What do Australian guidelines recommend for menopausal hormone therapy regarding indications, first‑line dosing, contraindications, duration, monitoring, and second‑line options?

Australian Guidelines on Menopausal Hormone Therapy

Critical Note on Evidence Availability

The provided evidence does not contain specific Australian guidelines (e.g., from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists or the Australasian Menopause Society). However, the Endocrine Society guideline 1 was co-sponsored and reviewed by the Australasian Menopause Society, making it the most relevant source for Australian practice. I will base recommendations on this guideline, which represents international consensus including Australian expert input.

Indications for MHT

Menopausal hormone therapy is indicated primarily for moderate to severe vasomotor symptoms (hot flushes, night sweats) and genitourinary syndrome of menopause in women under age 60 or within 10 years of menopause onset. 1, 2

• MHT is the most effective treatment for vasomotor symptoms, with benefits exceeding risks for the majority of symptomatic postmenopausal women meeting age/timing criteria 1, 3
• Genitourinary symptoms (vaginal dryness, dyspareunia, atrophy) are effectively treated with low-dose vaginal estrogen or systemic MHT 1, 2
• MHT should NOT be initiated for primary prevention of coronary heart disease, breast cancer, or dementia—these are not appropriate indications 1
• Secondary benefits include decreased risk of osteoporotic fractures and improved glycemic control, but these alone do not justify MHT initiation 2

First-Line Dosing and Formulations

Start with transdermal 17β-estradiol 50 mcg/24-hour patch applied twice weekly, combined with oral micronized progesterone 200 mg daily for 12-14 days per month in women with an intact uterus. 4, 5, 6

Estrogen Component:

• Transdermal 17β-estradiol is strongly preferred over oral formulations due to significantly lower cardiovascular and thrombotic risk (VTE OR 0.9 for transdermal vs OR 4.2 for oral) 4, 6
• Initial dose: 50 mcg/24-hour patch changed twice weekly (every 3-4 days) 6
• If symptoms persist after 2-3 months, increase to 100 mcg/24-hour patch twice weekly 6
• Maximum maintenance dose: 100-200 mcg/day depending on symptom control 6
• 17β-estradiol is explicitly preferred over ethinylestradiol or conjugated equine estrogens 7, 6

Progestogen Component (for women with intact uterus):

• First choice: Oral micronized progesterone 200 mg daily for 12-14 days every 28 days (sequential regimen inducing withdrawal bleeding) 5, 6
• Alternative: Micronized progesterone 100 mg daily continuously (avoids withdrawal bleeding) 5
• Second-line options: Medroxyprogesterone acetate 10 mg daily for 12-14 days per month, or dydrogesterone 10 mg daily for 12-14 days per month 5
• Critical: Never use progestogen for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection 5
• Women without a uterus require estrogen-only therapy with no progestogen 1

Route Considerations:

• Transdermal administration avoids adverse hepatic effects (increased SHBG, renin substrate, coagulation factors) that occur with oral estrogen 6
• Vaginal estrogen (low-dose) is appropriate for isolated genitourinary symptoms without systemic vasomotor symptoms 1

Absolute Contraindications

Do not prescribe MHT in the following situations: 1, 8

• Current or history of breast cancer or other hormone-sensitive malignancies 5
• Active or recent (within 1 year) venous thromboembolism or arterial thrombotic disease 1, 8
• Active liver disease 5
• Unexplained vaginal bleeding (must be evaluated first) 1
• Known or suspected pregnancy 1

Relative Contraindications Requiring Careful Risk Assessment:

• History of stroke or coronary heart disease (transdermal estradiol preferred if MHT considered) 7, 6
• Hypertension is NOT an absolute contraindication, but transdermal estradiol is strongly preferred over oral 7
• Migraine with aura (increased stroke risk; consider transdermal route and monitor closely) 7

Duration of Therapy

Use the lowest effective dose for the shortest duration consistent with treatment goals, with regular reassessment of risks versus benefits. 1, 2

• There is no arbitrary time limit for MHT duration—decisions should be individualized based on ongoing symptoms and risk profile 1, 3
• The "10-year rule" applies to initiation timing (within 10 years of menopause onset), not duration of therapy 1, 8
• Women who remain symptomatic may continue MHT beyond 5 years if benefits outweigh risks after thorough discussion 3
• For women with premature ovarian insufficiency, continue MHT at least until the average age of natural menopause (approximately 51 years) 7, 5

Monitoring Requirements

Annual clinical review focusing on compliance, symptom control, bleeding patterns, and reassessment of risks versus benefits. 7, 5, 6

• No routine laboratory monitoring (hormone levels, lipids) is required unless prompted by specific symptoms or concerns 7, 5
• Monitor blood pressure, weight, and smoking status annually 7
• Assess cardiovascular risk factors at baseline and periodically 7, 8
• Evaluate for any new contraindications or changes in risk profile 1, 8
• Baseline bone density assessment is recommended for women at risk of osteoporosis (age >65, family history, chronic steroid use) who will receive aromatase inhibitors or have premature ovarian insufficiency 7
• Investigate any unexpected vaginal bleeding promptly 1

Specific Monitoring for Transdermal Estradiol:

• Rotate patch application sites to minimize skin irritation 6
• If migraine worsens during MHT, consider changing dose, route, or regimen 7

Second-Line Options

For Women Who Cannot Use or Decline Systemic MHT:

Low-dose vaginal estrogen is the preferred second-line option for isolated genitourinary symptoms. 1

• Vaginal estrogen preparations provide effective local therapy without significant systemic absorption 1
• Ospemifene (selective estrogen receptor modulator) is an alternative for genitourinary syndrome of menopause 1
• Vaginal moisturizers and lubricants are available for those declining hormonal therapy entirely 1

For Vasomotor Symptoms in Women with Contraindications to MHT:

The evidence provided does not contain specific Australian guideline recommendations for non-hormonal alternatives. Based on the Endocrine Society guideline 1, other options are available but specific agents are not detailed in the provided evidence.

Alternative Estrogen Formulations:

• Oral 17β-estradiol 1-2 mg daily is a third-line option if transdermal delivery is not tolerated, though it carries higher cardiovascular and thrombotic risk 6
• Conversion ratio: 100 mcg/day transdermal patch ≈ 2 mg oral micronized estradiol daily 4, 6
• Combined tablets containing estradiol + dydrogesterone or estradiol + dienogest are available for continuous administration 6

Critical Clinical Pitfalls to Avoid

• Never initiate MHT in women over age 60 or more than 10 years past menopause onset without compelling reasons—absolute risks of adverse events increase significantly with age and time since menopause 1, 3, 8
• Never prescribe estrogen alone to women with an intact uterus—this dramatically increases endometrial cancer risk 7, 5
• Never use ethinylestradiol for hormone replacement therapy—this synthetic estrogen carries significantly higher thrombotic risk than bioidentical 17β-estradiol 6
• Do not use MHT for chronic disease prevention (cardiovascular disease, dementia, breast cancer)—current evidence does not support this indication 1
• Avoid starting with high doses—evidence shows no additional benefit and increased harm 5
• Do not assume menstrual cycles indicate fertility in women on MHT—ovarian function cannot be reliably assessed during hormone therapy 7

Age-Stratified Risk Considerations

Absolute risks of adverse events are substantially lower in younger women (50-59 years) than older women, making the risk-benefit ratio more favorable in recently menopausal women. 3, 8

• Per 10,000 women aged 50-79 taking estrogen-progestin for 1 year: expect 8 additional invasive breast cancers, 9 more strokes, 12 more deep venous thromboses, and 9 more pulmonary emboli, balanced against 6 fewer colorectal cancers and 5 fewer hip fractures 5
• Younger women (50-59 years) in the Women's Health Initiative had more favorable results for all-cause mortality, myocardial infarction, and the global index compared to older women 3, 8
• Stroke and venous thrombosis risks occur within the first 1-2 years of therapy across all age groups 5, 8