Has Estrogen Been Blamed For Cancer By Mistake?

An Update on Breast Cancer and Hormones

For decades there has been evidence and subsequent headlines about estrogen causing breast cancer.

For a quick recap:

In 2002, a study called the Women’s Health Initiative (WHI) was published.

It was a study that set out to determine if hormone replacement therapy (either estrogen + progestin or estrogen alone) would improve cardiac health of women.

This was done because in the decades prior, it seemed that women on hormones had better heart health.

The trial was stopped early due to increased breast cancer diagnoses in the estrogen + progestin group.

This was a massively publicized result, splashing across headlines.

About half of women on hormone replacement therapy at the time stopped.

Now 23 years later, the fear persists.

We now have a growing number of breast cancer diagnoses including women in their forties, so beyond persisting, the fear is growing.

A recent article was published on hormones as they relate to breast cancer.  It brings up some very interesting points that maybe we were pointing a finger at estrogen all this time when maybe progestin was to blame.

First, let's break down some terminology of hormones.

Types of Hormones

• Estrogen: we have three types of estrogen (estrone, estradiol, estriol)

These circulate at varying levels throughout our cycles, our lives and in pregnancies.

• Progesterone: also has varying levels throughout. This rises after we ovulate to support a pregnancy.

Preparation of Hormones

• Synthetic: a man-made form of a hormone

An example is birth control pills: both ethinyl estradiol and varying forms of progestin are synthetic

• Natural: extracted from a natural source, but not bioidentical (see below)

An example of this would be equine estrogen which was estrogen extracted from horse urine

• Bioidentical: made to have the same chemical structure as what we naturally produce

What is the evidence that estrogen is not to blame for breast cancer?

After all this time, estrogen may finally be getting exonerated.

Well, if we look back at the WHI, the group of women on estrogen alone (no progestin) actually had a decreased risk of cancer.  That suggests that estrogen then would not be to blame.

High-dose estrogen therapy was once used to treat breast cancer.  This was before we had medications called “estrogen blockers” (aromatase inhibitors such as tamoxifen). It was also before my time in practicing medicine.  The estrogen treatments were effective.

Women who undergo fertility treatments, particularly with ovulation induction (causing the ovaries to produce follicles) reach very high levels of estrogen.  This can even be up to 10 times the estrogen in a natural menstrual cycle.  There has been no increased risk of breast cancer in this population.

Women with a genetic predisposition to breast cancer (for example, BRCA1 gene) who take estrogen-only hormone therapy (after a risk-reducing surgery), have not had increased risk of breast cancer.

What is the evidence that progestin could be to blame for breast cancer?

Remember, progestin means a synthetic form of progesterone.

Birth control pills have been associated with increased risk of breast cancer and they contain synthetic hormones, including the progestin component.  The estrogen component has not been shown to have an effect on breast cancer risk.

In particular, a type of synthetic progestin called levonorgestrel (the type of progestin found in a hormone-releasing intrauterine device or IUD) has been shown to increase breast cancer risk when contained in a pill all by itself.  When combined with estrogen, it did not have this effect.

There is currently conflicting data as to whether the levonorgestrel IUD is associated with increased breast cancer risk.   

The Nurses’ Health Study showed a higher risk of breast cancer in women using progestin-only hormone replacement therapy.

Why does this seem to be the case?

The authors of this recent article illustrate that estrogen can actually affect the progesterone receptor on our cells.

A receptor on a cell is like a gate to enter the cell.  It may take some sort of unlocking, but once the correct molecule (or close enough) activates the receptor, the molecule (or hormone) can enter and affect change in the cell.

That means estrogen can open the gate or create more gates for progestins to enter our cells via their receptor.

When it comes to hormone replacement therapy,

Remember the WHI study used natural but not bio-identical estrogen plus synthetic progestin.

I use either prescription bio-identical hormones or compounded bio-identical hormones when using hormone replacement therapy for perimenopausal or menopausal women.  These have not been shown to have increased risk of breast cancer.

From this article which reviews a large amount of data, the synthetic form of progestin seems particularly culpable when it comes to breast cancer but ultimately this is very complex.

Resources:

Some of the information contained in this article is the result of my training, medical knowledge, and personal experience without a specific source to be cited.

This is not medical advice.

J. Kim, P.N. Munster,

Estrogens and breast cancer,

Annals of Oncology,

Volume 36, Issue 2,

2025,

Pages 134-148

https://www.sciencedirect.com/science/article/pii/S0923753424048804?ref=cra_js_challenge&fr=RR-1