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The Relationship Between Menopausal Hormone Therapy Formulation & Breast Cancer

By December 15, 2022December 28th, 2022No Comments

Menopausal hormone therapy has long been associated with increased breast cancer risk. For those taking the therapy long-term for longer than 5 years, this is a big problem.

However, scientists have found that not every hormone therapy is equal. Some can be a foe to those susceptible to cancer; some others are safe – the therapy formulations matter.

Which type of hormone is good for you? Read on to find out.


Breast Cancer Risk Depends on Menopausal Hormone Therapy Formulation

What Is Menopausal Hormone Therapy?

Menopausal hormone therapy, also known as hormone replacement therapy (HRT), is a well-established treatment for managing menopausal symptoms in women.

As women age, hormone levels fluctuate, so much so that the body experiences various conditions, from mild to severe, and loses the vigor it once had. This deterioration occurs because hormones like estrogen and testosterone are vital chemical messengers that regulate the activities of the cells.

The most common signs and symptoms of menopause are:


These conditions are collectively known as vasomotor, genitourinary, and sexual disorders, which aren’t life-threatening but will significantly decrease a woman’s quality of life.

Menopause can be even more debilitating than that. Since hormones play a role in bone health, menopause may cause bone-related diseases, such as osteoporosis or bone loss.

According to research, osteoporosis affects 1 in 10 women over 60 (typical menopause age) and can cause 20% of bone loss during this stage. Moreover, osteoporosis affects 1 in 2 postmenopausal women, most of whom suffer a fracture at some point.


Why Is Menopausal Hormone Therapy Used?

For this reason, hormone therapy emerges as a safe and efficient approach to resolving the suffering due to menopause.

Menopausal hormone therapy comes in various forms and routes of administration. The two main types of hormones include:

  • Estrogens (estradiol, estrone & estriol)
  • Progestogens (either a synthetic version called progestin or a bioidentical version called micronized progesterone)


You may have either estrogen-only or a combination of estrogen and progestogen. However, take estrogen-only therapy after a hysterectomy (a surgical procedure to remove the womb).

The route of administration also decides whether you’ll respond to the treatment and successfully relieve the symptoms. Some standard methods include:

  • Oral tablets
  • Skin patches
  • Gels, creams, & sprays
  • Pellet implants


Pellet implantation is the most effective way to administer hormones into the body. This approach bypasses the gastrointestinal system, causing no side effects related to digestion. Pellets are also stable, so you can control and adjust the dose during the treatment.


Menopausal Hormone Therapy and Breast Cancer


However, menopausal hormone therapy has been associated with an increased risk of breast cancer. Unfortunately, there is a clue.

Research has shown that compared to women who never take the therapy, those on hormones are more likely to have breast cancer after 5 years. Taking hormone therapy in the short term, like 1 year or less, may also increase the risk at a lower rate.

The longer you take hormone therapy, the greater the risk.

However, not every hormone is equal. For example, according to a recent study by the American College of Obstetricians and Gynecologists, hormone therapy only increases breast cancer risk in a formulation-dependent manner.

The study analyzed over 43,000 breast cancer cases out of 431,830 women from 1995 to 2014. Scientists found that not every type of hormone results in a side effect, with the estrogen-only formulation appearing safe.



Compared to women who never take therapy, those on estrogen-only treatment don’t have a noticeably increased risk of breast cancer.

The added risk of bioidentical estrogen is only 4%, while animal-derived estrogen is 1%. If you combine both types, the risk may decrease by 4%.


Combined Estrogen-progestogen

Nevertheless, the risk may otherwise increase if you combine estrogen and progestogen. Specifically, synthetic progestin is associated with breast cancer.

While the bioidentical version (micronized progesterone) does not affect breast cancer risk, synthetic progestin increases the risk by up to 28%. Thus, micronized progesterone may be the safer progestogen when prescribing hormone therapy.


Other Factors That Affect the Risk of Breast Cancer

Not everyone taking hormone therapy has the same risk. Multiple factors, including dosage, administration route, and treatment initiation time, lead to different outcomes.

As mentioned above, pellet implantation is the most efficient administration route of hormone therapy while minimizing the side effects.

Meanwhile, determining the appropriate dosage is a bit tricky. How much hormone you take depends on your current hormone levels. Doctors usually perform a blood test on you to identify your hormone status, then work out a plan that includes a regimen for you.

An earlier diagnosis is a better one. When you start taking menopausal hormone therapy is the most crucial factor affecting your breast cancer risk.

If you start the therapy from 50 to 59 years of age or within 10 years of menopause, you’re safe. In contrast, taking hormones beyond 60 or further than 10 years from menopause will result in a much higher risk.

If you’re susceptible to breast cancer, please consider this factor.


Pros and Cons of Hormone Therapy for Breast Cancer

The American College of Obstetricians and Gynecologists’ study concluded that breast cancer risk depends on formulations. Although the therapy generally leads to increased side effects, synthetic progestin is the main culprit.


  • Relieve the symptoms of menopause
  • Improve sleep & sexual health
  • Prevent osteoporosis & bone loss
  • Manage the effects of early menopause
  • Alleviate ovarian insufficiency (failure of ovarian functions)
  • Normalize hormone levels after a hysterectomy



If taken long-term (more than 5 years) using the wrong hormone types, dosage, or administration route, menopausal hormone therapy may:

  • Increase breast cancer risk
  • Increase other cardiovascular events (blood clots, stroke, & heart attack)
  • Increase thyroid & gallbladder disease risk


Overall, the benefits outweigh the risks. Please prioritize taking hormone therapy following the recommendations to manage menopause symptoms while minimizing the side effects. Also, check with your doctor before deciding to take the treatment.



Abenhaim, Haim A. et al. (2022). Menopausal Hormone Therapy Formulation and Breast Cancer Risk. Obstetrics & Gynecology Journal.


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