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Hormone Replacement Therapy and Ovarian Cancer Risk

Medically reviewed by Howard Goodman, M.D.
Written by Maureen McNulty
Posted on January 27, 2022

According to the American Cancer Society, a woman who lives in the United States has about a 1 in 78 chance of being diagnosed with ovarian cancer at some point in her life. However, multiple factors can increase or decrease a person’s likelihood of developing this cancer.

Hormone replacement therapy (HRT) can lead to a slightly increased risk of ovarian cancer.

What Is Hormone Replacement Therapy?

HRT is a type of treatment that some people choose to use while undergoing the transitional stages of menopause. During menopause, the ovaries stop releasing egg cells and quit producing hormones, which cause a person’s menstrual cycles to cease. For the 12 months following someone’s last period, they are said to be in menopause. The stage leading up to those 12 months is called perimenopause, and it can last for several years.The stage following a person’s year of menopause is called postmenopause, and it lasts for the rest of their life.

Decreasing hormone levels can cause people to experience several symptoms during the stages of menopause. Such symptoms usually first appear during perimenopause.

Symptoms related to the three stages of menopause include:

  • Lighter — or heavier — periods
  • Short, long, or irregular menstruation cycles
  • Hot flashes
  • Night sweats
  • Insomnia
  • Vaginal dryness
  • Urinary urgency (needing to urinate suddenly)
  • Changes in mood
  • Difficulty concentrating

Hormone replacement therapy can replenish the body’s hormone levels and lessen symptoms during all stages of menopause. HRT can also help maintain bone strength and combat the bone loss that often occurs during these years.

Some types of HRT are systemic — they travel throughout the entire body and can treat all of the possible symptoms. Systemic HRT may come in the form of a pill, gel, cream, patch, or ring. Other types of HRT include vaginal creams, rings, or tablets that a person inserts into their vagina.

Although HRT can be useful, it can also increase the risk of developing conditions like:

  • Blood clots
  • Stroke
  • Heart disease
  • Gallbladder problems
  • Certain types of cancer, including endometrial cancer (cancer of the uterus) and breast cancer

People who are interested in HRT should have a conversation with their doctor weighing the risks and benefits of this treatment.

HRT and Ovarian Cancer

Hormone replacement therapy is studied for a couple of different purposes related to ovarian cancer. Some studies have analyzed whether using HRT can lead to a higher risk of ovarian cancer or other types of cancer. Other studies have examined whether these medications are effective as a part of a person’s ovarian cancer treatment plan.

Is HRT an Ovarian Cancer Risk Factor?

Several cancer research studies have shown that HRT can lead to a slightly higher chance of a person being diagnosed with ovarian cancer.

In 2003, the first study linking hormone medications to ovarian cancer was published. A group of U.S. researchers in the cancer and gynecological fields studied more than 16,000 people who were postmenopausal in 40 clinical centers throughout the country. The researchers assigned each study participant to either take HRT or a placebo (sugar pill). After following up with participants an average of 5.6 years from the onset of a person’s participation, ovarian cancer rates were slightly higher in the control group than in the placebo group.

Similar results were reported in a British study of nearly 1 million women published in 2007. Researchers found that people who were currently using HRT were 20 percent more likely to develop ovarian cancer and 23 percent more likely to die from the disease.

It is important to note, however, that a person’s risk of ovarian cancer is low to begin with, so ovarian cancer is still rare for those who have used HRT.

More recently, a group of ovarian cancer experts published a report in which they combined data from 52 different studies that analyzed the link between HRT and ovarian cancer. This report also found an elevated risk of the condition among HRT users.

These researchers reported a few key findings:

  • Ovarian cancer risk is only slightly raised by HRT use. If 1,000 people approximately 50 years old underwent HRT, researchers concluded that the drugs would likely cause only one case more of ovarian cancer than the number of diagnoses seen in a like pool of people who didn’t use them.
  • Risk was elevated for only two types of ovarian cancer: serous tumors (the most common type) and endometrioid tumors.
  • Once a person stops using HRT, their risk of developing ovarian cancer drops over time, although it remains slightly higher 10 years later.

Taken together, these studies show that — though it is a slight one — HRT can be an ovarian cancer risk factor.

HRT and the Risk of Developing Other Cancers

Individuals who use certain types of HRT may also have an increased chance of developing endometrial cancer (cancer of the uterus). Risk depends on the hormones in a person’s HRT medication — estrogen, progestin (progesterone), or both. Use of estrogen on its own — estrogen replacement therapy or ERT — can put them at a higher risk of endometrial cancer.

Taking HRT containing both hormones, however, does not increase a person’s risk.

Postmenopausal people who still have their uteruses often take estrogen-progestin drugs, while those who have had a hysterectomy (surgical removal of the uterus) can take estrogen-alone HRT.

Using estrogen-progestin therapy can also raise a person’s breast cancer risk. However, it is a temporary risk. Once a person stops taking HRT, their chances of developing breast cancer will return to normal 3 years later. HRT medications that contain only estrogen do not increase risk, and may even lower it.

HRT has not been linked to an elevated risk of several other types of cancer, including colorectal cancer (cancer of the colon or rectum), lung cancer, or skin cancer.

HRT as an Ovarian Cancer Treatment

Ovarian cancer treatment usually involves an oophorectomy (surgery to remove the ovaries). This leads to sudden onset of the menopause cycle. Some people use HRT to help reduce menopausal symptoms as a part of treatment for this cancer. Research shows that using HRT may help people with ovarian cancer live longer.

Who Is a Candidate for HRT?

When deciding whether to use HRT, you should consider the possible positive and negative effects. HRT may be worthwhile for people with moderate or severe hot flashes as well as those who have gone into menopause early. It can also be an option for women who are experiencing bone loss when other bone-strengthening treatments aren’t working.

HRT may not be a good option for those who are older than 60 years old and those who began going through the menopause cycle more than 10 years ago. People who have a family history or personal risk of blood clots, stroke, liver disease, or cancer may also want to avoid HRT.

If you are concerned about your chances of developing ovarian cancer, talk to your health care team about whether HRT is right for you. If you choose not to use HRT, other treatments may be available.

Different prescription medications that do not contain hormones can help treat various menopausal symptoms. Additionally, symptoms tend to be milder if you avoid caffeine and alcohol, or manage stress levels through meditation or other relaxation exercises.

Reducing Ovarian Cancer Risk While on HRT

Certain strategies can help people minimize risk of developing health conditions while using HRT medications. Taking the lowest possible dose that still provides symptom relief can help. Additionally, when you stop using HRT as soon as possible after your menopausal symptoms disappear, you lessen your risk.

If you experience vaginal or urinary problems, but don’t have other symptoms like hot flashes, it may be a good idea to use a vaginal insert form of HRT rather than systemic medications, like pills that are taken orally. This is because the vaginal insert forms usually contain lower doses of hormones than systemic options. It is also because hormones delivered systemically are usually absorbed into the bloodstream, where they can affect other organs in the body

Adopting healthy lifestyle habits may also help protect against cancer. While they don’t seem to lower a person’s overall risk of ovarian cancer, practicing more of these habits may be linked to a smaller likelihood of developing certain types of ovarian cancer, including serous cancer and metastatic cancer (cancer that has spread to other parts of the body).

Healthy habits include:

  • Eating a balanced diet full of nutrients
  • Getting more physical activity
  • Maintaining a healthy weight
  • Limiting or avoiding alcohol
  • Quitting smoking cigarettes

Healthy habits can also reduce risk of other cancer types, including endometrial cancer.

Talk With Others Who Understand

On MyOvarianCancerTeam, the social network for people with ovarian cancer and their loved ones, more than 3,000 members come together to ask questions, give advice, and share their stories with others who understand life with ovarian cancer.

Have you undergone hormone replacement therapy? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Howard Goodman, M.D. is certified by the American Board of Obstetrics and Gynecology and specializes in the surgical management of women with gynecologic cancer. Review provided by VeriMed Healthcare Network.. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

A MyOvarianCancerTeam Member

I also went through ovarian cancer debulking and my pathology report said my tumor was not estrogen receptive. My oncologist said it was safe for me to use the vaginal insert form which i have been… read more

June 1, 2023
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