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My Thoughts on HRT

Letting you in on a secret, here’s one of my pet peeves: men or pre-menopausal women writing about hormones. Typically they omit the subject of post-menopausal hormones, OR if they do cover them, their conclusion is to use as little as possible for as short a time as possible. 

Just sayin’

I completely disagree!  I love the potential benefits of using hormone replacement therapy! As a post-menopausal woman, aiming for vibrant health as long as possible, as a physician and research geek, and the daughter and grand-daughter of women with breast cancer, I take hormone replacement therapy, and – unless information changes – will continue to do so as long as I’m able! I've looked into the subject very thoroughly, so if you're curious,here's a meandering through the science of hormones, with my personal take on the whole subject.

The most important point about HRT is to note that there are two completely different major categories: conventional and bio-identical HRT. Conventional (pharmaceutically unique, allowing patenting and profit) HRT has been the most studied, and I’ll wager you’ve heard more about the negative consequences (increased breast cancer but actually only the drug medroxyprogesterone, or Provera®, seemed causative) than the positive (many beneficial effects in many systems). I’ll also wager you’ve heard the re-assurance, “Oh, those hot flashes aren’t much, they’ll go away in a year or so.”

The most typical conventional prescriptions are an estrogen-type Rx (Premarin®) and the Provera® mentioned above – similar to progesterone in only one mechanism, but generally completely unlike any hormone naturally found in a real body, human or animal. Premarin®has some applications, Provera®has only one. (For a woman with excessive estrogen generated heavy bleeding, where natural progesterone is ineffective, various progestINS, including Provera, have a stronger anti-hemorrhage effect.) These were the formulations used in the Women’s Health Initiative (WHI) which was curtailed early because of an increased rate of cardiovascular disease and breast cancer in the study groups. Big newspaper headlines at the time have burned a permanent image in the brains of many people who continue to think that “HRT Dangerous to Women,” the word at the time.

Most physicians who currently endorse the use of menopausal HRT with enthusiasm use bio-identical, rather than conventional HRT. Bio-identical HRT uses compounds formulated to exactly match humanly produced hormones, must be individually dosed, and usually compounded, though a few pharmaceutical formulations qualify perfectly within the safety parameters as bio-identicals. The benefit and safety profile of bio-identical HRT is almost a complete opposite to that of conventional HRT.

Menopausal HRT and Women's Health

There are six major areas where properly prescribed HRT significantly impacts the health of a post-menopausal woman. Most physicians would agree about the first three, but are frankly not up-to-date on the last three, so often hesitate to recommend HRT.

1. Vasomotor Symptoms

HRT relieves the vasomotor symptom s(VMS) of menopause, namely hot flashes or flushes, and night sweats. Recent research clarified that the duration of troublesome temperature fluctuations can last close to 15 years, with 7 years being the average. Some women suffer quite dramatically, while many have moderate to severe symptoms. Difficult to quantify in terms of human suffering or cost, there is no doubt that the impaired sleep associated with nocturnal symptoms is hazardous to the health of the women with interrupted sleep.

Both conventional and bio-identical HRT relieve troublesome VMS.

2. Bone Density

HRT also resumes the beneficial effect of estrogen on bone health, lost to some degree at menopause, and resulting in rapid bone resorption and loss of bone density. I have used bio-identical HRT in women with significant osteoporosis and seen a reversal (improvement) in their annual bone density screens. Other hormones that work well with estrogen in a bone-building partnership include DHEA and Testosterone.

Estrogen is the key hormone here, and either bio-identical or conventional will help build stronger bones. Obviously, it works more easily to preserve bone rather than rebuild lost bone; starting estrogen earlier in menopause is likely more helpful than starting it later.

The conventional drug Provera® is suspected to cause a loss in bone density, as do many other medications including diuretics (for high blood pressure), corticosteroids, and those ubiquitous heartburn drugs that are so widely recommended for whatever kind of indigestion.

3. Urogenital Resilience

The final area of agreement is likely to be urogenital symptom relief. In menopause, the lining of the uterus and the distal portion of the urinary urethra undergo atrophy, transforming tissues that were once thick and soft into stretched, thin, and often painful tissues. Thinning of the vaginal tissues results in pain with intercourse, and for some women, pain just in ordinary movement or sitting. When the walls of the distal urethra thin, it’s harder to control the flow of urine: imagine the difference in squeezing shut a tube of thick velvet compared to a tube of paper. Loss of urethral control results in incontinence and increased urinary tract infections.

Women make three forms of estrogen: Estradiol is produced in the ovaries, is the most biologically active, runs high during reproductive years, and is most effective in systemic HRT at relieving symptoms. Estriol is made in the placenta, so is highest during pregnancy. Estrio in menopause is particularly effective on urogenital tissues, and has some systemic effects, though requires higher doses than estradiol to relieve menopausal symptoms. Estrone is the estrogen made in our fat cells (especially belly fat which also is excellent at converting testosterone to estrogen) and adrenal glands as well as ovaries, persists in menopause, and is the least welcome estrogen, associated with an increase in cancer, hypertension, and muscle pains. It can undergo conversion to estradiol in favorable circumstances.

Vaginal estrogens in the form of estriol can be used instead of or in addition to systemic HRT to thicken the walls of the vagina and urethra, although all other systemic effects will be lacking. (This is of course a plus for women avoiding HRT because they have had a hormone-sensitive breast cancer. Many oncologists are comfortable with the specific use of the estriol form of estrogen used just vaginally.) An estrogen-primed vagina, by the way, is a much happier vagina.

4. Cognition and Mood

Getting into the less acknowledged areasd, bio-identical (but not conventional) HRT can have a tremendous benefit on a variety of mental functions including reasoning abilities, memory, and moods as well. The clearest benefit has been seen using estrogen, and bio-identical estrogen has out-performed conventional estrogen in all areas: cognitive function, mood (estrogen as an anti-depressant), and prevention or reversal of dementia.

In a Stanford University study releasted in 2014, it was found that estradiol, but not Premarin®, preserves key brain function in postmenopausal women at risk for dementia. 

Although earlier adoption of estrogen is likely more beneficial in the prevention of dementia, estrogen has proved helpful prescribed later in life as part of the anti-dementia protocol so successfully used by Dr. Bredesen at UCLA, the program in which 9 out of 10 patients had significant return of lost cognitive function through his complex program.  

Progesterone also may play a beneficial role, as at least one study identified better preservation of cognitive function in women who retained significant levels of progesterone after menopause. In terms of prescription progesterone, bio-identical progesterone has a beneficial effect on sleep and mood for many women, although in higher doses (sometimes required), it can have a mildly sedating or outright fatiguing effect in oral doses. Switching to sublingual or vaginal dosing eliminates both possible results. The conventional drug, Provera®, typically has either neutral or negative effects on mood particularly, with mood swings, anxiety or depression joining weight gain and myalgia to comprise the down-side of synthetic progestins, the patent-able version of Progesterone. 

Hormonal treatment of menopause became popular decades ago and at that time, just estrogen was replaced until a significant number of women treated developed endometrial cancer. Since then, we have realized that some form of progesterone must be given to counteract the overgrowth of the endometrium in response to pure estrogen. Bio-identical progesterone works well, but until recently, did not come in any form that could be patented. ProgesTINS are NOT progestERONE, but rather synthetic analogues, different in every respect except that they DO prevent overgrowth of the endometrium. Their singular benefit to the patient is that they more powerfully reverse estrogen’s effect on the endometrium; in every other way they have greater adverse effects. They do however, reap a nice pharmaceutical profit for somebody.

5. Cardiovascular Risk

Among the many risk factors for cardiovascular (CV) disease, advanced age is primary, and for women risk increases particularly after menopause when we start to “catch up” with the rate of heart disease in men. Yet it has also been observed that estrogen can raise the risk for certain cardiovascular events such as blood clots, with resultant stroke or heart attack. What gives?

Many early observational studies (prompting the WHI) noted a 40-50% reduction in CV disease in users of estrogen particularly, but also in women using both estrogen and a progestin. In the studies to date showing an increased risk, it has largely been using oral forms of estrogen (bio-identical OR conventional) and in women with some pre-existing risk. On the other hand, increased risk of blood clots in women taking oral contraceptives has long been well-established. The WHI sought to answer that question and saw the well-known negative results: marked increase in heart attacks and strokes among women using Premarin®and Provera®.   However, a few years later, the results for the women just taking Premarin® showed a reduction in heart attacks, an increase in stroke risk – but much less than the Premarin®and Provera® increase. For some reason, little attention has been paid to a study from 1995  in which bio-identical progesterone boosted HDL (the protective form of cholesterol and the primary risk factor for CV disease) while medroxyprogesterone acetate (Provera®) lowered it. Other influences on CV disease were similar between the groups.

What really emerges from a host of studies is that ORAL estrogen is risky, that applied to the skin less so, and perhaps even protective. Transdermal estrogen yields the same lipid benefits as oral, but does not raise the levels of inflammation nor the blood-clotting tendency. 

There is agreement in research that transdermal estrogen therapy initiated when women are early in menopause has significant benefits to cardiovascular disease risk. It also appears that it is indeed possibly risky when started later in life in women who already have CV problems. The question remains open for older women (60+) who do not have CV problems. For older women, the question of increased blood clotting potential must be considered in light of all other contributors to the tendency to form blood clots.

6. Breast Cancer

Saving the best for last, what is the interaction between menopausal HRT and a woman’s risk of breast cancer? In the famed WHI study, treatment with Premarin®and Provera® resulted in an increased risk of breast cancer: 8 more per 10,000 women per year. Premarin® alone also resulted in an increase, but it was not statistically significant, meaning that the estrogen alone is not clearly risky or safe. In other studies, the trend remains: estrogen alone, transdermal or oral, does not increase risk, but paired with a conventional progestin, it does. Transdermal estrogen might be safer than oral.

As with CV disease, it is important to look at the setting for the woman considering HRT and how that affects her risk of breast cancer. Women wanting to reduce their risk of breast cancer will consider alcohol use, level of activity, vitamin D status, and many more. Furthermore, we know that the way in which estrogens are metabolized vary widely among women  depending on their level of health and their genetic strengths and weaknesses.

Back to my story: it turns out that one of the increased risk factors is the combination of two genetic weaknesses – referred to as snp’s - one in the methylation group (COMT) and one in the detoxification group (CYP1B1), and I actually have both of these weaknesses. (Full disclosure: an article about emerging recognition and treatment of genetic abnormalities is long overdue!) So my particular challenge, wanting all the other benefits of bio-identical HRT, is to address my genetic weakness. I manage this by keeping a normal weight, taking methyl-donating forms of several vitamins to lower my serum homocysteine level, limiting alcohol intake, including anti-oxidants in my food and supplement choices (I like curcumin), and consciously supplementing with detox-supporting supplements (SAMe, magnesium glycinate, and more). I keep my estrogen and progesterone levels moderate rather than high, and get regular thermograms for surveillance. Happily, I do also have a protective reserve of healthy detoxification genes other groups (CYP1A1 and GSTT1) and am able to live a fairly toxin-free, organic lifestyle.

I encourage you to step away from the commonly held MIS-conception that all menopausal HRT is dangerous and raises women’s risk of breast cancer and heart attacks. Remember instead that properly prescribed bio-identical HRT improves women’s quality and length of life, through its actions on our brains, bones, and sensitive tissues. Regarding heart disease and breast cancer, it’s important to use carefully prescribed and monitored HRT, and at all costs to avoid HRT containing synthetic progestins. Balancing your disease risks and optimizing health benefits is complex, it's not just a simple Rx to take to the pharmacy, but it can improve both the quality and length of your life. 



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