control pills; approximately 75 percent of women will experience a yeast infection during her lifetime, according to the L.A. Department of Health Services.

The ability of some natural compounds to help prevent and treat these conditions has been explored. Researchers from Charles University, Prague, Czech Republic, examined studies on different types of natural compounds and probiotics with antifungal activity, and determined garlic extract, tea tree oil and a range of lactobacillus strains may hold the ability to fight and prevent yeast infections.¹⁰ And a review from the University of Western Ontario noted probiotics may be able to maintain vaginal health and help prevent recurrent yeast and bacterial infection.¹¹

Polish researchers conducted an in vitro study to compare the activity of selected Lactobacillus species against Candida, and found the strongest and fastest activity against Candida was demonstrated by L. delbrueckii strains, which produced the largest quantities of hydrogen peroxide.¹² However, comparison of live active cultures of different strains and mixtures led the researchers to conclude pure compounds are less active than cooperative combinations of strains using different metabolites.

Intervention studies have been somewhat promising. In a randomized, placebo-controlled trial in 64 healthy women, researchers from the Canadian Research and Development Center for Probiotics in London, Ontario, provided oral capsules of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for two months.¹³ The intervention restored normal microflora from asymptomatic bacterial vaginosis in 37 percent of women, with a concurrent depletion in yeast and a reduction in pathogenic bacteria over the course of treatment. Another study from the University of Western Ontario found administration of L. rhamnosus GR-1 or L. fermentum RC-14 correlated with healthy vaginal flora in 90 percent of patients; seven of 11 patients with vaginosis converted to normal bacterial scores within one month.¹⁴ However, another study, conducted at the Department of General Practice, Victoria, Australia, that involved 235 women who took lactobacillus preparations orally or vaginally, or both, during an antibiotic course found the probiotics did not prevent post-antibiotic vulvovaginitis.¹⁵

Heather Granato

References

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2. Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2:CD001321, 2004. www.cochrane.org 

3. Johnson-White B et al. Prevention of nonspecific bacterial cell adhesion in immunoassays by use of cranberry juice. Anal Chem. 78, 3:853-7, 2006.

4. Liu Y et al. Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of Escherichia coli. Biotechnol Bioeng. 93, 2:297-305, 2006.

5. Kontiokari T et al. Randomized trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. 322, 7302:1571, 2001. http://bmj.com 

6. Di Martino P et al. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. World J Urol. 24, 1:21-7, 2006.

7. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 9, 3:1558-62, 2002.

8. Harrison GL, Memel DS. Urinary incontinence in women: its prevalence and its management in a health promotion clinic. Br J Gen Pract. 44:149-52, 1994.

9. Schauss AG et al. Reducing the symptoms of overactive bladder and urinary incontinence: Results of a two-month randomized, double blind, placebo-controlled clinical trial. Presented at FASEB 2006, San Francisco.

10. Hronek M et al. [Antifungal effect in selected natural compounds and probiotics and their possible use in prophylaxis of vulvovaginitis.] Ceska Gynekol. 70, 5:395-9, 2005.

12. Reid G, Burton J, Devillard E. The rationale for probiotics in female urogenital healthcare. MedGenMed. 6, 1:49, 2004. www.medscape.com/pages/homepages/ejournal/mgm 

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