Although the debate over the safety of hormone replacement still rages in the press, it appears some semblance of common sense is beginning to be heard. Yes, we need more confirming studies, but today’s women - myself included - cannot be put on hold and forced to wait another 10 to 20 years until all of the definitive studies have been completed. As with so many other issues in medicine, physicians have to use their best clinical judgment based on the information available now. Each woman needs to make these decisions with input from her own physician.

After all my years of practice, I still believe we should try to mimic the normal human physiology whenever possible. That’s why I use topical over oral hormones, cyclic over continuous progesterone, natural over synthetic hormones whenever possible and blood serum measurement of estrogen and progesterone to get the optimal therapeutic dosage for each individual woman. My goal with any patient is to give the lowest dose of hormone that corrects her symptoms and still gives her therapeutic levels of her natural hormones. However, no prescription drug, including hormones, is without side effects or totally free of risks. That’s why it requires a prescription: so your physician can safely develop a hormone program that is monitored and takes into account all your medical concerns. Because the Endocrinologist is the definitive hormone specialist, it’s ideal to have bioidentical HRT prescribed and monitored by an Endocrinologist. However, there is a shortage of Endocrinologists who treat menopause. For that reason it is important to seek out a gynecologist, internist or family practitioner who has acquired expertise in treating menopause with bioidentical hormone therapy and to take responsibility for educating yourself about menopause and its related conditions.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson was a medical writer and pharmacist before medical school and utilized these skills to research 450 medical journal articles to develop her book. She has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

I am frequently asked the question, “How long can I safely stay on my hormone therapy? and I usually ask the woman, How long do you want to continue to feel well?” In all seriousness, there are no long-term studies that enable me to answer this question. Taking hormones less than five years seems to carry very little risk. However, the longer you take hormones the higher your risk.

The North American Menopause Society and the Endocrine Society have addressed this issue. They recommend that all women be informed of potential risks and benefits and given the lowest effective dose consistent with treatment goals. If a woman wishes to continue HRT for an extended period of time, this is acceptable if she and her physician believe that the benefits of continuing HRT outweigh the risks.

A woman’s decision to initiate or continue HRT must be based on her own unique circumstances and risks. Many of the available studies have not attempted to evaluate the differences in risks among the different HRT regiments. However, new studies are beginning to appear that help sort out the risks for the different types of HRT. In a sense, the Baby Boomers are the “test generation” that started HRT in larger numbers. We will be the first to see the consequences, positive and negative, of being on HRT for 20, 30, and 40 years.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

To obtain a copy of "Outliving Your Ovaries" click here

All the adverse effects from the oral route of administration of estrogen as previously outlined in Outliving Your Ovaries can also occur from oral Prempro. However, the addition of the progestin seems to confer additional cardiac risk. Perhaps giving progestins daily instead of in cycles of 14 days each calendar month may be a factor in this increased risk. Earlier observational studies, like the Nurses’ Health Study, predominantly used oral cyclic progestins and did not show an increased risk of heart disease.

While estrogen increases the beneficial HDL cholesterol, adding a continuous synthetic oral progestin lowers HDL by 8 to 18%. Addition of oral, micronized progesterone causes little or no adverse effects on HDL. An animal study showed that adding MPA to estradiol blocks the conversion of estradiol to an important beneficial byproduct made in the liver called 2-methoxyestradiol.

In the Women’s Health Initiative, a randomized, placebo-controlled trial showed no change in the incidence of heart disease in women starting Prempro within 10 years of menopause when compared with placebo. Women starting Prempro 10 years after menopause had an increased risk of heart disease which increased the more time had elapsed since menopause.

The 2009 Danish Study, an observational study of 698,098 women, found those who took continuous combined oral HRT had a 35% increased risk of heart attacks compared to women who did not take hormones. In the women taking topical estradiol plus cyclic progesterone or cyclic progestin, there were 38% fewer heart attacks.

I had an acquaintance, Janet, who became newly menopausal and was exhibiting the typical symptoms. Her physician promptly started her on a daily combination pill containing synthetic estrogen and progestin. Within days of starting that therapy, she developed new onset chest pain sending her to the emergency room (ER). At the ER, Janet was evaluated and sent home and referred to a cardiologist who did stress testing and told her everything was normal. When she continued to have intermittent chest pain, her physician changed her to a combined topical estradiol/synthetic progestin patch. The pain lessened but she still had occasional chest pain. Not until she was finally put on topical estradiol with cyclic oral progesterone did she finally have resolution of her chest discomfort. Imagine the cost savings and the angst that would have been avoided if she had just been put on topical estradiol and cyclic progesterone from the beginning!

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

To obtain a copy of "Outliving Your Ovaries" click here

A very few lucky women sail through menopause with minimal symptoms. They have usually been very healthy prior to menopause. However, they are the exception. Most women will have at least some symptoms. These can range from a mild sensation of feeling warm, to a beet red face and drenching sweats that leave the sufferer with wet hair and clothes soaked in sweat. As you can imagine, this can be especially disconcerting to a woman who’s in the middle of a business meeting.

A woman may have trouble falling asleep or she may awaken at 3 a.m. unable to get back to sleep. Sometimes she has both! Sleep is the body’s time for rejuvenation when new tissues are made or repaired. When this vital restorative time is short- changed, symptoms like chronic fatigue, weight gain, irritability, palpitations, headaches, and migraines can develop.

Dizziness is another symptom that occurs in menopause. Episodes are usually mild and short-lived lasting only a few seconds. Occasionally dizziness may be debilitating. Alice was a 54-year-old woman who came for menopause management. She had been a confident businesswoman and she told me, “My life is falling apart and I feel like a cripple!” She was suffering off/on unpredictable bouts of dizziness of such severity that she would have to hold on to the wall to keep from falling. The dizziness had been going on for months, and she’d undergone a very extensive evaluation from a neurologist, a neurosurgeon and a cardiologist. Because all their testing showed NO cause for her dizziness, she was pronounced NORMAL and sent on her way! She had not actually sought me out for the dizziness but rather had resigned herself to her plight. However, after I started her on topical HRT, she never had another bout of dizziness. She was ecstatic to finally be rid of that debilitating symptom! I’ve never seen another menopausal woman with such severe dizziness but her case taught me to recognize the possibility that it may be related to low estrogen.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

To obtain a copy of "Outliving Your Ovaries" click here

When I was first starting my medical practice, menopausal problems were not taken very seriously. Hot flashes and premenstrual syndrome (PMS) were the source of a lot of jokes. Well, it isn’t funny when you feel awful and your life is falling apart. I can’t tell you how many times I’ve had women apologize for “wasting my time” with their complaints or tell me, “Thank you for listening to me.” I would always assure them that hearing their symptoms is essential for my finding the correct solution for their problem.

There are a few patients seared into my memory bank who forever changed my attitude about menopause. I once was called to do an endocrine consultation on Joan, a patient in the psychiatric ICU with “hirsutism” or excess facial hair. When I went to see Joan, she indeed had a moderate degree of facial hair. However, after reviewing her chart, I was astonished to learn that she’d been a banker with no prior psychiatric history. She’d undergone a total hysterectomy with removal of her ovaries for a benign condition the summer before and I was horrified to learn that she’d never been given hormone replacement.

After the surgery, her mental condition deteriorated to the point where she’d lost her job. She was put on various psychotropic medications but continued to do poorly. She’d become suicidal and ultimately was admitted to the psychiatric intensive care unit. It had not occurred to anyone that perhaps she needed hormones. When I started her on HRT, I saw firsthand how restoring deficient hormones can produce a total transformation in a person’s life. This woman eventually went off all her psychotropic medicines and was able to go back to her normal life. It still brings tears to my eyes as I think about how she was made to suffer needlessly. At the same time, it is incredibly gratifying when you can use your training and experience to help a person become whole again. That’s what drives most physicians - the desire to relieve suffering and help people.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson was a medical writer and pharmacist before medical school and utilized these skills to research 450 medical journal articles to develop her book. She has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

At the time of menopause, each woman has a window of opportunity during which she needs to make the important decision of whether to take hormones. As the estrogen levels fall, her body begins to go through degenerative changes that accelerate her risk of heart disease along with the other changes we have previously described. The sooner a woman starts HRT after menopause, the fewer degenerative changes she will experience. If a woman waits 10 years to start HRT, the heart protection from estrogen is greatly diminished. The same applies brain protection; once brain cells have been lost, it becomes difficult to retrieve normal function. However, for protecting bones, estrogen is effective even when started after age 75.

However, I would like to stress that each woman is an individual and if there are no contraindications to trying hormones, consider trying topical estradiol for a year to see if you experience any improvements. I recall Cora, an 82 year-old woman who was brought to me by her daughter June. Cora had never taken hormones after menopause.

June said, “Mom has always been so vibrant, energetic and happy and she loved to do gardening. However, for the past six months she just sits in a rocker and stares at the wall. I’ve taken her to several doctors and they have all told me that everything’s normal but this is not normal for my mother! Is there anything you can do to help her?” I examined her mother and the only abnormal lab result was her lack of estrogen. I told June, “I’m not sure how much benefit we can expect to see but let’s try her on estrogen and see how she responds.” A mere three months later, now with therapeutic estrogen levels, June told me with excitement, “I have my mother back! She’s smiling and happy and back to her old self.” Cora taught me to never give up on a patient just because they are older. Everyone deserves a chance to be better. People deserve to be treated as individuals not as statistics on a bell-shaped curve. I challenge my patients to become the outliers who defy the odds and do better than expected!

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson was a medical writer and pharmacist before medical school and utilized these skills to research 450 medical journal articles to develop her book. She has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

3. YOU CAN’T JUST GO BY “HOW YOU FEEL!”

I strongly endorse monitoring estradiol and testosterone blood levels to ensure appropriate dosage and effectiveness of hormone therapy. Monitoring estradiol levels in thousands of women since 1986 has led me to develop more precise hormone regimens producing blood levels comparable to a low physiologic range. As noted earlier, monitoring blood levels is especially important with topical therapy. Most post- menopausal women who see me initially have NEVER had their estrogen level checked!

Early heart disease and osteoporosis are both consequences of low estrogen and have no symptoms in many women. Hot flashes eventually go away in many women even without taking estrogen. Dosing hormones simply by “how you feel” is an archaic notion and other hormones like thyroid hormone and growth hormone are never dosed that way! It is time for menopause management to come into the 21st century and not be treated like a stepchild among other hormone deficiencies. A few lucky women go through menopause and never have hot flashes but this can be a mixed blessing. If you don’t have symptoms, you’re less likely to seek help. However, even without symptoms, you may still be at risk for the degenerative consequences of low estrogen.

For insidious problems like osteoporosis or heart disease, there are usually no symptoms until the woman has a fracture or heart attack. If estrogen dosage for such women is determined simply by “how they feel” we may be giving them an inadequate dose and putting them at increased risk. Objective measurement of blood estradiol ensures adequacy of dosage. Studies have shown a protective effect on bones from fairly low doses of estrogen. In one study of postmenopausal women treated with estrogen alone, those with higher estradiol levels had less progression of subclinical atherosclerosis on CIMT than those with lower estradiol. Recall that CIMT is an ultrasound measurement of the thickness of the two inner layers (the intima and media) of the carotid arteries that the American Heart Association recommends as the best way to screen for early risk of heart disease or stroke. I routinely rely on CIMT to assist me in assessing these risks in my patients.

In general, creams and gels produce lower blood estradiol levels ranging from 9.8 to 30 pg/ml that are similar to the lower doses of estradiol patches. The highest estradiol blood levels are achieved with the 0.1 mg estradiol patches and are typically in the range of 80 pg/ml.

More studies need to be done to determine the optimal level that protects us from the consequences of low estrogen while avoiding the adverse effects that may occur with the higher doses of estrogen. For the time being, a reasonable approach is to give the lowest estrogen dose that relieves symptoms and still falls within the lower physiologic range for a premenopausal woman.

4. IMPORTANCE OF ACCURATE BLOOD ASSAYS

When measuring estradiol levels it is very important that an assay be utilized which has the ability to detect the very low levels present in post-menopausal women. The estradiol assay used in fertility practices for women undergoing ovulation induction or in vitro fertilization is not appropriate. An assay with sensitivity at the low end of the scale is required to monitor estradiol therapy in menopausal women. The assay should be capable of measuring less than 1.5 ng/dL of estradiol or less than 1.0 pg/ml of free estradiol. Similarly for free testosterone, assays that utilize equilibrium dialysis are the most accurate at detecting the lower levels of testosterone seen in women.

When I first see a female patient, I may check estradiol blood levels several times in the first few months while adjusting their dosage. Once the levels are stable, I check them once a year unless symptoms develop or there is another dosage change. Since postmenopausal ovaries often continue to product testosterone, it is important to document low testosterone levels before prescribing testosterone.

For a woman with an intact uterus, withdrawal periods on cyclic progesterone and a normal yearly TVS, there is less need to monitor progesterone. “Withdrawal periods” is the medical term given to the monthly menstrual flow occurring in postmenopausal women prescribed estrogen with cyclic progesterone. When a woman is perimenopausal and still having periods, progesterone levels on day 21 of her menstrual cycle are a useful indication of her endogenous progesterone. If low, adding progesterone therapy may improve symptoms of heavy bleeding, PMS or insomnia.

5. SALIVARY HORMONE TESTING IS NOT RELIABLE

Many women ask me about salivary hormone tests. While dependent on the accuracy of the testing laboratory, you can measure hormone levels of estradiol, progesterone and testosterone in saliva. However, an important reason for measuring hormones is to be able to determine the optimal dose of the hormone preparation. Salivary hormone tests are notoriously unreliable for this purpose. Numerous studies have shown inconsistent and skewed results with the use of salivary hormone testing in women on HRT. That’s why I utilize blood hormone testing.

RECAP WHY IS IT IMPORTANT TO MEASURE ESTRADIOL BLOOD LEVELS? BLOG SERIES

WHY IS IT IMPORTANT TO MEASURE ESTRADIOL BLOOD LEVELS? PART 1

The content of this blog series is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. This blog series may discuss nutritional products and protocols that have not been evaluated by the U.S. Food and Drug Administration. These products or the information contained on this website is not intended to diagnose, treat, cure or prevent any disease. All website content is © Copyright 2012 by Marina Johnson MD - All Rights Reserved

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson was a medical writer and pharmacist before medical school and utilized these skills to research 450 medical journal articles to develop her book. She has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

To obtain a copy of "Outliving Your Ovaries" click here

Many women who initially see me for menopause have never had their estradiol level checked. Their previous physician may have diagnosed menopause with an elevated FSH, but usually no further tests are done. I’d like to go through various reasons why I believe it is important to monitor estradiol levels.

1. ESTROGEN IS A TWO-EDGED SWORD

I describe estrogen as a two-edged sword because it can be both protective and harmful depending on how your body uses it and on the amounts and duration of estrogen exposure. Endogenous estrogen refers to the levels of estradiol that a woman’s own body produces before menopause. Early in the book I outlined how estrogen is essential to many cellular functions throughout the body. In Chapter 22 - Risks of NOT Taking Estrogen, I listed the many symptoms and degenerative consequences that can result from a low estrogen state.

On the other hand, estrogen excess throughout a woman’s life is associated with increased risks of cancer. An increased risk of breast cancer is associated with longer exposure to endogenous estrogen, i.e. early menarche (starting your periods at an early age) and later menopause. Higher estrogen states seen with obesity increase the risk of breast cancer even more. Studies show women with a body mass index (BMI) over 35 have a twenty-fold increased risk of endometrial cancer.

Estrogen, estrone and testosterone can be produced from fat cells in obese postmenopausal women. These obese women also have lower production of a substance in the blood called sex hormone binding globulin (SHBG). SHBG serves as a carrier protein for storing estrogen in the blood. Lower levels of SHBG results in higher levels of available estrogen that thereby increases their estrogen exposure. In the Nurses’ Health Study of a subset of women on no HRT, an increased risk of breast cancer was seen in women with the highest endogenous estradiol compared to those with the lowest estradiol. A similar increased risk was seen in women on no HRT with the highest endogenous level of testosterone. However, in women on HRT with low testosterone, studies show that adding testosterone can be beneficial in lessening the risk of breast cancer.

These potentially protective and harmful effects of estrogen go back to the basic tenet of any hormone - adverse symptoms can occur with deficiency or excess while optimal function develops with the right level. I see this as an affirmation of the need to respect the balance among the different sex hormones. Monitoring estradiol and testosterone blood levels enables us to prevent a deficient state while guarding against excess levels. This is a standard practice when physicians prescribe thyroid hormone. Why should it be any different for estrogen and testosterone?

2. VARIABILITY OF TOPICAL ABSORPTION

While levels are consistent within a given individual, tremendous variability in the efficiency of absorption can be found from one woman to another and this constitutes another reason to measure blood levels. In a study of women given identical doses of topical estradiol there was considerable variation in blood levels with estradiol increases above baseline differing as much as 90 pg/ml from one woman to another. Studies have even shown differences in absorption when changing women from one patch to a different brand of the same dose. Despite such variations, absorption of topical estradiol is more stable and consistent than oral estradiol which peaks at 4 to 5 hours and is non detectable by 8 to 10 hours.

This phenomenon of variable absorption with topical patches, gels and creams has been documented in numerous studies. Importantly, estradiol blood levels tend to be consistent within a given woman once appropriate levels are achieved and frequent dosage changes are not generally required. Annual monitoring of estradiol blood levels is generally adequate to ensure therapeutic levels. With increasing age of the woman, drug metabolism may be slower, requiring dose reduction to prevent excess estradiol levels.

Since I routinely monitor blood estradiol levels, I have seen such variation in topical absorption in the thousands of women I have managed. This may also explain why some women who first start topical estradiol sometimes give up saying “it doesn’t work” and they switch to pills. Since you have learned of the lower risks from topical estradiol, it is worthwhile to persist in finding a topical product that works for you. In my clinical experience of managing over 100,000 female patient visits, I’ve found very few women who could not be managed with topical estradiol.

In general, thin women require higher estradiol doses while obese women with endogenous stores of estrogen in fat generally can be managed with a lower dose. Higher climate temperature in summer months may increase the need for higher doses of topical estrogen especially in women who are outdoors a lot and are very physically active. Women who take long hot baths will likely reduce estrogen absorption from estradiol patches because the hot water leaches estradiol from the patch. Taking showers does not have this effect. If a woman insists on long, hot, baths, she is best managed with topical gels and creams.

When a pharmaceutical drug is developed, in order to receive FDA approval, the manufacturer must show proof that their product has effectiveness and achieves significant blood levels. The pharmacology term for this is the “drug-response curve.” Studies are done to establish the optimal dose that will achieve certain blood levels and the desired therapeutic effect with the least adverse side effects.

Tomorrow: Why You Can’t Just Go By ‘How You Feel!' - Read Part 2

The content of this blog series is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. This blog series may discuss nutritional products and protocols that have not been evaluated by the U.S. Food and Drug Administration. These products or the information contained on this website is not intended to diagnose, treat, cure or prevent any disease. All website content is © Copyright 2012 by Marina Johnson MD - All Rights Reserved

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. Dr. Johnson was a medical writer and pharmacist before medical school and utilized these skills to research 450 medical journal articles to develop her book. She has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.

To obtain a copy of "Outliving Your Ovaries" click here

A recent study in Lancet Oncology looking at data from the Women’s Health Initiative (WHI) reported that the use of estrogen (Premarin) alone was NOT associated with an increased risk of breast cancer and the use of estrogen-progestin (Prempro) increased the risk of breast cancer. 

At first glance this may seem contradictory since estrogen has been traditionally associated with increased breast cancer.  Here’s a possible explanation.  The Million Women Study in England and the French E3N cohort study have reported that the timing for when estrogen is first started after menopause is a critical factor in determining breast cancer risk.  Women who started estrogen in the first 3-5 years after menopause had a higher risk of breast cancer than those starting estrogen AFTER 5 years. So starting estrogen more than 5 years after onset of menopause is considered a long gap time while starting estrogen immediately after menopause is considered a short gap time.

This is a complex issue so let me first give you some background to make it easier to understand. Most invasive breast cancers are the end result of a decades long evolution of increasingly abnormal premalignant cells. Estrogen is thought to promote breast cancer NOT by causing new cancer cells but rather by accelerating the growth of small, premalignant cells so they become detectable on clinical exam or mammogram. When breast tissue is deprived of estrogen at menopause for many years, it causes shrinkage of these premalignant cells.

Correlating this to the WHI study, recall that the WHI participants who were started on Premarin had been menopausal on NO estrogen for an average of 8 years.  Some of them were 20 years post menopause and had NEVER taken estrogen!  So you would expect to see less breast cancer because after so many years of being without estrogen whatever premalignant cells they had would have died off.  So that’s exactly what was seen with women in WHI.

Now if we’re postulating the TIMING as an explanation, why would you see increased breast cancer risk with the combination hormone pill called Prempro?  By the way, this increased risk of breast cancer with combined synthetic estrogen/progestin is a consistent finding in many studies.  A possible mechanism could be the addition of a daily progestin like the Provera found in Prempro that turns off apoptosis, a protective mechanism of the body that destroys early cancer cells. Another study reported another harmful effect of a daily progestin:  increased productions of RANKL, a protein molecule that stimulates breast cells to multiply and not die when they should.

So what does a woman do who’s considering HRT? Does she have to suffer miserably from hot flashes for 5 years to decrease her risk of breast cancer and then start estrogen?  Does she have a hysterectomy so she doesn’t have to worry about taking a progestin??  ABSOLUTELY NOT!!  First of all by depriving yourself of estrogen for 5 years, not only are you likely to be having the typical low estrogen symptoms like hot flashes but you’re also subjecting yourself to an increased risk of heart disease, osteoporosis, Alzheimer’s, sexual dysfunction and a poor quality of life!

The French E3N study in 53,000 women reported that women who took estrogen + progesterone had NO increased risk of breast cancer when they started HRT within 3 years of menopause.  So the take-home message from these studies is to avoid synthetic progestins and opt for natural hormones like estradiol and progesterone.  You can avoid the increased heart attacks and strokes seen in WHI by choosing topical estrogen in the form of patches, gels, creams and mists that are available at any drug store. It’s important for women to know that these pharmaceutical natural hormones (also called bioidentical hormones) are superior to compounded bioidentical hormones because they are required to meet higher standards for quality control and efficacy. 

Women need to know there’s a window of opportunity of 10 years from menopause when they will get the most protection from estrogen against heart disease, osteoporosis and Alzheimer’s.

The majority of women who go through menopause, get the classic symptoms: hot flashes, night sweats, insomnia, anxiety, depression, sexual dysfunction, and brain fog. For those who still have their uterus, menopause is easier to recognize because their periods stop. When a young woman in her 30’s or 40’s has a hysterectomy and has her ovaries removed, she will likely have severe symptoms.  However, for those women who have had a hysterectomy and still have their ovaries, the loss of estrogen may occur so gradually they don’t notice it.  Some of the subtle signs associated with estrogen loss can be:  weight gain especially around the waistline, crying spells for no reason, not being able to multi-task, dry skin, PMS, acne and sexual dysfunction.  Women are often treated with antidepressants and other drugs.  These are all symptoms that often resolve with estrogen therapy so it’s important for women to recognize this so they can ask their physicians about considering HRT.

This information is all explained in detail in my book, “Outliving Your Ovaries.“ My book is based on my review of 450 medical journal articles and supported by 30 years of clinical experience.  I wrote the book to give women a guidebook to sort out the confusion about HRT so they can better participate with their physicians in selecting the best HRT for themselves.  

1. Anderson GL, Chlebowski RT, Aragaki AK et al, “Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial,” The Lancet Oncology, Early Online Publication, 7 March 2012, doi;10,1016/S1470-2045(12)70075-X

2. Fournier A, Mesrine A, Boutron-Ruault MC, et al, “Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?” Journal of Clinical Oncology 27: 5138-5143.

3. Leslie Bernstein, “Combined Hormone Therapy at Menopause and Breast Cancer: A Warning—Short-Term Use Increases Risk,” Journal of Clinical Oncology 27: 5116-7

4. Fournier, A, Berrino, F, and Clavel-Chapelon, F, “Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study,” Breast Cancer Research and Treatment, vol 107, no. 1 (2008): pp 1033-1111.

5. Ory K, Lebeau L, Levalois C, et al, “Apoptosis inhibition mediated by medroxyprogesterone acetate treatment of breast cancer cancer,” Breast Cancer Research and Treatment, vol. 68 (2001): pp 187-198.

6. Schramek D, Leibbrandt A, Sigl V, et al, “Osteoclast differentiation factor RANK controls development of progestin driven mammary cancer,” Nature, published online 9/29/10doi:10.1038/nature09387.

7. Beral V, Reeves G , Bull D, and Green J for the Million Women Study Collaborators, “Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy,” Journal of the National Cancer Institute 2011;103:296–305

The average age for menopause is 50 to 55. I’ve seen an occasional woman who has regular monthly periods and then one month has her last period and never has another. However, this is the exception rather than the rule. Typically, women begin with perimenopausal symptoms in their forties. As a woman approaches the end of perimenopause, the periods become lighter and start to become more infrequent. She may skip several months without a period, and then finally the periods stop completely. When the decline in hormones occurs very gradually, a woman may not experience severe symptoms because her body has had time to compensate for the decline in estrogen and progesterone. Often the age of menopause is genetically determined and it is helpful to ask when an older sister or mother went through menopause. A catastrophic, stressful life event can bring on menopause earlier than expected.

Some women are elated when their periods have stopped and experience few adverse symptoms. Other women respond to the loss of estrogen with severe symptoms and find it difficult to do their work. Because of such differences, women experiencing great difficulties are sometimes written off as “hysterical” or hypochondriacal, which is very unfair to these women. Overall, there can be tremendous variation in how menopause is experienced by different women. Every time I think I have seen every “variation on the theme,” I see yet another woman who is having a slightly different experience.

After menopause, the adrenal glands continue to produce androstenedione, a hormone that is converted in fat cells to another form of estrogen called estrone. This is a reason why obese women may have less severe hot flashes. It also explains why thin women often require higher doses of estrogen to control their low estrogen symptoms.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD.
Dr. Johnson has no financial conflicts of interest or ties to any pharmaceutical company.
Her only objective is determining the most effective, safest therapy for patients.

"Outliving Your Ovaries is a book that should interest every member of the human race, including men. Most men have women in their lives (I have a wife, daughter, mother, sister, cousins, etc.) and most women have men in their lives who care about them. Women have a unique biology that I never understood before reading Dr. Johnson’s book.

Women need to understand that even making 'no decision' about replacing female hormones carries consequences! Dr. Johnson’s book bridges the huge knowledge gaps between the layperson and the pharmaceutical industry, between hype and the facts, between the layperson and medical researchers, between sound byte news reports and detailed medical analysis of studies and between patients and treating physicians. Her passion for patient care comes through on every page of the book and every word focuses on giving her menopausal patients and the physicians who treat them, the medical knowledge necessary to allow them to live long, productive, vigorous and healthy lives. Any woman approaching perimenopause or menopause and any man who cares for such a woman, should arm themselves with the knowledge provided by Dr. Johnson’s book. "

Mark W. Walker - Attorney

“I want to thank Mark Walker, a prominent business attorney and patient, who gave me very helpful comments and even did a survey of the women in his office asking their opinion about certain sections to improve clarity and relevance.” Acknowledgement Taken From ‘Outliving Your Ovaries’

Why I Recommend Pharmaceutical Bioidentical HRT

Let me tell you why I recommend bioidentical HRT. It is a therapy I have utilized in the 100,000 female patient visits that I have managed over the past 29 years since pharmaceutical topical estradiol was first introduced in 1986. I have had ample opportunity to see what therapies achieve results and what women tolerate with the fewest side effects.

An important concept regarding hormone therapy is that unlike most other prescription medicines, hormones are part of our biological make-up and are essential to the intrinsic function of our bodies. We've learned in previous chapters of the myriad biological actions of estradiol, progesterone and testosterone in a woman’s body. We have also seen that many of these actions are mediated through downstream byproducts of estradiol. So doesn't it make more sense to restore what's deficient rather than cluttering this complex, intricate system with an imitation, "wannabe" hormone?

HRT Is Not Without Risk

Female hormones have been in our bodies since we went through puberty. It is part of our original design since the beginning of time. Yes, there are some safety concerns about estrogen. So logically, if you've made the decision to take HRT, it makes sense to choose what appears to be the safer option. I have tried to fairly represent that bioidentical HRT is not without risks but the risks appear to be less with topical estradiol and progesterone than with imitation HRT. Should we wait another 20 years until large definitive, double-blind, placebo-controlled randomized studies produce more data in support of these findings? While some of the data are not supported by such scientifically rigorous studies, as a prudent physician needing to care for my patients today, I feel compelled to act on what is currently known and act accordingly, making adjustments as additional new studies provide us with more information.

The Goal Of Endocrinology

To those naysayers who contend that pregnant horse urine is “natural,” I choose the very same hormones, estradiol, progesterone, and testosterone that are present in a human woman’s body, not hormones from animals. Furthermore, you can take any natural substance that exists in the body, give it in excess amounts, and cause disease or death. For instance, something as essential to life as oxygen and water, given in excess, can be fatal. It is all about balance and respecting the normal physiology of the body. That is the goal of Endocrinology, a specialty that deals with diagnosing and treating diseases caused by too much or too little hormone(s.)

Bioidentical HRT is Often Given a Negative Connotation

Women are often surprised to learn that the bioidentical hormones, estradiol and progesterone, are available from pharmaceutical companies. That’s because the term "bioidentical hormone replacement" is often given a negative connotation. It often becomes a clash between pharmaceutical companies and compounding pharmacists.

Most pharmacists dispense prescription medications that are manufactured by pharmaceutical companies. Compounding pharmacists are trained to make individual hormone products from bulk raw materials. The physician writes a prescription for a particular hormone preparation and the pharmacist mixes it to those specifications. Pharmaceutical companies correctly assert that they have to meet higher manufacturing standards for quality control than compounding pharmacists. Pharmaceutical companies complain compounded hormone products are often given to women without the attendant information that outlines risks.

I Will Not Prescribe Prempro; or Any Oral Estrogen

I have no bias against pharmaceutical companies. They provide us with lifesaving and innovative therapies. However, I won't prescribe the most commonly prescribed HRT - Prempro or any oral estrogen - because it is not as effective as topical therapy and is associated with more side effects. As an advocate for my patients, it is my ethical responsibility to prescribe the safer, more effective therapy, and that principle governs all my professional decisions. The appropriateness of my choices has been demonstrated in the medical literature, and I have personally observed it in the thousands of patients I have treated over my clinical career.

Given The Choice I Will Always Choose Pharmaceutical Bioidentical

Having been a pharmacist, I am very supportive of the important role of compounding pharmacists. However, if I have a choice of a compounded or pharmaceutical bioidentical hormone product, I will always choose the pharmaceutical product because they have to meet stricter standards of quality control, and I achieve more consistent results when I monitor blood levels.

Compounding pharmacists play an important role in providing products for patients with allergies and other special needs. They can also compound products that are not commercially available. Pharmaceutical companies sometimes withdraw drugs from the market not because of poor efficacy but because there may not be enough market demand for their product. If a physician chooses to prescribe compounded hormones, it is imperative that blood levels be monitored. These patients need to be monitored in the same manner as any other patient receiving HRT. Patients also need to be informed that compounded HRT carries the same risks as pharmaceutical bioidentical hormones.

Talking to Your Doctor

Informing yourself of the risks and benefits of bioidentical HRT is important but since these are all prescription medicines, you will ultimately require the cooperation and advice of your physician. Your own physician can advise you if you have particular health issues which constitute a relative contraindication to bioidentical HRT. If you are having many menopausal symptoms, he/she will be more likely to prescribe HRT. All physicians want the best for their patients and are usually willing to listen and consider reasonable requests. If your physician believes that hormones are in your best interest, pharmaceutical bioidentical HRT is a good choice. Make a list of all your questions ahead of time and tell the scheduling person that you want an appointment to discuss hormone therapy. If you found Outliving Your Ovaries helpful, take a copy to your physician. Do not hesitate to seek out additional medical opinions about your individual condition - caring physicians will assist you in doing so.

Outliving Your Ovaries can increase your awareness of how hormones contribute to optimal health. Healing starts with your belief that it is possible. Use my book as a guide to educate yourself about your treatment options so you can ask meaningful questions and become a better partner in working with your physician.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD.

To obtain a copy of "Outliving Your Ovaries" click here

Studies show about eight of every 100 women of childbearing age - about 3.9 million women - go through natural menopause before the age of 40. Sometimes early menopause has a genetic basis and a 2006 study has attributed it to certain genes. In these families premature graying of the hair, sometimes as early as the 20s, is often seen. About 3.2 percent of women with premature ovarian failure also have Addison’s disease, an autoimmune disease of the adrenal glands. Addison’s disease is easily treated but it can be dangerous for women who don’t know they have it. If a genetic basis is suspected these women are well advised to consider having their families at an earlier age. If your periods stop and you suspect premature menopause, see an endocrinologist to confirm that it is truly menopause and not a temporary cessation from some other abnormality.

Most people are familiar with autoimmune diseases like hypothyroidism and diabetes, in which antibodies destroy the thyroid or pancreas. A similar process can result from antibodies that damage the ovaries. Certain environmental factors may contribute to premature menopause. If a woman has undergone chemotherapy or radiation for cancer, the treatments may permanently damage the ovaries.

The risk of menopause depends on the type and length of treatment (chemotherapy, radiation) and the age of the woman at the time of treatment. The physical symptoms for younger women are much as they would be at age 50, but the emotional impact is often greater. Women with premature menopause often struggle with depression. If they are still childless, they realize their dreams of giving birth are crushed because their reproductive years are over. They often feel somehow “less of a woman.” It’s like a one-two punch. The body is going through immense changes, and the psyche is being shattered. When menopause comes at such an early age, the woman is subject to a higher risk of heart disease, dementia, osteoporosis and other complications because she is subjected to more years of low estrogen. Because these women will likely receive a longer duration of HRT, it becomes even more important to select topical estrodial, a safer form of HRT.

In an open label, randomized, controlled crossover trial, women with premature ovarian failure were randomly assigned to either topical estradiol and vaginal progesterone or oral ethinyl estradiol and synthetic progestin. After 28 months, the women receiving topical estradiol and vaginal progesterone had lower blood pressure, better kidney function and less activation of the renin-angiotensin system compared to those receiving oral synthetic estrogens and progestins.

Such findings suggest important implications for the future cardiovascular health of women who undergo premature menopause. The North American Menopause Society and the Endocrine Society recommend that the findings from the Women’s Health Initiative (WHI) and the Heart and Estrogen/ progestin Replacement Study (HERS) should NOT be applied to women who experience premature menopause.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. 

In Response To Recent Social Media Question: 

Recently I was asked if “all women go through menopause the moment that their period stops?”  this is true ONLY if they are truly menopausal.  When women's periods stop, that could also be caused by various endocrine disorders, that when treated may lead to resumption of normal periods.

Women in their forties or fifties are often in the “sandwich” generation with responsibilities for children and husbands while caring for aging parents. It’s further compounded if they work outside the home. They may have been previously adept at this type of multitasking but now find themselves “overwhelmed.” These are obvious symptoms that get your attention and affect your productivity and well-being.

Mary came in to see me on a myriad of prescription medications. She relayed to me how she’d gotten on all those medicines. In her 40s when her periods started changing, she developed insomnia and depression. She was started on sleeping pills and antidepressants and initially felt better. When her periods stopped, she was put on Prempro and she gained 30 pounds in the first year. (women without estrogen often gain weight around their middle but it can also be worsened by oral estrogen.) Because of the weight gain and oral estrogen, she was diagnosed with high blood pressure and started on blood pressure medications. From the oral estrogen and weight gain, she developed high cholesterol and had to be started on cholesterol medications. Her weight gain continued and she developed fluid retention often seen with oral estrogen. She was then started on “fluid pills” (diuretics), to deal with her swollen hands and feet. She later developed anxiety and worsening depression at all the changes occurring in her body. Her antidepressants were increased and she was started on the strong, anti-anxiety medication (Xanax) which made her feel like a zombie throughout the day. She became sluggish throughout the day but she couldn’t sleep at night with her sleeping pills and was up doing laundry. Because of her fatigue, she was then started on Adderall, which is a potent amphetamine to give her energy! Her weight gain had also caused her to develop reflux and so she’d been given a potent acid blocker, (Nexium), which relieved the reflux but gave her bloating and constipation and she was miserable. So in essence she had been put on seven prescription medications when she probably just needed to be treated with topical bioidentical HRT.

I wish I could tell you Mary’s story is atypical, but sadly it’s an oft-repeated scenario that occurs in all too many women when their symptoms are simply treated with a drug instead of correcting the underlying cause of the symptoms. Often drugs are given to treat the side effects of the initial drugs that were given! In pharmacy circles, this is often called “polypharmacy.” After restoring appropriate levels of topical bioidentical estrogen, progesterone and testosterone, many of these prescription medications can often be gradually tapered off.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. 

To obtain a copy of "Outliving Your Ovaries" click here

When women learn I’m a physician specializing in menopause, they usually tell me their stories. Earlier this year, I sat next to Jane, a PhD researcher, who works for a prominent east coast research institution. She had been menopausal for 3 years and was terrified of taking hormones because she was fearful of breast cancer. Jane lamented, “Dr. Johnson, I can’t remember articles I’ve just read. I have to read and re-read them to make any sense of them. I keep incessant lists of everything to keep me on task. I’m afraid I’m going to lose my job!” I reassured her about the risk-benefit ratio for estrogen, told her about topical HRT and advised her to follow-up with a menopause specialist.

On another trip this month, I sat next to Jackie, a woman in her 60s who told me about her experience when she became menopausal 10 years ago. Jackie said,

“I was having awful hot flashes and could not think straight. I became paranoid and frightened, and I was afraid to be in any social situations. I asked my young doctor for help but he just told me that was something normal that would eventually pass. I relied on advice from an older woman friend, long menopausal. I coped by refusing to go out of my house for six months and staying in bed most of the that time. My husband was worried sick about me until finally I felt a little better.”

I submit to you in the 21st century, this is not an acceptable way to treat fifty percent of our population who will all eventually go through this life stage. In addition to the suffering of these women, think of the lost productivity. When you don’t have your mind, your quality of life is severely compromised.

When estrogen deficiency continues long-term, there is an increased risk for the development of Alzheimer’s disease. In June 2008, the Centers for Disease Control and Prevention reported that AD is now the sixth leading cause of death in the United States, surpassing diabetes. There are currently five million Americans with AD or dementia and more than half of them are women. This total figure is expected to increase to 10 million as the Baby Boomers age.

Estrogen has the following effects on the brain:

1. Modulation of synapses, the special junctions where nerve cells communicate with each other

2. Increase of cerebral blood flow

3. Mediation of important neurotransmitters and hormones

4. Protection against apoptosis (programmed cell death)

5. Increase in anti-inflammatory actions

6. Antioxidant effects

There are estradiol receptors throughout the brain especially in the basal forebrain located near the bottom of the front of the brain. This area includes the hippocampus that is important for memory and learning.

There is clearly an association between the length of time a woman maintains her own estrogen production and her ability to have normal mental focus and memory. When women undergo surgical menopause at an early age and do not take estrogen, they have a sharper decline in these mental functions than women who undergo natural menopause. A Mayo Clinic study of 3000 women followed for 30 years found that women who had one or both ovaries removed before menopause and did not take estrogen were more likely to develop dementia and Parkinson’s Disease.

Despite the biologic importance of estradiol in a woman’s mental function, studies in women receiving HRT have been less conclusive. The Nurses’ Health Study of 13,087 postmenopausal women followed for eight years showed no appreciable mental benefits in women who took oral estrogen or estrogen/ synthetic progestin as compared to those on no HRT. On the contrary, they showed an actual increased risk of mental decline in those women who started HRT at an older age. A possible mechanism for this is that oral estrogen increases C-reactive protein that has been associated with increased dementia. A few smaller studies have shown a modest benefit in improving cognitive function. The WHI Memory Study showed worsening of dementia in women taking Prempro; however, the dementia appears to be related to the use of continuous combined estrogen plus medroxyprogesterone acetate (MPA). MPA has been found to reduce mental performance in both animal and human studies. See previous chapter on Risks of Adding Oral Synthetic Progestins.

Achieving The Optimal Protective Effect of Estrogen

To achieve the optimal brain protective effect of estrogen, women are advised to start on topical estrogen soon after menopause. In light of the lack of protection seen in the WHI Memory Study, it seems prudent to initiate topical estradiol. In women with an intact uterus, cyclic progesterone should be used over a synthetic progestin. Women who start estrogen after age 60 have no reduction in their risk of AD probably because they have already developed degenerative brain loss.

The Cache Study on Memory Health and Aging: Estrogen Use Reduced Alzheimer's Risk by 50%

While estrogen has been shown to prevent the occurrence of Alzheimer’s disease, in studies specifically evaluating the effect of oral estrogen in women with established AD, no effect on progression of the disease was seen. A few small studies have shown topical estrogen positively influences postmenopausal memory and may offer some protective effect against the mental decline seen in AD.

Future research on treatment for AD should focus on such variables as the route of estrogen administration, the form of estrogen (conjugated estrogens versus estradiol), when estrogen is initiated following menopause, duration of estrogen treatment, and the effects of opposed versus unopposed estrogen to define which HRT regimens may have a benefit.

Excerpt from "Outliving Your Ovaries" © 2012 by Marina Johnson MD. 

To obtain a copy of "Outliving Your Ovaries" click here

Click Here For Study

Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, et al, Cache County Memory Study Investigators., Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study, JAMA (2002) 288(17):2123-9
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