Menopause Mondays: Understanding Hormone Replacement Therapy - Ellen Dolgen
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Menopause Mondays: Understanding Hormone Replacement Therapy

There is tons of contradictory information about hormone replacement therapy (HRT) circling the web. Women have been told it causes breast cancer when perhaps it doesn’t, forcing them to suffer through perimenopause and menopause symptoms like hot flashes, memory loss, insomnia and vaginal dryness without any hope for relief. In fact, MedPage published on January 16th that the Million Women Study that was previously used to conclude that HRT causes breast cancer was severely flawed due to information bias, detection bias, and biological plausibility. Shmirshky got down to brass tacks and asked an expert from PhysioAge Medical Group in New York City, Dr. Josh Trutt. PhysioAge specializes in bio-identical hormone replacement therapy, and you will be shocked by Dr. Trutt’s answers to our hard-hitting questions! This is part one of a two-part blog from Dr. Trutt. Check back next week for answers on HRT’s effects on cancer!

Q: First thing’s first: What do doctors mean when they say “natural” or “bio-identical” hormones (Harvard) and how do those differ from synthetic ones? Aren’t they all made in a lab?

A:  It’s true that even bio-identical hormones can be made in a lab; what matters, however, is that bio-identical hormones have exactly the same chemical structure as the hormones your body produces. The crucial distinction is not where they were made, but whether the hormones you use are identical to what your body matured with, versus an altered, patented medication. Bio-identical hormones are often referred to as “natural”, even though they may be made in a lab, because they are identical to what your body naturally produces.

Q: So the difference is that bio-identical hormones have the same makeup as your body’s natural hormones. But why should women care if hormones are “bio-identical”? We take synthetic medications all the time!

A: Certainly many synthetic medications can be beneficial. Hormones are in an unusual category, however, in that a great deal of misinformation has been disseminated about them. ProveraTM, a patented, altered imitation of progesterone, has been shown (like many other synthetic progesterone imitators, collectively called “progestins”) to increase a woman’s risk of breast cancer. Progesterone itself, however, has been shown NOT to increase the risk of breast cancer, and in some studies has actually protected against it! Similarly, Premarin (a collection of estrogens made from horse’s urine) increases the risk of blood clots, while transdermal bio-identical estrogen does not. Thus, the distinction that it is “bio-identical” is not merely intended to appeal to the Woodstock generation of naturalists; it identifies a category of therapy that is safer than the patented alternatives.

Q: I see. You’re saying that while some HRT can be harmful, there are different types and some are more safely recommended than others. But why should women use hormone replacement therapy when they enter perimenopause and menopause?

A: Books like Shmirshky have done women a great service in providing an outlet to voice their concerns and frustrations with the physical and emotional changes of menopause. Most women first look into HRT to address their symptoms of menopause—either proactively or reactively. Many of these women tell us, “You gave me my life back!” Improving your quality of life during the one or two years around menopause is certainly a valid reason to start HRT. From our standpoint, however, there is an even more compelling reason: improving your health for decades AFTER menopause! Estrogen has been well-documented in dozens of studies to drastically reduce your risk of heart disease, osteoporosis and Alzheimer’s disease—and HRT has been proven to decrease mortality in the women who use it.

Alzheimer’s Disease

Hormone replacement therapy is our single most powerful weapon against Alzheimer’s disease: women who start estrogen replacement within five years of menopause have HALF the risk of Alzheimer’s compared to women who don’t! This is not new information; it has been well-established for over a decade:

Journal of the American Medical Association (JAMA), 2002

These findings extend those of two previous prospective studies and provide new evidence to suggest a protective effect of hormone replacement therapy. As in the previous studies, the adjusted risk of Alzheimer’s Disease among long-term Hormone Replacement Therapy users was reduced to little more than half that of nonusers.

Zandi PP, et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County study. JAMA. 2002;288:2123-2129.

Lancet, 1996

We studied 1124 elderly women who were taking part in a longitudinal study of aging and health in a New York City community. Onset of Alzheimer’s disease was significantly later in women who had taken estrogen than in those who did not, and the relative risk of the disease was significantly reduced (Relative Risk= 0.40 [95% CI 0.22-0.85], p < 0.01), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used estrogen for longer than 1 year had a greater reduction in risk; none of the women who were taking estrogen at study enrollment has developed Alzheimer’s disease.

Tang MX et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet. 1996;348:429-432.

Many other studies came to the same conclusion, and I go over these with my patients when they come in for a consultation.

Q: Interesting! I’ve heard that HRT has side effects, though, and one of the most publicized is dementia. Is this true?

A: Despite all of these positive studies, somehow the Women’s Health Initiative found in their 2003 report that HRT increased the risk of dementia in women 65 and older– as early as 12 months after starting therapy!–yet did not increase the risk of mild cognitive impairment. In other words, they seemed to be saying that women on HRT blew right past mild cognitive impairment and quickly became fully demented within a year of starting HRT!

(Shumaker SA et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women’s Health Initiative memory study: a randomized controlled trial. JAMA. 2003;289:2651–2662.)

How do we explain this? The answer is that these were older women, who were placed on two drugs (Premarin and Provera) that are known to increase the risk of clots and strokes. These women did not suddenly develop Alzheimer’s– they developed mini-strokes, and likely had the onset of multiple stroke dementia. This is completely consistent with what we know about the WHI trial: within the first year of therapy, women over age 60 in the WHI trial who had not been on HRT previously did have an increased risk of strokes when started on Premarin and Provera– and women of any age who take Premarin have an increased risk of clotting. This is why we instead use transdermal estrogen and bio-identical progesterone, both of which do NOT increase clotting or strokes. In short, HRT is an astoundingly powerful preventative measure against Alzheimer’s– a devastating disease for which there is no effective treatment!

Q: The results are quite the contrary from what has been publicized for so long! Does HRT have any other benefits?

A: Even if there were no other benefits to estrogen use, I would encourage it for Alzheimer’s prevention alone. But in fact there are many other benefits, equally compelling from a public health standpoint:


Here again, estrogen replacement is one of the most powerful therapies we can offer women, and has minimal side effects compared with bisphosphonates (WebMD). Here are some studies:

Journal of the American Medical Association (JAMA), 2003

In older women, a dosage of 0.25 mg/day of [estrogen] increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects.

Prestwood KM, et al. Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. JAMA. 2003 Aug;290(8):1042-1048.

Maturitas, 2000

Prospective controlled cohort trial: 2016 healthy women aged 45-58 years, all less than two years menopausal. Staying on hormone replacement for 5 years reduced total fracture risk almost 40% (RR=0.61, 95% CI: 0.39-0.97) and forearm fracture risk 76% (RR=0.24, 95% CI: 0.09-0.69).

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women – results of the Danish Osteoporosis Prevention Study. Maturitas. 2000 Oct 31;36(3):181-93.

Jounal of the American Medical Association (JAMA), 1996

A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial studied 875 healthy women aged 45 to 64 years and found that Estrogen Replacement Therapy increases Bone Mineral Density at clinically important sites (hip and spine).

Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA. 1996 Nov 6;276(17):1389-96.

Again, this is not new information… here is a study from 22 years ago:

American Journal of Obstetrics and Gynecology, 1989

Estrogen use by postmenopausal women, especially when started within 3 years of the last menstrual period, prevents bone loss and reduces the risk of osteoporotic fractures. Withdrawal of estrogen therapy is followed by significant bone loss, suggesting that long-term therapy is needed.

Estrogens in the prevention of osteoporosis in postmenopausal women. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 2):1842-6.

Lest you think this is not accepted by mainstream physicians: The Endocrine Society (which provides consensus clinical recommendations of endocrinologists) stated in July, 2010:

Estrogen prevents early postmenopausal bone loss and augments bone mass in late postmenopause as effectively as the bisphosphonates, prevents hip and vertebral fractures, exerts a protective effect on osteoarthritis, and estrogen alone reduces total arthroplasty (joint replacement) rate.

J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S1–S6

And just this past year, in 2011, the National Osteoporosis Society released their Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis, stating:

We conclude that HRT has a role to play in the management of osteoporosis in postmenopausal women below the age of 60 years.

Menopause Int. 2011 Jun;17(2):63-5.

Cardiovascular Disease:

Of all the benefits of estrogen, none are better studied than it’s protective effects against heart disease. In 1996 the authors of a study of hormone replacement therapy noted:

“Over 90% of women will die from cardiovascular disease, which estrogen can prevent. Over 40 years of study have well documented the cardiovascular protective effects of estrogen.”

Ettinger B, et al. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 1996 87(1):6-12.

A 1998 review assessed the impact of estrogen use among women with particularly high cardiovascular risk. Seven studies of estrogen therapy in women with established coronary heart disease (such as coronary stenosis and prior heart attack) were reviewed:

“These studies all find fewer recurrent cardiovascular events and improved survival in the estrogen group when compared to the non-estrogen group. Analysis of the effect of estrogen in the 16-year follow up of the Nurses’ Health Study confirms that the protective effect of estrogen is even more pronounced among women with high baseline risk of heart disease.

Maturitas. 1998 Sep 20;30(1):19-26. Estrogen for women at varying risk of coronary disease. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School

And in 2000 the New England Journal of Medicine noted,

“Estrogen therapy alters the biology of the inner vessels (of the heart)… providing significant coronary artery benefits.”

Nabel EG. Coronary heart disease in women – an ounce of prevention. N England J Medicine. 2000;343(8):572-574.

So, the benefits of estrogen in preventing heart attacks, osteoporosis and Alzheimer’s are quite well documented.

Perhaps most importantly: Even the WHI trial showed that women who start HRT before age 60 decreased their overall mortality by 35%! A meta-analysis of 30 other studies found the same thing: if you start HRT before age 60, it decreases your risk of death from any cause, by about 35%. Of course this benefit may not last forever, but in a meta-analysis of 30 studies (14,000 women) it lasted for as long as the studies were carried out. (J Gen Intern Med 2004; 19:791-804)

Please note: This last point is not controversial. The Endocrine Society itself stated in it’s 2010 Scientific Statement on HRT,

“Menopausal Hormone Therapy was associated with a 40% reduction in mortality in women in trials in which participants had a mean age below 60 yr or were within 10 yr of menopause onset.”

(Executive Summary: Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement. J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S1–S66)

In my review of the data I found for various reasons that the true number is probably closer to 35% than 40%. Nevertheless it is remarkable to me that a finding that dramatic never makes the news, yet a tiny increase in breast cancer (caused by synthetic progestins) is trumpeted endlessly.

It is important to note that throughout these studies it is clear that the sooner you start estrogen therapy after menopause, the better. A 2008 review of hormone replacement therapy noted that:

“the window of opportunity for reducing mortality and coronary heart disease [requires] initiation of hormone therapy within 6 years of menopause and/or by 60 years of age, and continued for 6 years or more.”

Postmenopausal hormone therapy and cardiovascular disease in perspective. Clin Obstet Gynecol. 2008 Sep;51(3):564-80.

And a similar, related, issue is, it is not enough just to start therapy; adequate blood levels have to be maintained to benefit from it:

“The potential lethal consequences of osteoporosis are overwhelming. Estrogen is protective, but only when certain serum levels are maintained.

Fitzpatrick LA. Estrogen and bone health. Female Patient. 2004 Oct;29:40-46.

This is why I recheck serum levels in all my patients after initiating therapy. You can’t just use “the lowest dose for the shortest time period” to reduce menopause symptoms such as hot flashes, and still hope to significantly reduce your risk of osteoporosis and Alzheimer’s disease. This is one area in which Age Management doctors who have carefully evaluated the data separate themselves from well-meaning PMDs who offer the bare minimum to alleviate menopausal symptoms.

Thank you to Dr. Trutt for his expertise on HRT and bio-identicals and their effects on health. We have concluded that it is better to start hormone replacement therapy as soon as you enter perimenopause — all the more reason to make sure you pay attention to what your body is telling you, find a perimenopause and menopause specialist, and detect it early so you’re prepared to find the best path for yourself! Make sure you check Shmirshky next week for part two of Dr. Trutt’s blog, when we ask him the big question: Does HRT cause cancer?


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