HOW WOMEN CAN STAY YOUNGER LONGER

A transcript of the program originally broadcast on KSAT-TV on September 10, 2002.  Dr. Sherwyn Schwartz is entirely responsible for the contents of this narrative.

Some women in my practice have asked these questions:

1.                 When I go through menopause, will I need hormones, and are they safe?

2.                 How can I prevent osteoporosis and its deformities and fractures?

3.                 What can I do to feel young and active in my 70s and 80s? 

The answer to the first question has taken a topsy-turvy course over the last 40-50 years. 

Between 1960 and 1996, evidence slowly mounted to show that estrogen was a major protector of postmenopausal women from

·        Heart attacks

·        Strokes

·        Osteoporosis

·        Alzheimer’s disease. 

AS PROGESTINS WERE ADDED (TO WOMEN WHO HAD A UTERUS), THERE WAS

·        A drop in uterine cancer.  Women without a uterus did not need progestins.  These hormones, when added to estrogens in an on/off pattern (like birth control pills), induced menstrual periods.  If they are taken daily with estrogens, no menstrual period occurs after a few months. 

·        In all women, estrogens

o       Relieved hot flashes and

o       Associated insomnia. 

BY 2002, ESTROGEN COULD BE GIVEN ORALLY IN MANY DIFFERENT WAYS: 

·        Prempro (one of the most prescribed drugs in the United States) is made of an estrogen from mares’ urine (i.e.) Premarin and a progestin. 

·        Esterified estrogens (example: Estratest, Menest and Estratab).  A mixture of estrogens chemically altered to improve potency and absorption.

·        Estradiol (example Activella, Estrace and Ortho Prefest).  Identical to the estrogen found in premenopausal women.

·        Ethinyl Estradiol (Femhrt).  The same estrogen as found in birth control pills.

·        Estrone/Estropipate (example: Ogen and Ortho Est).  Identical to estrogen found in postmenopausal women. 

ESTROGEN CAN ALSO BE GIVEN AS A SKIN PATCH, SUCH AS ALORA, CLIMARA OR VIVELLE. 

THERE HAVE BEEN QUITE A FEW PLANT AND NATURAL SOURCES, PRIMARILY FROM SOY AND BLACK COHOSH. 

HOWEVER, BETWEEN 1996 AND 2002, THERE WERE STORMS BREWING AGAINST ESTROGENS FROM TWO LARGE, WELL-DONE STUDIES.

1.       The Heart and Estrogen/Progestin Study (HERS I & II).  It looked at

·        2,703 postmenopausal women with coronary artery disease and found an increased risk of disease after one year, a slight decreased risk of heart problems in year three to five. 

·        At the end of six to eight years there was no decreased risk of coronary artery disease at all.  Therefore, there was no heart protection benefit in these women who had coronary artery disease.   This was reported in the JAMA July 3, 2002. 

2.       The Estrogen Revascularization Atherosclerosis Trial (ERA) found

·        A similar lack of estrogens benefit in 309 postmenopausal women with coronary artery disease using equine estrogen and progestin. 

·        Coronary arteries that already had disease did not benefit from use of estrogens. 

BEFORE LATE JULY 2002, ESTROGENS/PROGESTINS WERE FOUND TO NOT HELP POSTMENOPAUSAL WOMEN WITH CORONARY ARTERY DISEASE. 

However, the major question (of estrogen’s necessity with a progestin for postmenopausal with a uterus and without coronary artery disease) was not answered until July of 2002. 

THE WOMEN’S HEALTH INITIATIVE (WHI) WAS STARTED IN 1993.  TO ANSWER OUR QUESTION OF IS HORMONE THERAPY NECESSARY AND HOW LONG:

Over 16,000 postmenopausal women who had a uterus were given Prempro, while 11,000 postmenopausal women who did not have a uterus were given Premarin.  It took over five years to find these women. 

By July 17^th of 2002, it was announced that the Prempro part of the study was stopped due to benefit not being worth the amount of risk that the patients were experienced.  The following were the results: 

·        29 % increased risk of heart attacks

·        41 % increased risk of strokes

·        26 % increased risk of breast cancer

·        37% decreased risk of colon cancer

·        34% decreased risk of hip fractures

·        200% increase risk in blood clots

At this time, the WHI data says that Premarin-only patients don’t have risk greater than benefits.  However, in the same July 17, 2002 JAMA article, the breast cancer demonstration project of greater than 44,000 women showed that women who took estrogens in higher doses than women take today over ten years had a two-time increased risk of ovarian cancer.  These were women who did not have a uterus or hysterectomy but had ovaries left.  The author of the study, however, was quick to say that the risk is low, as this was only preliminary data. 

At this time, because of the increased risk of breast cancer and vascular disease, authorities, such as Dr. Jan Schiffren, Director of the Menopausal Program at the Massachusetts General Hospital/Boston, were quoted by The Wall Street Journal, saying, “the conservative approach is for women to assume that all hormone replacement therapy brands carry the same risk and benefit as Prempro”.  Because most of the risk of the study was after five years, most M.D.’s assume it is best to limit all hormones to less than five years if possible.  Therefore, postmenopausal women with a uterus have little long-term use of estrogen therapy.  The jury is still out for women without a uterus on estrogen alone.  If a woman is taking Prempro for hot flash relief or other menopausal symptoms, those can be slowly tapered by her physician if possible.  Of course, any such decisions are up to the patient’s physician.  More research is needed to give women a better hormone replacement.  The first drug to come out of this research is Evista®/Raloxifene). 

EVISTA®/RALOXIFENE ACTS LIKE AN ESTROGEN TO DECREASE LDL (BAD CHOLESTEROL) BUT INCREASE RISKS OF BLOOD CLOTS.  BUT UNLIKE ESTROGENS:

·        Does not have to be given with a progestin, as there is a decrease risk of uterine cancer

·        None to a slight decreased risk of breast cancer

·        No rise of triglyceride as occurs in estrogen therapy

·        No relief of hot flashes like estrogen

IN 7,105 POSTMENOPAUSAL WOMEN THE MORE STUDY REPORTED IN THE JAMA OF FEBRUARY 20, 2002, UNLIKE ESTROGENS THERE WAS NO INCREASED CARDIOVASCULAR RISK THE FIRST YEAR BUT IN WOMEN WHO DID HAVE HEART DISEASE

·        There was a decreased risk of heart disease with women who took Evista.

·        In postmenopausal women, Evista had no effect on cardiovascular disease, however. 

At present, much research is ongoing to pick out the best parts of estrogen therapy and leave out the worst.  Therefore the answer to the first question is, you do not need to take long-term progestin/estrogen therapy, but new forms of estrogens are safer.  One needs to ask yourself, what am I trying to prevent or treat?  Estrogens treat hot flashes and should be given for a few months and then tapered off.  If they are not able to be used, a blood pressure patch, such as Catapres or an antidepressant class called SSRIs (Prozac, Paxil, Zoloft) can be given to treat the symptoms of menopause. 

·        If a woman has any risk of blood clots, any estrogen-like drug cannot be used.

·        If uterine or breast cancer is present in a close relative, Evista is safe, whereas estrogen is risky.

·        If a woman has heart disease, Evista is safe, whereas estrogen might not be.

It is still undecided on estrogen alone for treatment of women without a uterus.  But this should be answered by 2005 by the WHI.  Progestin, it seems, increases coronary artery disease and breast cancer.  We will await new studies to increase women’s choices, but remember all sources of estrogens (drug, plant or natural) must be considered identical until a study shows them to be different.  More research on these questions is actively ongoing. 

The answer to the second question needs a bit of background information.  UNDER NORMAL CIRCUMSTANCES MOST WOMEN BUILD BONES UNTIL APPROXIMATELY AGE 25.  SKELETONS ARE AIDED BY

·        3 glasses of milk per day while growing

·        Normal menstrual periods

·        Weight bearing exercise

·        No smoking

After age 25, bones continue to break down or resorb greater than rebuild until death.  Estrogen lack at the time of menopause amplifies bone loss that has already occurred. 

WOMEN WITH A

·        History of fractures without much trauma in a close relative

·        History of smoking

·        Weight of less than 125 pounds

·        History of prolonged inhaled steroid use

·        Excess thyroid hormone use

·        History of height loss

USUALLY HAVE EXCESS BREAKDOWN OF BONE THAT EVENTUALLY CAN LEAD TO OSTEOPOROSIS (this term means a woman whose bone mineral density is in the bottom 5% of all women).  This disease causes dowager’s humps and fractures to the spine and hip with minimal trauma.  This disease can only be diagnosed with an x-ray densitometer, as there are no symptoms.  This machine gives 1/10 the radiation of a chest x-ray and is very accurate.  It should be done sometime before menopause and then every one to five years after, depending on how many risk factors a woman has and what her bone mineral density is. 

MORE WOMEN SHOULD PREVENT AND/OR TREAT OSTEOPOROSIS BY

·        Take 1-1½ grams of calcium per day (will give examples)

·        Do weight bearing exercises greater than 30 minutes per day

·        Avoid smoking and carbonated drinks

·        Exercise to increase balance and flexibility, i.e. to decrease falling.  Examples are yoga, Tai Chi, etc.  If bone loss is present on densitometry, medications are often used. 

Bone loss is a very common problem.  A study of 200,000 women reported in the Journal of the AMA December of 2001, by Dr. Siris, showed early bone loss in approximately 40% of postmenopausal women that resulted in 80% increased risk of fracture.  Osteoporosis was found in 7% of postmenopausal women and this had a 4 times increase fracture risk. 

The relation of bone with estrogen came from two studies:  One from Dr. Lindsey, using mestronal and the second from Dr. Lufkin, using estradiol, which showed less spinal fractures with the use of hormones.  Many other studies also showed that estrogen slowed down bone breakdown.  Also, menopause accelerated bone loss that started at age 25 years old, as we just described.  It was therefore very natural to consider estrogens or estrogen-like drugs to be used to prevent and/or treat osteoporosis.  Because of estrogen’s risks, other compounds have been released and even more are under development in research.  The first to come out has already been discussed earlier in the show and this is Evista.  This has also been called a designer estrogen, or SERM.  As we have already discussed, there is no effect on the uterus, possibly some increased benefit on the breast but also has been show to decrease bone breakdown or resorption and therefore increases bone mineral density and decreases fracture risk.  The MORE study, which already has been discussed, in 25 countries, after three years showed that bone mineral density was found to increase by 2-3 percent and fracture risk was decreased by 30-40 percent.  However, there was a 3-times increased risk of blood clots versus women just given a placebo.  However, invasive breast cancer risk was decreased by 26%.  At present, several other SERMs are under development to try to get better effect on bone, breasts, lipids and blood clots.

A second class of drugs has already been out for several years, and they are called bisphosphonates, i.e., Fosamax and Actonel.  They decrease bone breakdown more than increasing formation of bone, resulting in bone mineral density increasing and fracture decreasing.  One study of postmenopausal women with fractures reported in the JAMA in December of 1998, by Dr. Cummings, looked at 44,032 patients.  Half were given placebo and half were given Fosamax.  Fracture risk was decreased by 44% in the spine and 36% in the hip without significant side effects.  Actonel is another drug to have come out, and similar effects have been shown.  JAMA of Oct 1999 reported a study of 2,458 women using Actonel had a 41% decreased fracture risk of the vertebrae and 39% decreased fracture risk of the hip.

Many new bisphosphonates are under development to decrease doing frequency (some as little as once or twice a year) and others to decrease side effects. 

A third class of drugs are the calcitonin sprays that have been shown to increase bone mineral density 1½ %, less than bisphosphonates but in a study of 1100 postmenopausal women, fracture risk decreased by 36%, only slightly less than bisphosphonates. 

A fourth, and new class of drugs, is being developed which are fragments of parathyroid hormone.  These are the first class of drugs to increase bone formation since there is no other drug that primarily does this.  It is hopeful that they will be able to combine with the other drugs that we have already discussed.  These drugs primarily decrease breakdown and do not increase bone formation. 

This is an exciting time in bone research.  Therefore the answer to the question, how can I prevent osteoporosis and its deformities, are primarily through lifestyle changes, i.e. stopping smoking, exercise, better diet.  At the same time if a woman does have disease, the drugs we have already discussed have been found to give some prevention and treatment of decreased bone mineral density.  There is, however, a lot of research ongoing and we can only expect better treatments for women with bone disease. 

THE ANSWER TO THE LAST QUESTION NEEDS A MANY-FACETED APPROACH,

AS IT IS THE MOST IMPORTANT AND YET MOST DIFFICULT.  THE ABILITY TO BE ACTIVE, AND YOUTHFUL IN ONE’S 70S AND 80S IS THE END RESULT OF WOMEN’S HEALTH. 

·        Healthy bones using a SERM, bisphosphonate or newer experimental drugs keep the bony skeleton healthy.  This is, of course, what carries the whole body around. 

·        A healthy heart and blood vessels gives a woman the energy to do anything she desires.  This goal comes from

·        LDL (bad cholesterol) less than 130 via either a low-cholesterol diet or statin drugs (Lipitor, Zocor, Pravachol, Lescol or newer drugs that are under development) if diet is without success

·        Blood pressure less than 140/90 if low-salt diet and weight reduction does not help.  Classes of drugs that have been used are ARBs.  Example, Diovan, Cozaar, ACE inhibitor inhibitors, example Accupril, Zestril, Vasotec and calcium-channel blockers, example Procardia, Cardizem.  These are examples of effective drugs, however, there are many others that have not been listed.  There are also several new classes of drugs under development.

·        If diabetic, keeping a hemoglobin-A1c (an average of three months blood sugars) less than 7% (less than 140 mg/dl) is very important.  Besides insulin and pills, there are lots of other drugs under development to help treat this disease.

·        An exercise program that benefits cardio flexibility and balance after clearance by your doctor.  A trainer can be very helpful in this area. 

·        A diet that is high in protein and complex carbohydrates and low in fat.  A dietician can direct change in this area, as bad habits of any kind are hard to change.

Therefore, staying younger longer is definitely possible in 2002.  It takes planning, understand and talking to your doctor, and in some cases, taking advantage through research of some possible treatments of 2006. 

If you have questions or comments,  please email to Dr. Sherwyn Schwartz.

© 1979- 2006 DGD