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Management of menopause
Karen Magraith
General practitioner1 SUMMARY
Immediate-past president2
Clinical senior lecturer3
During perimenopause and after menopause, women may experience diverse symptoms.
Christina Jang All women require a comprehensive assessment of their current health and risks for future
Senior lecturer4 disease, appropriate screening, and promotion of a healthy lifestyle.
Senior staff specialist5
Menopausal hormone therapy is the most effective treatment for menopausal symptoms.
President-elect2
It can be offered to symptomatic patients with no contraindications following an individualised
1
South Hobart, Tasmania discussion about the risk of harms versus benefits.
2
Australasian Menopause
Menopausal hormone therapy is recommended for women with premature ovarian insufficiency
Society
(menopause occurring before 40 years of age) regardless of symptoms, unless contraindicated.
3
Tasmanian School of
Medicine, University of Nonhormonal medications may improve symptoms for women who have contraindications to,
Tasmania, Hobart or do not wish to take, menopausal hormone therapy.
4
Faculty of Medicine, The
University of Queensland,
Brisbane Introduction In this article, the term ‘women’ only refers to
5
Department of The average age of menopause in Australian women cisgender women. Trans- and gender-diverse people
Endocrinology and is 51 years. Perimenopause typically lasts several may also experience menopausal symptoms and may
Diabetes, Royal Brisbane years before menopause, during which fluctuating benefit from appropriately tailored health services.
and Women’s Hospital
ovarian function and hormone concentrations affect
Management for menopausal
the menstrual cycle.1 Box 1 lists definitions related
Keywords
symptoms
to menopause.
estrogen, menopausal The management of menopausal symptoms
hormone therapy, Menopause can occur spontaneously, be induced by
(see Box 2) includes an assessment of the patient’s:
perimenopause, medical treatments (e.g. chemotherapy, radiotherapy) or
• general health, current symptoms and concerns
progestogen, tibolone by surgical removal of the ovaries. Approximately 75%
of women experience symptoms during perimenopause • risks of cardiovascular disease and osteoporosis

Aust Prescr 2023;46:48–53 and after menopause, with 25% experiencing moderate • need for screening and preventive activities.
[Link] to severe symptoms affecting their quality of life.3 During perimenopause, a menstrual bleeding history
austprescr.2023.014 Multiple symptoms typically occur (see Box 2), should be documented, noting any abnormal bleeding
including vasomotor symptoms (e.g. hot flushes, night
sweats), joint and muscle pains, mood changes, sleep
disturbance, low libido and genitourinary symptoms.
Box 2 C
 ommon perimenopausal or
Menopause is also associated with an increased risk of menopausal symptoms
osteoporosis and cardiovascular disease.4
menstrual cycle changes in length (longer or shorter)
and flow (heavier or lighter)
Box 1 D
 efinitions related to menopause vasomotor symptoms (hot flushes, night sweats)
mood changes
menopause—the final menstrual period or the
cognitive concerns (‘brain fog’)
permanent cessation of ovarian function
sleep disturbance
early menopause—menopause occurring at 40 to
44 years of age musculoskeletal symptoms
premature ovarian insufficiency—menopause occurring low libido
before 40 years of age; women may experience formication (sensation of insects crawling under
oligomenorrhoea and amenorrhoea during this time2 the skin)
perimenopause—from when the menstrual cycle starts genitourinary symptoms (vaginal dryness, dyspareunia,
changing until 12 months after menopause urinary urgency, urinary frequency, recurrent urinary
postmenopause—from 12 months after menopause tract infections)

48 This article is peer-reviewed © 2023 Therapeutic Guidelines Ltd

VOLUME 46 : NUMBER 3 : OCTOBER 2023

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that requires investigation, before considering Regimens used for MHT include:
systemic menopausal hormone therapy (MHT). • estrogen-only for women who have had a
Depending on individual symptoms, management total hysterectomy; unopposed estrogen is
may include nonpharmacological and pharmacological associated with endometrial hyperplasia and
(including hormonal and nonhormonal) therapies, potential malignancy
which are discussed below. • combined estrogen plus progestogen for
Any ongoing need for contraception should be women with a uterus:
determined.5
– cyclic combined MHT—continuous estrogen
Premature ovarian insufficiency (see Box 1) can be with a progestogen given cyclically (e.g. for
associated with increased health risks to women. 12 to 14 continuous days of a calendar month)
Women with premature ovarian insufficiency require
– continuous combined MHT—continuous
comprehensive assessment and management.
estrogen and progestogen
MHT is recommended regardless of symptoms
(unless contraindicated) until the usual age of • tibolone for women more than one year after
menopause, to reduce the risks of osteoporosis and menopause, particularly those with low libido.
cardiovascular disease.6 Women starting on MHT must be warned about
MHT is the most effective treatment for menopausal adverse effects, including nausea and breast
symptoms.4 It can be offered to symptomatic patients tenderness. Women should be reviewed after
with no contraindications following individualised 6 to 12 weeks of starting MHT to evaluate ongoing
discussions about risk of harms versus benefits and menopausal symptoms and any adverse effects. At
other therapies available. this review, dosage or formulation adjustments can
be made; for example, if vasomotor symptoms remain
Other established benefits of MHT include improved
problematic, the estrogen dose can be increased.
quality of life, and prevention of osteoporosis and,
Annual reassessment is recommended to ensure
potentially, cardiovascular disease.4,7,8 Estrogen
health screening is up to date and to review the need
therapy is suitable for the management of
for ongoing treatment.
osteoporosis or low bone density in women younger
than 60 years of age.9 Women prescribed cyclic MHT should expect a
Useful resources to assist practitioners in assessing regular vaginal bleed at the end of the progestogen
and managing menopause include: phase. Some women may have irregular bleeding
and spotting when starting cyclic MHT, and adjusting
• A Practitioner’s Toolkit for the Management of the
therapy can help (e.g. increasing the progestogen
Menopause from the Women’s Health Research
dose or duration). For both cyclic and continuous
Program at Monash University
combined regimens, bleeding and spotting often
• Menopause health professional tool from Jean settles over months, but if it persists beyond
Hailes for Women’s Health. 6 months, or becomes heavy or prolonged, it should
be investigated.
Nonpharmacological treatments for
menopausal symptoms There is no maximal duration of MHT defined. Many
Lifestyle modifications such as exercise, weight loss women wish to stop MHT after some time to assess
and reducing alcohol consumption may be helpful whether their symptoms still warrant treatment. Some
for some women. These measures may not reduce may elect to continue MHT indefinitely. This latter
the severity of symptoms but may make them more group must be counselled about the potential long-
manageable and improve overall wellbeing. term harms of MHT (see below).

Cognitive behavioural therapy can reduce the For a complete list of MHT formulations available in
impact of vasomotor symptoms and alleviate sleep Australia, refer to the Guide to MHT/HRT doses from
disturbance.10,11 the Australasian Menopause Society.

Menopausal hormone therapy for Estrogen

menopausal symptoms Estrogen is the primary component of MHT. Most
Menopausal hormone therapy (MHT) is indicated formulations contain either estradiol or conjugated
for treatment of menopausal symptoms. It is highly equine estrogens.12 Estradiol is preferred because
effective for alleviating vasomotor symptoms and may it is structurally similar to 17-beta-estradiol,
improve sleep disturbance, mood changes, cognitive the commonest naturally occurring estrogen
concerns and musculoskeletal symptoms.4 in premenopausal women. Various estradiol

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preparations are available (e.g. oral tablets or contraception such as a combined oral contraceptive
capsules, transdermal patch or gel). Systemic pill for MHT. This has the benefit of providing
estrogen should be started at a low-to-medium dose symptomatic relief, menstrual-cycle control,
and adjusted according to symptoms. and contraception.
Estrogen is effective for treating genitourinary
Tibolone
symptoms (e.g. vaginal dryness, urinary frequency,
Tibolone is a synthetic steroid that is metabolised
recurrent urinary tract infections).13 Genitourinary
into components with estrogenic, progestogenic and
symptoms often improve in women taking
androgenic actions. It is useful for postmenopausal
systemic MHT, but some require additional topical
women, particularly those with low libido. The usual
vaginal estrogen.
dose is 2.5 mg orally, daily.
Topical vaginal estrogen is only appropriate for
Clinical trials have demonstrated low-dose tibolone
managing genitourinary symptoms. Low-dose vaginal
(e.g. 1.25 mg orally, daily) may reduce both vertebral
estrogen (estradiol or estriol)12 is available as vaginal
and nonvertebral fractures. It can also be used to
tablets, pessaries or creams and does not require the
treat low bone density.16
addition of a progestogen.
Tibolone should only be prescribed to women who
Progestogens and combination preparations are more than one year after menopause as it can
Progestogens are required for women with a uterus cause vaginal bleeding. Women with a history of
who are prescribed estrogen-containing MHT. breast cancer should not be prescribed tibolone.
For perimenopausal women, cyclic MHT is used, Tibolone is associated with increased risk of stroke in
where a progestogen is given cyclically with estrogen women older than 60 years of age.16
(e.g. for 12 to 14 continuous days of a calendar
Cardiovascular disease risk and MHT
month). For postmenopausal women, continuous
Menopause is also associated with an increased risk of
combined MHT is used, where a progestogen is given
cardiovascular disease.4
continuously with estrogen.
Women who start MHT younger than 60 years of
If continuous combined MHT is used by
age, or within 10 years of menopause, have reduced
perimenopausal women, irregular bleeding frequently
all-cause mortality and risk of coronary heart disease.
occurs; cyclic MHT is recommended to minimise
These women also have fewer cardiac events on
irregular bleeding. Once a woman has been using
long-term follow up.17 These findings support the
cyclic MHT for 12 months, a trial of continuous
‘timing hypothesis’,18 where women who start MHT
combined MHT can take place.
close to menopause experience a cardiovascular
Several progestogens are available for use in MHT benefit, whereas those who start MHT several years
(e.g. micronised progesterone, dydrogesterone, after menopause do not experience this benefit.19
drospirenone, norethisterone, medroxyprogesterone At present there is no role for MHT in the primary
acetate). Their properties vary—for example, some prevention of cardiovascular disease; however, in
are more androgenic while others exert anti- women with premature ovarian insufficiency, MHT
mineralocorticoid effects. No randomised controlled may reduce the risk of cardiovascular disease and
trial data are available to guide choice.14 Micronised should be used until the usual age of menopause.
progesterone and dydrogesterone (which is structurally
similar to natural progesterone) may have a lower Contraindications to MHT
breast cancer risk than older synthetic progestogens15 Strong contraindications to MHT include undiagnosed
and, for most women, are considered first line. vaginal bleeding, and a history of breast or
Most progestogens are given orally as tablets endometrial cancers, or acute cardiovascular or
or capsules, either in a fixed-dose combination thromboembolic events. Other contraindications to
product with estrogen, or as separate preparations. prescribing MHT are listed in Box 3.
Transdermal patches contain a combination of Transdermal estrogen (rather than oral) may be
estradiol and norethisterone. A progestogen-releasing recommended for women with:
intrauterine device (IUD), the 52 mg levonorgestrel-
• a history of atherosclerotic heart disease or stroke
releasing IUD, can be used for up to 5 years in
• a history of migraine with aura
combination with estrogen. It has the added benefit
of providing contraception and managing heavy • treated cardiovascular disease risk factors
menstrual bleeding. (e.g. hypertension, dyslipidaemia)

Women younger than 50 years of age, without • increased risk of venous thromboembolism
contraindications, can use combined hormonal • hepatobiliary disease.

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Risk of harms associated with MHT Box 3 P

 recautions for menopausal hormone therapy (MHT)
For most women younger than 60 years, or within
10 years of menopause, the risks of MHT are low Contraindications to MHT Conditions where caution is
and outweighed by the benefits.4 Estrogen-only • hormone-dependent cancers including recommended with MHT
MHT is associated with endometrial hyperplasia and breast and endometrial [NB1] • past myocardial infarction, transient
potential malignancy due to unopposed estrogenic • undiagnosed vaginal bleeding ischaemic attack or stroke [NB3] [NB4]
effects, and therefore use is limited to women who • acute cardiovascular event • high risk of venous thromboembolism
have had a total hysterectomy. For conditions where [NB3]
• acute venous thromboembolism [NB2]
caution is recommended when prescribing MHT, • active liver disease [NB3]
• porphyria cutanea tarda
see Box 3.20 • migraine with aura [NB3]
• severe liver disease
• hypertriglyceridaemia [NB3]
Breast cancer
• hepatobiliary disease [NB3]
The Women’s Health Initiative trials found the • high risk of breast cancer
combination preparation of conjugated equine
• age older than 65 years and no prior use
estrogens+medroxyprogesterone acetate was of MHT
associated with an increased incidence of breast
cancer.8 Women taking conjugated equine NB1: MHT is generally safe to use in patients with treated stage 1 endometrial malignancy.
estrogens alone had a reduced risk of breast NB2: Consider transdermal estrogen for MHT if the patient is anticoagulated.
cancer,21 highlighting the role of progestogens. NB3: Exercise caution with oral estrogen; transdermal estrogen is preferred for MHT.
The risk of breast cancer has been linked to the NB4: Treated hypertension is not a contraindication to MHT use.
duration of MHT.14 Observational data suggest that Adapted from reference 20.
micronised progesterone and dydrogesterone may
confer a lower risk of breast cancer than older
synthetic progestogens.15
Gabapentin and oxybutynin may reduce the
Thromboembolic disease frequency and severity of vasomotor symptoms.
The North American Menopause Society no longer
Oral estrogen undergoes first-pass metabolism
recommends clonidine or pregabalin for treatment
in the liver and alters the hepatic production of
of vasomotor symptoms because of their adverse
coagulation factors. This is associated with a 2- to
effects; however, they are still used in some instances
3-fold increase in venous thromboembolism,
in Australia.10
but the absolute risk remains low. Estradiol and
estetrol theoretically have lower risks of venous Unlike vasomotor symptoms, genitourinary symptoms
thromboembolism, though strong evidence for this do not improve with time. Nonhormonal lubricants
is lacking. Transdermal estrogen does not carry can be helpful for vaginal dryness.
this risk and is the preferred option for women Complementary therapies and herbal preparations
with risk factors for venous thromboembolism or (e.g. black cohosh, phytoestrogens) have insufficient
cardiovascular disease.22,23 evidence of benefit, can cause adverse effects, and
are not recommended.20,24 Custom-compounded,
Nonhormonal drugs and other
bioidentical hormone therapy is also not
preparations for menopausal
recommended because of limited dose regulation and
symptoms
lack of safety data.4
Table 1 lists typical doses of nonhormonal drugs
used for vasomotor symptoms of menopause. Emerging treatments
Nonhormonal drugs may be useful for women with Emerging options for the treatment of menopausal
contraindications to MHT (see Box 3) or who do not symptoms include estetrol, an estrogen found in the
wish to take MHT. Generally, nonhormonal drugs are fetal liver, and neurokinin 3 receptor antagonists.20
less effective than MHT and do not confer the bone- Estetrol may provide some safety advantages
or cardiovascular-protective benefits of estrogen. through reduced effects on liver and breast
Most of the drugs have limited use because of their tissue.25 Neurokinin 3 receptor antagonists are
adverse effects.10 promising nonhormonal treatments for vasomotor
Selective serotonin reuptake inhibitors (SSRIs) and symptoms.20,26 A 2023 randomised placebo-controlled
serotonin and noradrenaline reuptake inhibitors trial reported the neurokinin 3 receptor antagonist,
(SNRIs) have modest effects on vasomotor fezolinetant, was effective and well tolerated for the
symptoms and may improve sleep and mood. treatment of vasomotor symptoms.27

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Table 1 N
 onhormonal drugs for vasomotor symptoms

Drug [NB1] Dosage Adverse effects

serotonin and noradrenaline reuptake inhibitors
desvenlafaxine 25 to 150 mg orally daily dizziness, nausea, sexual dysfunction

venlafaxine 37.5 to 150 mg orally daily

selective serotonin reuptake inhibitors

citalopram 10 to 20 mg orally daily dizziness, nausea, sexual dysfunction

escitalopram 5 to 20 mg orally daily

paroxetine [NB2] 10 to 25 mg orally daily

other drugs
clonidine [NB3] 25 to 75 micrograms orally twice daily dizziness, drowsiness, constipation

gabapentin 100 to 900 mg orally daily in up to 3 divided doses drowsiness, dizziness, possible withdrawal symptoms

oxybutynin [NB4] 2.5 to 5 mg orally twice daily dry mouth, drowsiness, blurred vision

NB1: All drugs listed in the table, except clonidine, are not registered by the Therapeutic Goods Administration for treating vasomotor symptoms.
NB2: Paroxetine should not be co-administered with tamoxifen; co-administration can cause inhibition of cytochrome P450 2D6 and reduce the efficacy
of tamoxifen.
NB3: Clonidine may be used but is no longer recommended because of its adverse effects.10
NB4: Oxybutynin may help symptoms of overactive bladder; however, it may cause adverse effects, particularly cognitive decline in older people.10

cardiovascular disease. Local vaginal preparations

Conclusion can be used for genitourinary symptoms only.
Women should be counselled on their therapeutic
MHT is highly effective for the relief of symptoms options and prescribed a regimen tailored to their
associated with menopause. For most women individual needs.
within 10 years of menopause or younger than
60 years of age, the benefits are likely to outweigh Conflicts of interest: Karen Magraith has received
the risk of harms. The benefits of MHT are not only honoraria for presentations from Mylan, Jean
limited to symptom control, but also good evidence Hailes for Women’s Health, and the Australasian
supports its role in prevention of osteoporosis and Menopause Society.

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