What is HRT? The History of Hormone Replacement Therapy (HRT)

Updated 05/29/2022

My friend Cindy is going through menopause, and it’s been a doozy. She’s having regular hot flashes and high irritability, among other symptoms. In short, she’s miserable! When I asked what she was doing about her symptoms, her response was “My doctor told me I should start hormone replacement therapy, but I just don’t know if I’m comfortable with that. Is it really necessary?”

That’s not a question I can answer lightly. There are so many pieces to the puzzle, so it has to be considered on an individual basis. But I was curious to know what exactly made her uncomfortable with the thought of HRT.

“I’ve heard so many conflicting things about it,” she said. “I just don’t know if it’s safe. Will I have even bigger health issues if I decide to try it?”

There has been a lot of controversy around HRT since its inception in the early 1900s. That’s because it was uncharted territory – we simply didn’t have any information about side effects when HRT was first being used. Since then, there have been many studies, including the large scale Women’s Health Initiative, but the results and methodology have been highly debated in the medical community.

For a long time, HRT was the go to treatment for menopause. Let’s take a look at why it became so popular, the information we’ve gained since its inception, and then I’ll offer up my thoughts on the subject and what I most often recommend.

Treating menopause

Menopause used to be seen as something women just have to suffer through. This myth still persists for some women, whose doctor’s dismiss their concerns and prescribe an antidepressant. Sure, living with the symptoms of menopause – the hot flashes, the bloating, the unpredictable mood swings and more – can lead to depression. But that’s just another symptom! We have to treat the root causes to correct the problem.

And here’s the thing – for far too long, menopause has been considered a “disorder.” In the 1940s-50, multiple books and publications pushed the use of estrogen therapy for these “disorders.” But in my opinion, the issue isn’t menopause, which is simpy a natural reproductive transition in women’s bodies, but the hormonal shifts that occur during this transition.

Still, the symptoms are uncomfortable and disruptive to women’s lives, and HRT can be quite effective in reducing those symptoms. The problem is, there’s also potential for some elevated risks of cancer, heart problems, and other serious issues.

What is HRT?

In simple terms, HRT is the replacement or balancing of hormones in a woman’s body through the use of synthetic hormones.

For over 70 years, menopausal women have been treated with HRT. The first brand sold in America was Premarin, which was made from conjugated equine (horse) estrogens. Concerns grew over this form of treatment as research showed increased incidence of uterine cancer in women who were using this form of therapy. Many years later, this finally prompted the drug company that manufactures Premarin to develop Prempro by adding a synthetic progestin.

History of HRT

How did estrogen therapy become the fifth most prescribed drug in 1975 (Bell, 1990). A lot of it, as with most drugs, comes down to media exposure and marketing. As I said earlier, there were a multitude of publications in the 40s and 50s that led to a steady increase in the use of estrogen therapy.

A wildly popular book by Robert Wilson called Feminine Forever, published in 1968, fueled the fire, encouraging the use of estrogen therapy to eliminate the emotional issues that come from menopause and make a woman “feminine forever.”

I have so many issues with this book, but the biggest is the idea that if a woman doesn’t replace those hormones she’s no longer a woman. Of course she is! But she may be a woman struggling, and there are ways to help reduce that struggle.

But let’s go back even farther. In 1933, an MHT product calle Emmenin, derived from the urine of pregnant women, was commercially produced and distributed. But this was expensive to produce, and ultimately, replaced by Premarin in 1941. Premarin was made from conjugated equine estrogens (Kohn, et al.).

In the 1970s, estrogen therapy declined after reports of increased risk of endometrial cancers were linked to the therapy. The FDA issued a warning on all estrogen products indicating a risk for blood clots and cancer.

In 1977, a book by Barbara Seaman titled Women and the Crisis in Sex Hormones identified several small studies linking HRT to breast cancer, stroke, and blood clots. This got people talking about the risks, but not for long.

Studies in the 1980s and 1990s, including the well known Nurses’ Health Study, began to report another benefit of HRT drugs: reduced risk of heart disease.

Studies also showed that adding progestin,( important to note here this is not the same as a progesterone), reversed the endometrial hypertrophy associated with endometrial cancer by over 97%.

Popularity of HRT surged again, and Premarin became the number one prescribed drug in 1992 (Kohn, et al).

Research and controversy

By the early 1990s, then, HRT was wildly popular. In fact, I heard more than once that some folks in the medical community almost considered it malpractice if you didn’t prescribe it to menopausal women.

In 1993 the Heart and Estrogen/Progestin Replacement Study (HERS) began, examining the effects of estrogen-progestin therapy on postmenopausal women with CHD. While, after the first year, incidence of cardiac events in women in the treatment group were higher than the placebo group. In the next three years, this was not found to be the case.

The study ultimately found that there was no benefit of hormone therapy for CHD. A second study HERS II, found the same results. Despite that information, in 1996, the United States Preventive Services Task Force (USPSTF) advised that all postmenopausal women consider using preventative hormone therapy (Kohn, et al).

In the later 1990s, however, many women began to question the use of HRT. Some of their questions included: “Do all women need it?”, “Why are all women put on the same dose and not different dosages?”, and “What is actually happening to the pregnant mare whose urine is being used as part of Premarin or Prempro?”. These women wanted to know if there was another alternative available to them. And these were all great questions!

On the flip side, many women were convinced that HRT was beneficial and would not have considered the possibility of stopping treatment. But in 2002, the results of an extensive women’s study (the WHI) looked at the effects of HRT (Premarin and Prempro — neither of which are bioidentical hormone forms); the findings overwhelmed the medical community, establishing that HRT in fact did NOT decrease a woman’s chance of getting heart disease, but rather definitively increased her risk of blood clotting, stroke and breast cancer.

As you can imagine, this was not the kind of news the medical community – or patients – wanted to hear. The publicity of these results led to new guidance for doctors and a drop in the use of HRT.

Later, however, these results were reanalyzed and these new studies showed that in younger women, the use of HRT could be beneficial to the cardiovascular system and reduce coronary disease and overall mortality rates (Cagnacci & Venier, 2019).

Current research has indicated that that there are differences between the effects for a 50-year-old woman placed on HRT and a woman who begins ten or more years after menopause. Researchers have been reexamining the data from the WHI study to see if there is a subset of women who might benefit from replacement hormones, as well as identifying subsets who should avoid it.

Alternatives to HRT

All of the confusion and controversy has led women to seek out alternative treatments to manage menopause symptoms. Those who stopped taking HRT found those symptoms rushing back, a huge disappointment after feeling the relief HRT provided. Still, the health risks of replacement hormones, particularly synthetic forms, scared them. To make matters worse, the pharmaceutical companies argued that there were no good or viable alternatives to HRT. But that simply isn’t true.

Today, there are many natural methods available that can help women ease the transition off HRT while at the same time providing the body with the care it needs to reduce or avoid menopausal symptoms. For help during this transition period, see our articles about ending hormone replacement therapy.

Bioidentical hormones – a new alternative

Numerous women have turned to bioidentical hormones as a superior form of HRT. These are female hormones – estrogen, progesterone, and testosterone – that are typically manufactured by our endocrine system, principally our ovaries, which naturally decline as the ovaries stop releasing eggs. “Bioidentical” means that the biochemical structure of the hormone is perfectly identical to the main hormones that are naturally produced in a woman’s body. Neither a horse’s hormone nor an artificially contrived formula, although similar in makeup, can replace what a woman produces naturally.

You may ask, “Why did bioidentical hormones take so long to come into play?” Pharmaceutical companies have had to create numerous nonhuman estrogens and progestins in order to patent their drugs, hoping that the small changes made to an estrogen or progesterone molecule would not have a negative impact on a woman’s body.

Today, unfortunately, we know that is often not the case. Birth control pills are an example of synthetic estrogens and progestins, and, as any woman who has ever taken them can confirm, each brand has different side effects. Some women, in fact, cannot tolerate birth control pills at all. The same can be said with hormone replacement therapy — bioidentical or synthetic! As we are all different, what works for one may not work for another.

In the 1990’s, pharmaceutical companies started developing and patenting methods of administering bioidentical hormones. One example is the Climara patch, which uses a sticky transdermal hormone delivery system. While Climara was patented in 1994, the estrogen, which is identical to human estradiol, cannot be patented; the patent was obtained by patenting the glue.

Moving into the Future of HRT

Many professionals believe that true bioidentical hormones can only be developed by a compounding pharmacy, and only after measuring a woman’s own hormone levels, and then customizing the dose. But in my experience, this approach is only required in a few cases, or for a short period in a woman’s life.

In any case, Mother Nature provides a woman’s body with numerous types of hormones and we cannot accurately reproduce her delivery methods or levels in the body. What we can do is estimate her methods and work alongside her. We can also observe a woman’s symptoms and see if we’ve found the right prescription. By helping to implement a good nutritional regime and supplements, appropriate exercise and other lifestyle changes, we have found that many women can manage their menopause symptoms very well!

There are times, however, when a woman can significantly benefit from a small amount of hormone replacement. I always recommend that you work through the challenges of menopause with your medical practitioner, especially if you have severe menopause symptoms, early menopause, or if you are compromising on your quality of life.

I told Cindy that I recommend a focus on lifestyle changes first, but if that doesn’t work then I do believe hormone therapy can help – as long as it’s bioidentical hormones. I told her, and I’m telling you, that there’s no need to suffer just because your body is making a natural transition. With all the right information, you can make an informed decision about bioidentical hormones, and begin to feel like the radiant, confident woman you were meant to be again!.

References:

Bell SE, Sociological perspectives on the medicalization of menopause. Annals of the New York Academy of Sciences, 1990. 592(1): p. 173–178. [PubMed] [Google Scholar]

Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas). 2019;55(9):602. Published 2019 Sep 18. doi:10.3390/medicina55090602

Kohn, Grace E et al. “The History of Estrogen Therapy.” Sexual medicine reviews vol. 7,3 (2019): 416-421. doi:10.1016/j.sxmr.2019.03.006

Wilson MDRA, Feminime Forever. 1968. [Google Scholar]

Reviewed by Dr. Mark Menolascino, MD