What You Need to Know About Menopausal Hormone Replacement Therapy (MHT)

I received this question from a reader 2 weeks ago:

Dear Dr. Oppitz,

A specific area I am dealing with and unfortunately many others are dealing with is a shift in hormones due to ovaries being removed.  I found out I had a BRCA mutation and was heavily encouraged to remove my ovaries which I did.  I was put on a hormone patch for a bit.  I wonder all the time if it’s wise or not to be on one.  Current guidelines say it’s safe to do short-term for BRCA patients.  But I wonder what short-term really means.  I also wonder if it’s best to stay on because of long-term risks for heart trouble and osteoporosis.  Different doctors have differing opinions.  Anyway, I think a lot of women due to mutation or breast cancer have ovaries removed and we are at a loss because doctors tell us most of the time estrogen is a bad idea, which I think I can understand.  But how do you take care of your body once a huge source of an important hormone such as estrogen has been removed?  Where does a person go from here?  I personally think a lot would benefit from a blog post on the topic.  I know I would!

-V.K.

Let’s start with the Global Consensus Statement on Menopausal Hormone Replacement Therapy (MHT) which are the core recommendations from the International Menopause Society.  MHT is the most effective treatment for vaso-motor symptoms (hot flashes, night sweats, etc) associated with menopause at any age.  Benefits likely outweigh risks for symptomatic women before the age of 60 years OR within 10 years after menopause.  MHT is effective and appropriate for prevention of osteoporosis-related fractures in at-risk women before age 60 OR within 10 years after menopause.  Standard dose estrogen alone may decrease coronary heart disease (CHD) and all-cause mortality in women under 60 AND within 10 years of menopause.  Estrogen + progesterone therapy (EPT) in women under 60 OR within 10 years of menopause shows a similar trend for mortality but in most randomized-controlled trials (RCT) there was no increase or decrease in CHD.  Local low-dose estrogen treatment (this means cream or suppository applied to vulva or inserted into the vagina) is recommended for women with symptoms limited to vulvo-vaginal atrophy (dryness, painful intercourse, recurrent urinary tract infections).  Estrogen therapy alone is recommended in women with a total hysterectomy.  Estrogen plus progesterone is recommended for women with a uterus.  MHT is an individual decision; quality of life, health priorities, and personal risk factors such as age, time since menopause, risk of venous thrombo-embolism, stroke, ischemic heart disease, and breast cancer should be considered when deciding whether MHT is appropriate and/or safe.  The risk of ischemic stroke is lower with topical dose MHT. 

The risk of breast cancer associated with MHT is primarily associated with addition of progestogen (synthetic progesterone) and duration; the risk is small and risk decreases after treatment is stopped.  The dose and duration of MHT should be determined and individualized by treatment goals and safety issues.  In cases of premature ovarian failure, systemic MHT is recommended until age 51.  No MHT is recommended in breast cancer survivors.  There is a slight increased risk after 4 years of systemic MHT most evident with estrogen+progestin; none to even less risk with estrogen alone.  With vaginal estrogen use there is no increased risk of breast cancer no matter the duration.

Consider these startling breast cancer risk statistics:

·        Regular alcohol intake increased risk of breast cancer 32-46%

·        Obesity increased risk of breast cancer 26-52%

·        Physical inactivity increased risk of breast cancer 7-33%

All of these are much higher than the risk conferred by MHT!!!

Here is a summary from a study in the New England Journal of Medicine published May 14, 2020:  “Estrogen alone reduced the incidence of and mortality from invasive breast cancer, while combination estrogen-progestin therapy elevated the incidence of but not mortality from breast cancer.

When considering perimenopausal/menopausal interventions (ie treatment), factor in the following:

·        Quality of life

·        Do No Harm (symptom relief with none to minimal impact on increasing risk of other diseases)

·        Disease prevention/risk reduction

·        Disease management

·        Opportunity for changes in health & lifestyles

·        Education about health choices

When determining the risk vs benefit, the 8 most important factors:

1.      The age of initiation of MHT (years since menopause, therapeutic window)

2.      Dose of estrogen

3.      Route of administration

4.      Type of progestogen

5.      Type of estrogen

6.      Estrogen alone or with progestogen

7.      Duration of MHT

8.      Considerations for women >65

Please read on for a more thorough discussion of the eight risk-to-benefit factors below.

There is a defined therapeutic window where the benefits of MHT outweigh the risks.  These benefits occur when MHT is initiated within 10 years of menopause to prevent urogenital atrophy, dementia, and possibly cardiovascular disease.  MHT should be initiated within 3-6 years of menopause to prevent and/or treat bone loss.  Timing of MHT is imperative to ensure maximum safety; the initiation of MHT should be considered for healthy symptomatic women who are within 10 years of menopause OR younger than 60 AND do not have contra-indications to use MHT.  There is an increased risk of side effects is MHT is initiated in women 60 years or older but extended use of MHT with the lowest effective dosage is acceptable with good clinical supervision, the lowest effective dose, method of delivery considerations, risk-benefit analysis, individualized treatment, joint decision; MHT should not be discontinued based solely upon age.  For anyone using MHT, at minimum you should be meeting with your prescriber annually for a physical exam and/or thorough lab testing along with a conversation on the risk vs benefits and how things are going.

Dose of estrogen is very important.  In the Women’s Health Initiative (WHI) observational study women using low dose estrogen (defined as <0.625 mg/day) as part of estrogen plus progestin therapy had a 71% lower risk of coronary heart disease (CHD) and a 69% lower risk of venous thromboembolism (VTE) over an average follow-up of 5.5 years compared with women using a conventional dose regimen.  Among women using estrogen plus progestin, the risk of CHD was more than double in users of high-dose estrogen verses women using a standard dose.  No relationship was observed between estrogen dose and cardiovascular events with estrogen alone.

Route of estrogen administration is also important.  Transdermal estrogen avoids the hepatic first pass and lowers the risk of thromboembolic effects (clots).  Transdermal estrogen does not confer added risk of VTE or stroke.  Oral natural estradiol was associated with lower hazard ratios for stroke than oral synthetic conjugated equine estrogen (CEE).  There is weaker evidence that natural estradiol is better than CEE for depression and anxiety.

Type of progestogen matters.  The risk of both breast cancer and cardiovascular disease is greater with synthetic progestins verses natural progesterone.

If a woman uses estrogen alone (only an option if the uterus has been removed), there is no increased risk of breast cancer—at least not for 20 years according to available data.  If a woman uses estrogen + progestin, the risk of breast cancer is 1/1000 after year 3 or 4.

How long should a woman use MHT?  MHT should be initiated in healthy symptomatic women within 10 years of menopause or if they are less than 60 AND do not have contraindications (see below).  For many perimenopausal women, vasomotor symptoms (hot flashes, nights sweats, etc) persist for an average of 7.4 years and for greater than 10 years in many women.  Moderate to severe vasomotor symptoms occur in 42% of women aged 60-65 and continue for many after age 65.  If a woman chooses to use MHT, annual evaluation is strongly recommended, especially after year 3 since there is a slight increased risk of breast cancer in those using both estrogen and progestin.  If a 65+ woman chooses to use MHT, they should consider switching to topical/transdermal application.  Deciding whether to continue or stop is a very individualized decision and many factors may influence this choice.  If a woman is 65 or older and has no contra-indications it may be appropriate to continue using MHT for quality of life.

Contraindications for MHT:

·        Unexplained vaginal bleeding

·        Estrogen receptor positive breast cancer, except in appropriately selected patients being treated for metastatic disease or with oncology involvement.

·        Endometrial cancer if beyond stage 2

·        Active or history of deep vein thrombosis or pulmonary embolism (topical dosage not considered a contra-indication)

·        Inherited high risk of thromboembolic disease (topical dosage may be considered only based on other benefits)

·        Active or within the past year arterial thromboembolic disease (stroke, heart attack)

·        Known or suspected pregnancy

·        Active liver disease

·        Chronic severe hepatic dysfunction (AST>twice normal)

·        Hypertriglyceridemia (topical dosage okay)

·        Dementia

·        Porphyria cutanea tarda

·        >10 years postmenopausal or after discontinuing MHT and then wants to restart

·        Specific contraindication to oral MHT:  history of stroke, coronary heart disease, inherited high risk of clotting

Cautious considerations for MHT:

·        Familial mixed hyperlipidemia or hypertriglyceridemia (triglycerides>300 mg/dL)

·        History of endometriosis, especially if advanced stages and >1 laparoscopy

·        Fibroids

·        A traumatic thrombophlebitis or history of thromboembolic event disorder if continued anti-coagulant treatment

·        History of gallbladder disease and no cholecystectomy

·        Seizure disorders

·        Migraine headaches

·        First degree relative with history of ovarian cancer

·        Endometrial cancer stages I & II

Possible side effects from MHT:

·        Nausea

·        Bloating

·        Dizziness

·        Weight gain

·        Fluid retention

·        Mood swings (progestogen related)

·        Uterine bleeding starting or returning

·        Breakthrough uterine bleeding

·        Headaches/migraines

·        Breast enlargement

·        Breast tenderness

·        Angioedema

·        Gallstones

·        Pancreatitis

Risks of MHT:

·        Slight risk of breast cancer after 3 years of use associated with estrogen + progestin

·        Endometrial hyperplasia/cancer if estrogen is given unopposed or inadequately opposed with progestogen

·        Venous thromboembolism (clot) associated with oral MHT

·        Gallbladder issues

·        Heart attack and/or stroke if initiated at 60+ years of age or longer than 10 years after menopause

·        Dementia (if started later and in older women)

BOTTOMLINE SUMMARY (OR IN CHRIS’ WORDS TLDR)

·        Menopausal Hormonal Therapy (MHT) can be a safe and viable option for some women in some cases.

·        The benefits and risks of MHT vary from woman to woman dependent upon their risk factors.

·        I do not recommend MHT for anyone that carries the BRCA1/2 genetic mutation; however, there are MANY non-hormonal options to help alleviate symptoms related to hormonal imbalance.

·        I NEVER recommend synthetic hormones under any circumstance, especially synthetic progestogen.

·        When MHT is used, I recommend using the lowest dosage for the shortest amount of time; that being said, some women do need to take MHT for life to manage their hormonal symptoms.

·        I am a huge fan of topical estriol for every peri/post-menopausal woman who is experiencing vaginal dryness, pain with intercourse, and/or recurrent urinary tract infections.

·        MHT should never be started in women 60 years or older.

·        MHT should never be started if a woman is 10 years or longer past menopause.

·        Any alcohol consumption, obesity, and physical inactivity increase your risk of breast cancer more than MHT.

·        Urinary and salivary hormone testing can help highlight your specific hormone imbalances and help me customize your treatment plan for optimal outcomes.

If you have more specific questions regarding your individual situation and how naturopathic medicine might help you manage your (peri)menopausal symptoms, please contact us today to schedule a complimentary discovery call with me!

Wishing you hormone harmony,

Rachel Oppitz, ND

P.S.   Please send more hormone related questions.