Tuesday, September 18, 2012

One-Size-Fits-All Is for Beach Cover-ups, Not Hormone Replacement Therapy

As a society, we have a tendency to think of menopause as a uniform experience. We generally suppose that all menopausal women have hot flashes, mood swings and require the same kind of treatment. But that's not accurate. Just as different women have different types of menstrual cycles in their younger years, different women experience different menopausal symptoms. Some may reach menopause early—or late. Some may have minimal symptoms while others experience severe changes. So just as every woman is unique, so her treatment should be.

This acknowledgement that one-size-does-not-fit-all is not a new concept to women and their physicians. Fortunately, the experts are now coming around to this reality, too—especially as it pertains to hormone replacement therapy (HRT). The North American Menopause Society (NAMS), the preeminent voice on menopause treatments, recently came out with a position statement recommending that HRT be prescribed on an individualized basis. "Current evidence supports the use of HRT ... when the balance of potential benefits and risks is favorable for the individual woman," the statement said.

This is a 180 degree turn from their recommendations after the results of the Women’s Health Initiative were announced in 2002.

HRT's Turbulent History
The Women's Health Initiative (WHI) was the  largest, most frequently referenced women's health study conducted in the 1990s and early 2000s. It was abruptly discontinued in 2002 when higher rates of breast cancer, heart disease, stroke and deep vein thrombosis and pulmonary emboli were found in women who were using Prempro, a conjugated equine estrogen and progestogen combination drug (EPT).

The second arm of WHI using Premarin alone continued. The results of this study were overshadowed by the Prempro study. And it too showed a slight increase in coronary heart disease, strokes and clotting problems. But it did not show a significant increase in invasive breast cancer.

Initially, the more the WHI study was reviewed, the less physicians prescribed any kind of HRT. In fact, both women and physicians began believing that all forms of HRT were dangerous—even bio-identical hormones. As a result, many conventional physicians stopped prescribing Prempro and other HRT. This left many women with serious symptoms that compromised the quality of their lives. Physicians tried antidepressants, anti-hypertensives and sedatives to control hot flashes, night sweats, insomnia and other symptoms.

There were several problems with the initial interpretation of the data from WHI:
  • The media’s pronouncement that all HRT was dangerous wasn’t accurate for all women across all ages using different kinds of HRT. WHI included women aged 50-79.  All participants were treated the same and lumped together following  a cookie cutter model...one size fits all. But, some of the participants were just entering menopause. Most were older and had never been on HRT or had been off it for a long time. This skewed the results. The majority of women were older aged 70-79; so the study results mirrored their experience. Increased risk of breast cancer, increased risk of heart attacks, increased risk of strokes and deep vein thrombosis. What physician would prescribe a drug for menopausal symptoms that had this profile of side effects? None that I know; so the safety review board appropriately halted the study before its completion. Unfortunately the entire world read headlines stating “HRT is bad for women.”
  • The headlines should have said “Prempro is bad for women.
  • The route of administration of these drugs was oral. Any time an estrogenic drug is swallowed there is an increased risk of deep vein thrombosis and pulmonary emboli. Think of the complications of birth control pills.  Heart attacks, blood clots and phlebitis. This is also true for conjugated equine (horse) estrogens like Premarin or natural estradiol like Estrace. Mother Nature never delivered estrogen through the stomach then processed it through the liver. Mother Nature released women’s natural estrogens directly from the ovary or fat into the bloodstream. So some of the complications at all ages simply had to do with the medications being administered orally. Topical low dose estrogens used in menopause, applied to the skin or vagina, have not been found to increase the tendency to clot. On the other hand, contraceptive rings and patches that are used for birth control with 50 times the estrogenic effect of HRT can still increase a younger woman's chances of phlebitis and pulmonary emboli.
  • Older women who have not been on hormones have much older cardiovascular systems. When a woman has her last period at age 51, on average, she has caught up to a man's risk of heart disease by age 65. Generally younger women are protected from strokes and heart attacks by their higher levels of estrogen. Once the estrogen levels drop, arteries lose their elasticity, cholesterol plaques progress more quickly, and cells including heart cells lose some of their vitality. If one then adds an oral estrogenic drug that enhances clotting to this significantly older cardiovascular system, there is predictably a greater risk of heart attacks, strokes and deep vein thrombosis. One out of two women currently dies of heart disease.
  • These were drugs. Drugs are not bio-identical. The estrogens were equine conjugated estrogens, Premarin.  It was not estradiol, estrone, and estriol--our natural hormones. The progestin or progestogen or progestational drug employed was medroxyprogesterone acetate (MPA). The brand name drugs containing this are PremPRO and PROvera. This is not natural progesterone.  It does not do what natural progesterone does. It is designed to protect the uterus from uterine cancer when a woman is on HRT. It's great for the uterus, but it's not healthy for the rest of a woman's body. In WHI and earlier studies MPA reversed the beneficial effects of estrogen on the cardiovascular system and cholesterol. Natural progesterone does not interfere with the benefits of natural estrogens on the cardiovascular system. Natural progesterone also protects the uterus and reduces a woman's risk of both breast cancer and uterine cancer.
In February 2004, the Premarin arm of WHI was terminated due to an excessive number of strokes overall. (Remember the tendency for oral estrogens to increase clotting in all women.) Even so studies began to be published which separated the absolute risk of various complications and benefits by age group. That's when things got very interesting.
  • In the Prempro group, EPT, there were still increased numbers of women with coronary heart disease, breast cancer, stroke and thrombotic disease across all age groups compared to placeboRanging from 5 additional heart attacks in women aged 50-59/10,000 women/year to older women aged 70 - 79 with 23 additional heart attacks/10,000 women/year. Breast cancer was similar: 5 additional cases of invasive breast cancer/10,000 younger women/year compared to placebo; 13 additional in the older cohort.  While none of these numbers are that large given the fact that this is per 10,000 women per year, there was still a very clear trend.
  • On the other hand, in the Premarin only group, ET, there was an unexpected reduction in heart attacks and breast cancer relative to placebo when women started Premarin shortly after going through menopause, i.e., in their 50s. Ten fewer cases of heart disease and breast cancer/10,000 women/year. Women who started Premarin in their 70s still had an increased risk of heart disease and breast cancer but it was a much smaller increase than the Prempro group. This was the first major finding which showed that not all postmenopausal women are the same. “Cookie cutter medicine dies...one size does not fit all.”
  • Another WHI follow-up study published in April 2007 showed that women who started Premarin, ET, within 10 years of menopause had no increased risk of heart attack, breast cancer or stroke. This resulted in a 30% decline in all cause mortality. That means there were fewer deaths in the group that took Premarin alone. 

This past spring follow-up studies covering an almost 12-year span of women who participated in WHI demonstrated even more interesting results. These studies reflected what happened to women after they stopped Prempro and Premarin.

Since Premarin is an oral estrogen, there was a slight increase in strokes and deep vein thrombosis while taking Premarin, which decreased after stopping the Premarin.

The lower risk of breast cancer was restricted to women without a history of benign breast disease or a strong family history of breast cancer. The researchers noted: “The continued post intervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence.” That’s tamoxifen they are referencing.

Summarizing all the above
Women who are experiencing hot flashes, night sweats cognitive dysfunction, fatigue and other  quality of life symptoms will get their lives back and live longer with less cardiovascular disease and breast cancer, not to mention osteoporosis and Alzheimer’s Disease if they start estrogen replacement therapy within 10 years of their last period or in their 50s. Topical or vaginal estrogen virtually eliminates the risk of excess clotting found with oral Premarin or any oral estrogen. Conventional doctors use any one of many topical estradiol products now available; Vivelle Dot is the most commonly prescribed. It is bio-identical.

Conventional doctors prescribe a progestin for women to protect the uterus from uterine cancer. Most see no reason for a woman to take progesterone or a progestin if the woman has had a hysterectomy.

The problem with this is that no one knows the optimum way to prescribe a progestin since MPA, PROvera in PremPRO, caused all the problems discussed above. What about Provera every three months? What about norethindrone, another progestin? Nobody knows.

Some conventional doctors are using natural progesterone, brand name Prometrium. But it is still not accepted as quite as good at protecting the uterus as the progestins.

How can we make this better? Safer?
There are physicians, like Dr. Jonathan Wright, who first studied the use of bio-identical hormones therapy (BHRT) in 1982. They have used combinations of topical estriol (an anti-cancer estrogen), estradiol and sometimes estrone combined with cyclical natural progesterone for 30 years and they haven’t seen the rate of breast cancer and heart disease that conventional medicine sees.

It’s topical--no increased clotting complications. It’s low dose--usually no periods. It’s bio-identical estrogens--has to be better than horse estrogens at reducing heart disease and breast cancer. And the estriol is a SERM. A selective estrogen receptor modulator. Flax seeds, the drug Evista, and soy are other SERMS that reduce the risk of breast cancer.

It’s natural progesterone which a woman’s body has produced month after month after month since she went through puberty. It’s not just good for uteruses; it’s great for breast and most other body tissues. Every month it helps a woman not have PMS and have a normal, pain free, cramp free period. It protects the breasts from over stimulation by estradiol. And it doesn’t negate the positive effects of estradiol like MPA. It also does a search and destroy mission every month routing out wayward cells or early cancer cells. It also keeps breast cancer from metastasizing. Progesterone is a good hormone. Better than any progestin. Thank you to the late Dr. John Lee who brought the public’s attention to progesterone.

Physicians using BHRT report a 50% lower rate of breast cancer in women who cycle progesterone instead of taking it daily. On the other hand, the U.S. Food and Drug Administration (FDA) and The Endocrine Society want further studies on BHRT. NAMS in its 2012 position statement “confirm(ed) its support of the US Food and Drug Administration (FDA) and other scientific organizations that have warned women about the potential harm from these bio-identical hormones,” meaning custom compounded hormones. Vivelle Dot and Prometrium are OK.

Randomized, controlled trials would be great. But all of these bio-identical hormones are natural. They can’t be patented so there isn’t a potential high profit motivating individuals or companies to do these studies. And we already have 30 years of observational studies from pioneering physicians who have treated patients for many years. BHRT should be the standard of care for HRT for men and women until someone proves that it damages patients. (Oh... men already use bio-identical testosterone. Men have always used bio-identical testosterone for replacement therapy. Not horse testosterone.)

A Tailored Approach
Lastly, are these lower rates of cancer and heart disease documented by BHRT prescribing physicians just due to BHRT vs HRT, including ET and EPT? No. Physicians who prescribe bio-identical hormone replacement therapy usually take a very holistic approach to patient evaluation and care.  They address diet, weight optimization, exercise, blood sugar control, stress management, other hormones, nutritional status, and the ability to detoxify and eliminate the many pollutants in our bodies and reduce our exposure to those in the world. 

Each woman is different. Some will sail through menopause without any symptoms. Others may find that they can take herbs, flax seeds or soy to control minor symptoms. Then, there are women whose lives fall apart due to incapacitating hot flashes, disturbed sleep, memory problems and inability to think clearly. These are the women who will benefit from BHRT.

However, before beginning any kind of BHRT, you and your doctor should consider the following:
  • Your current conditions and personal health history—particularly related to cardiovascular disease and breast cancer.
  • Family health history related to cardiovascular disease and breast cancer.
  • Your exposure to toxins.
  •  How long it has been since you started menopause.
  • The severity of your menopausal symptoms.
  • What type of HRT you may already be on, and for how long.
  • Your response to any HRT you may be on.
In addition, you will want to have several tests, including:
  • CRP
  •  Hormone levels
  • Adrenal function
  • Thyroid function
  • Vitamin D level
  • Iodine level
  •  Thermography to assess breast health
While NAMS does not endorse getting or monitoring levels of sex hormones, a former president of NAMS, Dr. Lila Nachtigall, said in a recent talk that women must have an estradiol level of 21 pcg/ml to maintain bone health. Higher to build bone. BHRT prescribing physicians, routinely monitor sex hormone levels.

If you'd like to explore bio-identical hormones or get advice on a personalized BHRT treatment plan, contact Vaughan Integrative Medicine at (336) 808-3627, extension 13, to make an appointment with Dr. Vaughan.

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