Study: Removing ovaries before age 50 may increase the risk of chronic conditions for some women


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Women under 50 years of age who have had or are considering removing their ovaries

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Checked Breast cancer survivors

Checked People with a genetic mutation linked to cancer risk

Checked Previvors

Checked Women under 45

Checked Special populations: Premenopausal women who are not at increased risk of ovarian cancer


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Removal of ovaries and fallopian tubes prevents ovarian cancer, but it may come with other health risks. Experts recommend removal of ovaries and fallopian tubes in women at high risk for ovarian cancer due to inherited mutations in BRCA or other genes linked to ovarian cancer risk. For these high-risk women the benefit of ovarian cancer prevention outweighs the risk of long-term complications. Based on a recent study, some researchers feel that for women who are not at increased risk for cancer, the risk for some chronic conditions is too high to consider removal of both ovaries. (11/1/16)

Contents

At a glance In-depth
Findings     Limitations                
Clinical trials Resources and reference
Questions for your doctor  


STUDY AT A GLANCE

This study is about:

Whether there is a connection between women who had their ovaries removed before age 50 and an increased risk of common chronic conditions, such as depression, asthma, coronary artery disease, and osteoporosis.

Why is this study important?

Researchers want to better understand the risks and benefits of ovary removal before age 50. Preventing ovarian cancer is a benefit of this procedure. However, ovaries produce hormones and removing ovaries at a young age can increase the risk for other diseases. Women need to understand the benefits and risks of ovary removal in order to make informed decision about the procedure. For women with an average chance for developing ovarian cancer, the risks that result from losing these sex hormones may not outweigh the benefit. 

Study findings: 

  1. Women who had their ovaries removed before age 46 were at increased risk of depression, hyperlipidemia (high cholesterol and/or triglycerides in the blood), heart disease, coronary artery disease, arthritis, lung issues such as asthma and chronic obstructive pulmonary disease, and bone loss (osteoporosis).
  2. Women who had their ovaries removed between ages 46 and 49 were at increased risk for depression, anxiety, hyperlipidemia, diabetes, arthritis, and cancer (all types).

What does this mean for me?

While the results of this study suggest that having ovaries removed before age 50 may increase a woman’s risk of some chronic conditions, it is important to note that the women in this study were not at increased risk for ovarian cancer. Generally, more work needs to be done to confirm and understand these findings. Women should work with their health care providers to weigh their personal risks for ovarian cancer and determine whether or not they want to remove their ovaries, and if so, at what age.

Women diagnosed with breast cancer before age 50 meet national guidelines for genetic counseling and testing to see if they have an inherited mutation that increases breast and/or ovarian cancer risk. These guidelines recommend removing the ovaries and fallopian tubes for women who have a mutation in BRCA1 or BRCA2. Women with mutations in BRIP1, RAD51c, RAD51d, and the genes associated with Lynch syndrome should consider removal of their ovaries.

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Expert Guidelines

The National Comprehensive Cancer Network (NCCN) creates guidelines for the management of risk in women at high risk for cancer. 

Guidelines for oophorectomy in high risk women

  • NCCN recommends risk-reducing salpingo-oophorectomy for women with BRCA1 and BRCA2 mutations.
    • For women with BRCA1 mutations the surgery is recommended between age 35 and 40 and upon completion of child bearing.
    • For women with BRCA2 mutations they state that delaying risk-reducing removal of ovaries and fallopian tubes until age 40-45 is “reasonable."
  • NCCN suggests that women with Lynch Syndrome, BRIP1 or RAD51C or RAD51D consider undergoing the surgery.

Guidelines for hormone replacement after salpingo-oophorectomy in high risk women

In their guidelines NCCN also states that hormone replacement therapy in women who have RRSO does not negate the reduction in breast cancer risk associated with the surgery. However they do highlight the limitations of the existing research .

The North American Menopause Society is a professional society of experts in the field of menopause. In 2017 they released a position statement on hormone replacement therapy, which includes the following: 

  • Menopause symptoms and a variety of symptoms and diseases are more likely to occur in women who have surgical menopause from ovary removal. These symptoms can have a major effect on quality of life and potential adverse effects on the cardiovascular system, bone, mood, sexual health and cognition, which have been shown in observational studies to be lessened by estrogen therapy. 
  • Unless contraindications are present, estrogen therapy is indicated for women who have removed both ovaries, to reduce their risk of sexual side effects, bone loss, heart disease and cognitive decline. For women who retain their uterus, endometrial protection (eg-progesterone) is indicated.

Specific to women with BRCA1 or BRCA2 mutations who have removed their ovaries to lower their risk for cancer, they include the following:

  • For women with BRCA1 or BRCA2 mutations who have not be diagnosed with breast there is some evidence suggesting that that hormone therapy use after oophorectomy does not increase the risk for breast cancer any further.
  • Considerations should be made about the benefits of estrogen to prevent health risks caused by surgical menopause.
  • Considerations should be made (based on a limited amount of data) about hormone therapy until age 52 with discussions about longer use based on the individual patient.

Questions To Ask Your Health Care Provider

  • I I had breast cancer before age 50. Should I consider genetic testing to see if I am at increased risk of ovarian cancer?
  • How do I know if I am at increased risk for ovarian cancer?
  • I tested negative for a mutation in BRCA despite having breast cancer before age 50.  Should I be concerned about my ovarian cancer risk?
  • What are my options for preventing ovarian cancer or detecting it early?
  • I had my ovaries removed to reduce my risk for ovarian cancer. What steps can I take to prevent or reduce long-term complications?
  • Can you refer me to a menopause expert?

Open Clinical Trials

IN DEPTH REVIEW OF RESEARCH

Study background:

There are differing opinions on whether or not women with average (1.5%) lifetime risk of ovarian cancer should have oophorectomy (removal of the ovaries) before menopause. Oophorectomy is recommended for women with a high (up to 50% lifetime risk) likelihood of developing ovarian cancer due to a mutation in BRCA1, BRCA2 or other gene associated with increased ovarian cancer risk, because the benefit of cancer prevention far outweighs the chance of other health problems. However, some women have their ovaries removed for other reasons. For example, women undergoing hysterectomy (removal of their uterus) for other reasons will sometimes have their ovaries removed at the same time. For many years, experts debated whether women with an average risk of ovarian cancer benefit from removing their ovaries, or if the risk of other complications is too high. Previous research from the same team found that “for most women without a cancer indication, the long-term risks of bilateral oophorectomy performed before menopause are greater than the benefits.” However, others have argued more research is needed.

Walter Rocca and colleagues from Mayo Clinic published work in 2016 in the journal Mayo Clinic Proceedings that provides more data on risks of oophorectomy before menopause.     

Researchers of this study wanted to know:

Does removing ovaries before age 50 increase a woman’s risk of common chronic conditions associated with aging?

Population(s) looked at in the study:

This study followed 1,653 women with intact ovaries and 1,653 women who had both ovaries removed before age 50 for about 14 years (some women were followed for a longer period and some for a shorter period). The oophorectomies were performed between January 1, 1988 and December 31, 2007. Study participants who had their ovaries removed did so while also having their uterus removed (hysterectomy) for reasons other than cancer treatment or managing cancer risk. Women who had their ovaries removed to help treat breast cancer or reduce their high genetic risk of cancer due to a mutation in BRCA were excluded from this study. 

Study findings: 

  1. Women who had their ovaries removed before age 46 were at increased risk of depression, hyperlipidemia (high cholesterol and/or triglycerides in the blood), heart disease, coronary artery disease, arthritis, lung issues such as asthma and chronic obstructive pulmonary disease, and bone loss (osteoporosis).
  2. Women who had their ovaries removed between ages 46 and 49 were at increased risk for depression, anxiety, hyperlipidemia, diabetes, arthritis, and cancer (all types).
  3. Women who received estrogen therapy were able to reduce some of these increased risks. 

Limitations:

It is very important to note that this study looked only at women with an average risk for ovarian cancer; it did not include women with increased risk of ovarian cancer (such as BRCA mutation carriers) or women who had their ovaries removed to reduce their risk of breast cancer. As such, these findings do not apply to these women where the benefits likely outweigh the risks.

The study had other limitations as well. The authors acknowledge a potential underestimation of some of the conditions that they looked at because some participants may not have had symptoms or did not request medical attention. Additionally, the researchers recognize that there may be a surveillance bias—the women who had their ovaries removed may have more contact with their health care providers after their surgery. Finally, some of the women in this study had their ovaries removed about 20 years ago when the surgeries and estrogen therapies were different.

Conclusions:

This study suggests that having an oophorectomy before age 50 may increase a woman’s risk of some chronic conditions, including heart disease, lung disease, coronary artery disease, anxiety, and depression. There are many reasons women with breast cancer or high risk for breast cancer may consider removal of their ovaries, such as reduction of breast cancer risk, treatment for ER/PR-positive breast cancer, and reduction of ovarian cancer risk associated with inherited mutations. All women should discuss the risks and benefits of oophorectomy with their health care providers to determine which choice is best for them. 

It is important to remember that national guidelines recommend removal of ovaries and fallopian tubes after completion of childbearing for women with mutations in BRCA1 and BRCA2. Women with mutations in BRIP1, RAD51c, RAD51d, and the genes associated with Lynch syndrome are advised to consider removing their ovaries and fallopian tubes to reduce their ovarian cancer risk. Women with inherited mutations in these genes or who are undergoing oophorectomy for other indications should be told of the long-term risks of ovary removal, but reminded that the benefits of preventing ovarian cancer far outweigh the risks of long-term complications.  

Women at average risk of ovarian cancer should speak to their health care provider about considering risk when presented with the option to remove their ovaries.

Posted 11/1/16

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