Dr. Tori Hudson, N.D.

Questionnaires were mailed to 8505 women in Canada who were randomly selected from the Quebec Pregnancy Registry. In the end, 3183 were included in the study. Others were returned to sender, or excluded due to missing data or multiple birth pregnancies. This analysis included cases of women who delivered a baby < 2500 g; these were compared to controls in which babies weight > 2500 g. A total of 424 cases (13.32%) were analyzed.

The questionnaire sought to quantify any association between the use of herbs, but specifically flax, chamomile, peppermint or green tea, either alone or in combination, with the risk of low birth weight. The researchers focused on the use of herbs during the second and third trimesters of pregnancy. While there was a checklist of 40 herbs, they were also asked to list others they used but were not listed.

After adjusted for variables, there was no statistically significant increase in low birth weight with exposure to any herb during the last second or third trimester and specifically no association with the four herbs they were especially curious about. What they did notice was that smoking tobacco during pregnancy and giving birth to a female each increased the risk of low birth weight. It is also known that lower economic status increases the risk of low birth weight.

Commentary: This study was motivated by the observation that the frequency of low birth weight in Canada had increased from 5.7% during 2001-2002 to 6.1% during 2005-2006. The use of herbal products during pregnancy is reported to be 9%. In addition, there is some laboratory research that found that high doses of yarrow, fenugreek or flax may lower fetal birth weight if taken during pregnancy.

While this current study found no significant association between any of the most frequently used herbs and low birth weight there was some small association for both green tea and flax although not statistically significant. In a 2010 study of 392 pregnant Italian women, a higher frequency of threatened miscarriage (21.6%) and preterm labor (21.6%) was found in 37 women who regularly used chamomile.

In the spirit of caution, I would recommend avoid green tea, flax and chamomile during pregnancy. Herbs considered historically safe include ginger root, red raspberry leaves, nettles leaf, partridge berry, lemon balm leaf, oat straw and dandelion root. Ginger has the benefit of documented safety in published research studies.

Reference

Moussally K, Bérard A. Exposure to specific herbal products during pregnancy and the risk of low birth weight. Altern Ther Health Med. March/April 2012;18(2):36-43.

If you go to your doctor’s office and get told to not come back for a pap smear in 1 year or 3 years or 5 years…. this may be an appropriate recommendation according to the pap smear guidelines, (based on pap smear history, risk of cervical dysplasia, age and history of human papilloma virus- HPV) but not the same as annual well-woman gynecologic health assessments. Our yearly visit is not dependent on receiving a pap smear or not. The yearly visit can identify disease risks, current medical problems, optimize prevention strategies, discuss lifestyle issues (nutrition, exercise, smoking, alcohol, stress) and establish a good working relationship with your clinician.

I was glad to see that The American College of Obstetricians and Gynecologists (ACOG), recently updated their guidelines for well-woman gynecologic visits.

Major recommendations include:

• The first gynecologic visit should occur between age 13 and 15 and should emphasize education (body image, weight management, immunizations)– I would add, nutrition, exercise, avoidance of smoking and alcohol)
• Pelvic examinations are not necessary to test for sexually transmitted diseases or to initiate oral contraceptives in healthy, asymptomatic testing. Currently, even a urine sample can test for common STDs and a blood test can test for herpes simplex.
• Annual examinations of the external genitalia should be performed in all women; complete pelvic examination is recommended for all women 21 years and older. Internal examinations (visualizing the cervix and internally palpating the uterus and ovaries) can be made jointly by clinician and patient with discussion and information.
• Annual pelvic examination is not necessary in healthy, asymptomatic women who have undergone a hysterectomy and removal of both ovaries if that surgery has been done for non cancerous and non pre-cancerous issues, and the woman has no history of a genital tract neoplasia or in women because of health status or age, would choose not to act even if abnormalities were discovered.
• Clinical breast exams by the practitioner are recommended annually, despite a lack of clear evidence of benefit.

It is reassuring to know that ACOG has addressed this issue of well-woman gynecologic exams as too many women and even too many practitioners, end up not receiving/advising these visits other than when done on pap smear intervals. It is important for all to realize that the “pap smears” and “well-woman visits/pelvic exams” are not synonymous. Furthermore, The Affordable Care Act mandates insurance coverage of yearly well-woman visits.

Reference

Committee on gynecologic practice, the American College of Obstetricians and Gynecologists. Committee opinion no 534: Well-woman visit. Obstet Gynecol 2012 Aug; 12:421.

A systematic review and meta-analysis was conducted using twelve electronic databases to evaluate the evidence for probiotics in the prevention and treatment of antibiotic-associated diarrhea (AAD). Studies that used one or more species of live microorganisms of Lactobacillus species, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus and/or Bacillus were included. Randomized trials were included if the probiotics were used as prevention, treatment or concomitantly with antibiotics to enhance treatment such as is the case in Helicobacter pylori. A total of 82 randomized clinical trials met the inclusion criteria. The majority of the interventions with probiotics were primarily Lactobacillus species, either alone or in combination with other species such as Bifidobacterium, Saccharomyces boulardii or Hansen species. Very few studies had used the Enterococcus, Streptococcus or Bacillus strains.

According to this systematic review, using probiotics as an adjunct to antibiotic therapy reduced the risk of AAD with a relative risk of 0.58 (or 42%). The species predominantly used were Lactobacillus rhamnosus or Lactobacillus casei.

Commentary: These results are affirming for those who already have this habit of using a probiotic for the prevention and treatment of AAD. We should remember though that AAD does not occur in the majority of patients taking antibiotics. What would be even more useful would be a study that determined which patients might benefit more. Examples could include studying probiotics with those antibiotics that are more likely to cause diarrhea. Another approach would be to study those who are elderly or those with a previous history of this problem. Another helpful approach would be to know which species may be indeed more effective at prevention and treatment of this particular clinical problem.

Reference

Hempel S, Newberry S, Maher A, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea. JAMA 2012;307(18):1959-1969

This study is the first randomized placebo-controlled trial of oral micronized progesterone (OMP) for hot flushes and night sweats, aka vasomotor symptoms (VMS). Postmenopausal women within 1 to 10 years of their last menstrual period and experiencing VMS that met the entrance required minimum for both frequency and intensity. The 133 women were randomized to receive either OMP 300 mg nightly at bedtime or placebo for 12 weeks. The average daily VMS score during the last 28 days of the study was the primary outcome. The average VMS score during the baseline was 17 per day. VMS scores improved in both the treatment and placebo groups, but the women taking the OMP received significantly more benefit than those receiving placebo. The differences between the two groups appeared by week 4. Both the frequency and severity decreased more than placebo. The OMP was also more beneficial in frequent-severe symptoms. The average reduction in VMS scores for women taking progesterone was 10.0 and for placebo was 4.4.

Commentary:

How progesterone acts to decrease VMS is not known although we do know that progesterone functions in the hypothalamus to increase core temperature, lower stress hormones that are increased in insomnia and interacts with neurotransmitters similarly to estradiol. One hypothesis is that progesterone alters the sweating threshold.

The primary reason why perimenopausal and recently postmenopausal women seek hormone therapy is for the relief of hot flushes and night sweats, collectively called vasomotor symptoms (VMS). Approximately 65% of postmenopausal women between the ages of 40 and 65 experience these symptoms. For about 7% of women, they experience moderate to severe VMS more than 50 times per week. In addition, VMS can occur for 10 years or more in some women.

In conventional medicine, both estrogens and progestins (synthetic version of a broader category called progestogens) are effective but many women are hesitant due to the complicated issues related to benefits versus risks. Also in conventional medicine, some of the antidepressants have less effect but still considerable ability to treat VMS. Changes in lifestyle, diet and the use of select vitamin and/or herbal preparations also offer many options, some as low as 20% reduction in VMS but others as much as 100%. Most of the research hovers in the 45-55% range of improvement.

Oral micronized progesterone (OMP) is a molecule that is identical to human progesterone- aka natural progesterone or bio-identical progesterone. It has been used in France for over 30 years and in the U.S. since 1998. OMP has many appealing clinical advantages than the synthetic progestogens (progestin). It does not increase blood lipids, has positive effects on the lining of blood vessels, can provide protection to the endometrium (lining of the uterus) when given with an estrogen and can have an added benefit as a sleep aid. Even more compelling is the fact that the progestins but not progesterone has been shown to increase proliferation in the breast tissue of primates and in two French studies, estrogen plus progesterone did not increase the risk of breast cancer where as estrogen plus progestins did. Lastly, in human breast tissue, progesterone (i.e. the natural progesterone) inhibits the proliferative effect of estradiol.

Previously, oral progestins have been shown to be effective for VMS, when given alone. And, when estrogen and progestins are given together, they are more effective than estrogen alone.

This current trial, the first randomized placebo-controlled trial on this issue, is meaningful for clinicians and perimenopausal and postmenopausal women in need of treatment for their VMS. Yet, one more small step for midlife women and one more option to choose from.

Reference

Hitchcock C, Prior J. Oral micronized progesterone for vasomotor symptoms-a placebo-controlled randomized trial in healthy postmenopausal women. Menopause 2012;19(8):886-893.

The purpose of this analysis was to determine whether soy isoflavones were effective in the alleviation of hot flashes in perimenopausal and postmenopausal women. Two large data bases, PubMed and the Cochrane Controlled Clinical Trials Register Database were searched for studies on this topic that were double-blind randomized controlled trials through mid December 2010. A total of 19 trials met the criteria for inclusion in this systematic review and another 17 trials were selected for their meta-analyses on the role of soy isoflavones on hot flash frequency and severity. An analysis of these 36 publications revealed that ingesting soy isoflavones, at an average of 54 mg per day for 6 weeks to 12 months did significantly reduce the frequency of hot flashes by 20.6% when compared with individuals taking placebo. When soy isoflavones were delivered in a supplement form providing an average of 18.8 mg of the isoflavone constituent genistein, the results were more than twice as effecting at reducing frequency of hot flashes than supplements with lower amounts of genistein. The authors concluded that whether or not soy isoflavone supplements were extractions of soybeans or chemically synthesized products, they were more effective than placebo in reducing the frequency and severity of hot flashes.

Commentary:

The effects of soy isoflavones have been studied in oh so many ways– heart disease, osteoporosis, diabetes, numerous cancers, hot flashes and more. From the hundreds of studies that were reviewed, North American Menopause Society position statement of October 2010 on the role of isoflavones in menopausal health reported that soy isoflavones are modestly effective in relieving menopausal symptoms. They also concluded that soy food consumption is associated with lower risk of breast and endometrial cancer and that the effectiveness of soy isoflavones on bone has yet to be proven and the role of soy in cardiovascular benefits is still unclear to draw any strong conclusions.

The results of the current review and meta-analysis of randomized controlled trials shows that about 54 mg of soy isoflavones per day or 18.8 mg of genistein per day has a modest effect on reducing the severity and frequency of hot flashes. For some women, this will be just enough to satisfy them, or warrant inclusion in their total treatment plan to alleviate hot flashes. I have found in my practice that supplementing with soy isoflavones can then be used with herbal products and/or hormone therapy, but lower doses of those may then be needed due to the partial improvement with the soy isoflavones.

Reference

Taku K, Melby M, Kronenberg F, Kurzer M, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause 2012; 19(7):776-790.

This paper was a retrospective analysis of data from 2710 men and 1143 women which included 626 postmenopausal women and overall, an average age of 30 or older in Seoul, South Korea. None of the study subjects were taking a calcium supplement and a 24 hour dietary recall was used to assess calcium intake.

Women with the highest calcium intake had lower total cholesterol levels and LDL cholesterol levels compared to those with the lowest calcium intake. With the coronary artery calcium scores (CACS) that were greater than 100 including different calcium intakes, dietary calcium intake was not significantly associated with CACS in either men or women. In addition, there were no negative effects of calcium on fasting glucose, insulin and platelet aggregation relative to all groups of dietary calcium intake. Higher phosphate levels did increase the risk for coronary artery calcification in men.

Commentary: There has been a longstanding advocacy for adequate dietary and/or supplemental calcium for the prevention and/or treatment of osteoporosis. There is also some evidence that calcium may be able to offer some vascular disease prevention by lowering cholesterol and blood pressure. Observational studies have even shown that women with higher calcium intake had a lower risk for death from cardiovascular disease and ischemic strokes (strokes due to lack of blood flow) when compared to women with lower calcium intake.

The lack of any detrimental effects of calcium on fasting glucose, insulin and platelet aggregation is reassuring as these are considered mechanisms by which calcium could have a negative impact on cardiovascular disease. Another mechanism by which dietary calcium intake might adversely affect cardiovascular disease is through vascular calcification.

The Women’s Health Initiative demonstrated that < 1000 mg calcium supplementation per day did not raise CACS. In the Auckland Calcium Study, calcifications of the aorta were decreased in the group with the highest dietary calcium intake.

However, there have been some recent studies that have demonstrated that there may be a positive relationship between higher blood levels of calcium and the increased risk for cardiovascular disease (myocardial infarction) and stroke, and others that show that calcium supplements might increase the risk of cardiovascular events while dietary calcium does not. Another observation is that the risk for cardiovascular events may be associated with the total of dietary and supplemental calcium intake. In a meta-analysis of 15 randomized blinded placebo-controlled trials, researchers evaluated 12,000 patients who were taking at least 500 mg of calcium supplementation per day (in addition to their dietary intake) and were older than 40. Calcium supplement intake was linked to a 30% increased risk for myocardial infarction. While this is considered only a modest increase, this would translate to about 36 more extra heart attacks over the course of two to five years in 12,000 women. In the midst of this controversy comes this retrospective study I have reported on today. It may be that we will have to rethink and reassess the role of calcium supplements in the prevention and treatment of osteoporosis and perhaps lower the recommendations from a total (diet and supplement) of 1200 mg/day to somewhere around 800 mg per day to find that sweet spot for bone and heart health without harm to either. Stay tuned for more news to come.

Reference

Hee Kim J, Won Yoon J, Won Kim K, et al. Increased dietary calcium intake is not associated with coronary artery calcification. Int. J Cardiology. 2012 Jun 14;157(3):429-31

This study was a prospective study using a detailed food frequency questionnaire. A total of 39, 876 female health professionals, with an average age of 54.6 were enrolled in the Women’s Health Study. A total of 38,022 women completed the questionnaire and were free of a diagnosis of age related macular degeneration (AMD). The main outcome measure was incident AMD and a reduction of vision to 20/30 or worse.

A total of 235 cases of AMD were confirmed during an average of 10 years of follow-up. Regular intake of docosahexaenoic acid and eicosapentaenoic acid in fish oil supplements and dietary fish was associated with a significantly decreased risk of AMD in women.

Commentary

Approximately 9 million adults in the U.S. over 40 have AMD. Another 7 plus million have early AMD with moderate or no vision loss but does in fact increase the risk of advancing to AMD. These prospective data indicate that fish oil supplementation and/or increased fish consumption of even just once per week may be a primary prevention strategy for AMD.

Reference

William G. Christen, ScD; Debra A., et al. Dietary omega-3 fatty acid and fish intake and incident age-related macular degeneration in women. Arch Ophthalmol. 2011;129(7):921-929

The purpose of this study I am reporting on here was to evaluate the effect of a red clover extract in postmenopausal women with depressive and anxiety symptoms.

One hundred and nine postmenopausal women were randomly assigned to take either 2 capsules daily of a red clover extract totaling 80 mg of isoflavones, or a placebo, for 3 months. At the end of the 90 days, there was a one week break, and the two groups switched to take the opposite pills for another 3 months. Their anxiety and depressive symptoms were measured using two common research methods, the Hospital Anxiety and Depression Scale(HADS) and the Zung’s Self Rating Depression Scale (SDS). These measurements were taken prior to the start of the red clover or placebo, then again at 90 days and 187 days.

After taking the red clover extract, women had a significant reduction (improvement) in the scores in both of the rating scales, with a 75% reduction for anxiety and 78.3% reduction for depression using the HADS tool, and an 80.6% reduction in the total SDS score. After taking the placebo pills, the HADS and SDS scores were only reduced by an average of 21.7%.

Commentary:

Depression and anxiety are two of those common conditions experienced by women, with an increase in occurrence during perimenopause/early menopause. It is thought that this increase in incidence is due to changing hormones and essentially less estrogen within the brain and therefore less estrogen interactions with neurotransmitters that affect mood and cognitive function. In addition, these women may also experiencing sleep disruption, aches and pains, hot flashes and more, that can easily impact mood and quality of life. Phytoestrogens, i.e. isoflavones such as those found in red clover extracts, can influence menopause symptoms through their ability to bind to specific estrogen receptors and through this mechanism, may be helpful in menopause symptoms, including depression and anxiety. Until this study, red clover has not been specifically studied for its specific effect using depression/anxiety scales, on depression and anxiety in menopausal women. Many herbs, including some plants with isoflavones have been studied in menopausal women for an array of symptoms including hot flashes, night sweats, mood, sleep, vitality, etc. Red clover has been previously researched for its effects on hot flashes and night sweats, with mixed results.

The current study re-vitalizes my interest in red clover for the management of perimenopause/menopause symptoms, and depression/anxiety in particular.

Reference

Lipovac M, Chedraui P, Gruenhut C, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas 2010;65:258-261

Over two thousand women with stage I, II or IIIA were enrolled in a study about two years after their breast cancer diagnosis. The use of a multivitamin pre-diagnosis and post-diagnosis was assessed with a questionnaire in Kaiser Permanente patients from Northern California. A yearly self-report and verification of their medical records was evaluated. Overall, 54% of the group reported using multivitamins pre diagnosis and 72% reported use post diagnosis. There were a total of 380 recurrences of breast cancer, 212 deaths from breast cancer and 396 total deaths out of the 2,236 women. The use of multivitamins after diagnosis was not associated with any outcome when compared to women who never used multivitamins. For those women who used multivitamins persistently from pre- to post-diagnosis, there was a decreased risk or recurrence, although not statistically significant, when compared to never users. There was a protective association in women who had been treated with radiation only and both radiation and chemotherapy. In addition, women who consistently used multivitamins before and after their diagnosis ate more fruits and vegetables, were more physically active and had better overall survival. In essence, those women who have a habit of multivitamin use before and after diagnosis and have overall healthier diet and exercise habits may improve their survival outcome after a breast cancer diagnosis.

Commentary: This study, called the LACE study is one of the larger prospective studies of breast cancer survivors that have examined multivitamin use and lifestyle factors in relation to breast cancer outcomes. Unfortunately, those women who only used the multivitamins in the 2 years after their breast cancer diagnosis did not receive any protective benefit. However, for those women who used multivitamins before their diagnosis and for the two years after, there was a possible associated reduction in breast cancer related outcomes and overall death. Specifically, those women who were in the top rung of healthy lifestyle habits by eating at least 5.5 servings of fruits and vegetables per day and some kind of physical activity at least 16 hours/week plus used multivitamins before and after diagnosis, they had a 60-70% reduction in the risk of dying from breast cancer or other illnesses.

Which ingredients in the multivitamins may be more or less important in this population remains to be answered. Other studies on breast cancer outcomes have looked more specifically at the antioxidants. The largest study is the Shanghai study that reported the use of vitamin C, E and/or multivitamins during the first 6 months after their breast cancer diagnosis was associated with a decreased risk of recurrence and overall mortality. In a sub analysis of the current LACE study, frequent use of vitamin C and E was associated with reduced risks of recurrence of breast cancer and vitamin E was associated with reduced risk of overall mortality.

While the results of the current study were small for a protective effect of multivitamins before and 2 years after diagnosis of breast cancer along with healthier diet and physical activity lifestyles, the trend is an important message for our patients.

Reference

Kwan M, Greenlee H, Lee V, Castillo A, et al. Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study. Breast Cancer Res Treat 2011;130:195-205.

Postmenopausal women with low bone density (osteopenia) but not osteoporosis were given green tea supplements for 6 months. A total of 171 women participated in the study in which there were four groups. Women in the placebo group and the placebo plus Tai chi groups received a total of 500 mg of a placebo per day. Women in the green tea and green tea with Tai chi groups received 500 mg per day of green tea polyphenols.

Women in the placebo plus tai chi and the green tea plus Tai chi groups attended three 1 hour tai chi exercise classes each week for 6 months. Each session had a warm up and a cool down period with a routine of a 24 form Tai chi style that was repeated 6 times during the 45 minute training period. Women in the non Tai chi groups who took placebo or green tea capsules continued their customary activity levels throughout the 6 month study period.

Bone density testing, bone formation markers, bone loss markers, serum and urinary calcium, creatinine, parathyroid hormone and muscle strength assessments was done at baseline, 1,3 and 6 months.

Results: In this study, green tea supplementation and Tai Chi exercise increased bone formation biomarkers and improved bone turnover rate. Tai Chi exercise increased parathyroid hormone. Green tea supplementation, Tai Chi exercise and the combination of the two together all had an effect on improving muscle strength in these postmenopausal women with low bone density.

Comments: Previous animal studies have shown that green tea polyphenols can function via several mechanisms and therefore improves bone health. Collectively, these effects of green tea extracts improves muscle health, slows muscle aging, decreases muscle lipid oxidation, slows bone loss and increases bone formation. Other studies have also shown that Tai chi exercise improves muscle strength and endurance which may provide bone protection by improving the neuromuscular function. While the results of the current study are certainly a logic for including green tea supplementation and Tai chi exercise as a bone supportive strategy, a high quality long term study that includes the measurement of bone mineral density as a primary outcome would be necessary to really confirm the full benefits to addressing low bone density and/or preventing osteoporosis and/or preventing further bone loss.

Reference

Shen C-L, Chyu M-C, Yea JK, et al. Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial. Osteoporosis Int 2012;23:1541-1552.