The Women’s Health Initiative (WHI) & how the misinterpretation of this study completely altered the management of menopause and perimenopause in the US. A gigantic medical mess with serious health, wellness and quality of life consequences that we are still recovering from 20 plus years later.

I think it’s important to talk about this to really understand why we treat women’s hormone replacement therapy (HRT) the way we do. I know it’s boring to hear about a study, but the findings of this study have very significantly impacted the way we approach hormone replacement therapy in perimenopausal and postmenopausal women.

Prior to being published (2002) nearly 40% of postmenopausal women were on HRT. At the time it was being used to manage the troublesome symptoms of menopause- specifically vasomotor (hot flashes) symptoms. However, it was also prescribed as a way to prevent some of the chronic diseases of aging including heart disease and cognitive impairment.

Why? Because the risk of heart disease does increase with menopause, and it was hypothesized that this was due to a decline in estrogen which could be counteracted with estrogen replacement Unfortunately, at the time there were only observational and animal studies that showed benefit. No randomized controlled trials with consideration for risks and benefits were available at the time (randomized controlled trials or RCT are the gold standard in providing objective data). The studies primarily looked at conjugated equine estrogen plus or minus medroxyprogesterone- because these were the most commonly prescribed hormones for HRT at the time of the study.

The study included women between the ages of 50-79 with a mean age of 63.

Findings of that initial study noted the following:
1. Combination HRT increases the risk of breast cancer
2. Combination HRT increases the risk of cardiovascular events (stroke, heart attack etc)

Aftermath of these findings:
1. A precipitous decline in prescriptions for menopausal hormone therapy
2. Mass panic in the medical community
3. knowledge and training of clinicians in the medical management of menopause became a lower priority

Limitations of the study:
1. The WHI study did not stratify or report results by age. The risk for cardiovascular disease increases significantly with age.
2. Many of the participants in the WHI study were 10 years past the onset of menopause.
3. The average age of WHI study participants was 63, the average age of menopause is 51.
4. Many of the women in the WHI study were not symptomatic with hot flashes

The KEEPS and ELITE trials were done as follow ups to test the timing hypothesis: Were the findings of the WHI study secondary to increasing time from menopause onset (greater than 10 years) and increasing age (average age of menopause is 51, while the average age of study participants was closer to 63).

KEEPS trial: a four-year randomized, double blinded and placebo-controlled trial (gold standard)
Over 700 women, aged 42-58 (average age 52), within 3 years of menopause onset (from 9 different clinical centers) were followed for 4 years.

The participants were monitored for signs of heart disease progression, increases in blood pressure and changes in lipid profile. Results of the study did not show any significant progression in heart disease and no effects on blood pressure. There was slight increase in good cholesterol and triglycerides, with a slight decrease in bad cholesterol noted with oral estrogen, this was not found with transdermal (patch) estrogen.

Additionally, no significant differences were seen in adverse events, including breast cancer, heart attack, transient ischemic attack (mini stroke), stroke, or venous thromboembolism (blood clot)– when comparing placebo with menopausal hormone replacement therapy.

As expected, there were clinical improvements in vasomotor symptoms (hot flashes), mood, sexual function and bone density with hormone replacement therapy (HRT) vs. placebo.

ELITE study: a six to seven year randomized, double blinded and placebo-controlled trial completed to compare the timing hypothesis. The study compared the effects of hormone replacement therapy on women less than 6 years past menopause and women greater than 10 years past menopause.

The results of the study showed that for women greater than 10 years past menopause, the progression of heart disease with placebo vs. HRT was similar. For women less than 6 years past menopause, the progression of heart disease with placebo vs. HRT showed a significant difference- with the HRT group showing slower progression of heart disease than the placebo group. Otherwise stated, the estrogen seemed to have a protective effect on the progression of heart disease in the treatment group that was less than 6 years past menopause, and in general, younger and healthier at baseline.

The findings of the KEEPS and ELITE studies support the use of hormone replacement therapy in young, healthy women early in menopause. In 2017 the North American Menopause Society released a position statement on hormone replacement therapy:

“For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome [vasomotor symptoms] and for those at elevated risk for bone loss or fracture.”

What does this all mean? Should we use HRT? The answer is, in the right patient, with an individualized risk assessment, HRT can make a world of difference in her quality of life. It can be a medically safe and even favorable way to manage the devastating vasomotor symptoms of menopause.

Ladies, there is no reason to suffer in silence, if you are having significant hot flashes and night sweats be sure to discuss your treatment options with your doctor.

I hope this article has been helpful in uncovering WHY we’re behind in women’s health- stay tuned for more information on menopause and treatment options in the coming weeks.

Sincerely,
Corsano MD- Your friendly neighborhood PCP

What the Women’s Health Initiative has taught us about menopausal hormone therapy
womens health initiative.pdf
The Menopause Society | Homepage