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Life Extension Magazine November 2013
As We See It  

Surprise Findings in Estrogen Debate

By William Faloon

Yale Study Shows That Premarin® Is Better Than No Estrogen

Yale Study Shows That Premarin® Is Better Than No Estrogen  

In 2013, a new analysis from the Women’s Health Initiative was published on women aged 50-59 who had undergone a hysterectomy. These women had significantly reduced levels of estrogen (in particular estradiol) production occurring in their bodies.

This study analysis, emanating from the Yale School of Medicine, estimated that between 2002 and 2011 a minimum of about 18,000 and as many as about 91,000 excess deaths occurred among hysterectomized women aged 50 to 59 years who did not take Premarin®.11

For women in this age group taking oral Premarin® (without progesterone), the reduction in deaths from coronary heart disease and colon cancer appear to outweigh the increase in deaths from breast cancer, stroke, and pulmonary embolism.


What makes this finding so compelling is that these women were taking oral Premarin®

  • without individualized dosing (to optimize tolerability);
  • without natural progesterone (to protect against unopposed estrogen on hormone-responsive tissues like the breast, potentially reducing breast cancer risk);39-42
  • without topical preparations (to avoid the first-pass effect of oral estrogen in the liver linked to inflammation and arterial blood clotting);46-48
  • without estrogen modifiers like indole-3-carbinol (to inhibit formation of estrogenic metabolites linked to increased risk of breast cancer);52,53
  • without enough vitamin D (to regulate breast cell proliferation);54-56 and
  • without being on a comprehensive program that involves ingesting healthy foods and reducing intake of dangerous ones.

The size of this analysis by Yale researchers makes a compelling argument that it may be better for estrogen-deficient women age 50-59 years to blindly take what many believe to be the worst estrogen drug (oral Premarin®) than to do without any estrogen at all.

In addition to the mortality benefit for women ages 50-59 years, hormone therapy in this analysis provided an improvement in quality-of-life measures during the first several years of treatment.

Women over 59 did not see these benefits with Premarin®-only therapy, nor would we expect them to. Aging humans have to be far more careful as to how they implement a hormone balancing program.

What few have yet to understand is that as women move through menopause, their estrogen blood levels can plummet to the range of hysterectomized females. We now know these low estrogen levels can cause significantly higher death rates, along with menopausal miseries.

The good news is this does not have to happen to women just because they are growing older. There are protocols using only natural bioidentical forms of estrogen and progesterone absorbed topically that, when combined with healthy lifestyle/supplement choices, can more safely induce a rejuvenating effect!

Findings from 27 Additional Studies on Hormone Replacement

No matter how prestigious the institution, or the size or quality of the study, one should always seek out confirmatory data when making a decision as substantive as restoring sex hormones back to youthful ranges.

From a mechanistic standpoint, when one understands how essential estrogen and progesterone are to a woman’s life processes, it would be logical to seek to maintain these hormones at youthful levels for life. But there is always concern about side effects.

To evaluate the worst case scenario, Life Extension researchers evaluated data derived from 27 published studies that looked at the long-term effects of many different forms of conventional estrogen and progestin drugs on menopausal women.12 Eight of these studies were observational, while 19 were randomized controlled trials involving 16,000 women followed for 83,000 patient-years. Some of the trials used hormone drugs we consider hazardous or suboptimal.

None of these trials follow the comprehensive natural hormone protocols to include nutrient support that Life Extension recommended decades ago.

We reviewed data from all these studies to ascertain the mortality risk in women taking conventional hormone replacement compared to those who did not. The pooled analysis from these twenty-seven independent studies showed that women under age 60 who replaced their sex hormones were 28% less likely to die!12

In the process of not dying, the quality-of-life measures showed clear benefit to women who restored their sex hormones.12

So what does this tell us? Since 2002-2004, warnings have emanated from the FDA, mainstream medical groups, and practicing physicians that replacing hormones in maturing women is dangerous. Yet the 2013 Yale study of hysterectomized postmenopausal women, plus an analysis of 27 hormone therapy trials using suboptimal hormone preparations in women age 60 years and younger, shows a mortality reduction in women who replace their sex hormones.

There is no question that improperly prescribed hormone replacement is going to increase cancer and vascular risks. But women no longer have to be subjected to outmoded prescribing practices. There is solid data to enable women of all ages to regain a more youthful hormone profile, using natural forms of estrogen and progesterone that have intriguing studies indicating reductions in cancer and vascular risks.

Natural Progesterone Protects Against Breast Cancer

Natural Progesterone Protects Against Breast Cancer

Compared to synthetic progestin that stimulates breast cell proliferation, natural progesterone has demonstrated a protective effect.

There are at least 17 studies showing that progestins significantly increase breast cell replication and growth largely due to stimulation of the estrogen receptor by progestins.42,45,57-71 In stark contrast, at least 11 studies have shown that natural progesterone does not induce estrogen-stimulated breast cell proliferation.68-78

Numerous studies have demonstrated an increased risk of breast cancer with the use of synthetic progestins.1,45,79-81 However, the use of natural (bioidentical) progesterone has not been associated with an increased risk of breast cancer.39-42,80,82

Quite to the contrary, research has revealed that natural progesterone decreases the risk of breast cancer. In a study published in the journal Breast Cancer Research and Treatment, 80,000 postmenopausal women using various forms of hormone replacement therapy (HRT) were followed for more than 8 years. Women who used estrogen in combination with synthetic progestin had a 69% increased risk of breast cancer, compared to women who had never used HRT. However, for women who used natural progesterone in combination with estrogen, the increased risk of breast cancer was completely eliminated with a significant reduction in breast cancer risk compared with synthetic progestin use.82

In another investigation, these same researchers found a 40% increased risk of breast cancer for women who used estrogen with synthetic progestin.80 Interestingly, in women who used estrogen combined with natural progesterone, there was a promising trend toward a reduced risk of breast cancer, compared to women who had never used HRT.80 In essence, natural progesterone appeared to protect women against the development of breast cancer. These findings confirm work done six years earlier that found a trend toward a reduced risk of breast cancer in 1,150 women using natural progesterone, compared to non-users of progesterone.83

Compelling research offers further insight into natural progesterone’s ability to defend against breast cancer. In a fascinating study, scientists administered estrogen alone, natural progesterone alone, estrogen plus natural progesterone, or placebo to 40 women prior to surgery to remove a breast lump. The hormones were applied topically to the breast for about 12 days before surgery. As expected, when given alone, estrogen caused a 62% increase in breast cell proliferation rates compared to placebo. Conversely, the addition of natural progesterone to estrogen resulted in a significant decrease in the estrogen-induced increase in breast cell proliferation rates. Even more impressive was the finding that the group receiving natural progesterone alone had a nearly 76% lower breast cell proliferation rate compared to the placebo group.72

Breast Cancer Is Not the Only Cause of Premature Death

With all the media attention and fundraising by support groups, you might be lulled into thinking the only disease women prematurely die from is breast cancer.

Each year, over 40,000 women in the United States do die of metastatic breast cancer.89 But there are a total of about 1,250,000 female deaths each year in this country.90 That means for every one breast cancer death, there are approximately 31 women who die from something else.

Many of those “something else” diseases relate to hormone deficiencies. That does not mean women should ignore breast cancer risk and blindly take hormone drugs. It does, however, bring into context the health issues maturing women really face. These “something else” deaths provide a rationale for the natural hormone restoration approaches long advocated by progressive physicians and the Life Extension Foundation®.

As you’ll read in an article in this month’s issue of Life Extension, there are prudent ways women can reduce breast cancer risk.