Menopause hormone therapy (MHT) for perimenopausal women

Menopause symptoms affect 80% of women1 and occur with similar frequency across ethnicities, though Māori women may be less likely to be offered menopause hormone therapy (MHT). 2  

This MedCase considers how to assess menopausal symptoms and develop a shared plan for individualised treatment using MHT.

Mrs F is a 47 year old Māori woman who presents with a 2-year history of worsening hot flashes that wake her each night. She is a teacher’s aide at the local primary school, but has had to take time off work over the past few weeks because she is exhausted.  She also tells you she has become more irritable and tearful both at home and at work.

Mrs F had a levonorgestrel intrauterine system (brand name: Mirena) inserted for iron deficiency and contraception two years ago. Since then, she has been amenorrhoeic. She has had no post-coital bleeding. She denies dyspareunia but tells you sex has become less enjoyable due to vaginal dryness.

On exam today, she is overweight (BMI 29, height 173cm, weight 85kg). Her blood pressure is 118/74 mmHg with normal heart rate. Her abdominal exam is unremarkable.

What is your differential diagnosis?

 

Assessing menopause symptoms

A diagnosis of menopause is made when there are new onset vasomotor symptoms (hot flashes, flushing, night sweats) and a change in the pattern of menstrual bleeding.3

  • Perimenopause is the time from onset of symptoms to the last menstrual period and lasts, on average, 4-8 years.
  • Menopause is said to have occurred when there has been no menstruation for one year.
  • Postmenopause starts one year after the last menstruation. This phase usually resolves within 5 years, though 10-20% of women still have symptoms 10 years after menopause.

Symptoms vary with time, reflecting the underlying hormonal changes of menopause. Eventually, symptoms of oestrogen deficiency predominate. However, oestradiol levels may fluctuate in the perimenopausal phase and women can experience symptoms of oestrogen excess at times (especially premenstrually), such as breast tenderness, headaches, irregular menses, and mood changes.


(Slide from the Pharmac Seminar on Women’s Health)
 

Despite experiencing a similar number of menopause symptoms (mean and median = 7) Māori women were half as likely to ever use MHT in a large New Zealand study (24% vs 54% for non-Māori).2 Actively screening for menopause-related symptoms can help identify Māori women who may benefit from therapy.

Mrs F has classic vasomotor symptoms of menopause along with mood and urogenital changes.

However, as she is amenorrhoeic from her Mirena, can you be sure her symptoms are due to menopause?

A thorough history and review of the patient’s previous medical conditions are usually enough to make the diagnosis. Blood tests are usually unnecessary. Levels of FSH, LH, AMH (anti-Mullerian hormone), oestradiol and testosterone fluctuate daily and results will not change management, which is based on symptoms in women at the normal age for menopause (>45 years).3

However, blood tests may be indicated if there may be other causes for symptoms, such as diabetes, hyperthyroidism or anaemia. If there is uncertainty, testing FSH may help to determine whether menopause is likely.

Mood symptoms are more difficult to disentangle. Consider past history: a patient with new mood symptoms and no previous history may be more likely to be experiencing mood changes due to the lack of oestrogen, while a patient with a history of previous anxiety or depression could have a recurrence of a primary mood disorder or recurrent symptoms precipitated by menopause.

Practice points

A good menopause history:3
  • Be alert for menopause-related symptoms in women aged >45 years.
  • Specifically ask about genitourinary symptoms: women often don’t report them, though they occur in 60% of postmenopausal women.
  • Record menstrual history, noting the date of insertion of any long acting contraceptive device.
  • Assess symptoms, ideally using a standardised symptom score such as the Australasian Menopause Society Symptom Score Sheet. This can be used to assess the effect of treatment on symptoms over time.
  • Establish any past history and risk factors for breast cancer, cardiovascular disease, thromboembolic disease and osteoporosis.
  • Ensure breast and cervical screening is up to date.
  • Ask about potential contraindications to MHT: uncontrolled hypertension; undiagnosed abnormal bleeding; previous breast or endometrial cancer or high-risk thromboembolic disease; active liver disease; previous cerebrovascular or coronary artery disease.

 

You get further history from Mrs F. She is usually well and takes no regular medications.

She last had blood tests 3 months ago, which showed no anaemia, and normal thyroid and liver function tests. She had impaired glucose tolerance with HbA1c of 45mmol/mol and has been trying to exercise more and follow a healthy diet. You note that she is a non-smoker and her last cardiovascular risk assessment was done at age 45 years, with a 5-year risk of 3%. She underwent pelvic ultrasound for investigation of heavy bleeding prior to Mirena insertion and the results were normal.

She answers negatively to the PHQ-2 questions for depression and has no previous history of a mood disorder.

You feel satisfied that Mrs F’s symptoms are likely due to perimenopause, and explain this to her. She is relieved and feels this makes sense.

You ask her if she would like to consider treatment, and she tells you she would. What treatment can you offer?

 

Who can have MHT?

There is now evidence to support MHT as first-line treatment for women aged <60 years or <10 years since their final menstrual period who have:

  • symptoms that affect their quality of life or daily functioning, AND
  • no contraindications (pregnancy; uncontrolled hypertension; undiagnosed abnormal vaginal bleeding; current or previous breast or endometrial cancer; active high-risk thromboembolic disease; active liver disease with abnormal LFTs; porphyria, prior cerebrovascular or coronary artery disease).3

Women who meet the criteria for MHT need an individual risk assessment to determine the most appropriate therapy. This is not something that can be done in a single consultation; offer follow-up consultations to allow women time to consider their options.

 

Risks associated with MHT

Unfortunately, confusing messages based on old data from the Women’s Health Initiative (WHI) study4 resulted in a reluctance to use MHT for many years (see here and here for a summary of the historical concerns). MHT can be used safely when based on individual risk assessment.3 Some useful summaries on the risks and benefits of MHT can be found on the NZ Formulary and the Australasian Menopause Society website.

A 2019 Lancet paper5  paper reported a slightly higher risk of breast cancer with use of estrogen and progesterone therapy (1.4 - 2 extra breast cancers at age 70 years for every 100 women who used hormones for about 5 years).  This paper also reported a small increase in risk of breast cancer for estrogen-only hormone users. It is worth noting that much of their data relates to older hormone therapy regimens, thus does not provide information on the MHT regimens currently in use.

Data from randomised controlled trials (considered gold standard) suggests cancer risks are as follows:

Combined treatment Oestrogen only treatment
*Breast cancer risk is increased by 1 event/1200 women/ year (by age late 50s), similar or less than the breast cancer risk from being overweight, or having two alcoholic drinks per day *No additional risk of breast cancer, at least up to seven years of treatment.
Ovarian cancer risk is not or negligibly increased Possible small increase in ovarian cancer risk 1 event/1000/year
Bowel cancer risk is lowered by 0.5 events/1000 women/year No change in bowel cancer risk
Endometrial cancer risk is slightly lowered

 Mrs F is a good candidate for MHT and can be offered treatment.

You discuss Mrs F’s individual risks and options for treatment. She has a low baseline cardiovascular risk, and no contraindications to MHT. She wants to try treatment, so you discuss what type of MHT she could consider.

 

How to select the best MHT formulation

Two key questions help determine the appropriate MHT formulation for your patient (see Health Navigator NZ for a summary):

1. Has she undergone hysterectomy?

  • If she has had a hysterectomy, estrogen-only therapy is appropriate
  • If she still has her uterus, she needs combination therapy with estrogen plus progesterone for endometrial protection.

2. Does she need contraception?

  • Perimenopausal women (within 12 months of the final period) require contraception.

Mrs F has her uterus and is perimenopausal, so she needs combined MHT with contraception. You consult the Australian Menopause Society guide for combined MHT and find that options include:7  
1.    The combined oral contraceptive pill (if no contraindications). Note this can be taken continuously to avoid vasomotor symptoms in the pill-free week
2.    Continuous estrogen (patch or tablet) plus cyclical progesterone, such as:

3.    Continuous estrogen plus continuous progesterone via the IUS (Mirena)

You agree that the third option is most appropriate for Mrs F. She already has her IUS in situ providing continuous levonorgestrel and contraception, and this can remain in situ for protection throughout the menopause. You focus your discussion on the types of estrogen therapy.

 

What type of estrogen therapy is best?

Choosing between an oral or transdermal estrogen preparation requires shared understanding of the risks along with patient preference. A full list of estrogen therapy options is available on the NZ Formulary website

  • Oral tablets are taken daily. Options include estradiol valerate (Progynova: fully funded), estradiol (Estrofem: part subsidy) or estriol (Ovestin tablets: fully funded).
  • Transdermal estradiol patches are usually  (Estradot: fully funded; Climara: no subsidy) avoid first-pass metabolism and may allow a lower dose of estrogen to be used.
  • Topical vaginal estriol (Ovestin cream or pessary: fully funded) is indicated for menopausal atrophy of the lower urogenital tract. It can be a useful treatment to start immediately while waiting for systemic estrogen therapy to reach full effect.

You give Mrs F information about oral and transdermal estrogen formulations. She would like time to consider the options and you agree to meet again in a week for a follow-up.

 

Practice points

Tips for individual risk assessment and therapy choices
  • Most risks associated with MHT are age-dependent.
  • Starting MHT in the first 10 years after menopause is associated with no increased cardiovascular risk and may offer cardiovascular protection.8
  • Risks vary based on the type, dose and route of MHT. Discuss options with your patient and offer follow-up consultations to allow her time to make a choice.

 

Mrs F returns to see you one week later and tells you she would like to start taking MHT and prefers an oestrogen patch to a tablet. However, she wonders if there might be a more ‘natural’ way to take hormones. She says a friend of hers saw a naturopath who did a saliva test then prescribed bio-identical hormones.

 

Bio-identical  hormones: what are they and should your patients use them? 

Some alternative practitioners prescribe so called ‘bio-identical’ hormones which are described as having exactly the same chemical and molecular structure as the hormones produced within the human body. They are often marketed as being ‘natural’ and therefore superior to ‘synthetic’ hormone therapy.

It is important to remember that all hormones are synthesised; the human endocrine system relies on hormone synthesis from precursors. Bioidentical oestradiol and bioidentical progesterone derived from plant precursors are used in regular MHT as well as by alternative providers.

Prescription grade bioidentical hormones have the advantage of known purity and regulation of dosage and have been studied extensively, which is not the case for potent compounded bioidentical hormones (see here for an information sheet on this topic). Consequently, the use of bioidentical compounded hormone therapies is not recommended.9  

Some alternative therapy providers offer testing of salivary or blood hormone levels to use as a guide for treatment. As described above, these hormone tests are not a reliable indicator for treatment, since hormone levels can fluctuate daily.

You explain to Mrs F that testing her blood or saliva is not useful, and that you can’t be sure about the safety or purity of bio-identical hormones. You recommend the prescription products as they are safe, and also cheaper; the oestradiol patch (brand name: Estradot) is fully subsidised.
Mrs F is satisfied that the combination of Mirena and transdermal oestrogen is the best for her. You prescribe the oestradiol patch at the lowest strength of 25 micrograms/24 hours. She tells you she has programmed an alert into her phone to remind her to change the patch on Wednesday and Sunday.

You explain to Mrs F that the patch may take a few weeks to take effect and suggest that she tries oestriol (Ovestin) cream for three months to help with symptoms in the meantime. She is happy to do this. You counsel her to start with approximately half the applicator-full of cream and increase gradually to the full dose, using it daily for a week then reducing to a  maintenance dose twice weekly. You plan a follow-up visit in 6 weeks.

At the follow-up visit, Mrs F tells you she finds the patches easy to use. The cream caused some stinging initially, but this has settled now. She generally feels better and says her mood and fatigue symptoms are much improved.

You agree to continue at the current dose of oestradiol for now, and continue the oestriol cream for at least another 6 weeks. After this, you can consider a trial of oestradiol alone, with 3-monthly reviews to ensure symptoms are adequately controlled.

Once stable, annual review is sufficient.

Patient information resources

 
References: 

  1. Women’s Health 2019, reproductive endocrinology Seminar 5. Pharmac Seminar
  2. Lawton BA, Rose SB, Cormack DM, Stanley J, Dowell AC. The menopause symptom profile of Māori and non-Māori women in New Zealand. Climacteric (2008)
  3. Diagnosing Menopause. Australasian Menopause Society
  4. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific MortalityThe Women’s Health Initiative Randomized Trials JAMA (2017)
  5.  Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet (2019)
  6. Manson JAE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomised trials. JAMA (2013)
  7. Information Sheet: Combined Menopausal Hormone Therapy (MHT) Australasian Menopause Society.
  8. Overcoming Barriers to Menopausal Hormone Therapy Healthed
  9. Information Sheet: Bioidentical Hormones for Menopausal Symptoms Australasian Menopause Society.
     

This MedCase was created in 2019 by Dr Vicki Mount, General Practitioner, MBChB, DipPaeds, with expert review by Dr Stella Milsom, Reproductive Endocrinologist, MBChB, Dip Obs, FRACP.

 

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