Why there’s so much confusion about HRT
There’s been an enormous amount of confusion and flip-flopping around hormone replacement therapy (HRT) practices and recommendations, it’s no surprise everybody feels confused. Medical practitioners included.
A lot of this confusion came from one, not quite accurate headline on an article summarizing the outcomes of the Women’s Health Initiative – a large research study looking at estrogens effect in reducing coronary heart disease, cognitive decline, and chronic disease.
Estrogen therapy was already approved for the management and treatment of menopausal symptoms including hot flashes, night sweats, and insomnia. It was observed over time that women who were on estrogen or combination hormone therapy for menopausal symptoms had lower rates of heart disease and mental decline. The Women’s Health Initiative (WHI) wanted to investigate if estrogen therapy could be used with the primary intention of reducing chronic disease and put HRT to the test using the gold standard method of testing: a randomized control trial.
Over 16,000 women participated in the study and were randomly assigned hormones or a placebo. The study was looking at estrogen specifically, but any women who still had a uterus was also given a progestin to protect against uterine cancer resulting in two hormonal groups – those only taking estrogens and those taking estrogens with a progestin.
This is an important piece of the study I feel needs recognition and clarification to better understand the depth of the confusion that developed around the study outcomes and continues to plaque us today. The first point is estrogen. The estrogens used in the study were conjugated estrogens (brand name Premarin) which are synthetic, chemically different in structure to what your body makes and contains both estradiol and estrone. There’s no way to identify how much risk or benefit was from estradiol, estrone or both taken together. Another important thing to know is that conjugated estrogens are considered unsafe today and are rarely prescribed due to the known risks.
The second point is the study used medroxyprogesterone acetate (MPA), a progestin, not progesterone. Progestins and progesterone are not the same thing. Unfortunately, progestins and progesterone are used interchangeably in medical literature and discussions despite being rather opposite in their risks and influence in the body. They are both Progestogens – a class of hormones that bind to progesterone receptors, and they both can limit endometrial (uterine) thickening but beyond that, there are more differences than similarities.
The WHI researchers added a progestin to the estrogen group of women who had a uterus to prevent the thickening the uterus’ lining, a known side effect of estrogen use, to reduce the risk of uterine cancers. Much like using conjugated estrogens to muddy the waters, adding in medroxyprogesterone acetate further complicated the results as there was now an estrogen effect and a progestin effect to tease apart.
The study was discontinued 3 years early due to an increase in the relative risk of developing breast cancer with hormone use. Not to go too deep into the weeds on relative versus absolute risk, and statistics, but it’s valuable to understand that the risk of developing breast cancer in the hormone group compared to the placebo group was not statistically significant. Meaning it was such a small change it could have been from chance. To put this into numbers, it was 1 extra breast cancer case per 1000 women. In the placebo group, 4 out of 1000 women developed breast cancer and in the hormone group, 5 out of 1000 women developed breast cancer. These are the numbers, and let’s remember that breast cancer and every woman effected is in no way trivial or insignificant.
An interesting result in the hormone group or the women receiving hormones versus the placebo, was a greater incidence of breast cancer cases in the woman taking both conjugated estrogens and progestins. The group of women taking only estrogen saw a reduction in breast cancer risk as time went on.
The headline that changed everything stated, “estrogen causes breast cancer”, not exactly wrong but clearly, it’s much more complicated. The fallout from that headline was an abrupt discontinuation of prescribing hormones regardless of menopausal symptoms, leaving many women without a treatment or support for disruptive and debilitating symptoms.
The WHI results have been re-evaluated over through an updated lens that includes decades more research and observations. Thankfully, better understanding of hormone risks and benefits have been identified bring more clarity and precision to the world of HRT.
Some of those revisions in recommendations include the type of hormone to use, how to administer the hormones, what age is appropriate to start and when to consider stopping.
We know that topical estradiol is the safer option for estrogen therapy. Patches are proving to provide the most stable and effective dose of estrogen with significantly lower risks of strokes or cardiovascular events. Oral estrogens pose a much higher risk of forming clots that can lead to strokes, heart attacks or pulmonary embolisms.
We also know that progestins are not the same as progesterone. Micronized progesterone, brand name Prometrium, is very similar in structure to the progesterone your body makes. It’s considered bioidentical and has a similar effect in the body as your naturally produced progesterone. Micronized progesterone can balance the effects of estrogen and limit the thickening of the uterine lining, alleviates menopausal symptoms, decreases anxiety, reduces insomnia and is neuroprotective.
Progestins, despite being able to protect the uterine lining, has a completely different chemical structure and studies are showing poorer outcomes compared to progesterone. The cellular and molecular mechanisms of progestins exert such extreme effects that it’s been shown to contribute to breast cancer, coronary heart disease, cognitive decline, and Alzheimer’s.
The age that you start HRT is another important piece to anyone’s decision to use HRT, it’s important to note that the average of women in the WHI was 63. Many of these women had been menopausal for over a decade before being started on HRT. Current research is pretty conclusive that starting HRT in perimenopause or very close to menopause provides the highest benefit with the least amount of risk. After 10 years of use, that risk: benefit ratio changes.
Hormone therapy can be an effective tool in managing menopause and truly raise a women’s quality of life. That said, it needs to be a personal decision and the details, like what hormones are used, how are they taken and what your menopausal status is, matters. Despite the benefits, there are still risks and those need to be thoroughly discussed and evaluated based on past health, current health, family history, lifestyle, and goals to make sure it’s the right thing for you.
Perimenopause, menopause, hormones, women’s health, and aging are complex and nuanced subjects. Individualized medicine, how I believe it should be practiced, is to take all the details into considering and help each woman decide what’s best for her. There is no one size fits all and hormones are not all good or all bad.
Hormone therapy, as with most of medicine is an ever-evolving practice. It’s important to know what’s driving decisions, recommendations, and the perpetuations of outdated information so you can ask the right questions and receive the best care.
Keeping you in pursuit,
Dr. Marsha✨