Perimenopause & Menopause

❍ At a glance

• Diagnosis is clinical in women over 45. Do not routinely measure FSH or oestradiol - they fluctuate widely in the perimenopause and a single normal result does not exclude it. If uncertain, a therapeutic trial of MHT is more informative than a blood test.
• Prefer transdermal over oral oestrogen. Patches, gel, and spray bypass first-pass hepatic metabolism and carry significantly lower VTE and stroke risk than oral preparations.
• Any woman with an intact uterus must have progestogen added to oestrogen therapy to prevent endometrial hyperplasia. The Mirena IUS is a legitimate and underused option for endometrial protection.
• There is no arbitrary time limit on MHT. Continue as long as the woman is symptomatic and benefits outweigh risks, with annual review. The "5-year rule" is not supported by current guidelines.
• GSM (vaginal dryness, dyspareunia, recurrent UTI): low-dose topical vaginal oestrogen is effective and appropriate even for women who decline systemic MHT, and for most women with prior breast cancer in discussion with their oncologist.
• POI (ovarian failure under 40): refer to specialist and offer MHT until at least age 51. These women face substantially elevated cardiovascular and bone risk without treatment.

❍ Perimenopause: diagnosis and symptoms

The perimenopause begins with the first menstrual irregularity caused by declining ovarian function and ends 12 months after the final period. The transition typically spans 4-7 years. Vasomotor symptoms (hot flushes, night sweats) occur in up to 80% of women; around 20-25% have symptoms severe enough to impair daily function and sleep.

Assess the full symptom burden, not just hot flushes. The perimenopause commonly causes: sleep disturbance (often the most functionally disabling symptom); mood changes including irritability, low mood, and anxiety (frequently misattributed to a primary depressive or anxiety disorder); cognitive symptoms ("brain fog", word-finding difficulty); joint and muscle aches; and reduced libido. Not all of these respond reliably to oestrogen, but they should be elicited and contextualised.

In women under 45 with suspected perimenopause, measure FSH and oestradiol on two separate occasions at least 4-6 weeks apart. FSH consistently above 25 IU/L supports the diagnosis. In women under 40 with consistently elevated FSH, diagnose premature ovarian insufficiency (POI) and refer.

❍ MHT: prescribing in practice

Route: Transdermal oestrogen (patches, gel, spray) is the preferred default. It is associated with significantly lower VTE and stroke risk than oral oestrogen because it bypasses first-pass hepatic metabolism.³ Use transdermal particularly in women with cardiovascular risk factors, migraine with aura, obesity, or a prior VTE (where transdermal may still be used after individual risk assessment).

Progestogen: Required in all women with an intact uterus. Options in NZ:

• Levonorgestrel IUS (Mirena): provides effective endometrial protection when used with systemic oestrogen. An excellent and underused option, particularly in women who want combined contraception during the perimenopause.
• Oral micronised progesterone (Utrogestan): lower VTE risk and possibly lower breast cancer risk than synthetic progestogens. Preferred when oral progestogen is used.²
• Combined transdermal patches: convenient, but options in NZ are limited; check NZF for currently funded preparations.

Women who have had a hysterectomy can use oestrogen alone.

Breast cancer risk in context: Combined MHT (oestrogen plus progestogen) is associated with a small increased risk - approximately 1 extra case per 1,000 women per year of use. Oestrogen alone carries a smaller risk. These numbers should be contextualised against lifestyle risks: obesity, alcohol consumption above 10 g/day, and physical inactivity carry comparable or greater breast cancer risk. Women with a history of breast cancer should discuss MHT with their oncologist; it is not uniformly contraindicated.

❍ Genitourinary syndrome of menopause (GSM)

GSM affects up to 50% of postmenopausal women and includes vaginal dryness, dyspareunia, vaginal and urethral atrophy, urinary urgency, and recurrent UTI. Unlike vasomotor symptoms, it does not improve spontaneously over time.

Low-dose topical vaginal oestrogen (estriol cream, vaginal tablet, or ring) is highly effective and not systemically absorbed at significant levels. It does not require progestogen add-back in women with a uterus. It is appropriate for women who decline systemic MHT, and for most women with prior breast cancer after discussion with their oncologist. If a postmenopausal woman is getting recurrent UTIs, prescribe topical vaginal oestrogen: it restores lactobacillus-dominant flora and significantly reduces recurrence.

Vaginal moisturisers (e.g. Replens) and lubricants are useful adjuncts but do not reverse atrophy. Recommend them alongside topical oestrogen where indicated, not as a substitute.

❍ Non-hormonal options

For women who cannot or choose not to use MHT: SSRIs and SNRIs (paroxetine, escitalopram, venlafaxine) reduce hot flush frequency by 40-65% and are the most evidence-based non-hormonal pharmacological option. Gabapentin has modest benefit. Clonidine has limited evidence and significant side effects. Fezolinetant (a neurokinin 3 receptor antagonist) has good emerging data but is not yet available in NZ.

CBT targeting hot flush beliefs and behavioural triggers reduces symptom distress and improves functioning without reducing flush frequency. It is particularly useful for women with significant health anxiety about menopause symptoms. Black cohosh, phytoestrogens, and other herbal preparations have weak or inconsistent evidence; they are not recommended for women with hormone-sensitive cancers and may interact with medications.

❍ The WHI in context

The 2002 Women's Health Initiative publication triggered a dramatic fall in MHT prescribing that persisted for over a decade and is still reflected in clinical conservatism today. The study found increased risks of breast cancer, VTE, stroke, and cardiovascular disease with conjugated equine oestrogen plus medroxyprogesterone acetate (MPA). Subsequent reanalysis showed that the cardiovascular risk was driven almost entirely by older women (mean age 63, over 10 years post-menopause) who had pre-existing atherosclerosis; the "timing hypothesis" established that MHT started within 10 years of menopause or before age 60 has a neutral or beneficial cardiovascular effect. The oestrogen-only arm showed a possible reduction in breast cancer risk. Absolute risk increases in the original study were small even before these refinements.¹

Current international guidelines (NICE NG23, International Menopause Society, British Menopause Society, Australasian Menopause Society) support MHT as first-line treatment for vasomotor symptoms in women under 60 or within 10 years of menopause, with the benefit-to-risk balance generally favourable.

❍ Premature ovarian insufficiency (POI)

POI is ovarian failure before age 40, affecting approximately 1% of women. Causes include idiopathic (most common), autoimmune (associated with Addison's disease, thyroid disease), chromosomal (Turner syndrome mosaicism, Fragile X premutation), and iatrogenic (chemotherapy, pelvic radiotherapy, bilateral oophorectomy).

Diagnosis requires two FSH measurements above 25 IU/L at least 4-6 weeks apart in a woman with oligomenorrhoea or amenorrhoea under age 40. A single elevated FSH is not sufficient. Once confirmed, refer to a specialist menopause or reproductive endocrinology service.

POI management differs from natural menopause management. These women face 10-15 additional years of oestrogen deficiency compared with the natural menopause age, with substantially elevated risks of cardiovascular disease, osteoporosis, cognitive decline, and all-cause mortality. MHT should be offered and continued until at least age 51. The combined oral contraceptive pill is an alternative in women wanting contraception, but provides less bone protection than physiological oestrogen replacement. Fertility is severely impaired but not zero; spontaneous ovulation occurs rarely, so contraception should be discussed. Psychological support is important given the profound impact of the diagnosis on fertility and identity.

❍ Referral criteria

Refer to gynaecology or a specialist menopause clinic for:

• POI under age 40
• Surgical menopause (bilateral oophorectomy), particularly in young women
• Complex breast cancer history requiring specialist guidance on MHT options
• MHT failure with persistent severe symptoms despite adequate dose and route optimisation
• Mixed genitourinary symptoms requiring urodynamic assessment