Menopausal Hormone Therapy And Breast Cancer Risk: All Progestogens Are Not The Same
Keywords: Copyright
Menopausal hormone therapy is the treatment of choice for the management of bothersome menopausal symptoms, for the treatment of urogenital atrophy and for the prevention of osteoporotic fractures in symptomatic women at risk . If given during the menopausal transition or soon after menopause, MHT may prevent cardiovascular disease . Hormone replacement therapy , furthermore, should be administered to all women with premature ovarian insufficiency irrespective of the presence of menopausal symptoms, unless contra-indicated, for the prevention of chronic disease associated with premature estrogen decline . The fear of breast cancer, however, deters many clinicians from prescribing MHT or HRT and makes women reluctant to receive it over the long term.
In conclusion, clinicians have to put the risk of breast cancer associated with MHT into clinical context: The risk associated with long-term estrogen use is much lower than the risk conferred by obesity, inactivity and alcohol use . Furthermore, the findings of this study are not relevant to women with POI, in whom risks are calculated in comparison to women with regular menstruation. In general, tailoring hormone therapy to the needs of the individual woman ensures its long-term safety.
Key Points: Gallbladder Disease And Migraine
- 1. ET or EPT increases the risk of gallbladder diseases.
- 2. Careful monitoring of gallbladder disease is required in women using oral MHT.
- 3. Non-oral MHT is recommended for women with gallbladder disease.
- 4. Because there is a lack of data on the relationship between MHT and migraine, it cannot be concluded that migraine is a contraindication for MHT.
Can Other Drugs Interfere With Hormone Therapy
Certain drugs, including several commonly prescribed antidepressants , inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the body’s use of tamoxifen because CYP2D6 metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.
The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its effectiveness is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.
Many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors, such as switching from an SSRI that is a potent inhibitor of CYP2D6, such as paroxetine hydrochloride , to one that is a weaker inhibitor, such as sertraline or citalopram , or to an antidepressant that does not inhibit CYP2D6, such as venlafaxine . Or doctors may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.
Other medications that inhibit CYP2D6 include the following:
- quinidine, which is used to treat abnormal heart rhythms
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Mht For Women In Menopausal Transition
Menopausal transition refers to the period from the moment of increased variation in menstrual cycle until the moment immediately prior to the last day of menstruation. It varies among individuals and is a period that often includes vasomotor symptoms such as hot flushes alongside frequent or excessive menstruation. Hot flushes vary among individuals but may appear from 1 year to 3 years prior to the last day of menstruation and are especially severe around the last day of menstruation. They may even last for several years. Approximately 75% of women aged between 45 years and 55 years suffer from symptoms of menopause, which may lead to low self-esteem, sleep disorder, and feelings of decreased energy. To evaluate the ovarian reserve during menopausal transition, measuring the serum level of anti-mullerian hormone , day 3 follicle-stimulating hormone , estradiol , and ovarian antral follicle count using pelvic ultrasonography is possible, but they are not used as indicators for predicting menopause. Additionally, because the function of the ovaries changes during this period, it is advised not to conduct a hormone test for menopause diagnosis .
Hormone therapies for treating the symptoms of menopause during menopausal transition are combination therapy of levonorgestrel releasing-intrauterine system with oral or percutaneous estrogen, low-dose combined oral contraceptives , and estrogenâprogestogen therapy .
Key Points: Cognitive Function And Alzheimer’s
- 1. If MHT is started in early menopausal women, a prevention effect against the reduction of cognitive function could be expected although the evidence from randomized controlled studies is lacking.
- 2. Executing MHT with the sole purpose of preventing worsening or treatment of current cognitive function is not advised.
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Should A Person Take Hrt
The benefits of taking HRT can vary from person to person. Some people decide that the benefits outweigh the risks.
HRT can help relieve the symptoms of menopause. It can also help reduce the risk of developing osteoporosis.
A person should discuss the benefits and risks with a healthcare professional before deciding whether HRT is right for them.
If a person decides to take HRT, they should attend all their breast cancer screening appointments.
Overall Survival According To History Of Mht Use
During follow-up, a total of 111 patients died of which 59 patients had a previous recurrence. There were 51 deaths in ever MHT users and 60 deaths among never users. KaplanMeier analysis showed a significant association between ever MHT use and a longer OS vs. patients who never used MHT . The crude HR for ever MHT use was 0.68 compared with never use. However, when adjusted for covariates, the statistical analysis showed no significant difference in survival between ever MHT users and never MHT users, HRadj 0.81 . There were significant effect modifications between ever MHT use and OS depending on axillary lymph node involvement and AI treatment but not with other patient, tumor, or treatment related factors.
Ever MHT use was associated with lower risk of death in node-positive patients with a HRadj of 0.48 but not in node-negative patients, HRadj of 1.27 . Moreover, any MHT use was associated with a lower risk of death in AI-treated patients with a HRadj of 0.41 , but not in non-AI-treated patients HRadj of 1.23 , adjusted Pinteraction = 0.015), see Table 2 and Figure 4.
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Is Hrt Safe To Use For The Menopause What The Science Says
The National Institute for Health and Care Excellence launched its first guidelines on how to treat the menopause. But dont expect this to be the final word on the subject. There is an ongoing debate about the pros and cons of hormone replacement therapy , and not all of it is based on sound evidence. So now might be a good time to take a look at what the science tells us.
Key Points: Cautions For Ht
- 1. For women with the uterus intact, estrogen must be administered together with progestogen to reduce the risk of endometrial hyperplasia and cancer.
- 2. It is better to start MHT immediately once symptoms appear before or after menopause.
- 3. There is no need to impose a limit on the duration of MHT as long as an effective minimum dose is used, if women are well aware of the potential benefits and risks, and a regular clinical follow-up observation is accompanied.
- 4. Bioidentical MHT may be administered in excessive or very low doses, with no guidelines established for administration and routine tests, including blood tests.
- 5. There is a lack of evidence of the effects and safety of complementary therapy.
- 6. DHEA and ospemifene may be effective in treating GSM.
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What Is Hormone Replacement Therapy
HRT medicines usually contain the hormones estrogen, progesterone, or both, to replace the hormones a womans body stops making after menopause.
HRT is different than hormonal therapy medicines that block estrogen to treat hormone receptor-positive breast cancer.
There are two main types of HRT:
-
combination HRT, which contains both estrogenand progesterone
Estrogen-only HRT usually is taken only by women who have had a hysterectomy .
Combination HRT usually is taken by women who still have their uterus. Estrogen-only HRT can cause the lining of the uterus to become too thick a condition called estrogen-associated endometrial hyperplasia. This can increase the risk of cancer of the uterus, called endometrial or uterine cancer. The progesterone in combination HRT helps to prevent thiscondition.
In combination HRT, both hormones can either be combined into one medicine or given as separate medicines. The same dose of estrogen and progesterone can be taken daily , or in different amounts on different schedules .
There are several ways to take or use HRT:
Systemic HRT effectively treats many symptoms of menopause, including hot flashes and night sweats. Topical HRT only works on vaginal symptoms, such as dryness and discomfort during sex.
Heart Disease And Strokes
HRT does not significantly increase the risk of cardiovascular disease when started before 60 years of age, and may reduce your risk.
Taking HRT tablets is associated with a small increase in the risk of stroke, but the risk of stroke for women under age 60 is generally very low, so the overall risk is still small.
Page last reviewed: 09 September 2019 Next review due: 09 September 2022
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Patient Characteristics And History Of Mht Use
A total of 814 patients were analyzed in this study. Of the 814 patients, 433 had a history of MHT use or were current users at the time of inclusion while 381 patients had never used MHT prior to inclusion . In the group of ever MHT users, 265 had used MHT for 5 years or longer while 159 reported fewer than 5 years of use. There were significant differences in patient characteristics depending on MHT status. Ever MHT users had a lower BMI and a higher ever use of oral contraceptives vs. never MHT users. Furthermore, ever MHT users were less likely to be alcohol abstainers than never MHT users .
Table 1. History of MHT use in relation to patient and tumor characteristics.
Key Points: Cerebral Stroke
- 1. The risk of stroke in younger postmenopausal women is rare, and a meta-analysis including a WHI study found no increased risk of stroke in women aged younger than 60 years or who were fewer than 10 years from menopausal onset.
- 2. The risk of cerebral stroke differs depending on the age range and MHT increases the risk of ischemic stroke in women aged above 60 years.
- 3. Lower-dose oral hormone therapy or transdermal hormone therapy could relatively reduce the risk of stroke.
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Does Hrt Increase The Risk Of Breast Cancer
Most types of HRT increase the risk of breast cancer. But the risk is higher for those using combined HRT, which uses both oestrogen and progestogen.
Vaginal oestrogens are not linked to an increased risk of breast cancer, whereas tibolone is.
Taking HRT for 1 year or less only slightly increases breast cancer risk. However, the longer you take HRT the greater the risks are, and the longer they last.
The risk of breast cancer due to HRT can also vary from person to person. Things such as what age you are when you first start taking HRT, other medicines you may be taking, and your general health can impact the risk.
People who begin HRT before or soon after the menopause may have a bigger risk than those who start HRT later.
Duration Of Recent And Past Exposures As Categorical Variables
Recent users of HRT comprised 56% of cases and 50% of controls ever exposed to HRT. Figure 2 and figure 3 show the associations between categorised durations of HRT and risks of breast cancer in women with recent and past exposures. The patterns of risks for recently exposed women were similar to those for overall exposures, but the risks were consistently higher and more pronounced, particularly for oestrogen-progestogen therapy. For women with past exposures, risks associated with longer durations of use of oestrogen-progestogen, particularly longer use of levonorgestrel and norethisterone , remained high, but for other hormones the risks were not statistically significant. Findings for recent exposures to different doses and applications also had similar patterns to the overall exposure analysis, but with higher odds ratios .
Recent and past use of oestrogen, oestrogen-progestogen, and tibolone in association with breast cancer risk. Odds ratios are with reference to never users and adjusted for smoking status, alcohol consumption, Townsend fifth , body mass index, ethnicity, history of other cancers, oophorectomy or hysterectomy, records of early and late menopause, menopausal symptoms, mammography or scans, family history, comorbidities, other drugs, and years of data. Cases are matched to controls by age, general practice, and index date
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Korean National Health Screening And Breast Cancer Screening
The breast cancer screening program includes a standardized questionnaire about the following risk factors for breast cancer: age at menarche and menopause, parity, history and duration of breastfeeding, history of oral contraceptives and HRT, previous diagnosis of a benign breast mass, and family history of breast cancer . Data on history of HRT were obtained from this questionnaire but it has limitations, as the question asking about any hormone medications to relieve menopausal symptoms is quite broad. Data on the family history of breast cancer were not used in this study due to the high rate of missing data. Breast density by mammography was divided into four categories according to the Breast Imaging-Reporting and Data System classification .
Comorbidities were defined by the ICD-10 codes, use of related medications, or an abnormal measurement in the health examination. Hypertension was defined as an ICD-10 code of I10-13/15, a history of related medications, or systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg. Type 2 diabetes mellitus was defined as an ICD-10 code of E11-14, a history of related medications, or a fasting glucose level of 126 mg/dL. Dyslipidemia was defined as an ICD-10 code of E78, a history of related medications, or a fasting total cholesterol level of 240 mg/dL.
This study was approved by the Institutional Review Board of the Catholic University of Korea . Anonymous and deidentified information were used in the analyses.
Not Being Physically Active
Evidence is growing that regular physical activity reduces breast cancer risk, especially in women past menopause. The main question is how much activity is needed. Some studies have found that even as little as a couple of hours a week might be helpful, although more seems to be better.
Exactly how physical activity might reduce breast cancer risk isnt clear, but it may be due to its effects on body weight, inflammation, and hormone levels.
The American Cancer Society recommends that adults get 150 to 300 minutes of moderate intensity or 75 to 150 minutes of vigorous intensity activity each week . Getting to or going over the upper limit of 300 minutes is ideal.
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What Is Already Known On This Topic
- Long term systemic use of hormone replacement therapy is associated with increased risks of breast cancer, mostly attributable to the progestogens medroxyprogesterone, norethisterone, and levonorgestrel
- After discontinuation of treatment, the increased risks decline, but remain raised for some years
- A recent large meta-analysis has reported higher than expected breast cancer risks associated with HRT
Can Hormone Therapy Be Used To Prevent Breast Cancer
Yes. Most breast cancers are ER positive, and clinical trials have tested whether hormone therapy can be used to prevent breast cancer in women who are at increased risk of developing the disease.
A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial found that tamoxifen, taken for 5 years, reduces the risk of developing invasive breast cancer by about 50% in postmenopausal women who were at increased risk . Long-term follow-up of another randomized trial, the International Breast Cancer Intervention Study I, found that 5 years of tamoxifen treatment reduces the incidence of breast cancer for at least 20 years . A subsequent large randomized trial, the Study of Tamoxifen and Raloxifene, which was also sponsored by NCI, found that 5 years of raloxifene reduces breast cancer risk in such women by about 38% .
As a result of these trials, both tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for this use regardless of menopausal status. Raloxifene is approved for use only in postmenopausal women.
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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.