Menopausal Hormone Replacement Therapy And The Risk Of Ovarian Cancer: A Meta
- 1Department of Reproductive, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- 2Department of Gynecology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- 3Department of Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- 4Department of Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
Background: Findings by epidemiologic studies on menopausal hormone replacement therapy and the risk of ovarian cancer are inconsistent. This study aimed to assess the association of menopausal HRT with the risk of ovarian cancer by histological subtype.
Methods: A literature search was performed in PubMed, Web of Science, and EmBase for relevant articles published from inception to August 2018. Pooled relative risk ratios with 95% confidence intervals were determined with a random-effects model.
This meta-analysis suggests that menopausal HRT may increase the risk of ovarian cancer, especially for serous and endometrioid tumors.
Strengths And Weaknesses Of This Study
Some limitations of this study arise from inevitable shortfalls in completeness and accuracy within any routinely collected dataset. A small proportion of women had missing information on smoking status, alcohol consumption, and BMI, but these were dealt with by multiple imputation. As we did not have reliable data for age at onset of menopause for all women, we estimated onset from the first menopause specific record before the earliest HRT prescription. For women with no such record we assumed onset within the most common age range of 50 to 54 years. We did not investigate the differences between continuous and sequential HRT because these regimens are prescribed at different times after menopause. As our cases and controls were matched by age, they would likely have been prescribed similar regimens, making a comparison infeasible. Our primary focus, anyway, was recent long term exposure.
Taking Estrogen With A Progestin Vs Estrogen Alone
Treating menopausal symptoms with estrogen and progestin together is known as estrogen-progestin therapy or combined hormone therapy. Although estrogen alone improves the symptoms of menopause, it increases the risk of cancer of the uterus . Adding a progestin to the estrogen lowers the risk of endometrial cancer back to normal. Because of this, EPT is given to women who still have a uterus . EPT can be given 2 ways:
- Continuous EPT means the same dose of estrogen and progestin is taken each day. Women often prefer continuous EPT because it rarely leads to menstrual-like bleeding.
- Sequential EPT means different amounts of each hormone are taken on specific days. There are different ways to do this. For example, estrogen can be taken by itself for 14 days, then estrogen plus progestin for 11 days, then neither hormone for 3 to 5 days. Other schedules involve taking progestin only every few months. This lowers the amount of progestin that you are exposed to. Monthly regimens are also thought to result in hormone levels that are more like the natural menstrual cycle. Cyclical EPT can produce bleeding like a menstrual period, but it can occur less often than monthly.
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Reminder For Prescribers About Licence Recommendations For Hrt
HRT should only be initiated for relief of postmenopausal symptoms that adversely affect quality of life and should be continued only as long as the benefit in alleviating menopause symptoms outweighs the risks associated with HRT use.
In all cases, a careful appraisal of all the risks and benefits should be undertaken before use. These should be reassessed regularly during use as a womanâs need for treatment and risk of adverse effects change over time.
A summary of the numbers of HRT-related breast cancers estimated from the new study, plus a summary other key risks and benefits of HRT use, is provided in table 1.
Table 2 provides revised estimates of relative and absolute risks of breast cancer per 1000 women with 5 or 10 years of HRT use from age 50 years from the new study. The table also provides a reminder of relative and absolute risks per 1000 women of other key risks and benefit in terms of reduction in fracture risk.
Hormone Replacement Therapy And Breast Cancer: An Overview
It is projected that by 2050, 1.6 billion women in the world will have reached menopause or the postmenopausal period, a significant increase, compared with a billion women in 2020. Of all menopausal women, around 75% are affected by troublesome menopause symptoms, such as hot flashes and night sweats. Around 84% of postmenopausal women experience genitourinary symptoms, such as vulvovaginal atrophy and incontinence.
Menopausal hormone therapy is the most effective treatment for managing these symptoms however, its effects on numerous aspects of female health remain uncertain, in particular with regard to breast cancer. The influence of MHT on breast cancer remains unsettled, with discordant findings from observational studies and randomized clinical trials, a factor that affects the decisions made by doctors concerning hormone therapy in menopausal women.
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Unanswered Questions And Future Research
In our study protocol we did not prespecify analyses relating to cancer stage or tumour type because these lay outside the main question of interest. Although information on risk related to individual progestogens could be improved, previous studies have shown that the associated risks between HRT and tumour types might differ, with higher risks of developing oestrogen receptor positive tumours and lobular tumours.11 Knowing the cancer stage could also address the question of risk differences between women of various body weights, to clarify whether systematic differences might exist in diagnostic delay. Other unknowns include questions about breast cancer survival rates and all cause mortality in women using HRT.13
Who Shouldnt Take Hrt
We worry about women who are at elevated risk of heart disease, have untreated hypertension, atherosclerotic plaque, or are at high risk for dementia or have changes already present in their brain on MRI scans, Pinkerton said.
You should also be wary if you have an elevated risk of blood clots or stroke, have had an estrogen-sensitive breast or uterine cancer, or liver issues.
The risks may go up at higher doses, the longer you use a medication, or as you age.
When looking for an alternative to hormones to treat hot flashes, David said, I tend to pick a drug that will benefit patients in another way. If she has a mood disorder, perhaps Effexor or another SSRI . If she has chronic pain, gabapentin.
Pinkerton also notes that clonidine patches, a high blood pressure treatment, has been helpful off-label, meaning it hasnt been approved for that purpose by the U.S. Food and Drug Administration .
Nonprescription therapies that have shown benefit in clinical trials include hypnosis, cognitive behavioral therapy, and possibly acupuncture, she added.
About half of all women in menopause end up with vaginal dryness, which is uncomfortable and can make sex painful.
For many, urination becomes an issue waking up frequently to urinate, leaking while sneezing, or embarrassing accidents.
Estrogen pills that are fired with a dispenser into the vagina, helps both dryness and urination problems.
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How Much Hormone Therapy Costs
The cost of hormone therapy depends on:
- the types of hormone therapy you receive
- how long and how often you receive hormone therapy
- the part of the country where you live
Talk with your health insurance company about what services it will pay for. Most insurance plans pay for hormone therapy for their members. To learn more, talk with the business office where you go for treatment. You can also go to the National Cancer Institute database, Organizations that Offer Support Services and search “financial assistance.” Or call toll-free 1-800-4-CANCER to ask for help.
Society And Public Perception
Wyeth, now a subsidiary of Pfizer, was a pharmaceutical company that marketed the HRT products Premarin and Prempro . In 2009, litigation involving Wyeth resulted in the release of 1,500 documents that revealed practices concerning its promotion of these medications. The documents showed that Wyeth commissioned dozens of ghostwrittenreviews and commentaries that were published in medical journals in order to promote unproven benefits of its HRT products, downplay their harms and risks, and cast competing therapies in a negative light. Starting in the mid-1990s and continuing for over a decade, Wyeth pursued an aggressive “publication plan” strategy to promote its HRT products through the use of ghostwritten publications. It worked mainly with DesignWrite, a medical writing firm. Between 1998 and 2005, Wyeth had 26 papers promoting its HRT products published in scientific journals.
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Hormone Replacement Therapy And Cancer
Hormone replacement therapy is often prescribed for women during menopause. Menopause is a natural phase of maturing womanhood, during which the ovaries produce significantly less estrogen, ovulation ceases, and menstruation ends. For many women, menopause has uncomfortable side effects. Hot flashes, sleep disturbances, depression, mood swings and anxiety may affect the menopausal woman. Additionally, menopause may also be accompanied by increased urinary tract infections, incontinence, vaginal discomfort due to a lack of estrogen-based lubrication and decreased bone density. HRT has been effectively used to mitigate these side effects and can be prescribed for women experiencing these unpleasant symptoms of menopause. Results from several clinical studies have demonstrated a correlation between the use of HRT and the development of breast cancer, as well as an increase from death caused by breast cancer.
What Is Menopausal Hormone Therapy
Menopausal hormone therapy also called postmenopausal hormone therapy and hormone replacement therapyis a treatment that doctors may recommend to relieve common symptoms of menopause and to address long-term biological changes, such as bone loss, that result from declining levels of the natural hormonesestrogen and progesterone in a womans body during and after menopause.
MHT usually involves treatment with estrogen alone or estrogen plus progestin, a synthetic hormone whose effects are similar to those of progesterone.
Women who have a uterusthat is, who have not had a hysterectomyare generally prescribed estrogen plus progestin for MHT. This is because estrogen alone is associated with an increased risk of endometrial cancer, but estrogen plus progestin is not. Estrogen is used alone only in women who have had a hysterectomy.
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Why Would A Woman In Menopause Take Hrt Some Women Take Hormone Replacement Therapy To Ease Menopausal Symptoms Hrt Is Medicine That Contains Hormones That The Ovaries Make Less Of As Women Age And Reach Menopause Hrt Can Be Taken As Estrogen Only Or As A Combination Of Estrogen Plus Progestin Combined Hrt Is Most Commonly Used Estrogen
Combined HRT may help relieve menopausal symptoms, protect against osteoporosis and reduce the risk of colon cancer.
Research shows that long-term use of combined HRT increases the risk of breast and ovarian cancer, heart disease, stroke and pulmonary embolism . The research suggests that the risks of long-term combined HRT use outweigh the benefits for most women.
The decision to take HRT is personal and should be made with the help of your doctor. Concerns about cancer, heart disease and stroke should be discussed when considering the benefits and risks of HRT.
When Do Menopause Symptoms Start And How Long Do They Last
Youve entered menopause when you havent had a period for 12 months in a row.
That moment ordinarily arrives between the ages of 48 and 55, generally after a transition with inconsistent bleeding.
Heat rises in the chest, face, and head, followed by flushing, perspiration, and sometimes chills. At night, you might find yourself waking up drenched with sweat.
Those sleep interruptions make fatigue the primary symptom of menopause around the world, Robin Phillips, a New York gynecologist and editor of The Menopause Bible: The Complete Practical Guide to Managing Your Menopause, told Healthline.
Doctors previously thought that vasomotor symptoms lasted from six months to two years, but they can last much longer. Half of all women who experience frequent hot flashes live with them for more than seven years, according to another major study .
If your first hot flashes come while youre still bleeding, the median is nearly 12 years.
African American women and women with more depression or anxiety also tend to endure symptoms longer.
We had women coming for help with menopause in their 60s, 70s, and 80s, David said. So we looked into the data.
The Mayo team found that more than 40 percent of women age 60 and up reported moderate or severe symptoms.
However, David pointed out that 60-plus women who were taking hormones had no hot flashes or night sweats.
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Implications For Clinicians And Policymakers
This study delivers more generalisable estimates of the different risks of breast cancer associated with specific progestogen components of HRT, while confirming no increased risks from short term use of oestrogen only, estradiol-dydrogesterone, and tibolone. Increasing duration of use was generally associated with increased risk, with tibolone and estradiol-dydrogesterone showing the smallest risks. The frequency of prescribing for treatments including dydrogesterone was, however, much lower than for those including norethisterone, medroxyprogesterone, or levonorgestrel.
What Hormones Are Used To Treat The Symptoms Of Menopause
The hormones most commonly used to treat symptoms of menopause are estrogen and progesterone. . Often, these 2 hormones are used together, but some women are given estrogen alone. Its important to know which hormones you are talking about when looking at the risks.
Common estrogen preparations used to treat menopausal symptoms include conjugated equine estrogens and estradiol, but several forms or types of estrogen are available.
There are also many progestins available, but medroxyprogesterone acetate , is often used with an estrogen to treat menopausal symptoms. Some preparations contain both an estrogen and a progestin.
Androgens are also sometimes used to treat menopausal symptoms. This is not common, though, and because only a few studies have looked at this practice, it isnt clear how safe it is in the long run.
Tibolone is a synthetic hormone drug that can act like estrogen, progesterone, and testosterone in different tissues of the body. Because this drug isnt available in the US, its not discussed here.
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You May Be Interested To Read
A large-scale study of HRT and the risk of breast cancer: Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. The Lancet 2003 362:9382
Menopause: diagnosis and management – National Institute for Health and Care Excellence guidance on diagnosing and managing menopause.
HRT and breast cancer risk: a blog post from the ICR discussing what research about HRT and breast cancer means for women.
Funding: This work is partially funded by the NIHR School for Primary Care Research and by Cancer Research UK through its Oxford Centre.
Conflicts of Interest: The study authors declare no conflicts of interest.
Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author and reviewer and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Do The Benefits Of Hrt Outweigh The Risk
Hormone replacement therapy is an effective treatment for relieving hot flashes from menopause. But the known link between hormone therapy and increased breast cancer among risks has discouraged many women and their doctors from choosing or recommending this treatment.
The type of hormone therapy , as well as the woman’s individual characteristics, risk factors, and severity of menopause symptoms, should be considered when weighing the risks and benefits of HRT. The decision to use hormone therapy after menopause should be made by a woman and their health care provider after weighing all of the potential risks and benefits .
The known association between HRT and breast cancer has prevented many breast specialists from recommending it for breast cancer survivors. Unfortunately, many women experience menopause symptoms after breast cancer treatment. Some forms of chemotherapy may also cause early menopause in premenopausal women.
In the past, doctors may have offered HRT after breast cancer treatment because there weren’t clearcut studies showing any harm. However, early in 2004, a study was stopped early after showing that cancer survivors on HRT were more likely to develop a new or recurrent breast cancer. Doctors now feel it is too risky to treat breast cancer survivors with HRT.
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Why Does Hrt Increase Breast Cancer Risk
Its not fully understood why HRT increases the risk of breast cancer, but research suggests that this is due to the higher levels of oestrogen. Some breast cancers can use oestrogen to help them to grow.
There are some factors that can influence the risk of breast cancer.
- How long you take HRT for. The longer you use HRT, the greater the risk
- The type of HRT you are taking. Breast cancer risk is greater with combined HRT than with oestrogen-only HRT
Estrogen Therapy And Cancer Risk
In women who still have a uterus, using systemic ET has been shown to increase the risk of endometrial cancer . The risk remains higher than average even after ET is no longer used. Although most studies that showed an increased risk were of women taking estrogen as a pill, women using a patch or high-dose vaginal ring can also expect to have an increased risk of endometrial cancer.
Because of this increased cancer risk, women who have gone through menopause and who still have a uterus are given a progestin along with estrogen. Studies have shown that EPT does not increase the risk for endometrial cancer.
Long-term use of vaginal creams, rings, or tablets containing topical estrogen doses may also increase the levels of estrogen in the body. Its not clear if this leads to health risks, but the amounts of hormone are much smaller than systemic therapies.
ET is not linked to a higher risk of breast cancer. In fact, certain groups of women taking ET, such as women who had no family history of breast cancer and those who had no history of benign breast disease, had a slightly lower risk of breast cancer.
The WHI study of ET did not report any results about ovarian cancer.
To put the risk into numbers, if 1,000 women who were 50 years old took estrogen for menopause for 5 years, one extra ovarian cancer would be expected to develop.
ET does not seem to have any effect on the risk of lung cancer.
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