HRT Clinical Reference — UK Guideline Summary

Irregular spotting is common in the first 3–6 months of continuous combined HRT. If bleeding started within the first 6 months and is light spotting, reassurance and review at 6 months is appropriate per BMS guidance. However, if bleeding is heavy at any time, persists beyond 6 months, or is new-onset after a period of amenorrhoea — investigate. BMS unscheduled bleeding guideline (July 2024) recommends pelvic ultrasound (endometrial thickness) and consideration of endometrial biopsy. Also consider whether the patient is truly postmenopausal — if she has been amenorrhoeic for less than 12 months, she may have been started on continuous combined prematurely; switching to sequential (Evorel Sequi or separate oestrogen + Utrogestan 200mg for 14 days/cycle) may resolve the bleeding.

BMS and NICE NG23 guidance supports transdermal HRT as the preferred route in women with BMI >30. Obesity independently increases VTE risk, and oral oestrogen adds further VTE risk on top of this. Transdermal oestrogen (patch or gel) at standard doses does not increase VTE risk beyond baseline, making it the safer choice. Consider Evorel 25 or 50μg patch, or Oestrogel 1–2 pumps daily, plus Utrogestan 200mg (14 days/cycle for sequential or 100mg daily for continuous) or Mirena 52mg IUS. If she is perimenopause — sequential regimen. If confirmed postmenopause — continuous combined is appropriate.

Post-hysterectomy = oestrogen only. No progestogen required (no uterus, no endometrial cancer risk). Oestrogen-only HRT has a more favourable safety profile than combined HRT — lower breast cancer risk. Start with a low dose — e.g. Evorel 25μg patch or Oestrogel 1 pump daily. Review at 3 months. Titrate upward if symptoms persist. If she had bilateral oophorectomy at 45 — this is POI/early menopause — higher doses may be needed and continuation to natural menopause age (~51) is recommended. NICE NG23 and BMS support HRT in this group to protect against premature bone loss, cardiovascular disease, and cognitive decline from prolonged oestrogen deficiency.

Use absolute numbers, not relative risk, for this conversation. BMS context: over 5 years, combined HRT with synthetic progestins adds approximately 8–10 extra cases per 1,000 women — comparable to the risk from obesity. Oestrogen-only HRT adds 0–3 extra cases per 1,000 women. Combined HRT with micronised progesterone (Utrogestan) appears to add no increased risk for up to 5 years per the Asi et al. meta-analysis. NICE NG23 (2024): HRT is unlikely to increase or decrease overall life expectancy. Risk returns to baseline after stopping HRT. The choice of progestogen matters — if she has a uterus, using micronised progesterone (Utrogestan) or Mirena IUS instead of synthetic progestogen minimises breast cancer risk while maintaining endometrial protection.

Previous VTE is a caution, not an absolute contraindication. Key guidance: transdermal oestrogen at standard doses does not increase VTE risk beyond baseline (NICE NG23, BMS). Oral oestrogen should be avoided. Assess thrombophilia risk — NICE NG23 suggests considering haematology referral before HRT in women at high VTE risk. Routine thrombophilia screening is not required before starting HRT. If she is deemed suitable — use transdermal oestrogen (patch or gel) plus micronised progesterone (Utrogestan) or Mirena IUS. Document the shared decision-making discussion. Avoid oral oestrogen and synthetic progestins where possible.

BMS and NICE NG23 guidance: switch from sequential to continuous combined HRT after at least 12 months of amenorrhoea — i.e., when postmenopause is confirmed. Switching before this point risks erratic, unpredictable breakthrough bleeding because residual ovarian activity causes endometrial stimulation that continuous combined regimens cannot predictably control. In practical terms: if a woman on sequential HRT has had regular withdrawal bleeds and then misses one — she may be entering postmenopause. After 12 months without a natural bleed (on sequential), it is appropriate to switch to continuous combined. Switch by replacing the progestogen with continuous daily progestogen, or by switching to a combined continuous product (Evorel Conti, Kliofem, etc.). Counsel about breakthrough spotting common in the first 3–6 months after switching.

First check: is the patch being applied correctly? Patches should be placed on clean, dry skin below the waist (buttocks, thigh) — not over the abdomen where absorption is less reliable. Avoid applying to the same site repeatedly. Has she been on the current dose for at least 3 months? Dose adjustments should not be made more frequently than every 3 months. If correct application confirmed and symptoms persist after 3 months at Evorel 50μg — consider checking a serum oestradiol (mid-patch, day 3–4). Target 200–400 pmol/L. If below range — increase to Evorel 75μg or 100μg, or add Oestrogel 1 pump daily alongside the patch (checking oestradiol does not become supra-physiological). Ensure the progestogen dose is increased if moving to a high oestrogen dose (refer to BMS dosing table). Also review whether low mood/fatigue might benefit from testosterone if libido is a component of her symptoms.

The Mirena 52mg LNG-IUS is licensed for 4 years for endometrial protection within HRT. However, BMS, FSRH/CoSRH, and BNF guidance supports its use for 5 years for this indication off-label — this is widely accepted practice in the UK. If the Mirena was fitted at 50 and she is now 54, she is within the 5-year off-label window supported by guidance. If it has been in place for more than 5 years — replace. If she no longer wishes to continue HRT, the Mirena can be removed — but ensure oestrogen is also stopped at the same time if she is postmenopausal. Do not remove the Mirena without stopping oestrogen — this would leave her with unopposed oestrogen and endometrial risk. Important: lower-dose IUS devices (Jaydess, Kyleena, Levosert) are NOT appropriate for endometrial protection in HRT regimens.

POI is diagnosed by FSH >25 IU/L on two separate occasions at least 4 weeks apart, combined with menstrual irregularity or amenorrhoea, in a woman under 40. NICE NG23: ensure the FSH results are not confounded by recent hormonal contraception. Both samples should ideally be taken off hormonal contraception. If diagnosis confirmed — this is POI. BMS advises HRT at physiological replacement doses (generally higher than standard menopausal HRT) until at least the average age of natural menopause (~51). This is to prevent the additional health risks associated with prolonged oestrogen deficiency: premature bone loss, cardiovascular disease, cognitive decline. Fertility implications should be discussed — POI does not mean impossible fertility (spontaneous ovulation can still occur), and specialist referral is appropriate. Psychological support should be offered — POI can be a significant diagnosis for a younger woman.

NICE NG23 specifically recommends testosterone for low sexual desire when HRT alone is insufficient. BMS extends this to include persistent fatigue alongside low libido. Brain fog and cognitive symptoms are not currently supported as primary indications by NICE NG23, though emerging evidence is building. BMS guidance acknowledges emerging data on cognitive function and energy but stops short of a formal recommendation for these indications alone. In practice: if a woman has optimised HRT and still has fatigue with some element of low libido — BMS guidance supports a testosterone trial. If her only symptom is brain fog with no libido component — current guidance does not yet firmly support testosterone as an indicated treatment, and this should be discussed with her as an emerging area. Ensure HRT dose is optimised and consider other causes of fatigue before initiating testosterone.

Migraine with aura is associated with increased stroke risk independently. Oral oestrogen has been shown to increase ischaemic stroke risk dose-dependently (Canonico 2016). The combination of migraine with aura and oral oestrogen therefore carries additional concern. BMS guidance: transdermal oestrogen is strongly preferred in women with migraine with aura. Transdermal oestrogen at standard doses does not increase stroke risk (Renoux 2010). In practice: use a transdermal patch or gel. If she has a uterus, add Utrogestan or Mirena. Avoid oral oestrogen. HRT may actually improve migraine in some perimenopausal women by stabilising oestrogen fluctuations — fluctuating oestrogen is a common migraine trigger. Keep oestrogen levels as steady as possible — patches provide steadier levels than cyclical oral preparations.

BMS guidance: arbitrary limits should not be placed on the duration of HRT use. Duration should be individualised, weighing ongoing benefits against risks at each annual review. NICE NG23 (2024): HRT is unlikely to increase or decrease overall life expectancy. Many women benefit from long-term HRT — particularly those with early menopause, surgical menopause, or POI where HRT protects against premature bone and cardiovascular disease. For women who started HRT for symptom control: review annually. If symptoms have resolved — a trial off HRT can be offered, with the understanding that symptoms may return and re-starting is appropriate. There is no maximum age or time limit specified in NICE NG23 or BMS guidance. Some women benefit from continuing HRT beyond 60 — this requires individual risk-benefit discussion with particular attention to breast cancer risk with combined HRT.

Personal history of breast cancer is a relative contraindication — not an absolute one. This requires specialist involvement (oncology/specialist menopause clinic). BMS and BGCS/BMS 2024 joint guidelines: the decision to start or continue HRT after breast cancer should be individualised, taking into account the tumour type, receptor status, prognosis, severity of menopausal symptoms, and patient preference. HRT has not been shown to significantly affect recurrence risk for all breast cancer subtypes — evidence is more complex than previously thought. In practice: for a woman 5 years post-ER-negative breast cancer with severe menopausal symptoms that significantly affect quality of life, specialist menopause input would typically be sought. Vaginal oestrogen (topical) has a very limited systemic effect and BMS guidance indicates it can generally be considered even in women with breast cancer history — with oncology awareness. Non-hormonal options for vasomotor symptoms include CBT (NICE NG23 supported), venlafaxine, clonidine.