Benefits and Harms

I have surveyed women’s attitudes about hormone use after menopause and discovered that virtually all are misinformed today regarding the benefits and especially the harms of this essential treatment. Hormone therapy has been prescribed for women since the 1950s and in my opinion this treatment has been a disaster. Many errors have been made in every respect imaginable. These errors have had disastrous results. Everyone knows this to be true. On the other hand hormone therapy has many potential benefits for women who suddenly loose them so they can’t have children any more as if they wanted any more in the first place.

There have been many studies done of hormones through the years with most of them showing significant benefit of hormone therapy for women after menopause. These were large studies that followed thousands of women for 20+ years. They found that estrogen alone and with progesterone prevented heart disease and had no effect on stroke. Other large studies showed that estrogen therapy with or without progesterone after menopause had a beneficial effect on life expectancy and the quality of life of those who used estrogen compared to those who never used estrogen.

The Women’s Health Initiative WHI was designed to be the definitive study of estrogen therapy in women after menopause. It was sponsored by the US National Institutes of Health to answer the following questions:

  • What is the risk for breast cancer in women using hormones after menopause?
  • What is the risk for heart attack disease in women using hormones after menopause? What is the risk for stroke disease in women using hormones after menopause?
  • What is the risk for pulmonary embolism disease in women using hormones after menopause
  • What is the risk for deep vein thrombosis in women using hormones after menopause?
  • What is the risk for dementia in women using hormones after menopause?
  • What is the risk for hip fracture in women using hormones after menopause?
  • What is the risk for vertebral fracture in women using hormones after menopause?
  • What is the risk for colon cancer in women using hormones after menopause?

The study had very little budgetary support from the NIH but Wyeth the maker of Premarin (CE) and PremPro (CE/MPA) volunteered to donate $500 million worth of medication so the study could proceed. The 20 academic medical centers that were chosen to do the study agreed to a meager budget. They wisely knew that participating in the largest prospective randomized hormone study ever conducted would be paper-publishing bonanza. Academic careers were made and stars were born as a result of the WHI but in my opinion the biggest losers were the very women the study was designed to help. The reason is results of the study were more negative than expected and that led to a media feeding frenzy. It was “man bites dog” when CE/MPA was shown to cause breast cancer and not prevent heart attack, which is exactly the opposite of what the study designers had expected the study to show. These negative results were sensationalized by the press and blown out of proportion. The US FDA was caught up in the hysteria too. Soon after the story broke they issued new stern warnings on all estrogen products that remain on them to this day with very little modification.

As I write these words 15 years have past since the WHI study results were announced my views of hormone therapy has evolved and matured. I see the risks and rewards for women and think that each needs to learn what these are and make their own choice. If they choose to use hormones we offer a unique approach to this therapy that has distinct advantages with very little risk and disadvantages.

With respect to the WHI what did they discover and importantly what was the entire hullabaloo over. Below is a summary table of the actual data with my interpretation.

Women’s Health Initiative Studies Results for the CE/MPA Group 16,000 Women

Condition Increased Annual Risk Table
Breast Ca 8/10,000
Heart Attack 7/10,000
Stroke 8/10,000
Pulmonary Embolism 8/10,000
Deep Vein Thrombosis 13/10,000
Hip Fx -5/10,000
Vertebral Fx -5/10,000
Colon ca -6/10,000

The interpretation of the table of risks seen in women taking CE/MPA is as follows: There was an increase risk for breast cancer 0.0008 per year, heart attack or 0.0007 per year, and stroke of 0.0008 per year. Pulmonary embolism is a blood clot that comes from the deep veins of the legs or pelvis. The risk for pulmonary embolism is increased by 0.0008 per year and for deep vein thrombosis 0.0013 per year. The benefits seen in the CE/MPA group include a reduction in hip and vertebral fracture risk of 0.0005 and 0.0005 respectively. Colon cancer risk fell by 0.0006 per year.

As you can see the risks and the benefits from use of CE/MPA in this study was minimal. The overall negative effect size from use of CE/MPA is very small. It is dominated by the two clotting abnormalities pulmonary embolism and deep vein thrombosis that together account for an increase risk of 0.0021 per year. This is due to administering estrogen orally, which increases clotting factor production in the liver. That is eliminated by administering estrogen topically and topical administration also allows the use of a dose 1/10 the size of the oral dose but with the same systemic effect. When the clotting risks are removed from the global risk equation the net risk of using CE/MPA in this group calculated obtained by summing the increased and decreased risks is 0.0007 per year, which in my view is low risk.

There are other ways the risks seen in the WHI can be reduced further. These include administering all the hormones topically rather than orally that avoids the first pass through the liver where 90% of hormones are metabolized. This permits use of 1/10th the oral dose. Using bioidentical hormones rather than artificial hormones like those used in the WHI and by most commercial pharmaceutical manufacturers. These products are what the body is accustomed to and prepared to use and metabolize unlike artificial commercial hormones with longer than normal half-lives and unnatural metabolites. Reducing the risk of hormone side effects by adding medications to control the metabolism of testosterone preventing it from increasing estrogen or causing virilization signs or symptoms. These features have been designed into Aurora Vaginal Cream that is specially formulated for the needs of women age 50 and older.