You’ve made that appointment for your yearly checkup; you are a patient patient as you peruse expired periodicals in the waiting room. You then have to pee into a cup, put on a ridiculous gown that doesn’t close and when the medical practitioner arrives, go though an exam that requires an undignified lithotomy position. (You know, with your feet in stirrups, your legs apart and your tush at the end of the exam table). The least that you should expect from all this is reassurance that you do not have cancer, or in the worst case scenario that the cancer has been found at an early stage and can be successfully treated. There are pap smears and HPV tests, pelvic bimanual examinations which allow the examiner to palpate pelvic abnormalities such as tumors, cysts or fixed, scarred and painful masses, blood tests and, of course, ultrasound. All these plus a carefully obtained medical history are used to rule out cervical and uterine cancer (as well as inflammation, benign cysts, and endometriosis), but the definitive tests for ovarian cancer still eludes gynecologists.

A quick review: Ovarian cancer is the leading cause of gynecologic cancer deaths, not because it is so prevalent but because it is usually found only after it has spread to other organs in the pelvis, abdomen or distant parts of the body. Our lifetime risk of developing this cancer is 1.4% which means that 1 in 71 women will develop ovarian cancer in their lifetime. One in 95 will die from it. Ovarian cancer is a cancer of older age…two thirds of cases occur after the age of 55…and the older we are the greater that risk.

Whenever you give your family medical history you are asked if you have first degree relatives (parents, siblings, and/or children) who have had or died from ovarian or early onset breast cancer. If so, this can triple your risk. And the risk of ovarian cancer is highest for BRCA gene mutation carriers. Testing for this mutation is recommended if you have a significant family history of ovarian cancer, female or MALE breast cancer, or multiple relatives with breast cancer and/or any of these combined with a high incidence of prostate or colon cancer. Mutations in the BRCA1 gene increase lifetime risk of ovarian cancer to 30 to 46% while mutations in BRCA2 are somewhat less of a risk but still high at 12 to 20 %. There are 3 sites for single mutations in these genes that are found in 2% of individuals who are Ashkenazi Jews (from Eastern Europe). So if you are Jewish and your ancestors came from Eastern Europe (this describes me)) and there is a relevant history in your family of these cancers, I would highly suggest you get the 3 site testing for the BRCA mutation.

(An aside… if there is no breast or ovarian cancer history and you are an Ashkenazi Jew, testing is not recommended “just to make sure”. I queried several physicians while visiting Israel a few weeks ago as to whether BRCA testing was routinely carried out in women who were of Ashkenazi Jewish heritage and the answer was a resounding no. But they do perform genetic testing on pregnant women for a wide range of potential diseases that are more prominent in the newborns of the families with this heritage. As our government discusses medical reform I would hope that they look at the system in Israel….where nearly everyone has medical coverage and choice options are available.)

So how can we diagnosis this relatively rare but often deadly cancer? Are there symptoms? Yes, but they are fairly non specific and are often ignored. They include pelvic or abdominal pain, urinary frequency or urgency, increased abdominal size (not just overall weight gain), bloating or difficulty eating or feeling full more than 12 times in a month. Yes this could be indigestion, a persistent urinary infection, overactive bladder or gas….but studies have shown that when women diagnosed with ovarian cancer where asked about a history of these symptoms, many had them. So if you are over 50 and experience these symptoms, see you doctor.

What about routine screening? Why can’t we simply do a pelvic exam, blood test, ultrasound or some combination of all these and find the disease at an early stage? After all, when ovarian cancer is confined to the ovary (stage 1) the 5 year survival is 90%, but falls to 33% when the diagnosis is made at stage III or IV.

A recent report in The New England Journal reviewed the current status and recommendations for ovarian cancer screening. First they reported on the tumor marker CA-125. This is a protein found at greater concentration in ovarian cancer cells than other cells and is elevated in blood tests of 80% of women with advanced stages of ovarian cancer. But there are some severe limitations to screening with this protein. High levels can be found in 1 to 2 % of normal women. CA-125 is elevated in only 50% of stage I cancers and it can be falsely elevated due to many benign and malignant conditions (endometriosis, fibroids, pelvic inflammatory disease, hepatitis, pregnancy, menstrual bleeding, recent abdominal surgery, breast cancer, pancreatic cancer, colon cancer, lung cancer and endometrial cancer). Currently, because it is so nonspecific, the American Cancer Society as well as the American College of Obstetricians and Gynecologists does not recommend its use as a routine screening test for ovarian cancer. They do feel it’s useful if an ovarian mass is found or if there is a significant family history putting a woman “at risk”. Most insurance companies and Medicare agree and won’t pay for a CA-125 test when it is ordered without a very specific indication!

There are other markers that have been investigated, some based on particular proteins produced by tumor cells or the presence of certain growth factors but to date, they have not been validated in large populations of women in randomized prospective studies. (Translation: Are the women who are given the tests diagnosed earlier than control women who are not tested?)

Ultrasound done with a vaginal probe (transvaginal) has been a mainstay for viewing pelvic tumors. So why not simply perform transvaginal ultrasounds on all women, especially those over 50? Multiple studies have unfortunately demonstrated that this type of imaging has not been as successful as we would wish. The positive predictive value has been reported to range from a mere 1% to 27%; which indicates that many of the women in whom a suspected tumor was found with ultrasound did not have ovarian cancer. And some had unnecessary surgery that resulted in surgical, medical and psychological complications as well as significant financial cost.

The New England Journal of Medicine article reviews several large studies. One included 25,327 women who were at average risk for ovarian cancer and who had annual transvaginal ultrasound. Among women with suspicious findings 364 patients underwent removal of the abnormal ovary but only 29 were indeed cancerous and only 14 (48%) of these were found early at stage I.

And what if women had both tumor marker blood tests and ultrasound? So far an American study has been equally disappointing. It is called the Prostate, Lung, Colon and Ovarian Cancer Screening Trial. Final results won’t be issued until 2014. To date a total of 34,261 healthy women between the ages of 55 and 74 have been randomly assigned to undergo either annual CA-125 testing plus transvaginal ultrasound or to receive “usual care”. Their test results were considered positive if the CA-125 was above 35IU and/or their ultrasound showed an enlarged ovary (it should shrink with age) or a cyst with solid areas. During 4 years of screening, 3388 women had positive results and 1170 or 34% underwent surgery with removal of the one or both ovaries. Only 5.1% of those who had surgery were found to have cancer and 72% of these cancers were stage III or IV. Moreover, 29 cases of ovarian cancer were diagnosed during the study period and were not detected by screening! In statistical terms (and we all have to use these) the positive predictive value of positive screening was only 1.0 to 1.3% during the 4 years of the study.

Bottom line: If you are not at what is deemed “at increased ovarian cancer risk” having a CA-125 blood test or a transvaginal ultrasound to screen for this cancer is not recommended by any of the major gynecologic or cancer societies. These tests may allow you (and your doctor) to feel that you are proactive but neither guarantee that you don’t have an early stage ovarian cancer nor do they reassure you that you won’t receive a future diagnosis of late stage ovarian cancer. If you are at risk because of family history, consider genetic testing. The current recommendation for BRCA positive women is to undergo surgical removal of the ovaries between the ages of 35 and 40 at the completion of child bearing or at the earliest age at which cancer was diagnosed in affected family members. If women who are BRCA positive chose to wait for surgery, the Comprehensive Cancer Network recommends CA-125 and vaginal ultrasound every 6 months although no one is sure that this will increase survival rates. Finally, if you have signs or symptoms of ovarian cancer (pelvic mass, pelvis or abdominal bloating, urinary frequency or urgency, increased abdominal size, bloating, difficulty eating or feeling of fullness) see you doctor… ultrasound and CA-125 may be warranted. When I perform these tests on my symptomatic patients I warn them that they may, however, be falsely positive or negative. Hopefully, in the future, my colleagues and I can do better.

By now (I would hope) we all know that there is a strong recommendation that all young girls and women get the HPV vaccine (Gardasil) to protect them from 4 types of human papilloma virus infection. A quick review: two of the types (16 and 18) are responsible for 70% of cervical cancers, as well as vaginal and anal cancer whereas the HPVs numbered 6 and 11 cause genital warts. The efficacy of this vaccine has been tested and supported by sufficient evidence to warrant FDA approval and CDC recommendation for its use for girls, adolescents and young women up to the age of 26. The protection will always be maximal for sexually naïve young women (a medical term that means they have not had sexual intercourse or other sexual activity which would foster HPV transmission).

The greatest incidence of HPV infection occurs within 5 to 10 years of first sexual experience. But even if such an infection should occur the chance that all the HPV types are present is very slim (see another article I wrote for this web site). Hence we continue to immunize young women when the opportunity arises (i.e. they are seen by an appropriate medical provider and they or their parents consent to this series of three shots given over a period of 6 months).

If we give the HPV vaccine to young women even if they have been sexually active or have evidence that an HPV caused disorder exists, why shouldn’t “older” women receive the vaccine and be granted some degree of immunity?

Women are waiting longer to get married (most of my patients are over 26 when they are ready to commit) and as we all know divorce rates are high. Indeed in the USA nearly 40% of men and women have married and divorced by the age of 55 and more than 25% of these people have remarried at least once. So without being judgmental lets just acknowledge that at least half of us will have new partners after the age of 26. Do the current HPV vaccine recommendations constitute age discrimination?

A large study sponsored by the pharmaceutical company Merck (they developed the quadrivalent or 4 type HPV vaccine called Gardasil) has recently been published in the journal Lancet and suggests that women in their late 20’s, 30’s and 40’s could benefit from prophylactic HPV vaccination. The study enrolled 3819 women between the ages of 24 and 45 in 38 international study sites. The criteria for entering the study were that they were not pregnant, had no history of genital warts or cervical disease. Roughly half received the vaccine while the other half received a placebo shot. They were then checked at day 1 (when they received the injection) and months 7, 12, 24, 36 and 48 with a pelvic examination and swabs taken from the cervix, vulva, and perianal areas to test for HPV. The women also were given Pap smears and their blood was tested for antibodies to the 4 vaccine type anti-HPV antibodies (which could have been silently present from previous infection but if not, should have appeared subsequent to the vaccination).
Those who developed an abnormality on Pap smear underwent colposcopy (a microscopic exam) and when necessary a biopsy and treatment. The study was meant to continue for 4 years, but after 2 years the researchers reported the following: The vaccine was 90.5% effective in preventing disease or infection related to HPV 6, 11, 16 and 18 (there were 4 cases out of 1614 treated women vs 41 in 1607 in the placebo group). And 83.1% effective in preventing disease or infection related to HPV 16 and 18 alone. (Remember those are the types that are most likely to cause genital cancer).

Clearly most of these women were not sexually naïve, the mean age of first sexual intercourse before enrollment was 19. Indeed 33.3% of the women were found to be positive to HPV 6, 11, 16 or 18 by blood testing or DNA cervical testing at the onset of the study. Most of these women were positive to only one HPV type, 1% of them were infected with two of the types in the vaccine and less than 1% were infected with 3 vaccine HPVs, while none of the women had all 4. Translated, this means that two-thirds of the women were susceptible to infection with all 4 of these HPV types, and of the remaining one-third, the current HPV vaccine could still protect them against the other three types of HPV.

Just in case you now wonder if the study is ethical…and what will happen to those women who did not receive the vaccine…the women in the placebo group will be examined every 6 months and treated if necessary. ( This is probably better than the care that most women in the USA receive). At the end of the trial the vaccine will be offered to all the participants.

This study has only 2 years of follow-up. The CDC and other organizations will probably wait for the final 4 year results before making substantial changes in their vaccine recommendations. And in this economy we also have to consider cost and insurance coverage. (The series of 3 shots usually run more than $400). But so far the results are significant.

I currently do not suggest HPV vaccination for all my patients in the 26 to 45 age group; however I will no longer exclude this vaccination for women who are at risk for HPV infection, no matter what their age!

I’ll try to report this one with a straight face and I suggest we all take a deep, (but not necessarily odorless) breath. A recent article in the prestigious journal Menopause published by the North American Menopause Society (NAMS) concluded that “onion consumption seems to have a beneficial effect on bone density in perimenopausal and postmenopausal non-Hispanic white women 50 years and older. Furthermore, older women who consume onions most frequently may decrease their risk of hip fracture by more than 20% versus those who never consume onions.”

Even I was surprised. And to think that ever since I felt that onions could cause bloat and flatulence (at least in my case), I advised others that from a nutritional standpoint they did little, but were simply added to improve the taste of many dishes! So let me correct myself and give more scientifically rendered facts: Rats fed a diet high in onions have been found to have a 17.4% increase in bone mineralization after 4 weeks compared to a control group. There are 3 compounds in onions that may be responsible. I will spare you their long scientific names. They are thought to inhibit the activity of the cells called osteoclasts that break down bone. The other 2 compounds may actually help build bone density by stimulating bone building cells (osteoblasts). These compounds belong to a family of flavonoids which in other studies have been found to have an estrogen like effect.

The next factoid used to support the supposition of bone support though onion consumption comes from Turkey. Women there have the lowest osteoporosis fracture rate in Europe and apparently that country has the highest per capita consumption of onions in the world. At the age of 50, women in the U.S.A. have an average lifetime risk of 15.8% of developing a hip fracture while women in Turkey have a 1% risk.

The authors of the article in NAMS analyzed the data from 507 perimenopausal and postmenopausal non-Hispanic white women gathered by the National Health and Nutrition Examination Survey (NHANES) between the years 2003 and 2004.These women were given a food frequency questionnaire. One of the questions was whether and how often they ate onions. They were then divided into 4 groups: less than or equal to once a month, twice a month to twice a week, three to six times a week and once a day or more. (This group must have had a lot of onion soup!) They all had bone density tests.

Then the statisticians went to work correcting for age, smoking, vitamin D levels, parathyroid level (this is a hormone that helps control calcium levels and bone density), calcium intake, exercise level, estrogen use (estrogen supplementation helps stave off bone loss) and body mass index (heavier women have denser bones). They then came out with the following numbers: The adjusted total body bone density measured in grams per centimeter squared (I’ll interpret this in the next paragraph) was 1.02g/cm squared in the group that consumed onions once a month or less, and rose to 1.06g/cm squared in the group that consumed onions once a day or more.

The “onioned” group had a 5% increase in bone density compared to the onion abstainers. That sounds very small but a percent of loss can mean a future increased risk of fracture by a factor of five or more.

So will I suggest onion consumption for bone strength to my patients? Not in lieu of 1200 to 1500 mg of daily calcium, 1000 units of vitamin D and weight bearing exercise. The authors of the article also pointed out that one of the compounds found in onions, called quercetin, may be toxic to genes when consumed in huge amounts. But to get a toxic amount (at least in rodents) 2 pounds of onions would need to be consumed.

So if you like onions go for it…I suspect that after this study the supplement and pharmaceutical companies will find a way to suggest you take their “onion like” product. Meanwhile I will do everything else to keep my bones supportive.

The HINI virus has had various names. I am in Israel as I write this;  in the beginning of its spread it was termed the Mexican flu, it then became the virus hazirim, or swine flu. In the U.S. the term swine flu was officially expunged perhaps due to concerns by the “other white meat” industry. So its numerical, virologic appellation has been adapted by everyone and is here to stay. This virus has previous unknown and constantly evolving genetic features. It is highly transmissible (but not through your bacon or pork chops) and has traveled the world, mostly via traveling people. It is truly an epidemic! In Israel they currently estimate that over the next year, 25% of the population will become infected. The number touted in the U.S.A is even greater….perhaps as high as 40%! To date, those who get really sick and/or even die are young, pregnant or have underlying medical problems. The incidence of H1N1, like seasonal flu, is expected to increase in the fall and winter when we are confined to closed interior spaces and more likely to transmit the virus from person to person.

H1N1 has received tremendous publicity. Prescription sales of Tamiflu (the antiviral medication that helps diminish length and severity of certain viral infections which to date includes H1N1) have rocketed. The U.S. government promises that if needed, stocks will be replenished. I receive daily bulletins from the CDC and WHO that if not hysterical, show great concern. For once I don’t feel that the media is making more of the H1N1 viral spread than it should. A vaccine is coming, but it looks like it won’t be in our pharmacies, hospitals or medical offices until the late fall. Meanwhile the FDA has approved the next general flu vaccine. It is directed against other flu strains that are expected to be in circulation as the weather cools. But this seasonal flu shot will not provide protection against the 2009 H1N1 virus.

In the midst of the impending H1N1 crisis please don’t forget… seasonal influenza viruses can be horrific….and indeed cause more than 200,000 hospitalizations and at least 36,000 deaths in the U.S. yearly. The latter statistic is especially significant for older people, young children and people with chronic medical conditions. Each year the WHO, FDA and CDC work together to identify the up and coming viral strains that will cause the most illness in the upcoming season. They then work with the vaccine manufacturers to develop the appropriate vaccine. I know that at the end of the flu year we have, in the past, been informed that there were other flu strains out there, and  that “they” got it wrong. But there is a far better chance that these organizations got it right.

There are 3 new strains of virus that will be included in the general flu shot this year. And according to the FDA “even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness and help prevent influenza-related complications”.

So start your fall and the getting-colder-season (at least in some parts of the country, I don’t know what the weather will be like here in sunny California) by getting your seasonal flu vaccine as soon as it’s available. A novel H1N1 vaccine will eventually be ready for consumer use….but not right away. So if you want this vaccine (and with all the warnings that inundate our media, most of you will), a second shot will be necessary. Once an H1N1 vaccine is available, initial supplies will go to vaccinate the most vulnerable groups…young children, young adults, pregnant women, healthcare personnel and those with chronic conditions. Eventually the hope is that it will be available for everyone.

This will be the winter of our viral discontent… But there is much we can do to help prevent viral spread. Stay home when you are sick (and make sure your children, significant others and friends do), wash your hands as frequently as possible, practice cough and sneeze protection, don’t greet others with the usual I-have-to be-polite handshakes and kisses.(I certainly hope Obama uses hand sanitizers!) If you come down with flu symptoms call your health practitioner (and if you are my patient, call me or my staff) at the onset of your symptoms. We no longer have to run tests to confirm the diagnosis. (The CDC has stopped counting specific cases). We will probably prescribe antiviral medication such as Tamiflu to help you get better quickly.

AND get your seasonal flu shot. Don’t wait for the H1N1 vaccine; when it’s available the media (and companies that produce it) will make sure you are informed. This year two shots will be better than one or none.

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