The Women’s Health Initiative (WHI) and its Impact on Menopausal Hormone Therapy Usage
What was the Women’s Health Initiative (WHI)?
The Women’s Health Initiative (WHI) was a prevention trial initiated in 1991 to explore treatments that might decrease morbidity and mortality in postmenopausal women, specifically cardiovascular disease, osteoporotic fractures, and cancer. Participants were given either a placebo (no treatment) or one or more of three active treatments: hormone therapy, calcium and vitamin D, and/or a low-fat, high-fiber diet.
However, when you hear the term “WHI,” it is almost always in reference to the menopausal hormone therapy (MHT) part of this trial because the results were the opposite of what was hypothesized about MHT preventing chronic diseases — and this drew a lot of media attention. This was the first randomized, controlled trial of this size to examine MHT products that had been prescribed to women for forty years (since 1950). This part of the study followed 27,347 women over 9+ years to learn about the development of new disease and mortality in relation to the use of hormone therapy products. In fact, participants that were in this study are still being followed today.
Which menopausal hormone therapy products were used in the Women’s Health Initiative (WHI)?
There are two hormones that are a part of most HT regimens used to treat menopausal symptoms: estrogen and progesterone. Traditionally estrogen has been seen as the treatment part of HT but when you give estrogen alone to women with a uterus (i.e., haven’t had a hysterectomy) it increases the risk of endometrial cancer. So, it’s important to use a progestogen (either progesterone or a progestin, a synthetic progesterone) in addition to the estrogen in order to mitigate this risk.
There were two products used in the WHI trial: one was an estrogen, and one was a combination of estrogen and a progestogen, a product that is or acts like progesterone. Women (10,739 of them) with no uterus received estrogen only in the form of Premarin® (brand name) — conjugated equine estrogens (generic name) — often referred to as CEE. For women who still had a uterus and needed the added progestogen to protect them from endometrial cancer, medroxyprogesterone — often abbreviated as MPA — was added via a product that combines medroxyprogesterone and conjugated equine estrogens called PremPro® (brand name) and this was what was given to the 8,506 women with a uterus.
As an aside, FDA-approved bioidentical estrogen was available and prescribed prior to the WHI trial, but Premarin (not bioidentical) was chosen as the study drug because it was the most widely used at the time.
How did the Women’s Health Initiative (WHI) influence the use of menopausal hormone therapy?
In 2002, the HT part of the WHI was halted because of increases in cancer, stroke and cardiovascular disease among women receiving MHT.
Immediately many healthcare providers stopped prescribing estrogen products and women stopped taking them. Without MHT, some women’s menopausal symptoms came back, and they looked for other remedies. Understandably, they were afraid of the products that had been used in the trial. It was at this point that prescriptions for compounded hormone therapy products began to increase as they were seen as a safer substitute. At the same time, the term “bioidentical” rose in popularity and bioidentical products were promoted by some as a safer alternative but without data to prove it.
A list of all hormone therapy options here.
A link to the WHI Study page is here.
The Other Parts
Part I: Hormone Therapy Overview, Defining Compounding and New Information from an Expert Committee
Part III: Defining Bioidentical and Explaining FDA approval
