Clinical overview
The climacteric is the physiological transition from reproductive to non-reproductive life — it spans the perimenopause (the years of escalating cycle disturbance and symptoms leading up to the last period) through into the early postmenopause. Menopause itself is a single retrospective point: the permanent cessation of menstruation caused by loss of ovarian follicular activity, diagnosed only after 12 consecutive months of amenorrhoea with no other cause. The median age in most populations is around 51 years; cessation before 40 is premature ovarian insufficiency (POI) and between 40 and 45 is early menopause — distinctions that matter enormously because these younger women need oestrogen replacement for protection, not merely symptom relief.
This is an HOTS objective because the central skill is not making the diagnosis — which in a woman over 45 is clinical and needs no blood test — but weighing the benefits and risks of hormone replacement therapy (HRT) for the individual in front of you, and counselling her accordingly. The climacteric is far more than hot flushes: it brings vasomotor instability, the genitourinary syndrome of menopause, psychological and cognitive symptoms, and longer-term consequences for bone (osteoporosis) and cardiovascular health. Modern practice has also been reshaped by a more nuanced reading of the Women's Health Initiative, the "timing hypothesis", and — within the last few years — an entirely new non-hormonal drug class targeting the hypothalamic thermostat directly. This chapter covers presentation, impact, assessment, and a contemporary, individualised management approach. It links to osteoporosis, contraceptive-modalities (contraception is still needed in the perimenopause), and hyperandrogenism.
Core knowledge
Staging and definitions
The STRAW+10 system stages reproductive ageing from the menstrual cycle, FSH, and ovarian markers:
- Reproductive — regular cycles.
- Menopause transition (perimenopause) — early: variable cycle length (persistent ≥7-day difference); late: an interval of amenorrhoea ≥60 days and rising, fluctuating FSH.
- Postmenopause — from the final menstrual period onward.
Key terms: perimenopause (the symptomatic transition, ending 12 months after the last period), menopause (retrospective, 12 months amenorrhoea), POI (<40 years), early menopause (40–45), and iatrogenic/surgical menopause (after bilateral oophorectomy, chemotherapy, or pelvic radiotherapy — often abrupt and severe).
The endocrinology
The driver is progressive depletion of the ovarian follicle pool. As follicles are exhausted:
- Inhibin B and anti-Müllerian hormone (AMH) fall first, removing inhibition of the pituitary.
- FSH rises (and later LH), at first intermittently — which is why a single FSH in the perimenopause is unreliable.
- Oestradiol fluctuates — sometimes high, sometimes low — before settling low in the postmenopause, when the dominant oestrogen becomes oestrone from peripheral aromatisation of adrenal androgens in adipose tissue.
The wildly fluctuating oestradiol of the perimenopause explains why this phase is often the most symptomatic, paradoxically more so than the stable low-oestrogen postmenopause.
Figure B3.1 — STRAW+10 staging, ovarian marker changes, fluctuating FSH and oestradiol, diagnostic testing rules, and perimenopausal contraception timing.
Clinical presentation
- Vasomotor symptoms (VMS) — hot flushes and night sweats, the cardinal symptoms, affecting up to ~75% of women and persisting a median of several years (sometimes more than a decade). The mechanism is a narrowed thermoneutral zone in the hypothalamus. Oestrogen withdrawal disinhibits the KNDy neurons (kisspeptin / neurokinin B / dynorphin) of the hypothalamic thermoregulatory centre, and neurokinin B signalling through the NK-3 receptor drives the flush — the molecular basis for the new neurokinin-antagonist drugs.
- Genitourinary syndrome of menopause (GSM) — vaginal dryness, burning, dyspareunia, and urinary urgency, frequency, and recurrent urinary tract infection, from oestrogen-deficient atrophy of the vulvovaginal and lower urinary tract epithelium. Unlike VMS, GSM is progressive and does not remit without treatment.
- Psychological and cognitive — low mood, anxiety, irritability, disrupted sleep, and "brain fog"; sleep is further fragmented by night sweats.
- Musculoskeletal — arthralgia and myalgia are common and under-recognised.
- Sexual — reduced libido, compounded by GSM and mood/sleep disturbance.
- Skin and other — reduced collagen, skin thinning, hair changes, palpitations.
Figure B3.2 — KNDy/NK3 thermoregulatory pathway for vasomotor symptoms and the main hormonal and non-hormonal treatment targets.
Long-term impact
- Bone — oestrogen withdrawal accelerates bone loss for the first 5–10 postmenopausal years, raising the risk of osteoporosis and fragility fracture (see osteoporosis).
- Cardiovascular — the loss of oestrogen's favourable effects on lipids and the vasculature contributes to a rising cardiovascular risk after menopause; the timing of any HRT relative to menopause modifies this (see below).
- Premature ovarian insufficiency carries the greatest long-term burden — earlier and steeper bone and cardiovascular risk — and so mandates replacement at least to the average age of menopause.
Assessment
Diagnosis
- In a woman over 45 with typical symptoms and menstrual change, the diagnosis is clinical — no FSH is required (NICE NG23).
- FSH testing is reserved for women under 45 (and especially under 40 to diagnose POI — two elevated FSH levels in the menopausal range, taken several weeks apart, with amenorrhoea), or where the picture is atypical.
- AMH is not used to diagnose menopause.
- FSH is uninterpretable in women using combined hormonal contraception or cyclical HRT.
Work-up before HRT
- Exclude alternative explanations for symptoms (thyroid disease, anaemia, depression).
- Always investigate abnormal or postmenopausal bleeding before attributing it to the transition or to HRT — exclude endometrial pathology (endometrial-carcinoma).
- Assess cardiovascular risk, VTE risk, breast-cancer risk, blood pressure, BMI, and contraindications to HRT.
- Document a personalised benefit–risk discussion — the core of this objective.
Management
Treatment is individualised and symptom-led. Many women need only reassurance and lifestyle measures; others benefit greatly from HRT; some cannot or choose not to take hormones and need effective non-hormonal options.
Lifestyle
Regular exercise, weight management, reduced caffeine/alcohol, smoking cessation, sleep hygiene, and a layered approach to flushing. Cognitive behavioural therapy (CBT) has good evidence for VMS, sleep, and mood and is recommended by NICE as an option alongside or instead of HRT.
Hormone replacement therapy — principles
- Oestrogen treats the symptoms and protects bone.
- A progestogen is mandatory if the woman has a uterus (endometrial protection against unopposed-oestrogen hyperplasia/carcinoma); oestrogen alone is used only after hysterectomy. The LNG-IUS is an excellent progestogen component (and provides contraception).
- Regimen: sequential (cyclical) HRT for perimenopausal women still having periods (produces a withdrawal bleed); continuous combined HRT for postmenopausal women (bleed-free).
- Route: transdermal oestrogen (patch/gel/spray) is not associated with the increased VTE or stroke risk seen with oral oestrogen, and is preferred in women with VTE risk, migraine, hypertension, obesity, or hepatobiliary disease.
- Tibolone is an alternative synthetic option for postmenopausal women.
Benefits and risks of HRT — the counselling core
- Benefits: the most effective treatment for VMS and GSM, prevention of bone loss and fracture, and — when started in women under 60 or within 10 years of menopause (the "timing hypothesis") — a favourable or neutral cardiovascular profile.
- Breast cancer: combined HRT confers a small, duration-dependent increase in risk that diminishes after stopping; oestrogen-only HRT carries little or no increase. This must be put in the context of baseline risk and lifestyle factors.
- VTE and stroke: increased with oral oestrogen; transdermal oestrogen does not carry this excess — hence route selection matters.
- Endometrial cancer: prevented by adequate progestogen; the risk arises only from unopposed oestrogen in a woman with a uterus.
- The 2024 NICE NG23 update presented detailed benefit/risk tables; note that the British Menopause Society contested some of the framing — counsel from NICE while acknowledging genuine uncertainty and individual variation.
Contraindications to systemic HRT
Current or past oestrogen-dependent cancer (notably breast), active VTE or thromboembolic disease, active liver disease, undiagnosed abnormal vaginal bleeding, and pregnancy.
Non-hormonal pharmacotherapy
- SSRIs/SNRIs (venlafaxine, escitalopram, paroxetine) and gabapentin or clonidine reduce VMS. Avoid paroxetine and fluoxetine in women on tamoxifen (CYP2D6 inhibition reduces tamoxifen efficacy).
- Neurokinin-3 receptor antagonist — fezolinetant (approved 2023) directly targets the KNDy/NK-3 pathway to reduce VMS without hormones.
- Dual NK-1/NK-3 receptor antagonist — elinzanetant (Lynkuet), FDA-approved in October 2025, is the newest non-hormonal option, reducing moderate-to-severe VMS with added benefit for sleep — a useful choice where HRT is contraindicated (e.g. breast-cancer survivors).
Genitourinary syndrome of menopause
Vaginal (local) oestrogen is highly effective and has minimal systemic absorption — it can be used long-term and is appropriate for many women in whom systemic HRT is contraindicated, including, after individual discussion, many breast-cancer survivors. Non-hormonal vaginal moisturisers and lubricants help; ospemifene is an oral SERM option. Local oestrogen does not require added progestogen.
Premature ovarian insufficiency
Offer HRT (or a combined hormonal contraceptive) at least until the average age of natural menopause (~51) for symptom control and, critically, bone and cardiovascular protection. Younger women often need higher oestrogen doses than older postmenopausal women.
Contraception in the perimenopause
Fertility declines but is not zero. Contraception is advised until 12 months of amenorrhoea if over 50, and 24 months if under 50. HRT is not contraceptive. See contraceptive-modalities.
Follow-up
Review at 3 months after starting/changing HRT, then at least annually — reassessing efficacy, bleeding pattern, side effects, and the evolving benefit–risk balance.
Figure B3.3 — Individualised menopause management ladder linking assessment, symptom targets, HRT construction, route selection, non-hormonal options, POI replacement, and follow-up safeguards.
Red flags / pitfalls
- Attributing postmenopausal or unscheduled bleeding to HRT without investigation — exclude endometrial cancer first.
- Missing POI — amenorrhoea under 40 needs FSH testing and, once confirmed, replacement; do not leave a young woman unreplaced.
- Unopposed oestrogen in a woman with a uterus — endometrial hyperplasia/carcinoma risk.
- Using FSH to "confirm" menopause in a woman on combined contraception or cyclical HRT — it is uninterpretable.
- Withholding vaginal oestrogen for GSM out of unfounded systemic-risk fears — local therapy is safe and effective, including for many cancer survivors after discussion.
- Defaulting to oral oestrogen in a woman with VTE, migraine, or cardiovascular risk — choose transdermal.
- Prescribing paroxetine/fluoxetine for VMS in a woman on tamoxifen — reduces tamoxifen efficacy.
- Assuming HRT provides contraception — it does not.
- Treating the flush and ignoring bone and cardiovascular risk — the climacteric is a window to address long-term health.
Evidence anchors
- NICE NG23 — Menopause: identification and management (2015; major update November 2024; last amended April 2026) — clinical diagnosis over 45, HRT benefit/risk tables, CBT, and non-hormonal options.
- The Menopause Society (formerly NAMS) — 2022 Hormone Therapy Position Statement (current) — "benefits outweigh risks for most symptomatic women <60 or within 10 years of menopause"; transdermal/lower-dose route advantages.
- British Menopause Society (BMS) and International Menopause Society (IMS) consensus statements on MHT and the timing hypothesis.
- NOFSA — National Osteoporosis Foundation of South Africa guideline (bone protection in the menopause; see osteoporosis).
- FDA approvals: fezolinetant (NK-3 antagonist, 2023) and elinzanetant (dual NK-1/NK-3 antagonist, 2025) for moderate-to-severe VMS.
- South African EML / NDoH Standard Treatment Guidelines — availability of oral/transdermal oestrogen, progestogens, and tibolone.