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Is HRT Safe for Women after Menopause?

Two Hormone Specialists Weigh-In On This Complex Question

Mia West
December 25, 2023
Medically-reviewed and fact checked by Ryan Lester, PA-C

Hormone Replacement Therapy (HRT) has been a decades long subject of ongoing debate, despite once being viewed as the standard of care for menopausal women. To debunk the myths that originated with the Women’s Healthcare Initiative (WHI), we’ve addressed the widespread misinformation surrounding HRT's alleged connection to breast cancer and heart disease. We’ve also conducted deep dives into its well-established benefits associated with preventing chronic diseases like cardiovascular and Alzheimer’s, as well as its unparalleled ability to relieve the seemingly endless number of menopause symptoms. However, a few crucial questions linger in the minds of most aging women: 

Can women safely embrace hormone optimization once they reach menopause? 

If so, how long should they stay on it for?

Well, like most complex systems, it depends. For clarity on this deeply nuanced women’s health topic, we turned to the expertise of Wellcore’s resident hormone specialist, Ryan Lester, Physician Assistant, and Wellcore advisor, Caleb Greer, Nurse Practitioner. Together, they guide us through the peri to post menopausal transition, as well as the safety and potential advantages of utilizing Hormone Replacement Therapy (HRT). After speaking to both, one thing was clear: timing is everything.

The Perimenopause, Menopause, and Postmenopause Phases - What are the differences?!

Perimenopause is the time at which a woman’s ovaries run out of eggs and stop producing follicles - this results in very low progesterone production. As a result, menstrual periods typically become more irregular and symptoms of progesterone deficiency start to appear; difficulty sleeping and anxiety, being the most common. 

As a woman progresses into late perimenopause, her ovaries stop producing estrogen. This results in the cessation of menstrual periods. After 12 consecutive months without a period, a woman has officially reached menopause (a formal medical diagnosis). Other scenarios that may mask the onset of perimenopause signs and symptoms are when taking oral birth control or in those that have had an endometrial ablation. A total hysterectomy (removal of ovaries and uterus) will quickly induce the estrogen and progesterone deficiency symptoms of menopause as well. This is considered surgically induced menopause. 

After that, she is considered postmenopausal. Vasomotor symptoms, hot flashes and night sweats, are the most common symptoms of the menopausal transition. Testosterone production steadily declines throughout this process as well. Lester further expands on how these losses can have both immediate and long-term consequences:

  • Low Estrogen: Hot flashes, night sweats, vaginal dryness, and brain fog are common symptoms. Moreover, the absence of estrogen increases the risk of osteoporosis, heart attack, stroke, Alzheimer’s disease, UTIs, macular degeneration, colon cancer, and cataracts.
  • Low Testosterone: Low sex drive, diminished well-being, and reduced sexual function are among the symptoms. Additionally, there is an increased risk of fat gain, loss of muscle mass and strength, and an increase in wrinkles due to loss of skin elasticity.
  • Low Progesterone: Sleep disturbances, anxiety, depression, and mood swings accompany the absence of progesterone. This deficiency also elevates the risk of breast, ovarian, and uterine cancer.

As a woman in the throes of perimenopause, the mentioned symptoms alone serve as potent motivation to continue with Hormone Replacement Therapy (HRT) after menopause, especially considering its potential to diminish the risk of chronic health conditions such as cardiovascular disease, breast, ovarian, endometrial, and colon cancers, osteoporosis, and Alzheimer’s disease. Nevertheless, these pivotal questions remain: When should a female start HRT and for how long is it safe to continue once started?

Breast Cancer: The Devil is in the Details

A prevalent belief, stemming from the WHI (Women’s Health Initiative) study, suggests that HRT causes breast cancer. For one, the study used non-bioidentical hormones, Premarin (conjugated equine estrogen and Provera (medroxyprogesterone acetate), which experts agree should no longer be used in HRT. Experts now advocate for bioidentical forms, such as estradiol and progesterone, as the safest and most effective options with over 50 years of research supporting this. 

Second, the group of women in the WHI who were only taking estrogen, despite using the non-ideal Premarin, were found to have nearly a 20% lower risk of breast cancer than the group taking both hormones, said Greer. Currently, the consortium of clinical data strongly suggests that taking bio-identical estradiol and progesterone reduces the risk of a woman developing and dying from breast cancer: full stop. The notion that these hormones cause breast cancer is categorically false.

Heart Disease: Timing is Everything

In the U.S., 1 in 4 (25%) women die of heart disease. Women are 10 times more likely to die from heart disease than breast cancer. In 2017, a mortality analysis was published in the Journal of the American Medical Association (JAMA) encompassing the entire 18-year follow-up pool of women from the WHI study. The results showed that there was no increased risk of all-cause, cancer, or cardiovascular mortality. Said differently, the non-bioidentical hormones used in the WHI didn’t shorten the women’s lives. Other landmark studies, like the Nurses Health Study, have further established a 40% reduction in coronary heart disease events and total mortality with hormone therapy started within two years of menopause onset. 

Despite this type of data, some still believe that long term HRT comes with an increased risk of disease and is only justified when a woman has severe symptoms. We believe that HRT has a significant positive impact on menopausal symptoms and female physiology as a whole, and that the alleged long-term risks are not supported by evidence and/or lack clinical significance. In our eyes and many like us, the benefits greatly outweigh the risks. 

“I have to remind my clients that aren’t experiencing rough menopausal symptoms that they won’t feel their bones losing density or their mitochondria losing their capacity until the threshold is met to instigate symptoms,” continues Greer.

Here is the important piece about timing. The WHI also demonstrated that women who started oral Premarin (conjugated equine estrogen) and Provera (medroxyprogesterone acetate) after the age of 63 or beyond the 10 window from menopause had an increased risk of heart attacks in the first year of taking hormones. This “increase in risk” amounted to 30 cases out of 10,000 women which is very low. To date, no studies have demonstrated this risk with oral bioidentical estradiol. 

Furthermore, studies, like EPAT, DOPS, and ELITE, strongly support the notion that oral estradiol reduces the risk of cardiovascular disease. So if you are considering starting estrogen and are more than 10 years from menopause, know that there may be (based on the WHI data on non-bioidentical hormones) a small increase in the risk of a cardiovascular event in the first year of treatment. Our take: given the immediate benefit to menopausal symptoms and the long-term positive impact on chronic disease risk (cardiovascular disease, bone health, dementia, certain cancers); the juice is likely worth the squeeze. 

Tailoring HRT to Individual Health Histories

While the advantages typically surpass the potential risks, Lester provides an overview of the considerations that could influence the appropriateness of HRT for postmenopausal women, taking into account their medical history and risk factors.

  • Cardiovascular Disease History: Women ten years past menopause with advanced cardiovascular disease should carefully weigh the risks associated with starting oral estradiol with their healthcare provider. If you are concerned with this risk, transdermal estradiol (cream or patch) is the safest form to use; however, studies continue to demonstrate that this form likely doesn’t not render the necessary blood levels to maximize the risk of future chronic disease - specifically cardiovascular disease, dementia, and osteoporosis.
  • History of Blood Clots: Although this is still debated amongst HRT specialists, women with a history of lung or leg blood clots may opt for transdermal estradiol (cream or patch) over oral administration to mitigate the risk of clotting. Again, the downside would be that this form is simply not as effective at reducing chronic disease risk.
  • History of Cancer: Those with a history of breast, uterine, or ovarian cancer in remission may still be candidates for HRT, however, they should carefully discuss the risks vs benefits with their oncologist.

Risk Benefit Analysis

A risk-benefit analysis is a comparison between the risks of a situation and its benefits to determine whether a course of action is worth taking or if the risks are too high. 

Esteemed longevity expert, Peter Attia, MD, who believes HRT is the most effective proven treatment for menopause symptoms, summarizes this best, saying, “...when it comes to HRT or any other therapeutic intervention, there are always risks and benefits. How they balance may depend on the individual patient, but to my eyes, the scale tips in favor of HRT more often than it tips against it. The reports of health risks are dubious at best, whereas the boons to menopause symptom relief, bone health, psychological and sexual well-being, and possibly risk mitigation for chronic diseases all have the potential to increase one’s chances of living healthier, happier, and longer.”


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About the Author

Mia West

A former journalist, Mia brings a high energy approach to communications rooted in insights, culture and brand DNA. She is driven by helping brands crystalize their story and foster meaningful, emotional connections with audiences. Over the years she has collaborated with prominent brands such as Petco, Keurig Dr Pepper, Jaguar Land Rover, Revlon, and Procter & Gamble Beauty, as well as many others in the retail, health & wellness, beauty, lifestyle, and sustainability realms. A California native, she lives in San Diego with her family at the beach.

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