Management of Menopause

1. Diagnosing menopause: do I need to measure FSH levels?

Elevated serum FSH is consistent with perimenopause/menopause. In the perimenopause FSH fluctuates widely thus FSH measurements can be uninformative: individuals may be symptomatic despite normal FSH, and normal FSH does not preclude a trial of HRT.

FSH levels should not be checked if the person is already using systemic HRT or is taking combined oral contraception.

• Individuals aged >45 years.  FSH measurement is not required to diagnose perimenopause in individuals aged over 45 years with symptoms suggestive of menopause. Do not measure FSH in this circumstance (unless the person is aged over 50 and wishes to stop contraception in which case if FSH is >30nmol/l contraception can be stopped after one further year).
• Individuals aged 40-45 years. Consider measuring FSH levels in individuals aged between 40 and 45 who have menopausal symptoms, particularly if there is uncertainty about the diagnosis. As FSH levels fluctuate widely in the perimenopause:-
  • a normal FSH does not exclude perimenopause as a cause of symptoms or preclude a trial of HRT.
  • under age 45 an elevated FSH (even if >30nmol/l) does not exclude future ovulation, and ongoing contraception should be recommended

Individuals aged under 40 years. FSH levels should be measured in all individuals under age 40 in whom a diagnosis of premature ovarian insufficiency (POI) is suspected. Careful consideration of other causes of symptoms is advised.

If serum FSH testing is indicated, when should the test be done?

Blood for serum FSH should be taken in the first few days after onset of a natural period (early follicular sample) to facilitate interpretation. If the person does not have a natural menstrual cycle, a serum estradiol taken on the same day as the FSH can be helpful to support interpretation of FSH results.

Please see full details on FSH testing for menopause and contraception.

2. When should I consider offering HRT?

Offer systemic HRT first line to medically eligible individuals (see section 3) with e.g. vasomotor, mood, cognitive and musculoskeletal symptoms of menopause, after discussing the short and longer-term HRT benefits (menopausal symptom control, bone protection, potential cardioprotection) and risks (breast cancer, ovarian cancer, thrombotic risk with oral estrogen), HRT side effects and giving advice about self-care). Note that ongoing menstruation does not contraindicate use of HRT. In individuals under age 45 always consider other possible medical, medication-related and psychosocial causes of the symptoms described.

Explain that although flushes and sweats will generally settle with HRT, not all symptoms experienced in menopause will respond to HRT. Explain that menopausal symptoms that do settle on HRT may well recur when HRT is stopped again.

HRT used for menopausal symptom control is additionally beneficial for bone health (and potentially for cardiac health if commenced soon around the time of menopause).  HRT is not usually used first line for management of low bone density in menopausal individuals without menopausal symptoms but may sometimes be considered.

2.1 Individuals with menopause before age 40 (premature ovarian insufficiency, POI)

In addition to menopausal symptom control, HRT is particularly important for bone health (and potentially cardiac health) in individuals who are menopausal before age 40 years (premature ovarian insufficiency, POI). We welcome referrals for individuals with POI. (Please refer those who wish to explore fertility options to Reproductive Endocrinology at the Edinburgh Fertility Clinic, where POI can be managed and they can also receive advice on assisted fertility).

Individuals with POI should be offered HRT at least until the average age of natural menopause (50-52 years) for bone and cardiovascular protection (unless there is a clear indication to HRT use). HRT for younger individuals can be in the form of combined oral contraception (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 offer tests for Fragile X premutation, Turner karyotype and autoantibody testing (thyroid and adrenal – and coeliac if symptomatic) to individuals with spontaneous menopause before age 40 to exclude associated conditions.

3. Medical eligibility for HRT

HRT should be offered as first line management option for eligible individuals with perimenopausal/ menopausal symptoms.

3.1 What common medical conditions contraindicate HRT?

There are few absolute contraindications to HRT use. HRT is, however, generally avoided during and after breast cancer and estrogen-sensitive gynaecological cancers (e.g. some endometrial cancers (dependent on grade and stage, many ovarian cancers). We would also advise discussion with the Menopause Clinic if HRT is to be considered for individuals who have a thrombophilia or personal history of VTE, or who have had an MI or CVA. See also British Menopause Society guidance at HRT and CVD and HRT after MI.

3.2 Can I prescribe HRT for individuals with migraines?

Yes. Migraine (with or without aura) does not contraindicate use of HRT but does affect choice of HRT preparation. Migraine (particularly migraine with aura) is a risk factor for ischaemic stroke. HRT containing transdermal estradiol has much less effect on thrombotic risk than HRT containing oral estradiol. So for people with migraine (especially migraine with aura), transdermal estradiol is preferable to oral estradiol to minimise HRT- associated thrombotic risk.

As changes in hormone levels and bleeding itself may trigger migraine, a 52mg LNG-IUD, which avoids the fluctuating progestogen levels associated with sequential HRT and minimises bleeding, may be a good option for the progestogen component of HRT.

3.3 My patient has had breast cancer – can I prescribe HRT?

It is generally recommended that systemic HRT is avoided during and after any breast cancer because of concern that it could increase the risk of recurrence or occurrence of a new primary breast cancer. Non-hormonal management options for menopausal symptoms should be offered first line, alongside self-care. Many people can, however, use low dose local vaginal estrogen to manage urogenital symptoms of menopause after breast cancer.

Please refer to Menopause Clinic for advice if:-

• systemic HRT is to be considered after any breast cancer
• low dose local vaginal estrogen is to be considered by an individual using an aromatase inhibitor after breast cancer
• any exogenous hormone (including low dose local vaginal estrogen) is to be considered by an individual with current breast cancer.

3.4 My patient has a family history of breast cancer – can I prescribe HRT?

Family history of breast cancer (unlike personal history of breast cancer) is not a contraindication to HRT. However, using combined HRT does increase the risk of breast cancer a small amount and this could be additional to inherited increased risk. Using estrogen-only replacement appears to have a smaller effect on breast cancer risk than using combined HRT. We cannot, unfortunately, quantify the additional breast cancer risk with HRT use for any individual based on their family history.

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 additional risk into consideration when deciding whether to use HRT for menopausal symptoms.

For context, lifestyle factors such as alcohol intake and obesity increase breast cancer risk to a similar or greater extent than HRT: this infographic from the British Menopause Society may be helpful when discussing risk.

3.5 My patient has had a VTE event / has a thrombophilia – can I prescribe HRT?

Everyone at elevated risk of VTE should avoid systemic HRT containing oral estradiol as it further increases thrombotic risk. Many people in this situation can, however, use systemic HRT containing transdermal estradiol. This minimises HRT effect on thrombotic risk, but because there could still be some adverse effect on thrombotic risk advice should be sought from the Menopause Clinic and / or Haematology.

Low dose local vaginal estrogen can be used for any vaginal or lower urinary tract atrophic symptoms.

3.6 My patient has had an MI / CVA – can I prescribe HRT?

In the past, HRT was always avoided if an individual had ischaemic heart disease or cerebrovascular disease. Current British Menopause Society guidance at HRT and CVD and HRT after MI indicates that use of HRT containing transdermal estradiol (ideally with micronised progesterone as the progestogen component) may be an option if menopausal symptoms are severe and the patient is using the recommended secondary prevention. Modifiable CV risk factors should also have been addressed. However, advice should generally first be sought from the Menopause Clinic.

Low dose local vaginal estrogen can be used for any vaginal or lower urinary tract atrophic symptoms.

3.7 My patient wishes to commence use of HRT after age 60. Is this appropriate?

Commencement of HRT after age 60, or more than 10 years after menopause, is generally avoided if possible, because of concern that after a long spell without the cardiovascular protective effect of estrogen, HRT could potentially be a cardiovascular risk factor. Note that this is a different situation from continuation of HRT at age 60 that was started close to the time of menopause.

4. Choosing type of systemic HRT

4.1 Should I prescribe estrogen-only or combined estrogen & progestogen HRT?

Most people using HRT require a progestogen to protect the endometrium from estrogen. Always ensure that you advise people that the progestogen part of their combined HRT is essential to avoid endometrial pathology.

Estrogen can only be used without a progestogen for endometrial protection if an individual has undergone total hysterectomy AND has no history of endometriosis. A progestogen may still be required after subtotal hysterectomy (see below).

Estrogen-only HRT appears to be safer in terms of breast cancer risk and thrombotic risk than combined HRT. Note that HRT using a 52mg LNG-IUD as the progestogen component is combined (not estrogen-only) HRT.

Can I prescribe estrogen-only HRT after sub-total hysterectomy?

Theoretically, a small amount of endometrial tissue could be left behind in the upper cervical canal after sub-total hysterectomy. Exposing any such tissue to unopposed estrogen could increase risk of endometrial malignancy. It may be possible to obtain advice on the likelihood of this from the individual’s surgeon. If not, a three-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 estrogen-only.

Can I prescribe estrogen-only HRT if there is a history of endometriosis?

Exposing residual endometriotic deposits to unopposed estrogen may cause endometriosis pain to recur and increases risk of malignancy (endometriotic tissue could be even more sensitive to estrogens than endometrium). Advice from the operating surgeon on the extent of remaining endometriosis can be helpful, but with a history of endometriosis, continuous combined HRT is probably the safest option in most cases.

4.2 Should I prescribe sequential or continuous combined HRT?

Any 52mg levonorgestrel-releasing intrauterine device (52mg LNG-IUD) can be used for 5 years after the date of insertion as the progestogen component of HRT (with separate estradiol) to offer a no-bleed continuous combined HRT regimen.  Note that the lower dose LNG-IUDs Kyleena and Jaydess cannot be used as the progestogen component of HRT.

Otherwise, if someone has menstruated within the last year and therefore likely still has some ovarian activity, sequential combined HRT should be chosen to reduce the risk of unscheduled bleeding.

Continuous combined HRT can be used for people whose last period was (naturally) at least one year ago.

If someone is amenorrhoeic on progestogen-only contraception we don’t know whether they would still be menstruating. We suggest considering a 52mg LNG-IUD for both contraception and endometrial protection or continuing a progestogen-only contraceptive and adding continuous combined HRT.

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 natural period every few months, you might give sequential progestogen for a year and then trial a switch. In a 45-year-old with vasomotor symptoms but regular periods, you might use sequential progestogen for 4-5 years before considering switching. If unscheduled bleeding occurs on continuous combined HRT, try switching back to sequential for another year.

Note that people will usually continue to have withdrawal bleeds on sequential HRT even if they are post-menopause. Ongoing withdrawal bleeds on sequential should not be considered a contraindication to switching to continuous combined HRT.

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 combined HRT. Most HRT users should aim to switch to continuous combined HRT by age 55 to optimise endometrial protection.

4.3 How do I choose an estrogen for HRT?

IMPORTANT:

Estrogen replacement must be used WITH a progestogen for protection of endometrium and /or endometriosis. IF YOU ARE PRESCRIBING SEPARATE ESTROGEN AND PROGESTOGEN COMPONENTS OF COMBINED HRT, YOU MUST ENSURE:-

• THAT THE PATIENT UNDERSTANDS THE IMPORTANCE OF THE PROGESTOGEN
• THAT AT EVERY REPEAT ESTROGEN PRESCRIPTION, THE PATIENT IS ALSO BEING PRESCRIBED A PROGESTOGEN
• THAT A 52MG LNG-IUD BEING USED AS THE PROGESTOGEN COMPONENT OF HRT HAS BEEN IN SITU FOR <5 YEARS

PLEASE NOTE THE SAFETY ADVICE ABOUT POTENTIALLY REDUCED EFFECTIVENESS OF ORAL PROGESTOGENS DURING USE OF INCRETIN-BASED THERAPIES.

4.3.1 Should I prescribe oral or transdermal estradiol in HRT?

HRT containing transdermal estradiol (estradiol patches, gel or spray) appears not to confer an increased risk of VTE or stroke in the general population, whereas HRT containing oral estradiol is associated with increased risk of thrombosis.

HRT containing transdermal (rather than oral) estradiol is therefore recommended for individuals aged over 60 years, and those with risk factors for venous thromboembolism or cardiovascular disease (eg BMI>30, smoker, migraine with aura, diabetes, cancer treatment, reduced mobility). Transdermal estradiol is also preferable to oral for individuals taking thyroxine and those with liver/gallstone disease. Route of administration does not appear to affect breast cancer risk.

4.3.2 What is the recommended range of estradiol doses?

If required for symptom control, estradiol doses up to 100mcg/24 hours estradiol patches, Oestrogel 4 pumps daily, and Sandrena gel 3mg daily can be considered. Note that guidance is currently emerging about use of >3 sprays of Lenzetto daily (it is as yet uncertain whether increasing to 4-6 sprays daily significantly increases the amount of estradiol achieved compared to use of 3 sprays daily, but the British Menopause Society recommends that up to 6 sprays daily can be trialled). If >3 sprays of Lenzetto are applied daily, 3 should be applied to one inner forearm and the remainder to the other inner forearm to facilitate absorption.

If increasing to these maximum estradiol doses does not achieve additional benefit for symptoms, the dose should be reduced again to the minimum that confers benefit.

We do not currently recommend use of estradiol doses higher than this for any individual.

In general, we try to avoid using oral estradiol doses above 2mg daily because thrombotic risk is estradiol dose-dependent.

Note:- If an individual is using a combined estradiol/progestogen patch or tablet, we do not recommend “topping up” with additional estrogen, as endometrial protection may not be adequate.

4.3.3 What is the equivalent dose of estradiol patch/gel/spray/tablet? Approximate equivalent estradiol doses with different preparations based on BMS HRT practical prescribing are as follows:-

	Low estradiol dose	Medium estradiol dose	High estradiol dose
Oestrogel (gel pump)	1 pump	2-3 pumps	4 pumps
Sandrena (gel sachet)	0.5mg	1-2*mg	3*mg
Lenzetto (spray)	1-2 sprays	3-4* spraysǂ	*5-6 spraysǂ
Patch	25mcg/24 hours	50-75mcg/24 hours	100mcg/24 hours
Oral	0.5mg	1-2mg	(3*mg)

4.4 How do I choose an HRT progestogen?

PLEASE SEE THE IMPORTANT SAFETY MESSAGES ABOUT ENSURING PROGESTOGEN PRESCRIBING AND COMPLIANCE (4.3 above).

4.4.1 How do I choose which progestogen to use for endometrial protection in HRT?

Side effects. 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 micronised progesterone, norethisterone, dydrogesterone, levonorgestrel and medroxyprogesterone acetate are listed in the East Region Formulary. Micronised progesterone may have fewer progestogenic side effects for some users than some synthetic progestogens.

Safety. Limited evidence suggests that HRT containing micronised progesterone could be associated with lower risk of breast cancer and VTE compared with HRT containing some synthetic progestogens. Individuals with risk factors for breast cancer or VTE should consider this option first line. Others may prefer the convenience of a combined patch or a 52mg LNG-IUD (also contraceptive). HRT containing dydrogesterone may – like HRT containing micronised progesterone – confer a smaller increase in breast cancer than HRT containing some other progestogens.

Recent evidence suggests a small increase in risk of meningioma associated with use of some contraceptive progestogens, including depot medroxyprogesterone acetate. There is not currently evidence to inform whether there is any effect of HRT progestogens (including medroxyprogesterone acetate) on meningioma risk.

4.4.2 HRT progestogen options

52mg LNG-IUD

All 52mg LNG-IUDs are effective for endometrial protection as part of HRT for 5 years after insertion (regardless of the person’s age at the time of insertion). They have the benefit of providing highly effective contraception, excellent control of bleeding and endometrial protection while delivering only a low, consistent systemic dose of progestogen.

If someone who is using HRT had their 52mg LNG-IUD inserted after age 45 and does not wish to have it replaced after 5 years, they can retain the IUD for contraception until age 55, but must also use combined HRT (rather than estrogen only) from 5 years after IUD insertion.

The lower dose Kyleena^® and Jaydess^® devices should not be used for endometrial protection as part of HRT.Micronised progesterone

The dose of micronised progesterone required for endometrial protection varies according to estradiol dose. Recommended doses are given below for per oral (PO) use. It is recommended that micronised progesterone is taken at bedtime as it can cause sleepiness (which can be a useful effect if taken at night).

	Estradiol dose
	up to and including:- 75mcg/24 hours patchOestrogel® 3 pumps daily Sandrena® 2mg dailyLenzetto® 4 sprays dailyoral estradiol 3mg daily	100mcg/24 hours patchOestrogel® 4 pumps daily Sandrena® 3mg dailyLenzetto® 5-6 sprays dailyoral estradiol 3mg daily
Oral micronised progesterone dose (sequential)	200mg* PO nightly for 14 consecutive nights in every 28 nights, taken at bedtime	300mg PO nightly for 14 consecutive nights in every 28 nights, taken at bedtime
Oral micronised progesterone dose (continuous)	100mg* PO nightly at bedtime (or 25 nights/28)	200mg PO nightly at bedtime (or 25 nights/28)

Notes on prescribing micronised progesterone:-

1. The product licence indicates use of micronised progesterone for 12 nights/28 for sequential use. We suggest 14 nights/28 because this is easier for users to remember.

2. The product licence indicates use of micronised progesterone for 25 nights/28 for ‘continuous’ use; we suggest that continuous use is easier, but if there is unscheduled bleeding on continuous micronised progesterone, a 3-night break can be taken in every 28-day cycle. Sometimes this will result in amenorrhoea, but there could be a scheduled withdrawal bleed (a single monthly bleed around the time of the 3-night break), which would not require investigation.

Vaginal use of micronised progesterone

If an individual has significant side effects with oral micronised progesterone and has not tolerated alternative progestogen options, as a last resort, micronised progesterone can be used vaginally at the same dose and in the same regimen as for oral use. The oral capsules can be inserted vaginally, or a specific vaginal capsule used – whichever is more cost effective. Vaginal use of micronised progesterone as part of HRT is off label, but is considered to provide adequate endometrial protection. If there is unscheduled bleeding after 3 months on vaginal micronised progesterone, however, a switch to an alternative progestogen is indicated.

Use of micronised progesterone for indications other than endometrial protection as part of HRT

Micronised progesterone is indicated only for endometrial protection as part of HRT. Patients sometimes request use of micronised progesterone alone without estrogen (often because of estrogen side effects), or alongside another HRT progestogen (e.g. 52mg LNG-IUD) for its somnolent effect. This is not licensed, is not supported by the BNF or the East Region Formulary, and we do not have evidence to inform health effects of such use.

Dose of other standalone oral progestogens used for endometrial protection in HRT

	Estradiol dose
	up to and including:- 75mcg/24 hours patchOestrogel® 3 pumps daily Sandrena® 2mg dailyLenzetto® 4 sprays dailyoral estradiol 2mg daily		100mcg/24 hours patchOestrogel® 4 pumps daily Sandrena® 3mg dailyLenzetto® 5-6 sprays dailyoral estradiol 3mg daily
medroxyprogesterone acetate (sequential)	10mg PO once daily 14 consecutive days/28		10mg PO once daily 14 consecutive days/28 (consider increase to 20mg if persistent unscheduled bleeding)
medroxyprogesterone acetate (continuous)	5mg PO once daily		5mg PO once daily (consider increase to 10mg if persistent unscheduled bleeding)
dydrogesterone (sequential)	10mg PO once daily 14 consecutive days/28	10mg PO once daily 14 consecutive days/28 (consider increase to 20mg if persistent unscheduled bleeding)
dydrogesterone (continuous)	10mg PO once daily

Unlicensed HRT progestogens

The British Menopause Society also supports use of 2x desogestrel 75mcg POP (150mcg total) daily for endometrial protection as part of HRT (with the advantage that this is also contraceptive).

Progestogens in combined HRT preparations

There are two combined estradiol/progestogen patches (Evorel Sequi/conti which contain the progestogen norethisterone and Femseven Conti which contains levonorgestrel). There is a range of combined estradiol/progestogen tablets containing norethisterone, dydrogesterone and micronised progesterone. These preparations can be convenient for patients, and they avoid the risk of inadvertent use of estrogen without a progestogen. There are not, however, combined preparations containing higher estradiol doses. We do not recommend ‘topping up’ a combined HRT patch or tablet with additional estradiol, as endometrial protection may be inadequate.

5. HRT and Contraception

5.1 Is HRT contraceptive?

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

Sequential HRT is not contraceptive. Continuous combined HRT may confer a contraceptive cervical mucus effect but should not be considered reliably contraceptive.

52mg LNG-IUDs offer both contraception and endometrial protection as part of HRT. Other progestogen-only contraceptives (progestogen-only pill, the etonogestrel implant, the progestogen-only injectable, and lower dose intrauterine systems like Kyleena^® and Jaydess^®) should not be used for endometrial protection but can be used for contraception in addition to standard sequential or continuous combined HRT. Combined hormonal contraception and HRT should not be used together. Please see FSRH Clinical Guideline: Contraception for Women Aged over 40 Years (August 2017, amended July 2023) | CoSRH and the RefHelp page on testing FSH for assessing need for contraception.

5.2 My patient is amenorrhoeic on progestogen-only contraception (eg implant, POP), should I start continuous or sequential combined HRT?

Bleeding pattern is unpredictable when HRT is added to a progestogen-only contraceptive, but addition of continuous combined HRT may be more likely to result in continued amenorrhoea than addition of sequential combined HRT. Use of a 52mg LNG-IUD for both contraception and endometrial protection as part of HRT should be considered as a good alternative option to achieve amenorrhoea and to avoid using two progestogens.

6. Duration of use of systemic HRT

6.1 How long can HRT be used for?

Use of HRT should be reviewed 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 (menopausal symptom control and bone protection) outweigh risks for them, continuation can be supported.

6.2 How should HRT be stopped?

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 an estradiol-only patch or gel preparation, by trimming the patches or reducing the amount of gel used, while continuing separate progestogen for endometrial protection until estrogen has been stopped completely.

7. HRT troubleshooting

7.1 Are there any supply problems with HRT?

Recent years have seen supply problems with various preparations of commonly prescribed HRT. The British Menopause Society publishes up-to-date advice on this on its website.

7.2 How do I manage bleeding on HRT?

New onset unscheduled bleeding in the first 3-6 months of use of HRT (or after a change of HRT) does not generally require endometrial investigation, but check that smear is in date, examine the vagina and cervix, and assess pregnancy and STI risk and test as appropriate.

Abnormal bleeding that predates commencement of HRT, heavy bleeding, bleeding associated with other gynaecological symptoms, bleeding that persists for more than 6 months after starting or switching HRT and new onset bleeding during established use of HRT may need to be investigated, particularly if the individual has risk factors for endometrial pathology (eg obesity, diabetes, polycystic ovaries) – please refer to Unscheduled Bleeding on HRT – RefHelp.

Whenever there is unscheduled bleeding on HRT, always check that HRT is being used correctly (including asking about any patch adherence/ gel drying problems), check for interacting drugs, including use of GLP1 agonists, consider pregnancy testing and STI risk assessment, check smear status and examine the cervix and vagina.

If pathology has been excluded, a 52mg LNG-IUD could offer better control of bleeding. Micronised progesterone and the progestogen in combined patches can be less effective for control of bleeding than some synthetic or oral progestogens: it is worth considering a change of progestogen type to try to control bleeding. Alternatively, if there is erratic bleeding on continuous combined HRT, consider switching to sequential HRT to establish a regular bleeding pattern.

Send a SCI Gateway advice request to the Menopause Clinic of you require support with optimising HRT for bleeding.

7.3 How do I manage HRT side effects?

• Breast tenderness and bloating 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 (micronised progesterone or dydrogesterone can be good options).
• Side effects like acne, adverse effect on mood and headache (sometimes limited to the progestogen-containing phase of sequential HRT) may respond to a change of progestogen. If side effects are cyclical, a 52mg LNG-IUD can be a good option in the perimenopause to avoid the stop/start sequential progestogen that is otherwise required.

If someone has side effects with all the formulary HRT progestogen options, they may consider off label use of micronised progesterone capsules inserted into the vagina (at the same dose and in the same pattern as with oral use – the oral capsules can be used vaginally if this is more cost effective than using specific vaginal capsules). There is not robust study evidence to demonstrate endometrial protection, but vaginal use is considered acceptable in this situation. If, however, there is persistent unscheduled bleeding with vaginal micronised progesterone an alternative progestogen should be used.

7.4 My patient has inadequate control of symptoms despite using a medium dose of estrogen – can I increase the dose further? 

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. It is important to manage expectation as to what HRT can achieve for such symptoms.

First consider other medical, medication-related and psychosocial causes of symptoms and check that the HRT is being used correctly. Ensure that patches are sticking fully to the skin for the entire application time and are not irritating skin, and that gel is drying completely on the skin. Thereafter, a trial can be considered of increasing estradiol dose above the standard medium dose (see table in section 4.3.3) if symptoms that are likely to relate to menopause have not responded (or have responded incompletely) to the medium estradiol doses.

We recommend stepwise estradiol dose increase, to maximum estradiol doses of 100mcg/24 hours estradiol patch/ Sandrena^® gel 3mg or Oestrogel^® 4 pumps transdermal daily/ Lenzetto 6 sprays daily. We recommend trying to avoid oral estradiol doses above 2mg if possible because effect on thrombotic risk (including risk of VTE and ischaemic stroke) appears to be dose dependent.

If you have already increased the estradiol dose to the recommended maximum above without benefit, try switching to an alternative estradiol preparation. For example, trial a switch from patches to spray or gel at equivalent dose. Some individuals seem to respond better to tablets than patches or gels (and vice versa). If all transdermal estradiol options have been trialled without benefit, and the patient has no risk factors for VTE/CVD/CVA (remember that this includes older age, higher BMI, smoking) you may wish to consider a trial of oral estradiol.

We do not usually recommend checking serum estradiol levels. This is because the test does not differentiate between endogenous and exogenous estradiol, and because there is no ‘normal’ serum estradiol that we would ‘aim for’.

If all suitable estradiol preparations have failed to improve symptoms, it may be that the symptoms will not respond to HRT. Non-hormonal management options can be offered, but self-care is key.

7.5 My patient’s private Menopause Care provider is requesting that I prescribe higher estradiol doses than are recommended in Lothian. What should I do?

Published evidence for health outcomes associated with use of HRT is based on studies that consider people using quite modest estradiol doses no higher (and often lower) than those that we recommend in Lothian.

In Lothian, therefore, we recommend titrating estradiol dose against symptoms only up to a maximum dose of estradiol 100mcg/24 hours patches (the licence limit) or equivalent, Oestrogel^® 4 pumps transdermal daily, Sandrena^® 3mg transdermal daily or Lenzetto^® 6 sprays daily. (We would generally avoid use of doses of oral estrogen above 2mg if possible because thrombotic risk with oral estradiol appears to be dose related).

We do NOT check serum estradiol levels as there is no optimum level that correlates with symptom control and because the evidence relates to the estradiol dose administered, NOT to the serum estradiol level achieved. Instead, we adjust dose within the standard range according to response of symptoms.

Some patients may have misconceptions that very high serum estradiol levels are normal pre-menopause and that they need to replicate these with HRT. They may be encouraged by private providers / the media to use several estradiol 100mcg/24 hours patches at the same time, or to combine different preparations e.g. ‘topping up’ with gel in addition to patches. In reality, while high estradiol levels are experienced for a few days in the middle of a natural menstrual cycle, average serum estradiol levels across the menstrual cycle are quite modest. Thus, estradiol levels for some patients receiving care outside the NHS are supraphysiological. We do not have evidence for safety of such high sustained serum estradiol levels, risk of tachyphylaxis is a consideration, and we don’t know how effective standard endometrial protection would be in this situation.

These high estradiol doses are essentially experimental, and we do not recommend their use.

7.6 What is ‘bioidentical HRT’, and is it recommended by the Menopause Clinic?

Information from the British Menopause Society on bioidentical HRT is available on their website at https://thebms.org.uk/publications/consensus-statements/bioidentical-hrt/.

Regulated ‘bioidentical HRT’ (use of which is supported by the British Menopause Society) contains estradiol in combination with micronised progesterone (rather than a synthetic progestogen) for endometrial protection. This combination can be offered in primary care as a standard HRT option.

Non-regulated custom compounded ‘bioidentical HRT’ is not supported by current guidelines. As a clinic we do not offer any such option, and we cannot give guidance on use. Care of individuals using such compounded ‘bioidentical HRT’ regimens should be undertaken by the provider.

8. Management of vulvovaginal and lower urinary tract atrophic symptoms

Hypoestrogenaemia associated with perimenopause/menopause (or other hypoestrogenaemic conditions) can cause soreness in the vagina (often particularly problematic during sex), vaginal dryness or smelly vaginal discharge, and urinary symptoms such as frequency, dysuria and sometimes recurrent UTI. It can exacerbate urinary incontinence. It can contribute to dryness and soreness of the vulval skin.

Sometimes the symptoms persist even when the person is using systemic HRT.

Low dose local vaginal estrogen 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. Vaginal estrogens can be used safely alongside systemic HRT.

Systemic absorption of low dose local vaginal estrogen products is negligible and benefit for prevention of severe vaginal atrophic and urinary tract atrophic symptoms including urosepsis can be very significant. This use is considered safe, with benefits outweighing risks for most individuals. HOWEVER, use of low dose local vaginal estrogen by individuals with a history of estrogen-sensitive breast or gynaecological cancer should generally be discussed with the Menopause Clinic or the individual’s oncology team. Use is usually acceptable after successful treatment of estrogen-sensitive breast cancer if the person is using tamoxifen but may not be ideal during use of an aromatase inhibitor e.g. letrozole, anastrazole, exemestane.

Low dose local vaginal estrogen is available as vaginal estradiol 10mcg tablets, an estradiol vaginal ring (Estring^®) and estriol 1mg/1g vaginal cream: choice of product depends on patient’s preference. Ultra-low dose vaginal estriol tablets and cream (e.g. Imvaggis^® and Blissel^®) are available for use if it is considered important to minimise estrogen exposure further.

Whether vaginal estrogen is used or not, regular non-hormonal vaginal moisturiser and a good lubricant for sexual intercourse are beneficial in menopause.

Vulval symptoms. It is common for people describing vaginal dryness / soreness to have dryness or soreness of the vulval skin. First line management would be avoiding vulval irritants and using an emollient to wash and moisturise the genital skin. Low dose local vaginal estrogen can also help with this, and a small amount of vaginal estriol cream can be applied around the vaginal introitus in addition to internal vaginal application.

9. What non-hormonal options do you recommend for menopausal symptoms?

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

9.1 Self care

Whether HRT is used or not, self-care is crucial for wellbeing in menopause. This might include:-

• avoidance of vasomotor triggers like caffeine, hot drinks and alcohol and nicotine which also disturb sleep)
• nutritious diet (including calcium and vitamin D for bone health)
• resistance and aerobic exercise (see the Royal Osteoporosis Society website for videos on building up resistance exercise for bone and muscle strength and the Lothian Exercise and Diet in Menopause patient information leaflet)
• good sleep hygiene (try Sleepio app)
• CBT and mindfulness techniques (Try the book ‘Managing hot flushes and night sweats: a cognitive behavioural self-help guide to the menopause’ by Myra Hunter and Melanie Smith).
• We recommend the TEDX talk ‘The Surprising Truth About Desire Everyone Needs to Know’ by Dr Karen Gurney to help people with low sexual desire to overcome barriers to sex.

9.2 Non-hormonal medical management options include:- 

• SNRI/SSRI (eg venlafaxine 37.5mg po od/bd or citalopram 10-20mg po od) used off label for vasomotor and mood symptoms (note that fluoxetine and paroxetine should not be used in combination with tamoxifen).
• Gabapentin 100-300mg tds po used off label for vasomotor symptoms.
• Oxybutynin 2.5mg po up to qds as tolerated for drenching sweats (be aware that this could potentially have an adverse effect on cognition for older individuals).
• (Clonidine is rarely used for vasomotor symptoms as there is not usually sustained benefit)
• The drug Fezolinetant has not yet been accepted by the East Region Formulary and cannot therefore be offered at present.

Can I prescribe testosterone?

Separate guidance to follow shortly.

SH, EG & CM 27.08.26