Hormone Replacement Therapy in Modern Clinical Practice

The hot flush that wakes you at 03:00, the sudden fog that steals a board‑room sentence, the invisible shift that hollows bones – the menopausal transition is blunt. Yet for many, relief sits in plain sight. Hormone Replacement Therapy (HRT) remains the single most effective intervention for menopause symptoms, and its influence stretches far beyond symptom control. This feature presents the full picture: what the therapy entails, who benefits, how it is delivered, and why timing, formulation, and personal history make a significant difference.

What HRT Means in 2025

HRT restores hormones that drop during the menopausal transition, easing physical and emotional disturbances that bruise daily life. UK practice keeps the term “HRT” for all mid‑life prescriptions, though some literature labels treatment started near age 50 as “hormone therapy”. Whatever the heading, the goal is the same: bring circulating levels of key hormones back to physiological territory.

Crucially, HRT is now viewed as an individualised toolkit rather than a single drug. The clinical indication – relief of vasomotor misery, protection after premature ovarian insufficiency, or gender affirmation – dictates dose, route and risk balance.

The Hormones at Work

Oestrogen

Central to every systemic regimen, oestrogen quells vasomotor episodes, counters vaginal atrophy, supports mood and guards bone mineral density.

Progestogen

For anyone with a uterus, a progestogen neutralises oestrogen‑driven endometrial proliferation, cutting the long‑term risk of cancer back to baseline.

Testosterone

Women produce testosterone too, and levels decline with age. When fatigue and decreased libido persist despite adequate oestrogen, specialist‑supervised off‑label testosterone can rescue sexual desire.

Who Receives HRT

Perimenopause and Menopause

Most prescriptions go to women aged 45 – 55 seeking respite from hot flushes, night sweats or mood disturbance. Diagnosis is clinical; hormone testing is rarely needed once classic symptoms and cycle change appear.

Premature Ovarian Insufficiency and Surgical Menopause

Menopause before 40, or abrupt loss of ovarian function after oophorectomy, brings decades of oestrogen deficiency. Here, HRT is essential for long-term bone and cardiovascular health, typically continued until at least age 51.

Gender‑Affirming Hormone Therapy

Transgender and gender-diverse individuals use similar molecules with different intentions. Feminising regimens combine oestrogen with testosterone suppression; masculinising plans use testosterone. Lifelong therapy is common, yet data on ageing with GAHT are sparse – a critical research gap.

Fun fact: Roughly 1.5 million HRT prescriptions were issued in England in 2024, double the number recorded five years earlier.

Routes of Delivery and Personalised Regimens

First‑pass metabolism makes oral oestrogen the only formulation linked with a measurable rise in venous thromboembolism (VTE) and stroke. Patches, gels and sprays bypass the liver, so transdermal oestrogen is first choice for anyone with thrombosis risk – body mass index over 30, migraine, family clot history or poorly controlled hypertension.

Two progestogen options dominate combined regimens: nightly oral micronised progesterone, which aids sleep, and the levonorgestrel intra‑uterine system, valued for dual contraception and minimal systemic exposure.

Sequential or Continuous?

1. Sequential (cyclical) HRT – oestrogen daily with progestogen for 12–14 days each month – suits perimenopausal women who still bleed.
2. Continuous combined therapy – both hormones daily – targets postmenopausal users aiming for a bleed‑free routine, accepting some spotting in the opening months.

Evidence‑Based Indications

Vasomotor and genitourinary relief tops the list. Moderate to severe hot flushes, night sweats or vaginal dryness that dent quality of life justify therapy.

Osteoporosis prevention is well documented. NICE and the British Menopause Society (BMS) place HRT among first‑line options for women under 60 at high fracture risk, especially when symptoms are present.

In premature ovarian insufficiency, HRT flips from optional to essential – a replacement that shields the skeleton, heart and possibly cognition from early hormone loss.

For transgender care, GAHT is medically necessary to align physical traits and mental health, though evidence on late‑life outcomes remains limited.

How HRT Benefits Patients

1. Rapid relief of hot flushes and night sweats
2. Reversal of vaginal atrophy, easing dryness, itch and painful intercourse
3. Maintenance of bone density and reduction in hip, spine and wrist fractures
4. Improved sexual function, especially when testosterone is added for hypoactive desire
5. Better mood stability and sleep, often via nocturnal cooling of night sweats

When HRT starts within 10 years of the last menstrual period, observational and re‑analysed randomised data show fewer coronary events and lower all‑cause mortality – the widely cited “window of opportunity”. Cognitive protection is less certain, but initiating before 60 does not raise dementia risk and may clear the so‑called “brain fog” of perimenopause.

Unpacking Risk without Alarmism

Learning from the Women’s Health Initiative

The 2002 WHI trial, halted early, sounded alarms on breast cancer and heart disease. Later age‑stratified analysis told a different story: women who began HRT in their 50s saw cardiovascular benefit and no early harm. The lesson is timing.

Breast Cancer Nuances

1. Oestrogen‑only HRT after hysterectomy shows little change, even a small reduction, in breast cancer incidence and mortality.
2. Combined HRT raises risk modestly – around 4–5 extra cases per 1,000 users over 5 years – and this falls after stopping.
3. Progestogen choice matters. Micronised progesterone and dydrogesterone are linked with lower risk than older synthetic versions, a finding highlighted by the BMS though not yet entrenched in NICE methodology.

Clot and Stroke Risk Driven by Route

1. Oral oestrogen increases VTE and ischaemic stroke via hepatic protein synthesis.
2. Transdermal oestrogen leaves clot risk at baseline, making it mandatory for anyone with thrombophilia, raised BMI or past thrombotic events.
3. Tibolone, an oral synthetic steroid, raises stroke risk in women over 60.

Age, Duration, History

Under 60 or within a decade of menopause: benefits outweigh risks for most.

Over 60 or late starters: weigh persistent symptoms against higher baseline cardiovascular and cancer risk.

No fixed stop date: annual review checks balance and patient preference.

Guideline Consensus and Divergence

1. NICE NG23 (updated Nov 2024) champions shared decision‑making, confirms transdermal oestrogen carries no extra clot risk and adds menopause‑specific cognitive behavioural therapy (CBT) as evidence‑based support.
2. BMS statements endorse the timing hypothesis, urge transdermal routes for VTE risk and highlight the lower breast cancer signal with micronised progesterone.
3. RCOG focuses on empowering patients to ask, “What are my options, pros and cons, and support?”

Clinicians must bridge methodological gaps, explaining why a micronised progesterone patch of evidence may sway choice even if not yet embedded in NICE tables.

Conducting a Patient‑Centred Consultation

1. Assess symptoms, family history, blood pressure, BMI.
2. Diagnose clinically in women over 45; reserve hormone tests for younger or uncertain cases.
3. Discuss absolute numbers: “Four extra breast cancer cases per 1,000 over 5 years” is clearer than “30 % rise”.
4. Prescribe lowest effective dose, favouring transdermal oestrogen when VTE risk looms.
5. Review at 3 months, then yearly. Side‑effects guide tweaks: lower dose for breast tenderness, switch progestogen if mood swings persist.
6. Advise on contraception – HRT is not a contraceptive.

When Hormones Are Not an Option

Lifestyle support remains foundational: weight optimisation, layered clothing, exercise, limiting alcohol and caffeine. Phytoestrogens and herbal remedies lack consistent proof and carry interaction or purity concerns; THR‑label products offer minimum quality assurance but not guaranteed benefit.

The Next Frontier

1. Licensed bioidentical hormones – body‑identical estradiol patches and micronised progesterone – merge “natural” appeal with regulatory rigour.
2. Compounded bioidentical mixes remain outside mainstream care due to inconsistencies in potency and a lack of safety data.
3. Drug delivery innovation: subcutaneous pellets releasing oestradiol for up to six months; micro‑dosed patches and nanotech gels aiming for zero skin transfer.
4. Pharmacogenomics could soon guide starting doses by analysing cytochrome P450 variants and receptor polymorphisms, reducing trial‑and‑error titration.
5. Research priorities: long‑term cardiovascular and bone outcomes in transgender cohorts, progestogen‑specific breast cancer risk in randomised settings, and definitive trials on cognition and dementia.

Practical Checklist for the Clinic

1. Confirm indication: symptom relief, POI protection, gender affirmation.
2. Match route to risk: transdermal for any clot predisposition.
3. Pair progestogen carefully if uterus intact – consider micronised progesterone or IUS.
4. Begin low, review at 3 months, and adjust if side effects outlast the adaptation window.
5. Continue as long as benefits outweigh risks; no arbitrary five‑year stop.

Conclusion

Prescribing HRT is like tuning a string quartet. Oestrogen, progestogen and testosterone each carry a line; tempo is set by delivery route; harmony comes only when every part meets the listener’s ear at the right moment. Get the balance right, and discordant symptoms resolve into a confident score.