Living longer with ovarian cancer: a drug that prolongs life
Ovarian cancer is the deadliest of all of the gynecologist cancers. The treatment of ovarian cancer is at first surgery to remove as much tumor as possible, followed by the standard chemotherapy of carboplatinum and paclitaxil. It is not uncommon for the cancer to return within two years, requiring the use of additional chemotherapy.
Researches have added other drugs in combination to extend disease-feee survival (DFS).
In 2017, bevacizumab (Avastin) was approved for advanced ovarian cancer. It extended DFS 4 months, but not overall survival.
A class of drug called PARP inhibitors has been studied. PARP is an enzyme that repairs DNA damage in cells. Inhibitors affect the DNA repair, and also work in BRCA mutation carriers.
Three PARP inhibitors have been approved in the US. They are used as maintenance therapy in women with recurrent ovarian cancer.
A study was done using olaparib (Lynparza) in women who were BRCA mutation carriers, diagnosed with Stage 3 ovarian cancer of the ovary, fallopian tube, or peritoneum. Stage 3 ovarian cancer means that the cancer has spread beyond the ovaries to the abdominal cavity. These patients were debulked surgically, then given platinum based chemotherapy which was at least partially effective. The women in the study were given either the olaparib vs. placebo.
They were followed for 41 months, at that time, 60% who received the drug were disease-free, vs. only 27% in the placebo group. Progression-free survival was 36 months longer in the study group.
Side effetcs occurred in 21% of patients compared to 12% in the placebo group. Most of these side effects were anemia, although !% of patients developed acute myeloid leukemia.
Most drugs that treat cancer are measured in months of disease-free survival. The fact that olaparib extended survival by 3 years is a tremendous advancement.
Marilyn C. Jerome, MD
Foxhall OB-Gyn Associates
PARP inhibitors extend survival in ovarian cancer, especially for women with a BRCA mutation.
OBG Management, Volume 31, No. 3, March 2019
I often talk to my patients in the office about the importance of exercise, strength and balance training, to prevent falls. The most significant cause of falling is lack of muscle strength. As we age, we naturally lose muscle strength unless we really work on it.
In the article written by Jane Brody and published in the New York Times on February 25, 2019, she states that falls are the leading cause of fatal and nonfatal injuries in the elderly. She also states that every 19 minutes, an older person dies from a fall. That is why I as a physician am so focused on prevention and treatment of osteoporosis. There are 2 million osteoporotic fractures in the US per year, most of which are preventable. Each fracture statistically takes years off your life, can decrease mobility, and can take away our independence, which, let's face us, is an important goal as we age.
The article by Jane Brody is excellent so instead of summarizing it I will just provide the link:https://www.nytimes.com/2019/02/25/well/live/falls-can-kill-you-heres-how-to-minimize-the-risk.html
Here are a few more thoughts. Avoid walking on the ice in bad weather. Don't use ladders. Let a younger person do it, or make sure someone in assisting you. Use very short leashes when walking the dog. So many people fall when getting tangled up walking the pooch. Don't walk two dogs or more dogs at once: a recipe for disaster.
And this one is important: Quit rushing! It is so much easier to trip when you are in a hurry.
Marilyn C. Jerome, MD
Foxhall OB-Gyn Associates
From the North American Menopause Society website, discussants Dr. Marla Shapiro, Past President of NAMS, and Dr. Cynthia Stuenkel, Past President of NAMS and professor at the University of California at San Diego
Once you have been diagnosed with osteoporosis, have had an osteoporotic fracture, or it has been determined that your FRAX score is high, treatment with medication is indicated. So many women have misconceptions about the medications, their risks and benefits. Let’s go through the categories of medication and options in each category.
This is a category of drugs that decreases re-absorption of old bone. We all have osteoclasts that are cells in our bones that remove old bone, and osteoblasts that put down new bone. Prior to menopause, the osteoblasts are more active than the osteoclasts, and new bone is formed at a higher rate than bone is lost. This changes at menopause, and with other conditions of low estrogen such as anorexia, prolonged lactation, and use of aromatase inhibitors. . Bisphosphonates work by decreasing the function of the osteoclasts.
There are 4 bisphosphonates: alendronate, risedronate, ibandronate, and zoledronate.
These drugs can be given orally or IV. All bisphosphonates decrease vertebral fractures from 35-65%. Both alendronate and zoledronate significantly reduce hip fractures also, and risedronate reduces non-vertebral fractures. If taken orally, the drug must be taken on an empty stomach with 8 ounces of water, and patients are advised to sit or stand for 30-60 minutes after ingestion to avoid reflux that could cause esophageal irritation. If the medication is taken with food or other drugs, the absorption of the drug is diminished and it will be less effective. These drugs remain active in the bone for some time after discontinuation of the drug. Alendronate specifically will remain in the bone for 5 years after the last dose, and the bone density will usually decline slowly during this time. This allows for patients to take drug holidays, without losing most of the benefits gained. Risedronate users had significant loss of bone in the first year after discontinuation.
Zolendronate is a once-yearly infusion. It cannot be given to patients with acute renal failure or a creatinine clearance of less than or equal to 35 mL/min.
Press reports have over-emphasized the side effects of this class of drugs. Side effects can include musculoskeletal aches and pains, gastrointestinal irritation and ulcers of the esophagus. More severe side effects including osteonecrosis of the jaw and atypical fractures of the femur are very rare, occurring in about 1/10,000 years of use. Since most women who take these drugs have a 20% risk of any fracture, and a greater than 3% risk of a hip fracture in the next 10 years, the risk/benefit ratio is far in favor of a benefit. Because of the long-term duration of effect of the bisphosphonates, it does not make sense to stop the drug during a dental procedure. It does make sense to have frequent dental exams while taking the medication, as osteonecrosis of the jaw, if caught early, is treatable. It also makes some sense to have any invasive dental work completed before starting bisphosphonate use.
Dosing of the bisphosphonates vary from orally weekly to monthly, and IV from every 3 months to yearly, depending on the drug. Patients with upper GI problems might consider intravenous administration, or a short-term trial of an oral agent.
Selective estrogen agonists/antagonists:
Raloxifene is a selective estrogen receptor modulator, or a SERM. This type of drug was designed by scientists to act like estrogen in certain parts of the body, while acting as an anti-estrogen in other parts of the body. Raloxifene acts like estrogen in the bone. Because of this, it is an anti-resorptive drug, preventing the resorption of old bone. It has been shown to reduce vertebral fractures. In the breast, raloxifene acts as an anti-estrogen, so a beneficial side effect is that it reduces the risk of postmenopausal breast cancer in women who have osteoporosis, even if they are at high risk of developing breast cancer.
This drug is taken orally, once a day and is usually well-tolerated. It can increase hot flashes, especially in women who are newly menopausal and who are still having vasomotor symptoms.
More serious side effects include blood clots in the legs and deaths from stroke, although the incidence of stroke is not increased. This drug is especially beneficial for women with osteoporosis who are at increased risk of breast cancer. Five years of use will reduce the subsequent risk of breast cancer by at least 50%.
Denosumab is a mono-clonal antibody that works in the cascade of molecules that affect the function of the osteoclast. The drug inhibits a pathway that leads to de-activation of the osteoclast, and thus less bone is reabsorbed. This drug has been available since 2010, and has been shown to reduce vertebral fractures by 68% and hip fractures by 40%. It is given subcutaneously by injection twice a year. Prior to administration, it is important to check the calcium level of the patient.
This drug is very well tolerated. It is believed that the risk of osteonecrosis of the jaw and atypical femoral fractures is very low. There is a significant increase in infections that were noted in clinical trials, but in practice, this risk is very low. Occasionally a patient will note musculoskeletal pain after injection, but again, this is infrequent.
Because the bone density can decrease significantly after this drug is stopped, and the fracture risk does increase in the first year, discontinuation of drug should be followed by a maintenance medication.
Calcitonin is administered as a nasal spray has been used for the reduction of vertebral fractures, but it is not as effective as other agents. It can be effective in women who have painful vertebral fractures by diminishing the pain.
Teriparatide or recombinant human parathyroid hormone stimulates the osteoblasts to produce more bone, therefore it is considered an anabolic (growth) hormone, rather than an anti-resorptive agent. It improves the micro-architecture of the bone, making it stronger. The drug is given daily and subcutaneously, therefore it is self-administered by the patient, and can only be given for two years. In animal studies, use more than two years increased the incidence of bone cancers, but this has not been seen in humans. After discontinuation of the drug, a patient must be switched to another medication to maintain the benefit.
This medication has been found to decrease the risk of vertebral and non-vertebral fractures. Side effects include nausea, dizziness, and muscle cramps, but since it is a daily dose, it can be discontinued easily.
Parathyroid hormone is often used in cases where the bone density decreases despite use of other drugs, or after a fracture has been sustained. Because it can only be used for two years, it must be part of a long-term strategy.
Estrogen is a potent anti-resorptive agent, and it is well known that bone density decreases significantly in the first five years of menopause. In the Women’s Health Initiative, vertebral and hip fractures were reduced about 35% by hormone therapy. Hormone therapy is approved for the prevention of osteoporosis in women at risk. Even very low dose estrogen patches have a benefit in the reduction of osteoporosis, although the benefit is dose-related. Hormone replacement therapy should be an important part of the conversation as a women enters menopause and considers her symptoms and goals, her family history and risk factors, and the type of treatment most suited to her individual situation. Most women can take combined estrogen and progesterone for at least five years with no increase in breast cancer, and longer if she is using estrogen only. After discontinuation of HRT, loss of bone density can be rapid and the benefit can be lost in two years, so monitoring bone density and adding another drug should be considered.
In the next chapter, we will look at drug holidays and try to put concerns about serious side effects in perspective.
Foxhall OB-Gyn Associates
The. American College of Obstetricians and Gynecologists. Practice Bulletin. Osteoporosis,
Number 129, September 2012
When you receive your mammogram report, you may note that at the end of the report it states that your breasts are dense and that this may limit the accuracy of the mammogram. This can be frightening to a patient: going through the procedure just to be told that it may miss a breast cancer because of dense tissue. What does that really mean?
The breasts are composed of glands and fat. The glands are composed of the lobules that produce milk and the ducts that bring the milk to the nipple. Fat surrounds the breast tissue. Most breast cancers arise from the ducts. Lobular cancers are less common.
We know that very dense breast tissue can increase the risk of breast cancer 4-6 times.
The reason for this is that the tissue that is dense is more actively growing and dividing which allows mutations that can lead to cancer. Also, the glandular tissue may be more hormonally sensitive.
According to the American College of Radiology, breast density is divided into four categories:
If your breasts are extremely dense or heterogeneously dense, they would be considered dense breasts. About 40% of women over the age of 40 will fit into this category.
Most women will fit into category 2 or 3.
So what does a mammogram look for?
A mammogram is looking for a mass which would often appear as an irregular white density, with irregular borders, sometimes containing calcifications. Non-invasive breast cancer or DCIS is microscopic disease, and often there is no mass present. Calcification that are clustered, fine, and irregular are often seen in breast cancer masses.
If your breasts are considered dense, what type of screening should you have? Is yearly mammography enough?
The answer to this depends on your age and other risk factors. Your physician should take into account your family history, BRCA gene status, a history of breast irradiation prior to the age of 30, and a history of previous breast biopsies. There are several models that can predict the risk of breast cancer taking into account multiple factors, but these models don’t take into account breast density as a risk factor.
The Gail Model risks takes into account your age, age at first menstrual cycle, age at first live birth, number of first degree relatives with breast cancer, how many breast biopsies you have had, and if any demonstrated abnormal cells.
The Tyrer-Cusick Model looks at age, weight, height, age of first menses and menopause, whether you have taken HRT and how long, your BRCA status if known, and and extensive family history of breast and ovarian cancer.
If either determines that your lifetime risk is greater than 20%, you would be considered at higher risk, and supplemental screening is optional. Remember that average lifetime risk of breast cancer is about 12%.
We know that mammography saves lives, because it can find invasive breast cancers before it spreads to lymph nodes. Whether additional screening with ultrasound of MRI actually saves lives has never been proven with studies. Most of the breast cancers found on sonogram or MRI that are not detected by mammogram are small and are lymph node negative. It is possible that some of these cancers are very slow growing and would have never been life-threatening.
Options for additional screening include 3D tomosynthesis, ultrasonography, or a breast MRI. Additional screening is recommended for women who carry the BRCA gene, or women who have had radiation to the chest (usually for Hodgkin’s disease before age 30). Insurance coverage for additional screening depends on the insurance carrier, and sometimes the state in which the study is done. An MRI can cost several thousand dollars, so insurance coverage criteria should be confirmed prior to administering the test.
Despite breast density, mammography, especially 3D mammography should always be the first screening tool used. A 2D mammogram will pick up 2-7 breast cancers per 1000 women screened. A 3D mammogram will pick up 3-9 breast cancers per 1000 women screened.
Adding sonography to a 2D mammogram will pick up 4-11 breast cancers per 1000. A 2D mammogram plus a contrast-enhanced MRI will pick up 12-17 breast cancers per 1000.
The decision to perform additional screening for breast cancer beyond a 2D or 3D mammogram is, in many cases, is a complex process, taking into account many factors, and breast density should be considered in that equation. By being better informed, and with the advice of your physician, an appropriate decision can be made for each individual woman.
Marilyn Jerome, MD
Foxhall Ob-Gyn Associates
OBG Management, Volume 27, Number 10, October 2015. Get smart about dense breasts.
Berg, et al.
The previous article about osteoporosis discussed the huge burden of this disease, and how important it is to treat patients with the diagnosis to prevent fractures.
Let’s look at some questions that many women ask.
What are the risk factors for osteoporosis?
When should you get your first scan and how often thereafter?
What is a dexa scan?
How do you interpret the results?
What is a FRAX score?
The typical women who has osteoporosis is Caucasian or Asian, menopausal and small-framed. Women are 4 times more likely than men to get osteoporosis, and they live longer which is another risk. Family history is extremely significant, as your bone structure is largely inherited. If your parent or grandparent broke a hip, your risk increases. Lifestyle with exercise and diet does make a difference, but probably less so than heredity. A history of fractures must be evaluated. Certain disease and medications increase the risk. Smoking and heavy use of alcohol also decrease the bone density.
Here is a list of medical conditions that increase the risk of osteoporosis:
Rheumatic and autoimmune diseases: ankylosing spondylitis, lupus, rheumatoid arthritis
Endocrine disorders: adrenal insufficiency, Cushing’s disease, diabetes, hyperparathyroidism, thyrotoxicosis
Gastrointestinal disorders: celiac disease, gastric bypass, GI surgery, inflammatory bowel disease, malabsorption, pancreatic disease, primary biliary cirrhosis
Lifestyle factors: low calcium intake, high caffeine intake, alcohol (3 or more drinks per day), active or passive smoking, high salt intake, sedentary lifestyle, falling, excess Vitamin A, aluminum from antacids, immobilization, being thin
Medications: anticoagulants (heparin), anticonvulsants, aromatase inhibitors, barbiturates,chemotherapy, glucocorticoids like prednisone, lithium, gonadotropin releasing hormone agonists, medroxyprogesterone acetate
Genetic factors: cystic fibrosis, hemochromatosis, Marfans, osteogenesis imperfecta,
parental history of hip fractures,
Hypogonadal states: anorexia, bulimia, athletic amenorrhea, hyperprolactinemia,
premature ovarian failure, menopause, Turner’s syndrome
Miscellaneous conditions: alcoholism, congestive heart failure, depression, emphysema, end stage renal disease, epilepsy, scoliosis, multiple sclerosis, muscular dystrophy, prior fracture as an adult, leukemia, lymphoma, multiple sclerosis, sickle cell anemia, and thalassemia
When should you get your first bone density scan?
All women should have a bone density scan by the age of 65, but women who have risk factors should be tested sooner. The bone density often decreases after menopause with the loss of estrogen, which is protective for the bones. If a women is at increased risk of osteoporosis, obtaining a DXA scan at menopause can serve as a baseline.
The frequency of testing depends on the results of the previous scan, and whether medication for osteoporosis is being administered, or if there are changes in medical history. Often, when a person is being monitored for low bone density, the test is repeated about every two years. If a person has a very good DXA scan, it might not be repeated for 5 years or more. If a women has a significant fracture, the bone density should be evaluated. In certain cases, the bone density may be evaluated after one year, if a certain intervention is being monitored.
What is a DXA scan?
A DXA scan, dual-energy X-ray absorptiometry of the lumbar spine and hip is the most commonly used test to evaluate bone density. Studies that evaluate the heel and wrist are predictive, but are not sufficient to monitor treatment effects.
The test is done by a trained technician. The patient lies on a table and the scanner passes over the lumber spine and hip after the patient is properly positioned. The amount of radiation of the x-ray is very low. The beams of the scanner are able to evaluate the density of the bone. The test is painless. Often, a vertebral fracture assessment is obtained. By lying on your side, the vertebrae are measured to see if there is any compression or fracture.
How do you evaluate the results?
After the test is completed, the technician will evaluate the scans that are obtained. A calculation, or T-score is obtained. The T-score compares your bone density to the bone density of a 30 year old women. The T-score is reported in standard deviations from the mean.
There are 3 possible results:
T-score: > -1.0 Normal bone density
T-score: > -1.0 to -2.5 Osteopenia ( low bone density but not osteoporosis)
T-score: <-2.5 Osteoporosis
The diagnosis of osteoporosis can be made without a bone density test. A history of a low-trauma fracture in a woman at risk would suffice for the diagnosis of osteoporosis. An example would be a vertebral fracture that resulted from a fall from the standing position vs. falling off a ladder. In most cases, women who have surgery for a broken hip should be treated for osteoporosis.
What is a FRAX Score?
A FRAX score is an assessment tool used to predict the risk of fracture in the next ten years.
The clinical risk factors that are part of the calculation include your age, sex, body mass index, previous fragility fracture, parental hip fracture, current smoking history, use of steroids (more than the equivalent of 5 mg of prednisolone per day for 3 months), alcohol use of more than 3 drinks per day, or other secondary causes of osteoporosis. Results are specific for race and gender. This tool is used to assess those with osteopenia, to determine if other factors increase the fracture risk and to determine if treatment is appropriate.
Generally, if you DXA scan falls into the osteoporosis range, medication is indicated.
If a patient has osteopenia, and her FRAX risk in greater than 20% risk of a major osteoporotic fracture in the next ten years, or a 3% risk of a hip fracture in the next 10 years, medication should be considered.
In the next edition of this series, we will look at treatments for osteoporosis: the pros and cons of medication therapy.
Marilyn Jerome, MD
Foxhall OB-Gyn Associates
The American College of Obstetricians and Gynecologists. Practice Bulletin. Number 129. September 2012. Osteoporosis
It's not too late to exercise: benefits for the heart (and a look at high-intensity interval training)
A study published in the Journal, Circulation, in January 2018, demonstrated that increasing your exercise routine in mid-life can improve your heart function and reverse some of the effects of aging. Poor fitness in middle-age is a risk factor for heart failure.
The study looked at 61 adults, aged 45 to 64, who were healthy but who lived a sedentary life style. The researchers divided up the group in two. In the control group, the participants were asked to do yoga, balance exercises, and strength training three times per week. The study group was given a moderate exercise plan, which was ramped up as the study continued. They were given high-intensity interval training as part of the routine. After six months, the exercise group was up to 5-6 hours of exercise per week. At least two days involved high-intensity interval training.
So, let’s define high-intensity interval training (HIIT) and its benefits. HIIT is defined as alternating hard-charging intervals of exercise which increases the heart rate to 80% of
its maximum capacity for usually 1-5 minutes, with periods of rest or less intense exercise.
To determine your maximum heart rate, you can use this formula: 220 minus your age.
Then, your target heart rate for exercise is 50-85% of that.
So for example, if you are 66 years old, your maximum heart rate would be 220-66=154.
50-85% of that is a heart rate of 77-131. 80% of 154 is 123. During the high intensity intervals you would want to get your heart rate up to 123. ALWAYS, BEFORE YOU START AN INTENSE EXERCISE REGIME, MAKE SURE YOUR DOCTOR ASSERTS THAT YOUR HEART IS IN GOOD SHAPE. YOU MIGHT NEED A CARDIAC EVALUATION IF YOUR ARE OLDER OR HAVE RISK FACTORS.
An example of a HIIT routine if you were a runner would be a 10 minute warm up, followed by 4 intervals of 4 minutes of fast running interspersed with 3 minutes of brisk walking, followed at the end by a 5 minute cool down.
Another example would be alternating 1 minute of high intensity exercise with one minute of less intense exercise, for a total of 20 minutes. This could be done walking, on a treadmill, bike, elliptical, or almost any other type of exercise amenable to changing intensity.
Scientists that have studied this type of training have found cardiac benefits. VO2 max is a measure of the maximum volume of oxygen that your body uses during intense activity during a specific amount of time. It is one of the best predictors of overall
health. If you are more aerobically fit, your heart pumps better and it takes longer for you to tire and become breathless. Studies have shown similar increases in VO2
max in comparing groups that exercised at 50 minutes versus those who exercised only
for 10 minutes with high-intensity intervals that added up to 1 minute total. Wow!
Same cardiac benefit for 20% of the time. Nice!
A study done by Martin Gabala at McMaster University in Canada, a leading expert in HIIT, demonstrated that obese sedentary adults that exercise three times per week for a total of only 30 minutes, about 10 minutes each time, with 3, 20 second high-intensity intervals, improved their VO2 max. It did not take much to improve cardiac function.
Studies that compared different types of interval training determined that longer high-intensity intervals had greater benefit, which would be expected. To get the maximum benefit, 4-5 intervals lasting 3-5 minutes were required.
Besides increased VO2 max, HIIT increased stroke volume in the heart, which is the amount of blood ejected with each heart beat. Calorie consumption with HIIT of 20 minutes is comparable to an endurance exercise of 50 minutes, but the effect on weight loss is less impressive. There is not enough data to suggest that HIIT is a more effective way to lose weight. In general, caloric restriction is far more effective way to lose weight than exercise. Studies have shown that the amount of weight loss is less than expected for the number of calories expended during exercise. But don’t despair, there are still many health benefits of exercise. ,
Of those who completed the study, about 86%, cardiac changes were noted that included increased fitness measured by oxygen consumption, and increased cardiac contractility or stretchiness, which increased the hearts ability to pump blood.
The authors of the study recommended starting an exercise regime sooner than later, before you develop joint problems or other health issues that can affect your ability to exercise. However, at any age, beginning an exercise routine can reduce the risk of heart disease, and help manage blood pressure and blood sugar. The benefits to your bones and preventing falls that can lead to fractures are also an important benefit.
In summary, beginning exercise at any age can have cardiac benefits, just make sure your heart can handle it. If you up the ante by doing high-intensity interval training you will get a similar cardiac benefit in less time. The longer the intervals you can sustain provide more substantial are the benefits. The bottom line, it is never too late to begin exercising!
Harvard Women’s Health Watch, Volume 26. Number 5, January 2019.
Regular exercise helps reverse age-related changes in your heart.
Circulation. Volume 137, Issue 15. April 10, 2018.
Randomized Control Trial: Implications for Heart Failure Prevention
Vox. How to get the most out of your exercise time, according to science, by Julia Belluz,
updated January 13, 2019.
Approximately 14,000 women die each year of ovarian cancer in the United States.
The average risk of getting ovarian cancer in your lifetime is about 1.4%, but if you have a family history or genetic mutation that predisposes to ovarian cancer, the risk can be as high as 40%.
Most women know that ovarian cancer can be silent until it is advanced to Stage 3-4.
The symptoms are vague and can be confused with gastrointestinal dysfunction, such as vague abdominal pain, indigestion, early satiety, and rectal pressure. The treatment of ovarian cancer involves extensive surgical removal of the uterus, tubes and ovaries, the omentum (fat that surrounds the intestines), lymph node dissections, and often removal of the peritoneal surfaces.
This is often followed (or can be preceded) by chemotherapy. Typically the cancer will recur within several years, and results in additional surgeries or rounds of chemotherapy.
The five year survival rates as reported by the American Cancer Society are 28% for Stage 3, and only 19% for Stage 4. If we could find ovarian cancer in earlier stages we could improve survival. We know that survival for Stage 1 tumors (confined to the ovary) is 78%, and if the tumor is confined to the pelvic organs, Stage 2, the survival is 61%. So how do we find the tumors earlier, when survival would be improved? Do yearly ultrasounds find the cancer earlier, and save lives.
Menopause Care Updates, published this month by the North American Menopause Society, reported on a study that addressed whether yearly ultrasound screening of women would change the stage at diagnosis and disease-specific survival. In total, 46,000 women were screened at the University of Kentucky from 1987-2017. The women who were screened had no symptoms and were over the age of 50, or over the age of 25 with a family history of ovarian cancer.
If a woman had an abnormal ultrasound, the study was repeated in 4-6 weeks to see if the abnormal finding was persistent. If it was, she underwent additional testing with a CA125, tumor morphology evaluation (looking at the size and complexity of the tumor), and Doppler flow evaluation which evaluated the blood flow to the tumor. A total of 699 women, or 1.5% were taken to the operating room for a surgical procedure. Of these women who had surgery, 71, or approximately 10% were malignant.
The disease free survival was assessed for these women who were screened, vs. women who wer not screened and whose cancers were detected clinically. Not surprisingly, the proportion of Stage 1 tumors was significantly higher in the women screened that those not screened. Disease specific survival at 5, 10 and 20 years was 86%, 68%, and 65% in those who were screened, vs. 45%, 31%, and 19% in those who were not screened.
On initial glance, this data is impressive, but when the experts looked at the data, things were not as clear. First, the incidence of ovarian cancer in the study group was much higher than expected. This could be explained by the study group including those at higher risk of ovarian cancer, those with a family history of ovarian cancer (23%) or a strong family history of breast cancer (43%).
Genetic carrier testing was not performed on these patients.
The rate of ovarian cancer in the study population was 271/100,000 patients screened, vs. only 11/100,000 in the control group. This disparity indicated that the group that was screened was a high-risk group, and clearly benefited from increased screening.
Other issues that need to be considered with widespread screening is the cost that is involved with annual additional testing. Another consideration is the risks of surgery in those 90% of patients found to have abnormal ultrasounds that do not have cancer. These patients would not have had surgery if they had not been screened this carefully, and some would experience side effects of the surgery which could be serious or life-threatening.
The final recommendations from this study was not to do routine ultrasound screening on patients at average risk of ovarian cancer. This is also the recommendation of US Preventive Task Force.
So this means that physicians should not recommend an ultrasound routinely, yearly, on patients at average risk of ovarian cancer. But,…..
Often patients come to the office complaining of vague symptoms of pain, rectal pressure, bladder pressure, abdominal distention, early satiety, or a change in bowel function. We must always consider ovarian cancer in a differential diagnosis, and order an ultrasound when indicated to rule-out ovarian pathology.
Even more important, as physicians, we should always consider a family history of breast, ovarian, pancreatic, uterine and colon cancer which can be related to genetic mutations that increase the risk of ovarian cancer. Genetic testing should be offered to patients at increased risk of cancer, as genetic mutations that increase the risk of cancer can be managed with increased surveillance and preventive surgery. Women with BRCA mutations have an increased risk of ovarian cancer, and should strongly consider risk-reducing removal of the ovaries and fallopian tubes after childbearing which drastically decreases their risk.
Marilyn Jerome, MD
Foxhall Ob-Gyn Associates
American Cancer Society
Menopause Care Updates, December 2018. North American Menopause Society, commentary by Mindy S. Christianson, MD
This topic was discussed in a recent version of NAMS Practice Pearl. The most pertinent studies were reviewed by Dr. Krista Varady, PhD, from the University of Illinois at Chicago.
Here is her assessment.
The cause of midlife weight gain is a combination of the following factors: loss of estradiol, age-related decreases in metabolic rate, and for some women, a more sedentary life style. Approximately 40% of women in menopause in the US can be categorized as obese.
There is so much conflicting information about which diet is the most effective for weight loss. It is difficult for physicians, and very confusing for the average women to know which strategy for weight loss has the best scientific data to back up its efficacy. Plus, the metabolism of women at midlife is very different from younger women, and also different than men, so finding studies specific or our sex and age group can be challenging.
Let’s compare low-fat diets to high-protein diets in midlife women:
Three studies of low-fat diets were randomized and controlled, which provides a high level of significance. In the first study, obese women were restricted to <30% fat, and calories were kept between 1200-2000 per day, depending on their weight. After 12 months, the average weight loss was 8.5%. If you started the diet at 180 lbs., you would lose about 15 lbs. in one year. In another study, a very low fat diet, <15% of calories consumed per day, women lost 7.7% of their body weight in 8 months. In another study, where fat was restricted to 20-35%, and calories restricted to a deficit of 500 calories per day, the participants lost 6.1% of their body weight in 4 months, about 11 lbs. for your 180 lb. women.
The Women’s Health Initiative looked at whether a low fat diet was effective in weight maintenance in mid-life women. In this study, more than 19,000 women were asked to restrict their fat intake to <20%, with no limitation in calories for seven years. In the first year, the women lost an average of 1.7%, but maintained about a 1% weight loss for the next seven years, indicating that fat restriction may be a strategy for long term weight maintenance.
Let’s look at the data for high-protein diets.
High-protein diets are effective in preserving muscle mass during weight loss. In one study, a high-protein low-calorie diet was compared to a low protein, low-calories diet, and both compared to an unrestricted diet. Both low calories groups lost the same amount of weight, 10% in six months. Again for our 180 lb. woman, this is 18 lbs. in 6 months. What was most important was that the difference in muscle mass was measured. The high-protein group last half as much muscle as the low-protein group. This is important because our muscle mass determines our resting metabolism: how many calories do you use up when you are at rest, not exercising. If you lose muscle mass, you require less calories to maintain normal functions, and you will need to restrict more to continue losing weight. Two additional studies had similar findings.
The bottom line was that restricted calories, regardless of protein composition of the diet, resulting in similar weight loss. Muscle mass was better preserved with high protein diets, but bone density was not as well preserved, and the benefit of the weight loss on insulin sensitivity was not as good as would have been expected.
Diets that incorporate fasting have become popular. One fasting day alternates with one day of “feasting” The idea is that on fasting days, caloric intake is limited to 500 calories, either at lunch or dinner. On non-fasting days. there is no restriction on what is eaten. Postmenopausal women lost about 11% of their body weight in 6 months with this regime, about 20 lbs. for our 180 lb. woman. Bone density was not affected by the alternative day fasting regime.
So, how do we compare these regimes. Caloric restriction, whether it be low-fat or high protein results in weight loss. High protein seems to be better for maintenance of muscle mass, but possibly sacrificing some loss of bone. What was not discussed was the effect on cholesterol and insulin levels, and the results if these diets were followed in the longer term.
These studies seem to raise many more questions.
Although all studies led to loss of weight, the rate of weight loss was slower than we might hope. For a person who needs to lose more than 20 lbs., it seems that a long-term strategy needs to be used. Rather than dieting, a lifestyle change might be a better approach. Increasing exercise and physical activity gradually can prevent injuries, and finding varied activities that are truly enjoyable may lead to a sustainable program. Incorporating short-term goals that are more easily obtainable may be more effective than going for the 50 lb. weight loss that will take several years to accomplish. Self-monitoring with diet apps that measure the caloric and nutritional value of foods can help to determine if your fat and protein intake are where you want them to be, and to understand the caloric value of portion size and the detriment of snacking and grazing. Many women do well with the structure of programs like Weight Watchers. A nutritionist may be helpful to organize a program individual to your lifestyle and personal preferences.
Unfortunately, long term success with sustained weight loss can be very difficult to obtain.
What is needed is more studies in women after menopause to understand their unique hormone issues how this changes metabolism, and which strategies provide the best success.
Marilyn Jerome, MD
Foxhall OB-Gyn Associates
NAMS Practice Pearl: Dietary Strategies for Weight Loss in Midlife Women, Krista A. Varady, PhD. released December 20, 2017
Two weeks ago I spent two days at the NIH at at a conference on osteoporosis: Pathways to Prevention: Appropriate Use of Drug Therapies to Prevent Osteoporotic Fractures. The goal of the meeting was to bring forward experts and the data to consolidate information regarding recommendations for treatments, understanding risks and side effects of medications, and to better understand gaps in our knowledge. This will hopefully lead to additional research to fill in these gaps.
Because this topic is so broad, I will break it down into smaller topics, and report the information as a series. Let’s start with the burden of the disease, a lecture given by Dr. Elizabeth Shanes.
Osteoporosis is a very significant public health burden. Approximately 10 million Americans have osteoporosis, but most of them do not know it. Osteoporosis is defined as weakness of the bones, resulting in increased risk of fractures. Fractures can lead to surgery, disability, immobility, loss of independence, and decreased life span. As we age, most adults want to maintain their independence and quality of life.
Here are some facts that we know for sure:
There are 1.5-2 million osteoporotic fractures per year in the US, mostly involving the spine, hip, wrist, and pelvis. Women will incur 70% of the burden of these fractures. 50% of women over the age of 50 will sustain at least one fracture in their remaining years. Caucasian women carry the highest risk.
The cause is low bone density which can be measured and monitored. The risk of osteoporosis increases with age. About 44% of women over age 50 have low bone mass. The risk of osteoporosis over age 50 is at least 10%, and may be as much as 30%.
Low bone density predicts fractures, both traumatic fractures as well as low-trauma fractures.As bone density decreases, the risk of fractures increases.
Once you break a bone, you are more likely to break more. If your break a vertebrae, you are 5 times more likely to break another vertebra, and 3 times more likely to break your hip. If you break one vertebrae, you have a 25% chance of breaking another within one year.
Adults who break bones have significant increased morbidity and mortality. After a broken hip, your risk of death in the next three months increases 5-8 times, and the increased mortality remains for the next 10 years. Studies show that other fractures including vertebral, femoral, tibial, multiple rib and other fractures are all associated with increases in mortality. About 25% of women who fracture a hip will live less than a year.
Fractures also decrease mobility. 50% of adults who break a hip will have difficulty walking one year later. Vertebral fractures are related to back pain and difficulty with managing tasks of daily living. Studies show that quality of life decreases after fractures, and the more fractures, the more rapid is the decline. Many people who fracture never regain their quality of life.
The cost to the healthcare system and individuals is dramatic. In 2005 there were 2 million fractures at a cost of 2 billion dollars. One hip fracture costs about $30,000 to treat. As the population ages, the healthcare costs related to fractures will increase. Those who are insured that fracture have twice as high health care costs as those who do not.
Fractures are preventable. All women should be encouraged to take adequate doses of calcium and Vitamin D, and exercise to improve muscle strength and balance. Fall prevention strategies should be discussed with patients. The biggest cause of falls is lack of muscle strength as we age.
Once osteoporosis has been diagnosed, medication is necessary to treat the disease. Many patients will be motivated to increase their calcium, Vitamin D and exercise at that point, but significant improvement in fracture risk is difficult to achieve. Short term use of certain FDA approved medications have been proven to prevent fractures. The long term strategies for drug use need further study.
Medications that prevent fractures are not being effectively. Bisphosphonates (Fosamax, Actonel, Boniva and Reclast) for osteoporosis treatment were approved in the mid-1990’s. Their use increased until about 2008 when media reports surfaced about side effects. The use of these drugs have sharply declined since then, although the risk are very, very rare. The perception by many patients is that the drugs do not work or make the bone more brittle, and the side effects are frequent. This is not true.
Since these reports, physicians have focused on treating those most at risk of fractures, rather than using the drugs preventatively, and have begun using drug holidays when appropriate.
Data indicates that even after hip fractures, less women are being treated for their osteoporosis. Less than 20% of women who break a hip are started on medication to prevent another fracture. New data tells us that for the ten years from 2005-2015, hip fracture rates were decreasing, then stabilized, and are now increasing. There have been about 11,000 more hip fractures and 2300 deaths attributed to the change in the trend. Medicare has markedly lowered reimbursement to doctors for osteoporosis testing in the office, so many practitioners no longer offer this service. The trend in decreased testing and concern of patients over side effects of medication, both contribute to the increase in fractures.
Physicians need to understand the concerns of patients about side effects, and understand the barriers to initiating and continuing treatment, including cost and insurance restrictions. Physicians also need to effectively communicate with patients the devastating effect of fractures, and learn how to prevent and diagnose complications sooner than later.
Here are Dr. Shanes final comments: “Osteoporotic fractures are common, costly, debilitating, disabling, and deadly. Although we have drugs to prevent them, those drugs are not being used.”
We have an opportunity to do better.
The next article in the series will look at who is at risk for a fracture, and who should be screened. We will also talk about how to interpret your results. Stay tuned.
Marilyn Jerome, MD
Foxhall OB-Gyn Associates
NIH: Pathways to Prevention: Osteoporosis
Elizabeth Shane, MD. Osteoporosis Fracture Prevention in the US, October 30, 2018