Summary: the hormonal and menstrual irregularities, metabolic dysfunction and adverse cardiovascular changes of PCOS (polycystic ovary syndrome) can be effectively treated with the right dietary and lifestyle interventions according to two recent studies. This is not surprising considering that excessive levels of insulin promote the development of ovarian cysts.

A study recently published in The Journal of Clinical Endocrinology & Metabolism offers excellent evidence that the metabolic and cardiovascular irregularities of PCOS respond well to the appropriate lifestyle changes. The authors state:

“Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce…Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS.”

They examined 59 obese girls with PCOS aged 12–18 years for menstrual irregularities,IMT (thickening of the inner layer of the arteries), waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and SHBG (sex hormone binding globulin) before and after a one year intervention of nutrition education, exercise training, and behavior therapy. The results were instructive:

“In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of −3.9 kg/m2) improved most CRF and decreased their IMT (by a mean of −0.01 cm). Testosterone concentrations decreased (by a mean of −0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (−42%) and oligoamenorrhea (−19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone and SHBG.”

These results illuminate the role of insulin resistance and its association with obesity and PCOS. The authors conclude:

“Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.”

These results add savor to another study published shortly afterward in The American Journal of Clinical Nutrition that offers evidence for the most effective protein/carbohydrate ratio for PCOS. The authors state:

“Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS)…The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS.”

They assigned 57 PCOS women to either a high protein (HP) diet (>40% of energy from protein and 30% of energy from fat) or a standard protein (SP) diet (<15% of energy from protein and 30% of energy from fat). Both diets were without caloric restriction, but dietary counseling was given monthly. At baseline and 3 and 6 mo, They took anthropometric measurements and collected blood samples at the beginning and after 3 and 6 months. The results support the replacement of carbohydrates with protein for women with PCOS:

“The HP diet produced a greater weight loss (mean: 4.4 kg) and body fat loss (mean: 4.3 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone–binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group.”

Considering that PCOS is driven by elevated insulin levels associated with insulin resistance the authors’ conclusion offers sound guidance:

“Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.”

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Summary: Magnesium, important for the human body for many reasons, can help with hot flashes due to menopause and treatment for breast and prostate cancer.

Hot flashes occur during the onset of menopause as abrupt changes in estrogen levels elicit vasomotor reactions through the hypothalamus, and they can also occur as estrogen levels are suppressed by chemotherapy in breast cancer treatment. A study recently published in the journal Supportive Care in Cancer presents evidence that magnesium helps to reduce menopausal hot flashes in breast cancer patients.

The authors derived a hot flash score from frequency and severity of hot flashes in breast cancer patients who had been experiencing at least 14 hot flashes a week, before and after taking 400 mg of magnesium oxide 400 mg for 4 weeks. The study subjects were allowed to increase the dose to 800 mg if needed. The results were impressive…

“The average age was 53.5 years; six African American, the rest Caucasian; eight were on tamoxifen, nine were on aromatase inhibitors, and 14 were on anti-depressants. Seventeen patients escalated the magnesium dose. Hot flash frequency/week was reduced from 52.2 to 27.7, a 41.4% reduction… Hot flash score was reduced from 109.8, a 50.4% reduction. Of 25 patients, 14 (56%) had a >50% reduction in hot flash score, and 19 (76%) had a >25% reduction. Fatigue, sweating, and distress were all significantly reduced. Side effects were minor: two women stopped the drug including one each with headache and nausea, and two women had grade 1 diarrhea. Compliance was excellent, and many patients continued treatment after the trial.”

These results are welcome because magnesium, the fourth most abundant mineral in the human body plays a vital role in hundreds of important pathways and is frequently subject to depletion. It is the ‘calming mineral’. The patients whose hot flashes were reduced likely obtained other benefits. The authors conclude:

“Oral magnesium appears to have helped more than half of the patients and was well tolerated. Side effects and cost ($0.02/tablet) were minimal.”

These findings are echoed in another report published in the Journal of Clinical Oncology. The author states:

“Hot flashes are common with natural menopause or induced estrogen deficiency from chemotherapy, tamoxifen, raloxifene, or the aromatase inhibitors. As many as 90% of perimenopausal women have hot flashes, and 40% of survivors of breast cancer rate their hot flashes rate the effect as “quite a bit” to “severe”.”

He notes that the common medications for hot flashes…

“…have potential adverse effects. Antidepressants can cause mental, emotional, and physical adverse effects. Megestrol acetate and medroxyprogesterone acetate, while effective, can potentially cause fluid retention, premenstrual symptoms, and deep vein thrombosis.”

He goes on to report clinical experience consonant with the previous study:

“Recently I saw two patients with breast cancer who volunteered that when they began magnesium supplements for reasons other than hot flashes, their hot flashes diminished within 24 hours and had not returned. In each case, the person was not expecting any relief from magnesium, so placebo effect is unlikely.”

It should be noted that men undergoing hormone blockade therapy for prostate cancer can also suffer from hot flashes. The potential benefits of magnesium apply to them too.

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Summary: The use of selective serotonin reuptake inhibitors (SSRIs, such as Prozac®, Celexa®, Lexapro®, Luvox® and Paxil®) taken during pregnancy—especially the first trimester—appears to increase the risk of autism spectrum disorders. There are evidence-based alternatives to SSRIs that support brain health without putting the fetus at risk.

A study recently published in the journal Archives of General Psychiatry draws attention to a risk of autism spectrum disorders (ASDs) born to mothers who took SSRI antidepressants during their pregnancy. The authors observe:

“The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.”

Therefore they set out to…

“…systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.”

In order to do so they compared the data for 298 children with ASD to 1507 randomly selected control children, along with the data for both their mothers. Their findings support a cautionary approach to the prenatal use of SSRIs:

“Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8).”

In other words, the increase in risk for the whole year before delivery was 220%, but limiting the investigation to the first trimester it was 380%. Interestingly…

“No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.”

Meaning that it wasn’t a history of mental health treatment the year before delivery but specifically the use of SSRIs that accounted for the increased risk of ASDs. The authors conclude:

“Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders.”

This would be a troubling dilemma were it not for the fact that therapies supporting brain health are available to treat depression. Serotonin production and signaling, when indicated, can be supported in a physiological and sustainable manner that promotes the brain health of mother and fetus. A categorization and description of key resources that applies to adults as well as children is available in the Parents’ Guide To Brain Health.

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Summary: women in the highest third of blood glucose levels were almost twice as likely to develop colorectal cancer over the course of the study.

More evidence that high blood sugar contributes to cancer is presented in a study just published in the British Journal of Cancer that examines the link between elevated fasting glucose and colorectal cancer in postmenopausal women. The authors state:

“It is unclear whether circulating insulin or glucose levels are associated with increased risk of colorectal cancer. Few prospective studies have examined this question, and only one study had repeated measurements.”

So they examined baseline fasting serum insulin and glucose values for 4902 non-diabetic women over 12 years, during which 81 cases of colorectal cancer turned up. The data showed a significant trend:

“Baseline glucose levels were positively associated with colorectal cancer and colon cancer risk: multivariable-adjusted hazard ratio (HR) comparing the highest (greater than or equal to 99.5 mg dl−1) with the lowest tertile (<89.5 mg dl−1): 1.74 and 2.25, respectively. Serum insulin and homeostasis model assessment were not associated with risk.”

In other words, glucose in the highest third almost doubles the risk. In this non-diabetic group an association with fasting insulin levels was not observed. However, I can say through extensive experience over 2-3 years having patients suffer through an extended glucose + insulin tolerance test that insulin can be often elevated later in the test but not in the fasting sample. The authors conclude:

“These data suggest that elevated serum glucose levels may be a risk factor for colorectal cancer in postmenopausal women.”

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Summary: any type of non-aspirin NSAID must be used only with great caution during pregnancy because they may significantly increase the risk of spontaneous abortion.

Research recently published in the Canadian Medical Association Journal alerts practitioners and pregnant women to the risk for spontaneous abortions caused by the gestational use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID). The authors state:

“We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.”

They examined data for 4705 women who had a spontaneous abortion compared to ten times as many matched controls, and correlated associations between different types and dosages of non-aspirin NSAIDs with having the spontaneous abortion. Their data raises some serious alarm:

“Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43). Specifically, use of diclofenac (OR 3.09), naproxen (OR 2.64), celecoxib (OR 2.21), ibuprofen (OR 2.19) and rofecoxib (OR 1.83) alone, and combinations thereof (OR 2.64), were all associated with increased risk of spontaneous abortion. No dose–response effect was seen.”

In other words, there as an overall 243% increase in the risk for spontaneous abortion. The increase was over 300% for diclofenac (Voltaren®) and more than 200% for ibuprofen. The authors express the gravity of their concern supported by the data in their conclusion:

“Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy.”

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Summary: the most extensive study to date reveals a modest but significant increase in breast cancer risk from alcohol consumption that should be balanced against the risk for cardiovascular disease.

An important study just published in JAMA (the Journal of the American Medical Association) goes further than all previous studies in examining the association between modest alcohol consumption over extended periods of time and breast cancer. The authors state:

“Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and “binge” drinking) and consumption at different times of adult life are not well understood.”

This new study is important because it followed women over a longer period of time and included for factors that can also alter breast cancer risk such as pregnancy, ionizing radiation, etc. in 105,986 nurses over 28 years as the authors set out to…

“…evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption.”

Their data show that the amount of alcohol rather than frequency of drinking is associated with breast cancer risk, and that age doesn’t matter:

“During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week. Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk.”

Analysis of their data also revealed a trend for a 10% increase in breast cancer risk for each 10 gram increase in alcohol consumption. The mechanism is not certain, but because the greatest impact was on hormone receptor-positive breast cancer it is likely related to the tendency for alcohol to increase circulating levels of estrogen. The authors conclude:

“Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk.”

As with everything else in medicine, the information needs to be considered in the context of each woman’s individual health and family history, including the balance of risks for cancer and heart disease.

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Not surprisingly considering the profound importance of our microbial ecology for immune and barrier tissue health, a study published in the journal Clinical Infectious Diseases offers evidence that probiotic organisms applied intravaginally can put a halt to recurrent urinary tract infections. The authors state:

“Urinary tract infections (UTIs) are common among women and frequently recur. Depletion of vaginal lactobacilli is associated with UTI risk, which suggests that repletion may be beneficial. We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women.”

They treated 100 young women with a history of recurrent UTI with antimicrobials for an acute UTI, randomized them to receive either the probiotic or placebo daily for 5 days, then once weekly for 10 weeks. The subjects were followed up at 1 and 10 week intervals with urine cultures and PCR for the probiotic by vaginal swabs. What did the data show?

“Recurrent UTI occurred in 7/48 15% of women receiving Lactin-V compared with 13/48 27% of women receiving placebo. High-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI…”

The microbial ecology is as important in the genitourinary region as elsewhere. I have a preference for a multi-species formula for this purpose.

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A study just published in PloS Medicine (Public Library of Science) offers more evidence that alcohol consumed in moderation can promote overall health and successful aging for women. The data presented also helps to firm up guidelines for determining amounts that are beneficial and harmful. The authors state:

“Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.”

They defined “successful ageing” as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations, and applied this to the 13,894 Nurses’ Health Study participants who survived to age 70 or older for whom they had comprehensive and continuously updated health data. This was correlated with habits of alcohol consumption. Their data paints an interesting picture:

“…light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios were 1.0 (referent) for nondrinkers, 1.11 for ≤5.0 g/d, 1.19 for 5.1–15.0 g/d, 1.28 for 15.1–30.0 g/d, and 1.24 for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios were 1.29 and 1.47 for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 for those drinking only 1–2 days per week.”

In other words, consuming 30 to 45 grams of alcohol per day conferred a 24% increase in the odds for successful aging. Moreover, drinking 5-7 days per week increased the odds of a good outcome by 47%. The authors conclude:

“These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.”

So how much is 30 to 45 grams of alcohol? A ‘standard drink‘ = 10 grams of pure alcohol. A 750 ml (regular size) bottle of red wine with a typical 14% alcohol volume equals approximately 8.3 standard drinks (82.8 grams of pure alcohol). A 30 ml (one ounce) shot of 80 proof (40% alcohol volume) is 9.4 grams of pure alcohol (just shy of one standard drink). An ounce of stronger spirits like 94 proof gin or vodka is 11.12 grams of pure alcohol.

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Adding to the damage list associated with sleep-disordered breathing, a study just published in JAMA (The Journal of the American Medical Association) offers evidence that sleep apneas and hypopneas can contribute to serious cognitive impairment. This is not surprising considering the importance of oxygen for brain health. The authors state:

“Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults. Cross-sectional studies have linked sleep-disordered breathing to poor cognition…”

So they designed their study to…

“…determine the prospective relationship between sleep-disordered breathing and cognitive impairment and to investigate potential mechanisms of this association.”

Defining sleep-disordered breathing as an apnea-hypopnea index of 15 or more events per hour of sleep, they examined polysomnography (‘sleep study’) data for 298 women without dementia collected between January 2002 and April 2004. They then used data collected  between November 2006 and September 2008 to correlate hypoxia, sleep fragmentation, and sleep duration with cognitive status (normal, dementia, or mild cognitive impairment). What did the data reveal?

“Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% vs 44.8%). Elevated oxygen desaturation index (≥15 events/hour) and high percentage of sleep time (>7%) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR, 1.71 and AOR, 2.04, respectively).”

In other words, the higher strata of sleep-disordered breathing doubled the risk for dementia. Interestingly…

“Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”

Clinicians need to bear in mind the serious metabolic, cardiovascular and cognitive penalties of sleep-disordered breathing and question patients about tell-tale signs such has heavy snoring and daytime somnolence. The authors conclude:

“Among older women, those with sleep-disordered breathing compared with those without sleep-disordered breathing had an increased risk of developing cognitive impairment.”

This study cohort was all female subjects, but I can think of no reason why the same consideration does not apply to male patients.

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It doesn’t hurt to have a reminder of the power of lifestyle factors to reduce chronic disease such as this study just published in JAMA (the Journal of the American Medical Association) in which the authors correlated several of them to the risk of sudden cardiac death. As they note, sudden death is often the first sign of heart disease:

“Sudden cardiac death (SCD) accounts for more than half of all cardiac deaths; the majority of SCD events occur as the first manifestation of heart disease, especially among women. Primary preventive strategies are needed to reduce SCD incidence.”

Sudden cardiac death means dying within an hour of the onset of symptoms. For their purpose they defined a “healthy lifestyle” as not smoking, having a body mass index (BMI) of less than 25, exercising for 30 minutes per day or longer, and to exceed 40% of the alternate Mediterranean diet score (defined as a high intake of vegetables, fruits, nuts, legumes, whole versus refined grains, fish and moderate alcohol. What did the data show?

“All 4 low-risk lifestyle factors were significantly and independently associated with a lower risk of SCD. The absolute risks of SCD were 22 cases/100 000 person-years among women with 0 low-risk factors, 17 cases/100 000 person-years with 1 low-risk factor, 18 cases/100 000 person-years with 2 low-risk factors, 13 cases/100 000 person-years with 3 low-risk factors, and 16 cases/100 000 person-years with 4 low-risk factors. Compared with women with 0 low-risk factors, the multivariable relative risk of SCD was 0.54 for women with 1 low-risk factor, 0.41 for 2 low-risk factors, 0.33 for 3 low-risk factors, and 0.08 for 4 low-risk factors. The proportion of SCD attributable to smoking, inactivity, overweight, and poor diet was 81%. Among women without clinically diagnosed coronary heart disease, the percentage of population attributable risk was 79%.”

Considering that the benefits of diet and exercise can be further enhanced by customization according to functional metabolic-genomic assessment needs and more effective time-saving interval training respectively, it is likely that even these significant percentages can be further improved. The authors conclude:

“Adherence to a low-risk lifestyle is associated with a low risk of SCD.”

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