Archive for the ‘Women’s Health’ Category

Omega-3 fatty acids work differently for men and women

Monday, August 23rd, 2010

There are fascinating and profound biological differences between men and women, so it’s not surprising that a study just published in Nutrition, Metabolism and Cardiovascular Diseases proves that there is a gender difference in the blood ‘anti-stickiness’ benefit from omega-3 fatty acids. The authors begin by stating:

Increased platelet aggregation is a major risk factor for heart attacks, stroke and thrombosis. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) reduce platelet aggregation…Recent in vitro studies have demonstrated that inhibition of platelet aggregation by LCn-3PUFA is gender specific. We examined the acute effects of dietary supplementation with EPA or DHA rich oils on platelet aggregation in healthy male and females.

Platelet aggregation is the ‘sticking together’ or clotting of the sub-cellular blood platelets. Blood that is too ‘sticky’ or clots too easily is a risk factor for heart attacks and strokes and a hindrance to the blood perfusion of tissues. The authors dosed males and females with EPA or DHA rich oil and measured the post-supplementation platelet aggregation. What did the data show?

EPA was significantly the most effective in reducing platelet aggregation in males…whereas DHA was not effective relative to placebo. In contrast, in females, DHA significantly reduced platelet aggregation at 24 h (while EPA was not effective. An inverse relationship between testosterone levels and platelet aggregation following EPA supplementation was observed.”

This paper follows another recent study reporting that cholesterol levels vary with the menstrual cycle. Practitioners must bear in mind these and other gender differences. The authors conclude:

“Interactions between sex hormones and omega-3 fatty acids exist to differentially reduce platelet aggregation. For healthy individuals, males may benefit more from EPA supplementation while females are more responsive to DHA.

DNA methylation—a key factor in breast cancer prognosis and treatment

Monday, August 16th, 2010

Landmark research just published in PLoS Genetics (Public Library of Science) brings to light two important points in breast cancer diagnosis and treatment. First, the authors prove that defects in methylation (addition of a methyl group) a critical process for maintaining DNA health, is a powerful prognostic indicator for breast cancer outcome. The authors first observe:

“Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics…We investigated DNA methylation profiles in over 160 well annotated breast tumor samples and found significant relationships with standard and other known predictors of prognosis, as well as established risk factors for disease: alcohol intake and dietary folate.”

They measured the methylation patterns of critical genes primary breast tumors from 162 women. Their findings are compelling:

Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly associated with altered methylation…”

The second valuable point confirms the role of alcohol intake and folate status, both known to impact methylation capability.

“Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly associated with methylation class membership.”

The authors’ conclusion indicates the profound importance of assessing and protecting methylation capacity:

Breast cancer prognostic characteristics and risk-related exposures [alcohol and folate status] appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.”

I use measurements of urinary methylmalonate and formiminoglutamate, objective indicators of important methylation cofactors. One or both of these is typically abnormal in patients with breast cancer. In my opinion, measuring this and treating methylation abnormalities with physiological interventions should be part of the standard of care for breast cancer.

Menstrual pain changes the brain, meditation helps

Saturday, August 14th, 2010

The authors of a paper just published in the journal Pain report that pain from primary dysmenorrhea (PDM) can produce structural changes in the brain that make the subsequent experience of pain worse. The authors note:

“Prolonged nociceptive [painful] input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero-nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization.”

The authors tested their earlier hypothesis that loss of inhibition [calming] of orbitofrontal networks [neural circuits in the frontal areas in the region of the eyes] could result in increased pain and negative feelings with menstrual pain. They used a type of brain MRI called voxel-based morphometry to measure differences in the amount of  gray matter (GM) in subjects with and without PDM. What did their data show?

Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affected regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top-down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain.”

The most striking and important finding was articulated in their conclusion:

“Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.”

Interestingly, another paper in the same issue of the same journal offers EEG evidence that meditation reduces the negative experience of pain.

“In this study we compared a group of individuals with meditation experience to a control group to test whether any differences in the affective appraisal of pain could be explained by lower anticipatory neural processing.”

The authors used anticipatory and pain-evoked ERP (event related potentials measured by electroencephalography) data and pain unpleasantness reported by test subjects to determine whether experience with meditation made a difference. What did the data show?

“More experienced meditators perceived the pain as less unpleasant relative to controls, with meditation experience correlating inversely with unpleasantness ratings. ERP source data for anticipation showed that in meditators, lower activity in midcingulate cortex relative to controls was related to the lower unpleasantness ratings, and was predicted by lifetime meditation experience.”

Meditators also had less medial prefrontal cortical activity engaged in anticipating pain unpleasantness. The authors concluded:

“Our data is consistent with the hypothesis that meditation reduces the anticipation and negative appraisal of pain…”

Cholesterol levels vary with the menstrual cycle

Friday, August 13th, 2010

A study recently published in The Journal of Clinical Endocrinology & Metabolism proves that we must take the menstrual cycle into consideration when testing cholesterol in cycling women.

“The objective of the study was to evaluate the association between endogenous [internally produced] estrogen and serum lipoproteins across the menstrual cycle.”

The authors found that total and LDL cholesterol were lower during the luteal phase (second half, when progesterone is higher) than the follicular phase:

More women were classified above the desirable range (LDL ≥130 mg/dl or total cholesterol ≥200 mg/dl) when measured during the follicular phase [first half].”

HDL was higher when estradiol had peaked, corresponding also to lower LDL and triglycerides.

Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women’s cholesterol.

Bicycle riding and erectile dysfunction

Saturday, July 24th, 2010

The standard bicycle seat can deliver a significant insult to the nerve and blood vessel supply to the male genitalia. There have been numerous studies investigating the relationship between bicycle riding and erectile dysfunction. The authors of a paper published a while back in The Journal of Sexual Medicine that reviewed the science set out to:

“…summarize accumulating data on the safety of bicycle riding based on medical evidence categorized by levels of evidence, including case reports, observational studies, case control studies, mechanistic studies, and population-based epidemiologic investigations. The secondary aim was to address the concerns of bicyclists and propose measures to minimize the risk of ED associated with bicycle riding.”

The mass of data revealed a clear picture and yielded specific recommendations:

Bicycle riding more than 3 hours per week was an independent relative risk for moderate to severe ED. Therefore, bicycle riders should take precautionary measures to minimize the risk of ED associated with bicycle riding: change the bicycle saddle with a protruding nose to a noseless seat, change the posture to a more upright/reclining position, change the material of the saddle (GEL), and tilt the saddle/seat downwards.”

The authors note in their conclusion:

“Straddling bicycle saddles with a nose extension is associated with suprasystolic perineal compression pressures, temporarily occluding penile perfusion and potentially inducing endothelial injury and vasculogenic ED.”

In a subsequent paper published in the same journal this year the authors revisit the problem and begin by noting:

“For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications.”

They conducted a comprehensive review of the scientific literature and found that further studies had firmly established the risk of cycling-related sexual dysfunction and extended it to females:

“There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists.”

The authors of a review published earlier in European Urology caution practitioners to be aware of this widespread phenomenon. They report that a range of problems have been documented:

“The most common bicycling associated urogenital problems are nerve entrapment syndromes presenting as genitalia numbness, which is reported in 50–91% of the cyclists, followed by erectile dysfunction reported in 13–24%. Other less common symptoms include priapism, penile thrombosis, infertility, hematuria, torsion of spermatic cord, prostatitis, perineal nodular induration and elevated serum PSA, which are reported only sporadically.”

They conclude by exhorting practitioners to be alert:

“Urologists should be aware that bicycling is a potential and not an infrequent cause of a variety of urological and andrological disorders caused by overuse injuries affecting the genitourinary system.”

Perhaps this could contribute, at least to some degree, occurrences of ‘cyclist road rage’. Are there any remedies or recommendations for cyclists to follow? Another study in The Journal of Sexual Medicine investigated the condition in police officers:

“The average bicycle police officer spends 24 hours a week on his bicycle and previous studies have shown riding a bicycle with a traditional (nosed) saddle has been associated with urogenital paresthesia and sexual dysfunction.”

The officers manifested the typical problems, but also demonstrated some improvement when using a ‘no-nose saddle’:

“(i) With few exceptions, bicycle police officers were able to effectively use no-nose saddles in their police work. (ii) Use of no-nose saddles reduced most perineal pressure. (iii) Penile health improved after 6 month using no-nose saddles as measured by biothesiometry and IIEF. There was no improvement in Rigiscan® [nocturnal erection] measure after 6 months of using no nose saddles, suggesting that a longer recovery time may be needed.”

It only makes anatomical sense that insult to the nerves and blood vessels that supply the genitalia could cause sexual dysfunction in both males and females.

Probiotics treat mastitis better than antibiotics

Monday, July 12th, 2010

Clinical Infectious DiseasesA study published last month in the journal Clinical Infectious Diseases offers an interesting surprise about the treatment of mastitis (infection of the breast).

Mastitis is a common infectious disease during lactation, and the main etiological agents are staphylococci, streptococci, and/or corynebacteria. The efficacy of oral administration of…two lactobacilli strains isolated from breast milk, to treat lactational mastitis was evaluated and was compared with the efficacy of antibiotic therapy.”

What happened to the women who took probiotics instead of antibiotics?

“On day 21, the mean bacterial counts in the probiotic groups were lower than that of the control group…Women assigned to the probiotic groups improved more and had lower recurrence of mastitis than those assigned to the antibiotic group.”

Of course there is the obvious advantage of not decimating the patient’s microbial ecology. This impressive result, summed up in the authors’ conclusion, is worth bearing in mind if you’re nursing a baby who caring for someone who is:

“The use of L. fermentum CECT5716 or L. salivarius CECT5713 appears to be an efficient alternative to the use of commonly prescribed antibiotics for the treatment of infectious mastitis during lactation.”

Nuts for young girls

Saturday, July 10th, 2010

Cancer Causes & ControlA useful study was just published in the journal Cancer Causes & Control that examines the effect of nut consumption by young girls on breast disease and breast cancer.

“We examined the association between adolescent fiber intake and proliferative BBD [benign breast disease], a marker of increased breast cancer risk, in the Nurses’ Health Study II.”

They gathered data on diet and the emergence of breast disease confirmed by pathology for 29,480 females. A definite pattern emerged:

“Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD… High school intake of nuts was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk…than women consuming <1 serving/month.”

Taking into consideration other research I think we have to accept the likelihood that the beneficial fat in nuts confers some of the benefit. This adds to the weight of evidence in favor of nuts in a wholesome and preventative diet:

“These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.”

Taking an aromatase inhibitor for early breast cancer? Check your vitamin D…

Monday, July 5th, 2010

MaturitasA paper just published in the journal Maturitas (the journal of the European Menopause and Andropause Society) is a reminder the importance of vitamin D in breast cancer treatment. As the authors observe:

Aromatase inhibitors (AI) treatment leads to an increased risk of bone loss and fractures.

The authors examined a group of women with early breast cancer (EBC) and baseline Vitamin D deficiency (<30 ng/ml) who were treated with aromatase inhibitors. They followed serum levels of Vitamin D, bone mineral density (BMD), calcium intake, and the increase of serum 25(OH)D from 3 months of Vitamin D supplementation. What did their data show?

“At baseline [the beginning of AI therapy], 88.1% had 25(OH)D levels <30 ng/ml, 21.2% had severe deficiency (<10 ng/ml), and 25% of the participants had osteoporosis…We found a significant association between 25(OH)D levels and BMD…Plasma 25(OH)D levels improved significantly at 3 months follow-up in those treated with high dose Vitamin D supplements.”

This is only one aspect of the crucial role of Vitamin D in breast cancer prevention and treatment. The authors’ conclusion should be borne in mind by all those caring for or dealing with breast cancer:

“Our study suggests a high prevalence of commonly unrecognized Vitamin D deficiency in women with EBC treated with AI, a known osteopenic agent. Our results support the need for a routine assessment of 25(OH)D levels and, when necessary, supplementation in these patients.

For a discussion of aromatase inhibitors versus tamoxifen see this recent post.

Tamoxifen versus aromatase inhibitors for breast cancer prevention and treatment

Friday, July 2nd, 2010

Cancer InvestigationA paper recently published in the journal Cancer Investigation summarizes the evidence in favor of aromatase inhibitors (that block the synthesis of estrogen) over tamoxifen (which antagonizes the estrogen receptors). As you probably already know, tamoxifen’s side-effects are potentially very serious. It has come to my attention that clinicians assisting women in the prevention and treatment of breast cancer may not be aware of the evidence advanced by the authors:

Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective in reducing recurrence. As distant recurrence has been associated with poorer survival and death, reduction in this type of early recurrence event may lead to improved survival over the long term. Recent data from major clinical trials are beginning to bear out this contention.”

European Journal of Surgical OncologyThis is not the first time that evidence establishing the superiority of aromatase inhibition over tamoxifen has been presented. Consider this paper published earlier in the European Journal of Surgical Oncology in which the authors observe:

“The aromatase inhibitors (AI)…have demonstrated superior disease-free survival (DFS) over tamoxifen in several trials. As the choice of adjuvant endocrine treatment for early breast cancer (EBC) is evolving from tamoxifen to the AIs, this review compares the AIs with tamoxifen to help surgeons choose a treatment plan that provides the greatest reduction of recurrence risk for their patients.”

The authors note the weight of already accumulated data:

Trials of the AIs versus tamoxifen have established that patients benefit from longer DFS (disease-free survival), and in some cases distant DFS, after the use of an AI as initial adjuvant therapy, as switch therapy following 2–3 years of tamoxifen, or as extended adjuvant therapy following 5 years of tamoxifen.”

Their conclusion carries additional significance considering that we have natural aromatase inhibitors that are equally useful in preventing excessive conversion of testosterone to estrogen in men (a common problem).

“The advantage in DFS associated with AIs over tamoxifen use should prompt physicians and patients to consider the use of an AI as the initial adjuvant endocrine therapy or, alternatively, switching patients who currently take tamoxifen to an AI for the remainder of adjuvant endocrine therapy.”

Bear in mind that is but one point in the constellation of factors, including proportional steroid hormone production, metabolism, elimination and receptor function, that need to be measured with the appropriate tests to evaluate and correct the hormonal milieu for estrogen receptor stimulation.

Incorrect testosterone supplementation can increase cardiovascular risk

Thursday, July 1st, 2010

New England Journal of MedicineAn important paper just published in The New England Journal of Medicine is a reminder that supplementing any hormone to levels above the normal physiological range can backfire. The authors intent was to investigate the safety and efficacy of testosterone treatment in older men with mobility limitations.

“Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter or a free serum testosterone level of less than 50 pg per milliliter were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months.”

Things turned out so poorly that…

“The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.”

As the data came in a worrisome picture clearly emerged:

“…the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group…The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period.”

There is an extremely important practical message here buried in the data for anyone interested in hormone replacement/supplementation and the practitioners caring for them. The authors made a supplementary appendix available with more detailed data. It showed what we always see when hormones are applied transdermally (through the skin by gel, cream or patch): in time they accumulate to levels of elevated beyond the range of what is physiologically normal (when we properly measure the bioactive free-fraction hormones). Higher than normal hormone levels cause problems, including symptoms similar to hormone deficiency due to receptor desensitization. This applies to any hormone. Deep in the supplemental appendix we find that the free testosterone went as high as 82 pg/mL during gel supplementation. The functional (physiological) range we use for males age 51-60 is 36-65 pg/mL, for males over 70 years it’s 15-45 pg/mL.

Another important point: the protocol for this study did not even include how much testosterone was being converted into estrogen by aromatase activity. Elevated estrogen is a serious risk factor for men. For hormone supplementation to be effective and safe we must properly assess all aspects of production, accumulation, receptor function, metabolism and elimination.