Menopause Hormone Therapy: Timing Doesn’t Matter

It’s Ok When You Have Symptoms, but Don’t Use It for Prevention.

The National Women’s Health Network has always supported menopause hormone therapy (HT) for symptom relief. Most symptoms associated with menopause are worse immediately before or after periods finally stop, but some, like vaginal dryness, can cause problems for women many years after menopause. But what about using hormones for prevention? Does it matter when women start hormones when the reason they’re taking them is to prevent problems in the future? A new study has confirmed that taking hormones immediately after menopause does not reduce risk factors for heart disease, nor does it prevent cognitive decline. The study results are a nail in the coffin for the “critical period” hypothesis, the idea that menopause HT would work to prevent heart disease and other conditions, but only if treatment started immediately after menopause. The critical period hypothesis was developed after the Women’s Health Initiative found that taking menopause HT later in life did not prevent these conditions.

We’ve created this consumer health information because it is important for women of all ages, and the clinicians who take care of them, to understand what we now know about taking hormones to prevent chronic conditions such as heart disease, Alzheimer’s and cognitive decline.

Kronos Early Estrogen Prevention Study (KEEPS)

Who, Where, and When:

  • 727 healthy women took part in the study. They were on average 52 years old at the beginning of the study.
  • Women in the study had gone through natural menopause less than three years before starting the study.
  • Most women had some symptoms of menopause.
  • Women were screened to determine that they had very few risk factors for heart disease. They did not have high blood pressure or cholesterol levels and were not overweight.
  • Everyone was followed for 4 years.
  • The study was funded by Kronos Longevity Research Institute, a private foundation, without drug company funding. The federal government funded the study of cognitive effects.
  • Participants were seen by researchers at nine study sites.
  • 71% of the participants were White, 7% Latina, 8% African American, 3% Asian/Pacific Islander.

What Was KEEPS Designed to Test?

The KEEPS researchers wanted to find out if menopause HT given to women shortly after menopause could prevent cognitive decline and lower the risk of heart disease. They believed “natural” hormones, those chemically identical to the hormones made by women’s bodies would be most effective. For that reason, researchers used the following design:

  • Patch vs Pill vs Placebo: The study tested the effects of natural estrogen given via a patch (brand name Climara) vs. the most commonly used estrogen pill, which is derived from pregnant horses (brand name Premarin), vs. placebo.
  • Progesterone vs Placebo:  Women with a uterus also took natural progesterone (brand name Prometrium) vs. a placebo.
  • Random Pills and Patches: Women were randomly assigned to either menopause HT or placebo and everyone was given look-alike pills and patches to mask who got the real treatment.
  • Ultrasounds and X-rays: All participants were given special ultrasounds and x-rays to evaluate the thickness of their arteries and the amount of plaque build-up at the beginning of the study, and every year thereafter.
  • Repeated Memory Tests: Women were given special tests of their memory and asked about their mood at the beginning of the study. The tests were repeated at 18, 36 and 48 months, and scheduled in a way that allowed researchers to look at the effect of estrogen alone vs. estrogen plus progesterone.

What Did KEEPS Find?

The KEEPS researchers announced their findings to the press in October 2012. The heart disease results were not officially published until July 2014. The memory and mood results have still not been published. We are concerned about the long time lag between the researchers’ announcement and the publication of the results. Publication of study results in a medical journal provides much more information than a press release, information that is vital for informed decision making. We note which findings have not yet been reviewed and published.

  • Menopause HT had no effect on the age-related progression of hardening of the arteries. (published July 2014) [1]
  • Menopause HT had no effect on blood pressure, either positive or negative. (published July 2014)
  • Menopause HT did not improve memory, or prevent age-related memory decline. (announced 2012 [2], not yet published)
  • Menopause HT did not affect overall mood; one questionnaire showed an improvement in depression symptoms, another questionnaire did not. (announced 2012, not yet published)

What Does the Network Think?

This study is another blow to the old-fashioned idea that women’s femininity decays after menopause, and that the only way to age healthfully is to “replace” hormones with pills, patches, creams, and sprays. An entire generation of physicians and women were shaped by this message, and millions of women took menopause HT, not to treat any symptoms, but because their doctor (and pharmaceutical companies) told them it would help them stay young and healthy.

But sometimes old attitudes (and the pharmaceutical industry’s profit motive) die hard. Proponents of menopause HT are still outspoken in support of the idea that women’s bodies aren’t equipped to age healthfully without taking hormones. Their latest attempt to justify their opinion was the theory that the timing of menopause HT is crucial. The publication of the KEEPS study results should put an end to that theory, and to the continued promotion of menopause HT as a prevention strategy.


  • [1] Harman S, Black D, Naftolin F et al, "Aterial Imaging Outcomes and Cardiovascular Risk Factors in Recently Menopausal Women:  A Randomized Trial," Annals of Internal Medicine 2014; 161(4): 249-260
  • [2] KEEPS Website, Study Finds Estrogen Therapy Improves Depression and Anxiety in Recently Menopausal Women Without Adverse Cognitive Effects, Tempe, AZ: KRONOS, 2012. Retrieved on June 22, 2015 from:

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