Unveiling the Truth of Estrogen Replacement Therapy


One of the most complex health-care decisions facing women today is whether or not to use prescription hormones for menopause. Most women feel stuck between a rock and a hard place. Do I suffer through menopause-related depression, anxiety, lack of sleep, hot flashes, and an increased risk of dementia? Or do I perhaps increase my risk of cancer?


For many women, the tools and advice needed to make this decision are difficult to find and not widely available. In this blog, we will break down the medical jargon to allow you to form your own judgments and decide what is right for you.


History of HRT:


In the late 1990s, receiving hormones at menopause was unquestioned and usually automatically prescribed. This recommendation was primarily based on the Nurses’ Health Study, one of the largest prospective investigations into women’s risk factors. The study revealed an 11% reduction in the risk of coronary artery disease (CAD) in women who took part in hormone replacement therapy (HRT). CAD is the leading cause of death in American men and women.


The first formal clinical trial to test women’s hormones was in 1993- the Women’s Health Initiative. The study was a 15 year multiphase trial of over 160,000 post-menopausal women. The focus was on the use of HRT to prevent heart disease. The study had 2 arms:

  • Estrogen therapy alone for women without a uterus.

  • Estrogen and progestin therapy for women with a uterus. (Progestin was found to protect the uterus from cancer, which estrogen alone could potentially initiate.)


But the study came to a halt in 2003 when early data suggested that HRT in both arms of the study increased the risk of blood clots and stroke. The estrogen and progestin group also showed an increase in breast cancer.


When this information was released to the public, it was sensationalized by the media. Almost overnight, nearly 80% of American women who had been taking HRT stopped cold turkey. Physicians no longer felt comfortable prescribing hormones, and HRT usage diminished.


Almost 20 years later, this study is still perceived as the world’s most comprehensive source of information regarding the risks and benefits of HRT. HRT usage is still very low and many doctors are still not prescribing it.


The Truth about the WHI Study


Almost immediately after the release of the study’s results, independent scientists and researchers began raising concerns about the validity of the study’s approach and the relevance of the findings. Investigators concluded the initial interpretations of the study were in part incorrect and contrary to the results.


One scientist involved in the early leadership of the study, Dr. Langer, has since said, “Good science became distorted and ultimately caused substantial and ongoing harm to women for whom appropriate and beneficial treatment was either stopped or never started.” Dr. Langer is now speaking publicly about the many faults of the study and misconstruing of the findings.


A close look at the WHI:

  • The trials were conducted predominantly on women many years after menopause, in their 60s and 70s.

  • While the results warned against the use of HRT for all women, only about 30% of participants were of the age when HRT is recommended.

  • Many of these women had pre-existing conditions, such as smoking and obesity, that increased their risk of stroke and blot clots. This was not accounted for in the results.

  • Many women already suffered from CAD. Women’s arteries typically begin to harden after menopause- so being given HRT post-menopause would have decreased effectiveness.

  • The dose of estrogen used was far too high. The researchers used a dose of estrogen more appropriate for menopausal women starting HRT, which is considered by most experts as too high for older women.

  • The trial was designed to highlight long-term hormone therapy to prevent chronic disease in older women, but the results were generalized to apply to younger women on short-term therapy for menopause symptoms. Later analysis of the WHI results demonstrated younger participants saw a decreased risk of cancer, bone fractures, and death.

  • Both the estrogen and progesterone used in the study were synthetic. The estrogen used in the study was Premarin. This is estrogen from the urine of pregnant horses.

Dr. Langer believes the study’s release favored “fear and sensationalism over science,” ultimately overstating the risks in order to achieve “maximum publicity.”


A 2013 study estimated as many as 91,610 American women died prematurely between 2002 and 2012 due to the lack of estrogen therapy.


The Truth about HRT:


In the WHI study, the group only taking estrogen saw a 23% reduction of breast cancer. Even seven years after the WHI, the prospect of breast cancer among participants remained low. Another study updated the results of the WHI to demonstrate no increase in breast cancer among those taking estradiol and progestin.


In studies performed since the WHI, it seems that risks of HRT are associated with the type of progestin used. Medroxyprogesterone acetate (MPA), the type of progestin that was used in the Women’s Health Initiative trials, has been shown to raise one’s risk considerably, whereas other progestins such as micronized progesterone carry lower risk.


HRT has been demonstrated to:

  • Help prevent osteoporosis and associated injuries.

  • Decrease the risk of heart disease.

  • Slow the progression of atherosclerotic plaques, which lead to heart attacks and cardiac death.

  • Improve symptoms related to vaginal atrophy.

  • Reduce the incidence of coronary heart disease by 50%, if started within 10 years of menopause.

  • Alleviate menopausal symptoms.

  • Improve sleep, muscle aches, and pains in menopausal women.

  • Help alleviate depressive symptoms.

  • Increase skin collagen content, thickness, elasticity, and hydration.

  • Lower risk of death by 39% for women who started HRT before menopause.

The Importance of Estrogen:


Estrogen plays a role in nearly every system in the human body. Estrogen exists in 2 forms- estrogen that exists solely inside the brain and estrogen produced in the ovaries or with body fat. Both types play different roles.

  • Estrogen manufactured in the body protects our heart and bones.

  • While estrogen made in the brain protects our memories, thoughts, and feelings.

Brain estrogen has a call-and-response relationship with body estrogen, responding to its actions and inactions via the HPG axis that connects our brains to our ovaries. Aside from this back-and-forth, the brain makes a lot of its estrogen in-house and has its own hormonal ecosystem. Unfortunately, there is no good way to currently measure the estrogen in our brain. Hot flashes, night sweats, brain fog, insomnia, weight gain have all been shown to be a result of low estradiol in the brain.


To learn more about estrogen and the importance of HRT, Dr. Johnson recommends the book, Estrogen Matters. This book was written by Avrum Bluming, an oncologist who reveals more truths about HRT and estrogen.


To learn more about the Johnson Center's approach to hormone therapy, click here.

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