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 160,000 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: menopausal 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 menopausal hormone therapy products. In fact, participants that were in this study are still being followed today.
We offer results from the non-menopausal hormone therapy parts of the trial see below.
Which menopausal hormone therapy products were used in the Women’s Health Initiative (WHI)?
There are two hormones that are a part of most MHT regimens used to treat symptoms: estrogen and progesterone. Traditionally estrogen has been seen as the treatment part of MHT but when you give estrogen to women with a uterus (i.e., she hasn’t had a hysterectomy) it increases the risk of endometrial cancer. So, it’s important to use a progestogen (either progesterone or a progestin) in addition to the estrogen in order to mitigate this risk.
There were two products used in the WHI trial: one was Premarin® (brand name) — conjugated equine estrogens (generic name) — often referred to as CEE and one was PremPro® (brand name), a combination of CEE and a progestin, medroxyprogesterone — often abbreviated as MPA. Women (10,739 of them) with no uterus received Premarin® and women who still had a uterus (8,506) received PremPro®.
How did the Women’s Health Initiative (WHI) influence the usage of menopausal hormone therapy?
In 2002, the MHT 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.
What did the follow up analyses show about the risks and benefits of MHT?
Over the years there have been new analyses of the data which showed varying risks and benefits depending on a person’s age and how many years since menopause she starts hormone therapy, with younger women closer to menopause generally facing a more favorable risk profile.
What were the outcomes of the non-MHT parts of the Women’s Health Initiative?
The Dietary Modification Trial (~48,800 women, low-fat diet with more fruits/veggies/grains vs. usual diet)
Findings: The low-fat diet didn’t significantly reduce rates of coronary heart disease or overall cardiovascular disease, and a related analysis found no significant effect on breast cancer or total cancer incidence, partly because many women in the intervention group didn’t stick closely to the diet. Longer follow-up did show some benefits in the low-fat+ fruits/veggies/grains: breast cancer deaths were significantly reduced, a reduction in diabetes requiring insulin, and a modestly slower age-related physical decline over 12 years.
The Calcium + Vitamin D Trial (~36,300 women, 1,000mg calcium + 400 IU vitamin D vs. placebo)
Findings: Calcium plus vitamin D did not significantly reduce overall hip fracture rates compared with placebo, though it did modestly help preserve bone density (hip bone density was about 1% higher in the supplement group). In participants who took 80% or more of their supplements, hip fracture rates dropped by 29%. There was also a tradeoff — supplementation reduced hip fractures but increased the risk of kidney stones.
A link to the WHI Study page is here.
