Sunday, November 30, 2014

Confused Over Estrogen? You’re Not Alone ...

“Who needs estrogen? Doesn’t it cause breast cancer, strokes and heart attacks?” That is the general public consensus over the past 12 years since the Women’s Health Initiative headlines announced

“Hormone replacement therapy (HRT) associated with a 38% increase in stroke risk.” Though that is a pretty scary headline, it’s not relevant for most women considering HRT.

It is very easy for a younger woman to say “I am not going to take hormone replacement therapy (HRT) when I go through menopause. I’m going to age naturally.” However, when that same woman starts experiencing perimenopausal and menopausal symptoms, she may change her mind. Not all women need hormone replacement therapy when they go through menopause. But some do. For some women, HRT—including estrogen—is essential for a full, productive and joyful life.

First let’s look at how menopause progresses. Menopause is actually when the ovaries stop producing sufficient amounts of progesterone and estrogen for a woman to have a period. Blood estradiol (E2) levels drop below 40pg/mL and follicle-stimulating hormone (FSH) rises above 28-35. This causes hot flashes, night sweats, mood and memory problems, more bodily pains and other symptoms. Frequently these symptoms ease off over time; unfortunately, accelerated aging has already begun.

And that is not all that is going on in menopause. Menopause also is a veritable stress test on a woman’s adrenal glands. These are the small pyramid-shaped glands that sit on top of each kidney. They are the organs that help us respond appropriately to a specific stress. These daily stresses are short lived, hopefully. Then there are bigger chronic stresses...not enough money, job loss, a marriage that turns sour, aging parents or a special needs child. All these demand more work from your adrenal glands day in and day out.

Normally as the ovaries begin shutting down, a healthy woman’s adrenal glands start producing extra steroid hormones that swim into the woman’s fat and are made into estrone (E1)—a weaker estrogen than E2 that is made by the woman’s ovaries. Some women will do just fine on these modest levels of estrone as their ovaries slowly shut down. These are the women who will say, “What’s the big deal? This is so easy. I like not having periods. I’m not having hot flashes, I feel fine.”

On the other hand, some women are chronically exhausted and do not have any reserve. Their adrenal glands are already working at maximum capacity already. These women may start experiencing many disabling symptoms because their adrenals cannot ramp up enough to cover the woman’s estrogen needs.

What determines the severity of symptoms as women progress through menopause?
Lifestyle makes a huge difference. Dr. Thierry Hertoghe, a fourth generation endocrinologist in Belgium, recommends certain lifestyle changes. Adopting the following habits before or during menopause will reduce symptoms. Optimal hormone production of estrogen, progesterone, testosterone, and even growth hormone depends upon eating an adequate number of calories and following a Paleolithic diet with animal protein and a variety of foods which are preferably organic. Adequate body fat and a healthy weight enhance hormone production. Avoiding alcohol, a vegan diet, tobacco, marijuana, caffeine, sugar, dairy products, cereal grains including wheat, and too strenuous physical activity all improve symptom control in menopause.

It’s also important to balance adrenal and thyroid hormones. Too much or too little will profoundly affect menopausal hormones.

Lastly the rate of fall of hormone levels is critical. Premenopausal women who have their ovaries removed or women who are acutely stressed emotionally or physically may go into full-blown menopause with incapacitating symptoms. Both may need HRT in the short-term to let their bodies adjust.

What are symptoms of estrogen deficiency?  
Increased fatigue 24/7, which is always there. It doesn’t vary with the time of day. Low-grade depression. Loss of libido. Poor memory—especially for nouns and people’s names. “Remember to bring the... the... thingamajig!” Poor short-term memory “Why did I walk into this room?” Hot flashes, especially when stressed out. Night sweats that may be mild or drenching but always wake you up interfering with sleep. Joint pain, osteoarthritis. Bladder infections. Vaginal dryness or itching. Decreased vaginal lubrication during sexual intercourse. Heavy, light or irregular periods.

For some women, symptoms may start as early as the late 30s or early 40s. By age 51, the average age of the last period, most women have had many of these symptoms for some time. Without HRT, some women will continue to experience severe symptoms and accelerated aging for years. Some women never stop having hot flashes and night sweats. These come from the brain. Not the skin. It is a strong indicator that these women may benefit from estrogen therapy. For others, symptoms may diminish, but they too will still experience some accelerated aging.

What are the physical signs that a woman can see in the mirror?
Pale face and skin. Dry mouth and eyes. Dry, dehydrated skin. Small, thin vertical wrinkles above the upper lip and at the corner of the eyes. Smaller, droopy breasts. Loss of hair on the top of the head and loss of body hair. And increased facial hair due to persistently normal testosterone levels as estrogens drop.

What diseases are caused by loss of estrogen?
Infertility, premature aging of all organ systems, osteopenia and osteoporosis, cardiovascular disease and Alzheimer’s disease among others. This is not to say that menopause is the only cause, but it tends to accelerate the processes.

Is HRT safe?
What about the Women’s Health Initiative (WHI)? Didn’t the study in 2002 prove that HRT was dangerous for women? Yes, that is exactly what that study announced. (But the risks were actually fairly small while the head lines were huge.) Further studies on various subgroups will be addressed below.

But that study did not study bio-identical hormones. It studied two drugs, Premarin, which is made from pregnant mare’s urine, and Provera, medroxyprogesterone acetate (MPA). Both of these compounds function as drugs in a woman’s body. They are not bio-identical and natural hormones. They have some of the same effects as our natural hormones, but they also have side effects like any drug.

Secondly, these drugs were not delivered directly into the blood stream like the ovaries or adrenals deliver hormones. These drugs were swallowed and went through the stomach to the liver and caused other side effects because of this. It is best to copy Mother Nature. The pharmaceutical equivalents to bio-identical hormones are Climara®, Vivelle® or Minivelle® patches, and some gels and sprays containing E2. Oral Prometrium® is the brand name for oral progesterone. It is imperative to understand that these natural hormones were not studied by WHI.

Third, a small but real risk for any woman starting estradiol or Premarin or even birth control pills (BCP) is that it may unmask a pre-existing breast or uterine cancer. Estradiol feeds cancer; it does not cause it. The same goes for men starting testosterone. It may unmask an already existing prostate cancer. So women and men need to be monitored more closely for the first year or so of hormone therapy. Thermography of the breasts effectively does this. It picks up rapidly growing tumors. And mammography picks up slower growing tumors. Both can be useful along with breast exams. 

Many physicians were not surprised with the initial results of WHI. If a woman swallows estrogen, even if it is a bio-identical estrogen, it is going to increase her risk of clotting. Think of women who are on birth control pills, they have an increased risk of blood clots, heart attacks and strokes just like women who swallowed Premarin, Prempro or even E2. Most of these increased risks diminished after women stopped the drugs in the study.

Fourth, WHI studied horse estrogen with MPA. Since 1997, it has been known that MPA in laboratory tests reversed the cardiac benefits from taking estrogen. Supplemental estrogen alone improved menopausal women’s good cholesterol and maintained good glucose control in the PEPI trial. When Prometrium, i.e. natural progesterone, was added to these women’s regimen, it did not have any negative effect. On the other hand when Provera/MPA was added to these women’s regimens good cholesterol and blood sugar control plummeted. These, in combination, increase a woman’s risk of having a heart attack or stroke. In 2002 WHI demonstrated this outcome in female patients, not just in their lab work. The headlines should have read: Prempro is dangerous and oral estrogen is dangerous. Not all HRT is dangerous.

Physicians who have been prescribing bio-identical estrogens, natural progesterone and sometimes testosterone have been doing so for more than 40 years in this country and Europe. They have not seen the increased incidence of breast cancer or heart disease. They have seen woman who live fuller, better lives with stronger bones, reduced chances of getting Alzheimer’s disease, reduced risk of breast cancer, and reduced risk of heart attacks. This is called a large observational study by independent clinicians.

The PEPI trial only examined lab work in patients that reflected their risk of cardiovascular disease. WHI looked at clinical outcomes for patients. It looked at several illnesses. Breast cancer and cardiovascular disease were of primary concern. WHI did not study progesterone, but only Premarin with and without MPA.

Those who took MPA (Prempro) developed more disease. Women who were on Premarin alone (no MPA) and started it less than 10 years after menopause had a 23% lower risk of breast cancer compared to women who did not take any hormones, and a 63% better chance of surviving breast cancer if they got it (compared to placebo patients), and a 38% reduction in all-cause death even if they got breast cancer. More of them were alive and well 10 years later than those on placebo. And the placebo patients fared better than the Prempro patients who continued to have a higher risk of breast cancer and cardiovascular disease even after stopping the drug. My advice: Don’t take Prempro.

Who should not take estrogen?
Women who have untreated breast or uterine cancer. Avoid oral estrogens in liver disease and in women with a history of or increased risk of a clotting disorder or cardiovascular disease.

What options are available for treatment?
Some women do not need “treatment”. They do fine with lifestyle changes. Some use a variety of drugs to manage symptoms. These may include anti-inflammatories, antidepressants, sleeping pills, vaginal lubricants and anti-anxiety drugs. They may include medication for diabetes, hypertension, and hypercholesterolemia.

Other women will be able to take herbs including black cohosh, Pueraria mirifica (a type of kudzu from Thailand), red clover, flax seeds, maca and/or soy phytoestrogens. All of which have estrogenic effects. These women may say: “What’s the big deal? Everything is fine; I can take these herbs and I feel great.”

Then there are women who have severe night sweats or hot flashes, significant memory and mood issues, who cannot perform their jobs, and whose lives change radically as their estrogen levels drop. These are the women who need to consider hormone replacement therapy.

What levels of E2 are necessary for a woman to feel her best?
This is going to vary dramatically depending upon the woman’s height and shape. Women who are short and curvy, who grew “out” instead of up when they were in grade school and are under 5’4” have always been exposed to a lot of estrogen. So they will feel comfortable with higher estrogen levels when they need hormone replacement therapy.

Women who are 5’4” to 5’7” and have somewhat smaller breasts will feel comfortable with slightly lower estrogen levels because they were exposed to a lower amount of estrogen as they went through puberty and life.

Women who are very tall (think of a runway model who is flat-chested) typically have very low estrogen levels going through puberty and they feel comfortable with low levels of estrogen in menopause. So, the amount of estrogen that a woman is going to need throughout her life and in menopause, if she in fact needs HRT at all, is going to vary.

The “normal ranges” for E2 vary with the time of the month, but the best time to check the highest estrogen levels in a premenopausal woman is on the 21st day of her cycle, and the normal ranges are 30 - 200 pg/ml. This is a wide range and that is because there is not one best level for all women. Dosing must be individualized. Many women feel their best during the second week of their cycle—after the period is over and before ovulation, when estrogen levels rise. Typical levels on the 7th day are 40-100 pg/mL. These may be the preferred ranges for menopausal women.

Height and history matter and need to be taken into account. While there is not one magical level, we do know that a minimum of 21 pg/mL of E2 is needed to maintain bone health. Most physicians find that postmenopausal woman feel better with higher levels than this. Frequently, brain function requires higher levels. Most physicians treat for symptom relief regardless of the levels.

The treatment for low estrogen in women is human estradiol, E2. This is available in gels and patches. It is also available in pill form, Estrace. All of these will raise a woman’s estrogen level and relieve the symptoms mentioned above.

What does conventional medicine say?
When researchers went back and teased out different subpopulations of WHI, they found that the headlines that said HRT is bad for women did not apply to women who were younger. And in 2013, a global consensus statement was published on Menopausal Hormone Therapy (MHT) formerly called HRT. It was endorsed by seven different societies including The North American Menopause Society (NAMS).
  • They concluded that MHT is the most effective treatment for vasomotor symptoms (hot flashes and night sweats) associated with menopause at any age. Benefits are more likely to outweigh risks for symptomatic women before the age of 60 years or within 10 years after menopause. (After WHI, they had recommended SSRI’s and other drugs to control vasomotor symptoms.)
  • MHT is effective for the prevention of osteoporosis-related fractures.
  • Standard-dose estrogen-alone MHT may decrease coronary heart disease and all-cause mortality in women before the age of 60 years or within 10 years after menopause. (The complete opposite of what was reported in WHI.)
  • Local low-dose estrogen therapy is preferred for women whose symptoms are limited to vaginal dryness or discomfort with intercourse.
  • The option of MHT is an individual decision in terms of quality of life and health priorities as well as personal risk factors such as age, time since menopause and the risk of venous thromboembolism, stroke, ischemic heart disease and breast cancer. (The patient always has the final say. Risk analysis is critical.)
  • The risk of venous thromboembolism and ischemic stroke increases with oral MHT. (Not topical or vaginal HRT.) Observational studies point to a lower risk with transdermal therapy. 
  • The risk of breast cancer in women over 50 years associated with MHT is a complex issue. The increased risk of breast cancer is primarily associated with the addition of a progestogen to estrogen therapy and related to the duration of use. The risk of breast cancer attributable to MHT is small and the risk decreases after treatment is stopped. (Increased risk with estrogen AND progestogens/MPA/drugs. This has not been demonstrated with natural progesterone.)
  • The dose and duration of MHT should be individualized.
  • In women with premature ovarian insufficiency, systemic MHT is recommended at least until the average age of the natural menopause.
  • The use of custom-compounded bio-identical hormone therapy is not recommended.
  • Estrogen as a single systemic agent is appropriate in women after hysterectomy but additional progestogen is required in the presence of a uterus.
Most integrative doctors would agree with all but the last two recommendations.  

What is the best available treatment?
It will vary with the specific patient, as it should. This is individualized treatment.  Integrative physicians who prescribe bio-identical hormones usually use custom-compounded bio-identical hormone therapy individualized to the patient. Conventional physicians and societies disagree and are more comfortable with pharmaceuticals. Integrative doctors use a combination topical or vaginal cream utilizing 80% estriol and 20% E2, (Biest 80/20). This is combined with progesterone in most women and sometimes testosterone is added if indicated.

Estriol is a very weak estrogen, approximately 70 times weaker than E2. It functions like a selective estrogen receptor modulator (SERM) like Evista or flax seeds. This combination is very similar to the natural level of hormones that women have in their own bodies for most of their lives.

Many physicians who prescribe Biest find that their patients have a lower incidence of cardiovascular disease, osteoporosis, Alzheimer’s and breast cancer or uterine cancer especially when combined appropriately with natural progesterone.

If a woman’s only complaint is facial wrinkles, vaginal dryness or pain with sex, estriol by itself works well when applied locally.

What is the best way to take bio-identical estrogen?
The best way is going to be topically, since swallowing estrogen in any form is going to turn on one’s liver and increase the production of clotting factors. If women opt for oral estrogens, the risk is still going to be much lower than it is for someone taking birth control pills since they contain “chemicalized” estrogens that are 200 fold stronger than bio-identical estrogens.

But if one wants the lowest risk of cardiovascular complications, she should take the estrogen topically. It can be applied to the neck, inner arms, inner thighs, the genitalia or may be used vaginally. It should not be applied anywhere around the breasts. To achieve uniform levels, topical estrogen is best used twice a day.

Occasionally, women can use it once a day. It is possible to get Biest or E2 in the form of sublingual drops and troches; however, there is still potential for this being swallowed, so from a purist perspective, applying the estrogen topically is the best. Sometimes, women find that topical estrogen loses its effectiveness over time and Dr. Jonathan Wright, the father of bio-identical hormones in this country, found that these women need to use it vaginally, as the vagina never gets tolerant to application of estrogen. It will continue to allow the women to absorb the estrogen without interference for a lifetime.

Pharmaceutical bio-identical estrogen products, like estradiol patches, are convenient. The primary drawback to these from an integrative perspective is that the woman is not getting the benefit of estriol. Also some women need ½ or ¼ a patch and this is awkward.

Women should recheck estrogen levels after being on estrogen replacement therapy after two months. This does not mean you have to wait two months to feel better.

If a woman is severely low on estrogen and needs estrogen, she will notice a difference in how she feels mentally within a couple of hours of putting on the estrogen. This does not mean all of her hot flashes will be gone. It may take several weeks for the hot flashes to go away and sometimes, hot flashes can actually even get worse transiently.

Women can also experience some breast tenderness transiently as their clearly deficient levels of estrogen are slowly increased as they stay on the topical estrogen. This is a bit of a nuisance, but it is not dangerous and it should not last more than two to three months.

I've had a hysterectomy; do I need progesterone?
Conventional doctors agree. Many women are told by their OB/GYNs or their primary care doctors that if they have had a hysterectomy, they do not need to worry about taking a progestin or progesterone. Integrative physicians disagree.

It is true that they do not need progesterone or a progestin to protect them from uterine cancer if they don’t have a uterus. However, almost every single one of a woman’s trillion-plus cells in her body has progesterone receptors. All of these cells depend on a dance that occurs between estrogen and progesterone, so most integrative physicians recommend that women with or without a hysterectomy take natural progesterone. This is combined with an estrogen cream or can be taken separately as a pill once or twice a day.

What tests are available to determine whether a woman is menopausal and to monitor therapy?
It is important to check E2 and FSH levels prior to initiating estrogen therapy. Menopause is defined by a low level of E2 (under 20-40 pg/mL) along with an elevated FSH (over 28-35).

24-hour urine testing of sex hormones and cortisol has been available for some time, but this is awkward. Streamlined testing is available through Precision Analytical Labs. Only four urines are sampled throughout the day. These are collected on filter paper which is allowed to dry completely and mailed to the company. These test not only levels of E2, E1, and estriol (E3), but also the breakdown products. This can tell a woman if she is actively increasing her risk of breast cancer. There are certain breakdown products, specifically 4-hydroxyestrone that is highly carcinogenic. If a woman produces this in excess or does not fully metabolize other estrogen breakdown products, then this will increase her risk of breast cancer.

The good news is that once one recognizes that this is occurring, one can take action to stop it. Supplements including di-indole methane (DIM), sulforaphane, resveratrol, and other methylating cofactors reduce this risk substantially. Whether a woman has a family history or does not, this is a very useful test to guide therapy. It is not a good test for menopausal women to get unless they are on HRT, since the estrogen levels are too low to show break down products. But once started on therapy, they can be very reassuring or give one a course of action. Some physicians and pharmacists recommend getting salivary tests and these are very convenient; however, they are very difficult to interpret once a woman is on hormones. Either blood work or urine samples do a better job of this.

What are the symptoms if one overdoses on estrogen?
Breast enlargement and tenderness, fluid retention and irritability are the hallmarks of estrogen excess. Dr. Uzzi Reiss, an OB/GYN in Los Angeles who wrote the book “Natural Hormone Balance for Women”, describes his estrogen “quick check”:
  • Feel your breasts. If they are tender, painful and full, you are on too much estrogen. If, on the other hand, your breasts are losing their fullness or seem to be dropping, you may need more estrogen.
  • Check your rings. If your rings do not slip off and on easily, you may have too much fluid retention due to estrogen. 
  • How well are you sleeping? If you wake up drenched in the morning, you have too little estrogen on board and you need more. If you have difficulty falling asleep or experience restless nights, you might not have enough estrogen. Even if you have a few hot flashes overnight, you need more estrogen.
  • Lastly, check your mind and mood. For many women mental clarity and mood are extremely accurate measurements of estrogen replacement. Not enough estrogen means that your mind is a little foggy in the morning, you may feel a little bit down or confused, and not in good control of your mood. If you have too much estrogen, you might feel uptight, irritated and bossy, but your mind will be clear and your energy level will be good.
Can I ever stop it?
Whenever you want to. If the benefits you experience do not justify taking the treatment, then work with you doctor and taper off of the hormones. When you discontinue the hormones gradually, over several weeks to months, the body has a chance to adjust. Bodies, especially brains, do not like to stop anything abruptly.

Final Thoughts
Menopause is a natural event for every woman who survives to experience it. Some women breeze through it into their golden years. Other women suffer needlessly or take numerous medications to control the symptoms and the consequences of accelerated aging.

There is a reason to be respectful of the power of hormones; there is no reason to be afraid of them. Most women fear breast cancer caused by HRT. Physicians who have prescribed bio-identical hormones for decades see less breast cancer and the tumors are easier to treat. WHI also showed a decrease in breast cancer for women on estrogen and again better survival if a woman developed breast cancer.

And get clear on this ... thriving in menopause is not just about the hormones. Its lifestyle, stress management, sleeping soundly, having good social support, etc. Working with a health care provider who is knowledgeable, open-minded and can individualize treatments with the patient is optimal.

On Thursday, December 18, 2014, join me for a free talk to learn more about the safe and appropriate use of natural estrogen. Email for details and to reserve a seat.

1 comment:

Anonymous said...

I have no ovaries, but cannot tolerate drug company estrogen. It is too potent and throws me into insulin resistance and horrible water retention. I have to use something because of drenching sweats every 20 minutes and 1 hour of sleep per night. Compounded estrogen is the only thing my body can tolerate. I also need testosterone because of oophorectomy.