New Therapy for Treating Moderate to Severe Hot Flashes in Menopause

The Food and Drug Administration approved a new drug for the treatment of hot flashes associated with menopause this month. Its commercial name is Veozah and chemical name is fezolinetant.  It is a neurokinin 3 receptor antagonist which works by binding to and preventing the activities of the NK3 receptors in the brain which helps the brain regulate body temperature.

This type of drug was sorely needed because the standard treatment for menopausal hot flashes involved the use of hormones which are contraindicated in women with some types of  heart disease, strokes, high risk of blood clots, vaginal bleeding and liver disease. For women with these clinical conditions, where hormones could not be used, physicians often tried the off-label usage of antidepressants.

Eighty percent of menopausal women experience hot flashes which can consist of sweating, flushing and chills lasting for varying periods of time. While menopause is considered a normal part of healthy aging these sudden and unpredictable hot flashes are disabling . Menopause is a natural normal change in a women’s life usually occurring between ages 45-55 when a women’s periods cease, associated with a decline in the production of estrogen and progesterone. It is defined as menopause when a woman has not had a menstrual period for 12 months.

The new drug is taken orally once a day with instructions to take it at the same time each day if possible. Prior to initiating therapy with Veozah, patients should have blood tests examining liver function.  After initiating therapy, patients should have their liver function blood tests every three months for at least one year.

The most common side effects of the medication are abdominal pain, diarrhea, insomnia, back pain, hot flushes (which it is supposed to prevent) and elevated liver blood tests (hepatic transaminases).  The drug should not be taken if a patient is taking any medication which is metabolized by the CYP1A2 system. The most common drugs using this pathway are Cipro and Fluvox. There is additionally a contraindication to the use of Technetium contrast material for imaging studies while taking this medication. GoodRx has not released the price of the medication just yet, nor has the manufacturer.

This sounds like a promising medication for a very disturbing health problem. However, I would like to see at least six to nine months of real-world use in the USA before I prescribe it to determine just how safe and effective this product is.

Talcum Powder Does Not Cause Ovarian Cancer

Katie O’ Brien, PhD, of the National Institute of Environmental Health Sciences in North Carolina reported a study in nearly 250,000 women over an 11 year span that showed that talcum powder does not contribute to the development of ovarian cancer, The study was published in JAMA, the Journal of the American Medical Association.

The study found that in women who used talcum powder in the genital area, a total of 61 cases per 100,000 persons years was detected. When they compared that to women who never used talcum powder in that area, they found 55 cases of ovarian cancer per 100,000. The difference between users of talcum powder developing ovarian cancer by age 70 compared to nonusers was just 0.09%.

The concern about talcum powder use and cancer occurred in 1976 when asbestos was found in talcum powder. Most talcum powder is felt to be asbestos free today.

Benefits of Exercise on Blood Pressure and Prevention of Atrial Fibrillation

Junxiu Liu, MD, of the University of South Carolina published an article in the September 15 , 2014 edition of the Journal of the American College of Cardiology showing that exercise and improving fitness levels prevented an age related expected rise in patient systolic blood pressure. His study followed 14,000 men for 35 years. Sedentary men started to see their systolic blood pressure rise at about age 46. Men who were fit delayed this rise in blood pressure until they were 54 years of age. The effect on the diastolic blood pressure was even more pronounced when looking at fitness levels. Men with low fitness ratings elevated their diastolic blood pressure to above 80 by age 42. Those men with a high fitness level did not see the rise in diastolic BP until they were beyond age 90. His research suggests that “highly fit men are likely to reach abnormal BP readings a decade later or more than sedentary men.

In an unrelated study published in the same issue, researchers in Texas found that regular aerobic exercise prevented the hearts left ventricle or main pumping chamber from developing stiffness. The stiff ness of the ventricle contributes too many common cardiovascular conditions effecting older patients. They found that low levels of casual lifelong exercise such as four (4) sessions of 30 minutes per week throughout adult hood was sufficient to keep the ventricle from stiffening.

Marco Perez, MD of Stanford University looked at exercise levels in women and the development of the heart arrhythmia atrial fibrillation. He found that sedentary women were much more likely to develop this pathologic arrhythmia than women who exercised regularly. Obesity and being overweight is a risk factor that increases your chances of atrial fibrillation. Regular exercise by obese women reduced this risk by about nine percent (9%).

The message is very clear that keeping moving and being active improves your blood pressure control and reduces your risk of developing many cardiovascular related problems. My advice is find some activity you enjoy doing and make sure you try it several times per week to gain the natural benefits the exercise provides.

No Need For Routine Pelvic Exams?

The American College of Physicians created controversy and discord with the American College of Obstetrics and Gynecology by stating that women without symptoms of pelvic disease and of average risk” do not benefit from pelvic exams as part of routine care.” This recommendation received major media coverage. ACP panelist Russell Harris MD of the University of North Carolina in Chapel Hill in an interview with the University of Pennsylvania on line journal MedPage Today added further confusion to the recommendations by saying that “Our guidelines really have to do with women who do not have symptoms, who do not have a discharge or bleeding or pain. Our guidelines talk about screening of asymptomatic women who are not pregnant. Those women simply don’t need the exam. It’s not something that is useful for them.” The article goes on to say that “the guideline also does not apply to women who are due for cervical cancer screening.”

The concern is that the exam is intrusive in a private area and most findings lead to evaluations that lead one down an investigative path that is expensive, invasive and studies show very little yield in terms of finding preventable disease. This is based on the groups’ review of 52 published studies between 1946 and 2014.

Once again organized medicine has shown a way to be confusing, divisive and contributing to the appearance that the right hand does not know what the left hand is doing. The ACP and the American College of Obstetrics and Gynecology should have discussed this issue and released a joint recommendation which makes sense. The ACP guidelines suggest we should be visually inspecting the cervix which requires a speculum exam and using cervical swabs for cancer and or human apillomavirus. How much extra time and cost is involved if the clinician with the patient’s pre approval digitally and manually palpates the uterus, ovaries and rectum for the presence of unsuspected anatomical abnormalities? Is this, in fact, another effort by the American College of Physicians, and the American Board of Internal Medicine, to dumb-down and accelerate the training of future physicians? If we do not perform a certain number of pelvic exams on normal individuals how is one going to recognize an abnormal exam? This is the same type of short sighted thinking that led to the Institute of Medicine and US Preventive Task Force recommending that we do not teach women how to perform breast self -examination to detect breast irregularities? It reminds me of the recommendations years ago to stop doing chest x rays on smokers for the detection of lung disease and lung cancer because it was low yield and not cost effective. Funny how 20 years later the recommendations now call for screening low dose CT Scans of the Chest on smokers 55 years or older who have been smoking for many years.

I will continue to discuss the issue of a pelvic exam with my patients and suggest they discuss it with their gynecologist as well. I believe that 15 -20 years down the road the guidelines will once again insist on examinations of the uterus and ovaries when the politics of the times is not solely set on reducing health care costs! Hopefully those new suggestions will not be fueled by an increase in advanced gynecological cancer due to 20 years of no one examining their patients.

DNA Test to Replace Pap Smear

The Pap smear or Papinicolou Cervical Cancer Test is designed to detect early cancer of the cervix. It requires expert technique in obtaining the specimen during a speculum pelvic exam, expertise in applying the swab obtained specimen to a glass slide and preparation of the slide for transport to a cytology lab for microscopic evaluation. The microscopic evaluation is supposed to be performed by a specially trained and certified cytologist but they are in very short supply. The result is that there is great variability and suspected variation of accuracy in this test.

We now know that cervical cancer is a sexually transmitted disease (STD) of the human papilloma virus particularly HPV strains 16 or 18. Roche Molecular Systems has obtained FDA approval for its HPV DNA molecular test looking for fourteen high risk HPV strains. If a woman is found to have strain 16 or 18 health care professionals are advised to proceed to testing with colposcopy. If one of the other strains is found it is suggested that a Pap smear be performed to screen for the need for colposcopy. The FDA approval came after testing 48,000 women and comparing the accuracy of Pap Smears versus the DNA testing.

The new FDA approval allows clinicians to use the HPV testing alone or in conjunction with Pap smears.

Aspirin for Breast Cancer?

In an observational study published in the Journal of Clinical Oncology in 2010, Drs. Michelle Holmes and Wendy Chen of the Harvard Medical School showed that women with breast cancer who took one aspirin per week had a 50% lower chance of dying from breast cancer. They have been trying to set up a randomized blinded study of 3000 women with breast cancer to test this finding using the gold standard of research but they have been unable to raise the $10,000,000 required for a five year study. Pharmaceutical companies see no profit in aspirin and prefer to use their research money on medications that are potentially more profitable. Government agencies seem to feel the same way opting to test new cancer drugs pushed by pharmaceutical companies rather than finance an inexpensive available product.

The authors believe aspirin, if proven to be effective in randomized trials, is a less expensive alternative for women who cannot afford or cannot tolerate hormonal therapy post-surgery for five years. Great Britain, through its national health service has decided to study the effects of aspirin on four cancers, with breast cancer one of them, in a study that will not be completed until 2025. Drs. Holmes and Chen believe that with proper funding their study of women with stage 2 and 3 breast cancer, would answer the question of aspirin’s efficacy within five years.

The Business of Medicine Should Not and Can Not Replace Care and Compassion

Well over a year ago I advised my 80 something year old patient and her children that due to progression of her Parkinson’s disease, and her frail nature, she needed a higher level of assistance and care if she wished to remain in her home.  She was extremely unsteady walking and several courses of physical therapy had not improved the situation. The patient was feisty and would only allow help to come for 4 hours per day despite having a long term care policy that paid for significantly more.  She lost her balance recently, fell and landed on her back. She could not get up or get to a phone or her alert bracelet and was found seven hours later on the floor by her aide arriving for work.  In the Emergency Room x-rays revealed several acute fractures of her vertebrae that accounted for her severe pain with movement and inability to stand, bear weight or walk.

I hustled over to the ER and examined her and called the interventional radiologist to see if he could perform a procedure called a kyphoplasty that would cement the fractures and remove the pain. It was early Friday afternoon and the traditional back specialists were unavailable until the next day.  The radiologist came promptly, was professional and very pleasant explaining that he could do the procedure but because she took a baby aspirin for prevention of stroke, he would not perform it until the aspirin wore off in 5 – 7 days because of fear of excessive bleeding around the spinal cord.  He suggested we send her home with pain medications and round the clock assistance or keep her in the hospital until the aspirin wore off and he felt comfortable performing the procedure.  He was courteous and a credit to any profession. 

Since the patient was in great pain with any movement, I chose to admit her to the hospital while we sorted things out.  I admitted her as an inpatient because she is extremely elderly and frail with medical conditions that led to this injury which an expert had just told me required surgery to fix. She could not walk or transfer to a chair or wheelchair to get food, water or get to the bathroom. She had no arrangements for additional help at home to assist her. She could not, in my professional opinion, go home safely at this point.  

The next day I was making rounds late in the day for me at noon, reviewing the situation with the patient and her son when the physician’s assistant (PA) for the back surgeons, Andy, walked in and introduced himself. They had not seen her Friday evening or Saturday morning and this was their first contact with the patient.  My consult request and phone call had been quite clear. I wanted to know how they viewed the injury and what options did they feel were best to fix the problem. I additionally asked them how their approach would differ, if at all, from the approach of interventional radiology.  I had seen Andy around the facility and said “hello” but never formally met him so it was an introduction for me as well. 

“Hi, my name is Andy, and I work for Doctors Y and Z.  We have a little problem with your insurance.  You have a Medicare Advantage plan and we are not part of that plan. Most of the time, about 95% of the time, we eventually get paid for our services but we need to know how we will get paid for performing a procedure on you to fix your back before we proceed further. In these situations we usually ask the patient to pay the bill up front ($1000 – $1200) and then we submit the charges to your insurance company. If we get reimbursed from the insurance we return the money to you.”  

I took a deep breath and wondered if maybe I was overreacting to the brusque inappropriate presentation to a groggy senior who had been given a narcotic 30 minutes before for pain and was really in no condition to listen to any presentation or sign away informed consent.  I cut Andy off in the middle of a sentence and reminded him that I had requested an opinion. The son, an attorney by trade took up the fight and reminded the PA just how inappropriate his initial remarks were and that in this case money was not a problem but the manner of dealing with an elderly confused patient was.  I played mediator at this point and got the PA to explain that his employers had done several thousand of these procedures and handled many more complications than most interventional radiologists and that their success record spoke for itself.  He outlined a slightly different approach and once we got him talking about the reasons for his invitation onto the case, justified calling his group.

I am all in favor of physicians being paid for their professional services. This could have been handled differently by calling me first and informing me that they had concerns about payment and insurance and letting me address the issues. It could have been handled far gentler by answering the questions asked first and suggesting options and then reviewing the problems with the insurance. Had the gentleman performed a history and or exam rather than rely on the ER PA’s evaluation the day before, he would have seen that the patient was not in a position to comprehend what he was saying or sign for a procedure.  

This is not a criticism of PA’s or Nurse Practitioners. It is a criticism of any practitioner who does not answer the questions asked by the referring physician or question the referring physician about payment before arriving for the consult if they have questions about getting paid for their time and expertise.

The post script is that the son wisely chose to use this group based on their talents and experience and put aside the rude and insensitive communication by the PA. The surgery went well and the patient will go home after spending three nights in the hospital. 

There is still one obstacle to overcome. The hospital ignored my written order to make her status inpatient and made her status observation which will prevent her from receiving any post-surgery therapy or care which is paid for by her insurance. I will fix that. Keeping the phone number on my phone contact list of the Office of the Inspector General who investigates Medicare irregularities opens doors in situations like this. It does not change the fact however that as practitioners we need to be much more thoughtful when we discuss financial issues before medical issues if we wish to continue to be considered a profession rather than another business.

Walking Reduces Stroke Risk

Barbara Jefferis, PhD, of University College London UK presented data in the journal Stroke that indicated that older men who added a long walk to their daily routine significantly reduced their risk of having a stroke.  The association was independent of activity level or walking pace. Men who walked 8 – 14 hours per week had about a one third lower risk of stroke compared to men who walked no more than three hours per week or at all. The risk was about 2/3 lower for men who walked more than 22 hours per week.  Walking is recognized to be the predominant form of physical activity in older adults and its impact in reducing stroke risk is important to understand.

The study looked at 3,435 men followed over a ten year period.  The lead researcher said there is no reason to believe that the protective effect does not apply to women as well.

This is one of several studies published over the last few months that extol the benefits of modest age related exercise to preserve function and independence.  We have seen the benefits of an after dinner walk on blood sugar levels documented in recent studies. In a recent British Medical Journal article (BMJ 2013, 347:f5555) researchers reviewing 60 research trials conclude that exercise benefits patients with arthritis rather than being sedentary. We have seen other studies linking seniors with active leisure activity life style exhibiting improved cognitive function compared to seniors with a more sedentary leisure life style.

From a doctor’s perspective the advice is simple. Find something you enjoy doing that is active and aerobic such as walking, running, cycling, swimming, dancing, roller skating or roller blading and engage in this activity regularly to protect your health and independence.

 

Do Probiotics Prevent Diarrhea and Antibiotic Related Colitis in Seniors?

Probiotics are medication containing bacteria that normally reside within a healthy intestinal tract and aid in digestion and the production of a solid stool.   Physicians and scientists have known for years that when a patient is given an antibiotic to treat a bacterial infection, that antibiotic works against the invading pathological bacteria as well as the bacteria that normally reside within us and keep us healthy. The theory for years is that by destroying the healthy normal flora of the intestine we are paving the way for virulent pathological and opportunistic bacteria such as clostridium difficile to invade the gut and produce antibiotic related colitis. The hope has been that by giving the intestine back the normal bacteria in the form of a pill containing normal gut flora, we can prevent diarrhea and even the more severe antibiotic related colitis when prescribing antibiotics appropriately to fight a bacterial infection.

Initial small Meta-analysis studies supported the notion. Based on these small studies private firms have produced over the counter probiotics such as Align and a series of prescription only probiotics for human consumption. Hospital and health systems have invested money in purchasing and prescribing probiotics to senior citizens given antibiotics to stave off diarrhea or antibiotic related colitis.  A new large study performed in South Wales and England looked at almost 3,000 patients aged 65 or older who were being treated with antibiotics while hospitalized.   Patients were treated with either a placebo pill or a probiotic pill containing two strains of Lactobacillus acidophilus, Bifidobaceterium bifidum and bifidobacterium lactis, for 21 days and between antibiotic doses.

Despite the probiotic administration, diarrhea occurred in 10.8% of the patients given probiotics and 10.4% of those given placebo. The researchers then went on to analyze the stool of half the diarrhea patients and found that Clostridia difficile was an uncommon finding in both groups. The probiotics did not produce any measurable adverse effects in the patients taking them.

The PLACIDE study was by far the largest study of the effectiveness of probiotics done to date. Its result speaks against the routine use of these agents to prevent antibiotic related diarrhea or colitis. There will be additional studies in the future.

The science of the composition of our intestinal flora is in its infancy. Studies have shown that genetically alike individuals have similar bacterial gut patterns. Studies have also shown that if you develop antibiotic related colitis and receive an enema containing stool from a genetically identical individual, your chances of recovering from previously resistant antibiotic related colitis are much better.   It could be that there will be different compositions of bacteria in future probiotics for genetically different individuals.  More research is needed.

New Medications for the Treatment of Hot Flashes

Menopausal related hot flashes are an annoying and life altering symptom plaguing millions of adult women. Pfizer and Ligand Pharmaceuticals received approval this month for a new drug named Duavee to treat hot flashes in women who still have a uterus.

Duavee is a combination drug pairing conjugated estrogens with a selective estrogen receptor modulator (SERM) named bezedoxifine. Normally estrogens are paired with progestins with the progesterone used to prevent cellular hyperplasia in the uterus reducing the chance of a malignancy developing.  While this new medication is designed for women with menopausal related hot flashes, it is unclear whether it provides any less of a side effect or cancer risk than current estrogen and progesterone combinations.   It is additionally recommended as a treatment for osteoporosis.  Like most estrogen products, it should be used for the shortest time possible.

Several months ago the FDA approved a non-hormonal treatment of hot flashes with an antidepressant named paroxetine and marketed under the name Brisdelle.  Paroxetine is also marketed as an antidepressant under the brand name Paxil which has been available to treat depression for many years.

It is always wonderful to have new medications available to treat chronic and severe problems.  However, it remains to be seen what clear advantages Duavee brings to clinicians.