Once leading the charts as #1 most prescribed drug in the US, Hormone Replacement Therapy has had ups and downs

Let me start by strongly recommending to those who are interested a book by Elizabeth Watkins, called The Estrogen Elixir: A History of Hormone Replacement Therapy in America. This book provides an extensive history of hormone replacement therapy, and does a comprehensive analysis of the pros and cons leaving the reader to decide what is best for them.

“Estrogen deficient woman are nothing but the walking dead.” – Marie Hoag

“I’ve seen estrogen make princesses out of witches.”  – Anonymous

“I’m what is known as perimenopausal. “Peri”, some of you may know, is a Latin prefix meaning ‘SHUT YOUR FLIPPIN’ PIE HOLE”.”  – Celia Rivenbark

Before a woman reaches menopause there is a period of time that can be described as a hormonal rollercoaster, or in the medical community ‘perimenopause’. Above are a few quotes from women who cared to share their thoughts about such a time in their lives. There are often physical symptoms, including irregular and/or heavy bleeding, insomnia, night sweats and/or hot flashes, worsening PMS, migraine, vaginal dryness and abdominal weight gain. To go along with these, there are also many emotional symptoms that may occur, I assure you few are positive. Hormonal replacement therapy has been suggested as a possible treatment for these symptoms in the short term, as well as many of the chronic diseases that women face in the long term which historically have been associated with menopause. 

Menopause is an issue that has been studied and dealt with vigorously by women trying to avoid the symptoms, doctors trying to help their patients, and of course pharmaceutical companies trying to take advantage of the opportunities. In the middle of the 1900s a common theory stated that these symptoms and other chronic diseases are caused by an estrogen deficiency, and so replacement therapy would be beneficial. In the 1960s a book called Feminine Forever by Robert Wilson went viral (or whatever the equivalent at that time was), and sales of estrogen supplements skyrocketed. However in 1975 two studies were published showing the connection between estrogen replacement therapy and increase in endometrial cancer, causing sales to plummet. In the coming decades, sales of the hormones recovered and kept increasing. Progesterone, another hormone heavily involved in the menstrual cycle was added to the therapy and helped to improve the risks of endometrial cancer that were created from estrogen therapy. In fact sales increased so much that in 1992, Premarin (a mixture of estrogens obtained from natural sources) was the single most prescribed drug in the United States. It remained number one or two for the remainder of the century. 

Where did the drive and support for hormonal replacement therapy come from?

I’m going to skip the issue of big pharmaceutical companies and their incentives to make money, and even though much can and should be said about this subject I want to touch on some other very interesting points.

Celebrity influence is something that has always amazed me. I never understood why the simple fact that someone is famous gave them so much influence on our lives, and why we treat them like gods. We shower them with gifts and offerings, hang on to and record every word they say, and we are quick to follow their advice as if they have divine powers. The fact that they may not be experts in the certain area that they are speaking about is not relevant much of the time. Suzanne Somers was, and still is, a huge advocate for the entire supplemental industry, and she made her rounds on talk shows bragging about it. She eventually got to the most powerful woman in the world, Oprah, who continued the conversation, making it about women taking control of their health. What was not mentioned was the amount of endorsement money people like Suzanne Somers were taking in from the advertising and links she had on her website.

There is no doubt that these, along with other celebrities played a major role in the trends and popularity of hormonal therapy, but the research and science behind it is much more important to me, and I hope to you too. As we know, hormone levels (estrogen and progesterone) dramatically decrease after a woman goes through menopause. There was once a belief that replacing these hormones, either one or both can lead to a reduction in long term chronic diseases such as cardiovascular disease, dementia, and osteoporosis. A number of studies tested the use of estrogen, a combination of estrogen and progesterone, and placeboes to see the outcomes over several years. It’s important to note that most of the trials were terminated early due to dangerous adverse effects. This being said, there were some positive effects on the outcome of long term chronic diseases.

A study published in 2011 described a population of women that had been treated with estrogen for five years, then the treatment was discontinued. The study recorded their health conditions for a period of ten years after the estrogen treatment finished. Compared to a population that had not received hormonal therapy in the past, the study showed a reduced risk for invasive breast cancer in the treatment group. During this period there was no significant difference in risk for chronic heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality.

Two additional studies showed a decrease in the incidence of diabetes in women taking both estrogen and progesterone. One study showed up to 35% reduction in diabetes for women who previously had been diagnosed with coronary heart disease. The other study showed a small but statistically significant reduction in diabetes over five and a half years of follow up. An estrogen only study initially showed promising results, but in the long run (three to six years) had no effect on incidence of diabetes.

What are the downsides and dangers?

In 1991/1992 two large studies were planned by the Women’s Health Initiative in an attempt to put an end to the uncertainty of the debate about hormone replacement therapy. One of these studies gave estrogen alone in comparison with a placebo, the other gave women estrogen and progesterone together. The results caused another big hit in sales of the hormone replacement industry.

The study treating women with both estrogen and progesterone wanted to mainly look at outcomes for coronary heart disease, but was stopped early due to increased risks for coronary heart disease as well as breast cancer, stroke and pulmonary embolisms. The study however did show decreased risk of colorectal cancer and hip fractures in the group that was treated with hormone therapy, but concluded that “Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women”.

There was no noticeable difference in the risk of other types of cancer between the two groups. Risk of impaired cognitive function more than doubled in the group taking hormones, and the risk of gallbladder disease also was increased in the group taking hormones.

The study treating women with estrogen alone was also stopped early. In 2004 the Women’s Health Initiative published their findings, showing no difference in coronary heart disease between the two groups, but the group taking estrogen had an increased chance of stroke. There was however a decrease in hip fractures, but similarly to the other study, this too concluded that the risks outweigh the benefits, and there was no justification in being treated with estrogen to prevent chronic disease.

What’s the bottom line?

The previous paragraphs may have been a little confusing or tough to follow, so as a whole I would like to sum up the major findings.

Hormone Replacement Therapy (Estrogen)

Increases risk of: Endometrial carcinoma, stroke, thromboembolic events, gallbladder disease.

Decreases risk of: Invasive breast cancer, breast cancer mortality, fractures.

Hormone Replacement Therapy (Estrogen + Progesterone)

Increases risk of: Invasive breast cancer, coronary heard disease, stroke, thromboembolic events, breast cancer mortality, lung cancer mortality, gallbladder disease, impaired cognitive function.

Decreases risk of: Diabetes, fractures, colorectal cancer (statistical significance is borderline).

The following organizations recommend against taking hormone replacement therapy in order to prevent chronic disease: US Preventive Services Task Force, The American Heart Association, The American Congress of Obstetricians and Gynecologists, and The Canadian Task Force on Preventive Health Care and the American Academy of Family Physicians. Does anybody endorse it? No, but The North American Menopause Society does not give a yes or no answer, and states that individuals should choose as they please while taking the appropriate evidence into account. And of course, Suzanne Somers.

 

 

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