There are few absolute contraindications to HRT use.

HRT is generally avoided after breast cancer and oestrogen-sensitive gynaecological cancers e.g. some endometrial cancers and many ovarian cancers.

We also advise discussion with the Menopause Clinic if HRT is to be considered for individuals who have a thrombophilia or history of VTE, or who have had an MI or CVA.

Migraine, with or without aura, does not contra-indicate use of HRT but may affect choice of HRT preparation.

As changes in hormone levels may trigger migraine, the Mirena IUS may be a good option as it avoids the fluctuating progestogen levels associated with sequential HRT.

Similarly, transdermal estradiol offers relatively more stable serum estradiol levels than oral estradiol, and is associated with lower thrombotic risk. Migraine with aura is an independent risk factor for ischaemic stroke.

Family history of breast cancer, unlike personal history of breast cancer, is not a contra-indication to HRT.

Taking combined HRT does increase risk of breast cancer therefore women who already have elevated breast cancer risk because of family history or because they carry a BRCA or other relevant gene mutation should take this into consideration when deciding whether to take HRT for menopausal symptoms.

For context, lifestyle factors such as obesity and alcohol intake significantly increase breast cancer risk. This infographic from the British Menopause Society may be helpful when discussing risk.

Fatty liver increases insulin resistance and CVD risk, therefore HRT can be advantageous if commenced at the appropriate time. Transdermal estradiol with either IUS or Utrogestan is recommended. LFTs should be checked 3 monthly until HRT dose is stable and with any dose increases.

If abnormal LFTs are due to cirrhosis, advice should be sought from the specialist menopause service.

Despite the higher proportion of AD in women, there is no conclusive evidence that HRT prevents the onset of AD in older menopausal women who start HRT.

There is limited evidence that it may be beneficial in younger women but further studies are required.

Offer HRT to medically eligible individuals with vasomotor, mood or cognitive symptoms of menopause, after discussing the short and longer-term benefits and risks and alternative management options.

Note that ongoing menstruation does not contraindicate use of HRT. Explain that menopausal symptoms may well recur when HRT is stopped again.

Ideally HRT should be commenced within 10 years of the LMP. Starting HRT beyond this interval may miss out on the ‘window of opportunity’ for cardiovascular and cerebrovascular benefits.

There is an increased risk of stroke if oral HRT is commenced after age 60. Use transdermal options in this age group. 

Coronary heart disease may be increased if HRT is commenced after age 60, but not if it commenced prior to this age and still continued

• Serum FSH levels should be measured in individuals aged under 40 in whom a diagnosis of premature ovarian insufficiency (POI) is suspected. 2 samples 4-6 weeks apart are required.
• FSH levels should be considered to help diagnose menopause in individuals aged between 40 and 45 who have menopausal symptoms, including a change in the menstrual cycle
• FSH measurement is not required to diagnose perimenopause in individuals aged over 45 years with symptoms suggestive of menopause.
• FSH >30nmol/l is consistent with perimenopause. However, FSH measurements can be uninformative in the peri-menopause. Individuals may be symptomatic despite normal FSH, and normal FSH does not preclude a trial of HRT.

Oestrogen-only HRT can only be prescribed after a total hysterectomy, otherwise a progestogen is required for endometrial protection. A progestogen is also required after hysterectomy if there is a history of moderate/severe endometriosis (see below)

Oestrogen-only HRT appears to be safer in terms of breast cancer risk than combined HRT.

There is a theoretical possibility that a small amount of endometrial tissue may be left behind in the upper cervical canal after sub-total hysterectomy.

Exposing any such tissue to unopposed oestrogen would risk endometrial malignancy.

A three to six month trial of combined sequential HRT may help to clarify - if there is no withdrawal bleeding, it is likely to be safe to switch to oestrogen-only preparations.

Exposing residual endometriotic deposits to unopposed oestrogen may cause endometriosis pain to recur and increases risk of malignancy (endometriotic tissue appears to be more sensitive to oestrogens than endometrium).

BMS guidance is to use a combined preparation even if there has been a hysterectomy for endometriosis.

The Mirena^® 52mg levonorgestrel-releasing intrauterine system (LNG-IUS) can be used for 5 years as the progestogen endometrial protection component of HRT to offer a no-bleed HRT regimen with separate estradiol

(Faculty of Sexual Reproductive Health (FSRH) guidance, but outwith product license)

Otherwise, for individuals who have menstruated within the last year and are therefore likely to still have some ovarian activity, sequential HRT should be chosen to reduce the risk of unscheduled bleeding.

Continuous combined HRT can be used in individuals whose last period was at least one year ago.

There is no right or wrong answer as to when to switch from sequential to continuous combined HRT. Aim to do this when you might reasonably expect normal periods to have ceased.

In a 50-year-old having a period every few months, you might give sequential for a year and then trial a switch. In a 45-year-old with vasomotor symptoms but regular periods, you might use sequential for 4-5 years before considering switching.

If unscheduled bleeding occurs, try switching back to sequential for another year.

With regard to health risk, continuous combined HRT is associated with a slightly greater increased risk of breast cancer, but a lower risk of endometrial cancer than sequential HRT.

HRT containing transdermal estradiol (estradiol patches or gel) appears not to confer an increased risk of VTE or stroke.

Oral HRT is associated with increased risk of thrombosis. Transdermal HRT should therefore be used in preference to oral HRT by individuals aged over 60 years and those with risk factors for venous thromboembolism or cardiovascular disease e.g. BMI>30, smoker, migraine with aura, diabetes, cancer treatment, reduced mobility.

Transdermal estradiol is also preferable for individuals taking thyroxine and those with liver/gallstone disease.  However, patient choice must be considered as this will improve compliance.

A medium, 2mg oral estradiol dose is roughly equivalent to a 100mcg/24 hours estradiol patch or 1-1.5mg estradiol gel.

Equivalent estradiol doses in different preparations are described in this British Menopause Society factsheet

Different progestogens are associated with different side effects. If an individual has a side effect with one progestogen in HRT, it can be helpful to try a different progestogen. HRT options containing norethisterone, dydrogesterone, levonorgestrel (Mirena) and medroxyprogesterone acetate are available.

Evidence suggests that HRT containing dydrogesterone or micronised progesterone may be associated with lower risk of breast cancer and VTE compared with HRT containing some synthetic progestogens.

Micronised progesterone (Utrogestan) received SMC approval in December 2022 and is now included in the preferred list of the GGC formulary.

Mirena is effective for 5 years for endometrial protection as part of HRT (regardless of the individual's age at the time of insertion).

If an individual had their Mirena inserted after age 45 and does not wish to have it replaced after 5 years, they can retain the Mirena for contraception until age 55, but must use combined HRT (rather than estrogen only) from 5 years after Mirena insertion.

Levosert is also a 52mg LNG-IUS but is not licensed for use as part of HRT.

Sequential HRT is not contraceptive. Continuous combined HRT may offer a contraceptive cervical mucus effect but should not be considered reliably contraceptive as it is not taken according to missed pill rules.

Note that it is established practice that contraception can be stopped at age 55 years.

The Mirena LNG-IUS offers both contraception and endometrial protection as part of HRT. Other progestogen-only contraceptives (progestogen-only pill, the etonogestrel implant, the progestogen-only injectable, and other intrauterine systems) should not be used for endometrial protection but can be used for contraception alongside standard sequential or continuous combined HRT. Please see FSRH Clinical Guideline: Contraception for Women Aged over 40 Years

Use of HRT should be reviewed and documented on an annual basis.

HRT-associated health risks, particularly breast cancer, increase with age and duration of use. However, there is no maximum age or duration of use and if an informed individual without medical contraindications considers that HRT benefits outweigh risks for them, continuation can be supported

Menopausal symptoms tend to recur on stopping HRT, and many individuals find it helpful to gradually reduce the estradiol dose over several months when stopping HRT. This can be easiest to achieve with a patch or gel preparation.

Unscheduled bleeding: new onset unscheduled bleeding in the first 3-6 months of use of HRT, or after a change of HRT, is not uncommon and does not generally require investigation.

Heavy bleeding, bleeding associated with other gynaecological symptoms, bleeding that persists for more than 3-6 months after starting or switching HRT and new onset bleeding during established use of HRT may need to be investigated.

Investigation is indicated if the individual has risk factors for endometrial pathology such as obesity, diabetes, polycystic ovaries. Always assess compliance, including patch adherence problems, check for interacting drugs, consider pregnancy testing and STI risk assessment, check smear status and examine the cervix. If a patient is using a transdermal cyclical product, please ensure these have been used in the correct sequence. If referral is required please use USOC via the PMB pathway

If pathology has been excluded, a Mirena LNG-IUS could offer better control of bleeding.  Alternatively, if there is erratic bleeding on continuous combined HRT, consider switching to sequential HRT to establish a regular bleeding pattern.

Lower oestrogen dosing is associated with better bleeding profiles, so it may be worth considering reducing the oestrogen dose if the patient feels able to do so.

Breast tenderness, bloating and headache are common when HRT is started and often settle with time. If symptoms persist, try reducing the estradiol dose, changing the route of estradiol administration or changing the progestogen. Dydrogesterone, the progestogen in Femoston products, can be a good option.

Side effects like acne and adverse effect on mood, sometimes limited to the progestogen-containing phase of sequential HRT, may respond to a change of progestogen.

Vasomotor symptoms generally respond well to HRT, but other menopausal symptoms like mood change and 'brain fog' do not always respond as reliably, even if estradiol dose is increased.

We suggest seeking advice from us before increasing estradiol dose above 2mg oral estradiol/100mcg/24 hours estradiol patch or Sandrena gel 1.5mg transdermal daily. Younger individuals may well require higher doses.

Please note increased estradiol doses should be accompanied by a corresponding increase in progestogen dose.

See British Menopause Society fact sheet

If you have already increased the estradiol dose without benefit, try switching to an alternative route of estradiol administration if otherwise clinically suitable as some individuals seem to respond better to tablets than patches or gels, and vice versa.

Currently, there is no licensed testosterone product for women.  As there is no evidence that it improves any symptoms other than weak evidence of libido, it should not be routinely included in HRT.

NICE and BMS menopause guidance states that testosterone replacement can be used in addition to HRT for the indication of low sexual desire associated with menopause. There is inadequate evidence to support use of testosterone for other symptoms associated with the menopause, such as low energy levels, brain fog or reduced muscle tone.

As testosterone for low libido associated with menopause is 'off-label’ it is out-with the remit of the GGC Formulary. If being considered, prescribers should:

• refer to NHSGGC Unlicensed Medicines Policy and Off-label or unlicensed use of medicines for further information on prescribing ‘off label’ medicines.

• refer to the GGC Prescribing Advice for Menopausal Women: Testosterone

If advice is still required, please contact Sandyford for email advice at ggc.menopausesupport@nhs.scot

Regulated 'Bioidentical HRT', use of which is supported by the British Menopause Society, contains estradiol in combination with micronised progesterone (Utrogestan^®) for endometrial protection, rather than a synthetic progestogen.

This combination may be associated with a smaller increase in breast cancer and VTE risk than combined HRT containing some synthetic progestogens.

Information from the British Menopause Society on bioidentical HRT is available at: Bioidentical HRT - British Menopause Society (thebms.org.uk)

Low dose vaginal oestrogen is extremely effective for urogenital atrophic symptoms, although it can take 3-6 months of use for benefit to be noticeable and long-term continuation is advised to prevent symptom recurrence.

Systemic absorption of low dose local vaginal oestrogen products is negligible and thus vaginal oestrogen is considered safe for most individuals.

HOWEVER use of local vaginal oestrogen by individuals with a history of oestrogen-sensitive breast or gynaecological cancer should generally be discussed with the Menopause Clinic or the individual's oncology team. Low dose local vaginal oestrogen is generally acceptable during Tamoxifen use but not during use of an aromatase inhibitor.

Local vaginal oestrogen is available as low dose vaginal estradiol tablets, estradiol vaginal ring and estriol cream as per the patient's preference. Very low dose vaginal estriol tablets and cream are available for use if it is considered important to minimise oestrogen exposure. Vaginal oestrogens can be used safely alongside systemic HRT.

Some people don't want to take HRT or have been advised against it for medical reasons.

Vasomotor symptoms generally improve with time. It can help to avoid vasomotor triggers like alcohol, caffeine and hot drinks, to layer clothing and bedding and consider cognitive behavioural therapy/ mindfulness techniques and sleep apps.

Medical management options include:

• Clonidine is licensed for vasomotor symptoms and is effective in some women.

• Please see BMS information on alternatives 02-BMS-TfC-Prescribable-alternatives-to-HRT-03A-JUNE2022.pdf (thebms.org.uk)

GGC guidelines

• [CG] Hormone Replacement Therapy and Cardiovascular Disease (nhsggc.org.uk)
• [CG] Hormone Replacement Therapy Prescribing, Gynaecology (nhsggc.org.uk)

Yes. We welcome referrals for individuals with POI. Please refer those with fertility wishes to the Assisted Conception Unit, GRI, where POI can be managed and they can also receive advice on assisted fertility.

Unless there is a clear contraindication to HRT use, individuals with POI should be offered HRT until the average age of natural menopause (50-52 years) for bone and cardiovascular protection and possibly reducing risk of Alzheimer’s Dementia.

HRT for younger individuals can be in the form of COC or HRT according to their preference and medical eligibility.

At age 50-52, the individual may opt to trial stopping HRT or to continue for ongoing symptom control.

We may offer tests for Fragile X permutation, Turner karyotype and autoantibody testing (thyroid and adrenal) to individuals with spontaneous menopause before age 40 to exclude associated conditions.