NB Blog - Unscheduled bleeding on HRT

Sometimes in General Practice you’ve got to get out of your comfort zone and dive head long into an area with which you are both uncomfortable and unfamiliar. It’s the nature of being an expert generalist - there will always be gaps and areas that go off your radar and need to be brought back into focus. The phrase ‘unscheduled bleeding on HRT’ brings me out in a cold sweat and a dash to the nearest member of our women’s health team begging for advice…..

So it is with great thanks that one such colleague recently highlighted the excellent BMS guideline on unscheduled bleeding in HRT, that was published last month. It’s a great resource, endorsed by a number of bodies including the RCOG and RCGP, and answers many of those key questions I have, such as ‘what is unscheduled bleeding?’, ‘what dose of progestogen do you need for the various doses/types of oestrogen?’, ‘what does adjusting HRT actually mean?!’. It has a simple flow chart (page 6) and some easy to use tables as reference. 

The background to this guideline will come as no surprise. HRT prescribing has sky rocketed with an average 13.6% annual increase every year over the last decade in women aged >50. Unscheduled bleeding is common, affecting 38% on sequential HRT (sHRT) and 41% on continuous combined HRT (ccHRT), leading to a 43% increase in urgent suspected cancer gynae referrals. Reassuringly this has not equated to a relative increase in more cancer diagnoses. This guideline aims to make sure those women at highest risk of cancer do get urgent assessment, while those at lower risk can be safely managed (initially) in primary care to help reduce anxieties, unnecessary HRT cessation, and ease the burden on urgent referral pathways. 

Some useful points and areas to highlight include:

• When should we switch from sHRT to ccHRT? Once over age 45 switch from sHRT to ccHRT after 5 years of sHRT use or by age 54 (whichever comes sooner). 
• What dose of progestogen do you need vs oestrogen dose? Appendix 1 (page 42) summaries the oestrogen doses of the different formulations (and which doses are off license) and gives the progestogen doses required e.g. if on ccHRT with a 100mcg oestrogen patch this is ‘high dose’ and if using micronised progesterone we need to use the higher 200mg daily dose to cover this. 
• Be aware limitations in the evidence for endometrial protection of progestogens with high dose oestrogen. It’s worth being aware that there is limited evidence on optimal doses of synthetic progestogens (e.g. norethisterone, medroxy progesterone) and micronised progesterone if using high dose oestrogen.
• If in doubt think Mirena. Whilst there is uncertainty around optimal regimes for some progestogens, this is not the case for the 52mg LNG IUD - studies have shown it offers sufficient endometrial protection across all oestrogen doses for peri- and postmenopausal women, can be used for 5 years, and gives added endometrial protection for women with BMI ≥30.
• What is unscheduled bleeding on HRT? This is defined as irregular bleeding which occurs after initiating, or changing, a HRT preparation which should be ‘bleed free’ (i.e. bleeding on ccHRT or bleeding in addition to the scheduled monthly withdrawal bleeds on sHRT). 
• Once other causes of bleeding have been considered (e.g. infection, cervical cause) assess endometrial cancer risk to guide next steps (see table P6 for full detail):
  • Major risk factors include (but not limited to): BMI >40 (obesity remains the strongest risk factor), Lynch syndrome.
  • Minor risk factors include (but not limited to): BMI 30-39, progesterone dose not proportional to oestrogen dose for >12 months, diabetes.
• Who needs an USS or referral? (See P20/21 for detail)
  • Referral on the urgent suspicion of cancer pathway (i.e. what used to be the ‘2 week wait’) if unscheduled bleeding PLUS 1 major or 3 minor risk factors (irrespective of bleeding pattern or interval since starting/changing HRT).
  • Urgent USS (within 6 weeks) if unscheduled bleeding PLUS 2 minor risk factors, or > 6 months since starting HRT, or > 3 months after a change in dose or preparation of HRT, or bleeding that is heavy (flooding, clots), persistent (most days for >4 weeks) or prolonged withdrawal bleeds (> 7 days). 
  • Women at low risk not covered by referrals above can be managed in primary care with HRT adjustments for up to 6 months before considering USS. 
• How do I adjust HRT? This will inevitably depend on a number of factors (see table 6, P29 for more detail), but the BMS recommends we offer all women the 52mg LNG IUD as this is the most effective method to reduce unscheduled bleeding.