Wednesday, September 15, 2010

Do Women Develop Bladder Cancer, and what are the Risks?

Like men, women can develop cancer of the bladder. The most common type is called urothelial carcinoma, previously known as transitional cell carcinoma. It is the 8th most common cancer in women, and of all new bladder cancer diagnoses a year, women make up 20% of them. It has been either under-diagnosed, under –appreciated or under-suspected in women because the usual presenting sign of bladder cancer, blood in the urine, can often be assumed to be a urinary tract infection, which women experience commonly, and thus not suspected.

Bladder cancer is most often non-invasive at diagnosis, but requires periodic bladder endoscopy, xrays and bladder treatments to reduce the risk of recurrence which can be high. In about 15% of cases, bladder cancer is diagnosed as being “muscle-invasive”, which in healthy patients is best treated by complete bladder removal. This requires either reconstructing a “new bladder”, or having a urinary ostomy to drain urine. Chemo and radiation are sometimes necessary when bladder cancer is invasive.

Risks for bladder cancer are toxins, most commonly smoking, environmental exposure to arsenic, and certain “aromatic amines”, or chemicals used in the coloring/dye industry, which are less common these days. Theories exist that certain nutrients, when excreted in the urine, and after contacting the bladder lining on a chronic basis, can lead to tumor formation. However, a recent report published in Cancer investigated whether eating meat contributes to bladder cancer, via potential carcinogenic compounds found in meat, related to cooking and processing. Prior evidence connecting meat and carcinogenesis has been inconsistent.

Nitrates and nitrites, found in meat, are hypothesized to promote carcinogenesis. They are used to preserve color and flavor. They are converted to compounds that have been shown to induce tumors in many different organs, including the bladder.

Following over 300,000 men and women over a 7 year period between the ages of 50 and 71, of whom a fraction developed bladder cancer, food questionnaires were answered as a part of a very large Diet and Health Study.

What was found?

There was a borderline, statistically significant increased risk of bladder cancer only for those who were the highest consumers of red meat, mainly from processed red meat and not unprocessed. No association was seen with beef, bacon, hamburger, sausage, or steak. Overall, there was only an association with dietary nitrites in those that were the highest consumers. The researchers conclude that this study provides some limited evidence for an association between dietary nitrites and bladder cancer. This underscores the common sense approach to eating, which is, all things in moderation, but it’s no reason to skip the BBQs.

Thursday, September 2, 2010

Phytoestrogens: What are they, and are they safe for women?

Phytoestrogens are a group of naturally occurring, plant-derived compounds that have either a weak estrogenic, or anti-estrogenic effect. They are often called “dietary estrogens”, and are used widely by women to treat the symptoms of menopause. Their popularity has increased after several large women’s health trials alluded to health risks in women taking hormone replacement therapy for menopausal symptoms.

Phytoestrogens can be divided into three groups:

Flavinoids, such as genistein, naringenin, and kaempferol

Coumestans, such as coumestrol

Lignans, such as enterodiol, and enterolactone.

The most widely known and studied phytoestrogens are the isoflavones found in red clover and soy: genistein, formononentin, biochanin, and daidzein.

Urologists have known, rather assumed, that diets high in soy, such as in Asia, have a protective effect on men against development of prostate cancer. However, in women there has been conflicting evidence. Some studies show a protective effect against breast cancer, while some in vitro studies differ on whether they hinder or potentiate tumor cell growth. Some phytoestrogens are weakly estrogenic and bind the estrogen receptor, but are approximately 1000 times weaker than estradiol. Other phytoestrogens exhibit a blocking effect on the estrogen receptor. The isoflavones in soy show mainly an agonist effect, namely, a weak estrogen effect.
Does this mean that soy compounds can lead to “side effects” such as endometrial hyperplasia or cancer- this of course is not known.

More intrigue: Genistein antagonizes the inhibitory effect of tamoxifen on breast cancer cell growth in vivo. This raises more questions than answers.

Recently, a group of researchers from Austria set out to clarify the safely profile of phytoestrogens by analyzing all known studies published in English. 174 randomized controlled trials comparing phytoestrogens to placebo were identified, however in 82, no side effects were discussed. Mean treatment duration was short at approximately 6 months.

Various categories of side effects were studied: GI, Gyn, urinary, neurological, musculoskeletal, etc. The most common side effects seen among the women were GI complaints, such as: nausea, vomiting, heartburn, gastric irritation or pain. Women older than 55 yr old had a higher rate of these GI symptoms. Studies in US and Europe were less likely to report GI side effects. The length of the study, such as 6 months vs. 24 months did not lead to a higher incidence of side effects. Actually, fewer side effects were observed the longer women were taking phytoestrogens. Other side effects noted were muscle pain and sleepiness.

Of potential gynecological side effects, the side effects of vaginal spotting, nipple discharge, breast pain/enlargement, breast cancer, endometrial hyperplasia, and pelvic pain were reviewed. One study showed a higher rate of endometrial hyperplasia with atypia after 5 years of phytoestrogen supplementation. However there was no observed increased risk of endometrial cancer or breast cancer in any individual study or meta-analysis. There was no indication of other side effects that can occur with hormone replacement such as stroke, blood clots, heart attack and breast cancer.

The authors were cautious but did conclude that based on the available data, phytoestrogens can be used over a 2 year period. They did not however comment on their efficacy in controlled menopausal symptoms. Overall, only GI upset was seen to be the category of significant side effects, while over a 2 yr period, no endometrial or breast cancer was observed. This comprehensive review that these researchers took highlights the recurrent theme when treating oneself with medication or “natural products” when it involves hormone manipulation: that we may not know the true long term (>5 yrs) effect, they may be safe in the short term, there is sometimes conflicting data, and they should be taken in moderation. Just because compounds occur in nature doesn’t confer on them an automatic sense of “safety” or “health”. And certainly, eating a soy burger may have less fat than a regular burger, but only eating soy burgers is not going to make you live to 100 (without hot flashes).