Previous changes

July 2025 — minor update.  Added information regarding the management of women with endometriosis who may still require combined HRT following hysterectomy.

January to April 2025 — reviewed. A literature search was conducted in January 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring to improve clarity and navigation. The recommendations have been updated in line with the National Institute for Health and Care Excellence (NICE) clinical guideline Menopause [NICE, 2024a] and other relevant literature. A section detailing the investigation and management of unscheduled bleeding on hormone replacement therapy (HRT) has been added in line with guidance prepared on behalf of the British Menopause Society, in partnership with the British Society of Gynaecological Endoscopy, British Gynaecological Cancer Society, Faculty of Sexual & Reproductive Healthcare, Getting It Right First Time (GIRFT), Royal College of General Practitioners and the Royal College of Obstetricians & Gynaecologists [BMS, 2024]. 

February 2025 — minor update. Information that the tricycling regimen has been identified as a major risk factor for endometrial cancer if used for over 12 months has been added to this topic. 

November 2024 — minor update. Updated to reflect the new guidance in NICE Menopause: identification and management [NG23], November 2024. Specifically relating to the risk and benefits of HRT. Prescribing information updated to show that dydrogesterone is contraindicated for use in people with (or history of) meningioma.

October 2022 — minor update. Information that exogenous oestrogens may induce or exacerbate symptoms of hereditary and acquired angioedema has been added to the adverse effects section of this topic. 

March 2022 — minor update. Added detail to recommendation regarding progestogen regimes in non-hysterectomised women taking sequential HRT.

October to November 2020 — reviewed. A literature search was conducted in August 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring to improve clarity and navigation. The lowest age-range of the topic has been changed from 40 to 35 years, to include the diagnosis and management of suspected premature ovarian insufficiency (POI). The recommendations have been updated in line with the National Institute for Health and Care Excellence (NICE) clinical guideline Menopause [NICE, 2019] and other relevant literature. Additional options for non-hormonal therapy include the use of paroxetine, clonidine, gabapentin, or cognitive behavioural therapy (CBT) for the management of vasomotor symptoms. Additional information for women with hypothyroidism has been added to the section on Managing co-morbidities. A new node on Referral has been added to the topic, to improve clarity and navigation.

April 2020 — minor update. Minor typographical error corrected.

March 2017 — minor update. More information on results of the Collaborative Group on Epidemiological Studies of Ovarian Cancer has been included in the topic, and a link to the meta-analysis has been included [Collaborative group on epidemiological studies of ovarian cancer, 2015].

December 2016 — minor update.

• Information that a combined oestrogen/bazedoxifene acetate product (Duavive®) is available for postmenopausal women with a uterus (with at least 12 months since the last menses) for whom progestogen-containing therapy is not appropriate, has been added to this topic [ABPI, 2016]. Minor text change on the effectiveness of gabapentin for reducing hot flushes has also been added. 
• Information on the risk of ovarian cancer associated with hormone replacement therapy (HRT) has been clarified, in line with the manufacturers' updated Summary of Product Characteristics [ABPI, 2016].
• The adverse effects of HRT have been updated to include angioedema, and advice that people requiring thyroid replacement therapy should have their thyroid function monitored regularly while taking HRT has been added [ABPI, 2016].

November 2016 — minor update. Information on testosterone removed from the section on management without HRT.

October 2015 — reviewed. A literature search was conducted in October 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with recommendations in the National Institute for Health and Care Excellence (NICE) draft guideline Menopause [National Collaborating Centre for Women, 2015]. The topic has also been restructured.

February 2015 — minor update. Testosterone implants have been discontinued. References to testosterone implants have been removed from the topic.

December 2014 — minor update. The recommendations for managing women with current or previous breast cancer have been re-written for the purposes of improved clarity.

July 2014 — minor update. Update to the text on the use of unopposed oestrogen in women with an intact uterus. The manufacturers of Evorel^® advise that if oestrogens are administered alone for prolonged periods, the risk of endometrial cancer may remain elevated for at least 10 years, even after stopping treatment.

March 2014 — minor update. Text amended to clarify the recommendations on how to stop cyclical combined HRT patches and continuous combined HRT patches.

May to June 2013 — reviewed. A literature search was conducted in April 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. No major changes to clinical recommendations have been made. However, the evidence summary on risks associated with the use of hormone replacement therapy has been updated in line with two recent Cochrane systematic reviews.

March 2012 — minor update. Estraderm TTS 25^® and Estraderm TTS 100^® patches have been discontinued. The prescriptions for these products have been removed. 

January 2012 — minor update. Added updated information from the manufacturer's Summary of Product Characteristics (SPC) stating that venlafaxine may alter glycaemic control in people with diabetes mellitus. 

January 2012 — minor update. Lundbeck Ltd in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA), has published new safety data regarding the association of citalopram and escitalopram with dose-dependent QT interval prolongation. This topic has been updated to reflect this advice. 

May 2011— interaction between SSRIs and tamoxifen added as stated in the most recent Summaries of Product Characteristics (SPCs). 

April 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made. A prescription for estriol 0.01% vaginal cream (Gynest^®) has been added. 

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

December 2010 — minor update. Premique^® cycle tablets and Premarin^® vaginal cream have been discontinued. The prescriptions have been removed. 

July 2010 — minor update. Harmogen tablets (estropipate 1.5 mg) have been discontinued. The prescriptions for this product have been removed. 

May 2009 — minor update. Estraderm TTS50^® patches and EstraCombi^® patches are being discontinued during May to July 2009. The prescriptions for these products have been removed. Estraderm TTS25^® and Estraderm TTS100^® patches will continue to be available.

March 2009 — minor update to the evidence section for antidepressants. Text discussing a sensitivity analysis for antidepressants is now included. Advice from the Medicines and Healthcare products Regulatory Agency (MHRA) that tibolone increases the risk of breast cancer recurrence in women with a history of breast cancer has been included. Issued March 2009.

September 2008—minor correction to Changes section. 

March 2008 — minor text update to the basis of the recommendation about possible risks of HRT.

October 2007 to January 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

July 2006 — minor update. The Commission on Human Medicines' (CHM) update on the risk of endometrial cancer with HRT and tibolone has been included. Evorel Pak^® discontinued and prescriptions removed. 

May 2006 — minor update. Estradiol 100 mg implant discontinued and prescriptions removed. 

November 2005 — minor technical update.

July 2005 — updated to incorporate the Referral guidelines for suspected cancer published by the National Institute for Health and Clinical Excellence. 

February 2005 — correction to table in line with Long-term benefits of HRT: results from the Women's Health Initiative study. 

November 2004 — updated to include the latest review of the evidence on long-term safety of HRT from the Committee on Safety of Medicines (CSM). 

March 2004 — reviewed. Validated in May 2004 and issued in July 2004.

June 2001 — rewritten. Validated in July 2001 and issued in October 2001.

April 1998 — reviewed.

September 1997 — written.

New evidence

Evidence-based guidelines

• NICE (2026) Fezolinetant for treating moderate to severe vasomotor symptoms associated with menopause. National Institute for Health and Care Excellence. https://www.nice.org.uk/ [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2025.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2025.

Systematic reviews and meta-analyses

No new since systematic reviews or meta-analyses 1 January 2025.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 January 2025.

New policies

No new national policies or guidelines since 1 January 2025.

New safety alerts

No new safety alerts since 1 January 2025.

Changes in product availability

• New product calcitriol 0.25 and 0.5 microgram is licensed for the correction of the abnormalities of calcium and phosphate metabolism in patients with renal osteodystrophy, and for the treatment of established post-menopausal osteoporosis. See more here. 
• Evorel Gel, the third transdermal estradiol gel on the market, is licensed for once-daily use on the arms, shoulders or inner thighs, cyclically or continuously; a progestogen is required in those with an intact uterus. See more here.

Basis for recommendation

The information on the clinical features of menopause and perimenopause is based on the National Institute for Health and Care Excellence (NICE) clinical guideline Menopause: identification and management [NICE, 2024a], Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society [Lambrinoudaki, 2022], publications from the British Menopause Society Menopause Practice Standards [BMS, 2022a], and Cognitive Behaviour Therapy (CBT) for Menopausal Symptoms [Hunter, 2022], and the Endocrine Society Treatment of symptoms of the menopause [Stuenkel, 2015], The 2022 hormone therapy position statement of The North American Menopause Society (NAMS) [NAMS, 2022], and expert opinion in review articles [Hill, 2016; Hickey, 2017; Delamater, 2018; Monteleone, 2018; Pinkerton, 2020; Santoro, 2021; Herson, 2022].

Basis for recommendation

The recommendations on assessment are based on the National Institute for Health and Care Excellence (NICE) clinical guidelines Menopause [NICE, 2024a], and Suspected cancer: recognition and referral [NICE, 2025], Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society (EMAS) [Lambrinoudaki, 2022], the Endocrine Society clinical practice guideline Treatment of symptoms of the menopause [Stuenkel, 2015], the British Menopause Society (BMS) Menopause Practice Standards [BMS, 2022a]; the AACE and American College of Endocrinology (ACE) Position statement on menopause - 2017 update [Cobin, 2017], the North American Menopause Society (NAMS) position statements on non-hormonal management of vasomotor symptoms [NAMS, 2023] and on hormonal therapy [NAMS, 2022], the College of Sexual and Reproductive Healthcare (CoSRH) clinical guideline Contraception for women aged over 40 years [CoSRH, 2023], and expert opinion in a review article [Pinkerton, 2020].

Basis for recommendation

The recommendations on when to identify menopause and perimenopause are largely based on the National Institute for Health and Care Excellence (NICE) clinical guideline Menopause: identification and management [NICE, 2024a], the European Menopause and Andropause Society (EMAS) care pathway Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society [Lambrinoudaki, 2022], the College of Sexual and Reproductive Healthcare (CoSRH) clinical guideline Contraception for women aged over 40 years [CoSRH, 2023], the British Menopause Society Menopause Practice Standards [BMS, 2022a], the Endocrine Society guideline Treatment of symptoms of the menopause [Stuenkel, 2015], the North American Menopause Society position statement The 2022 hormone therapy position statement of The North American Menopause Society [NAMS, 2022], and expert opinion in review articles [Hill, 2016; Hickey, 2017; Delamater, 2018; Monteleone, 2018; Pinkerton, 2020; Santoro, 2021; Herson, 2022].

Not routinely using blood tests such as serum follicle-stimulating hormone (FSH) to diagnose menopause

• NICE reviewed the available evidence from 21 studies of low- to moderate-quality, to determine the diagnostic accuracy of age, menopausal symptoms, biochemical measurements (FSH, anti-Müllerian hormone, antral follicle count, inhibin B, inhibin A, and oestrogen), and ultrasound features (ovarian volume) to diagnose perimenopause and postmenopause. These indexes were considered both individually and in combination.
  • The evidence showed that when examined in isolation, no indication (age, vasomotor symptoms, biochemical measures, endocrine changes, or ultrasound features) was found to accurately diagnose the menopause. However, algorithms either as combinations of menstrual (classifying women according to the time since their last period), hormonal (classifying women according to their menstrual history, surgical history, age, FSH and oestradiol levels), and historical (classifying women according to their menstrual history, surgical history, and age) allowed for the correct classification of both premenopausal and perimenopausal women.
• The NICE guideline development group concluded that:
  • Age over 45 years and amenorrhoea for at least 12 months are sufficient clinical indicators for the routine diagnosis of menopause.
  • Biochemical measurements, hormonal tests, and ultrasound tests are not useful in the routine diagnosis of menopause and perimenopause and should not be used to diagnose these conditions in women aged over 45 years.
• This approach is supported by the EMAS care pathway [Lambrinoudaki, 2022], which advises not measuring FSH in menopausal women over 45 years of age.
• The recommendation that FSH levels should not be measured if a woman is taking combined hormonal contraception or high dose progesterone is based on the NICE clinical guideline, which notes that the diagnostic accuracy of FSH levels may be affected by women taking hormonal treatment.
  • The CoSRH clinical guideline [CoSRH, 2023] notes that women using combined hormonal contraception have suppressed levels of estradiol, FSH, and LH even if measured during the hormone-free interval, so these investigations cannot be used to assess menopausal status.
• The recommendation that FSH levels should not be measured if a woman is taking hormone replacement therapy (HRT) is based on the CoSRH clinical guideline, which notes that measurement of FSH is unreliable while taking HRT, as serum levels can be very variable and may be suppressed. 

When to consider using serum FSH measurements to diagnose menopause

• The recommendation about women aged between 40–45 years with menopausal symptoms is based on the NICE clinical guideline, the BMS standards of care [BMS, 2022a], and the EMAS care pathway.
• The recommendation about women with a suspected diagnosis of premature ovarian insufficiency (POI) is based on the NICE clinical guideline.
• The recommendation about women aged over 50 years using progestogen-only contraception, including depot medroxyprogesterone acetate (DMPA), is based on the CoSRH clinical guideline. CKS notes that this recommendation differs from that in the NICE clinical guideline, which recommends that gonadotrophins including FSH should not be measured in women using hormonal treatments. 
  • The CoSRH clinical guideline notes that during perimenopause, isolated serum estradiol, FSH, and LH levels can be misleading and should not be used as a basis for providing advice about stopping contraception. Ovulation may still occur with risk of pregnancy, particularly in young women with a diagnosis of POI. It recommends serum FSH measurement can be used to advise about stopping contraception in women over 50 years of age using progestogen-only contraception who are amenorrhoeic.
  • The recommendation to recheck the FSH level after 1 year if it is in the premenopausal range is based on the CoSRH clinical guideline.
• The EMAS care pathway recommends considering the use of FSH measurement in aged 40–45 years who report a change in their menstrual cycle and menopausal symptoms.  If menopause is suspected in women, aged under 40 years of age, further assessment is recommended to explore the possibility of premature ovarian insufficiency. 
• The NICE clinical guideline does not give any specific guidance on how to test for or interpret serum FSH levels.
  • The information that a single serum FSH level more than 30 IU/L indicates a degree of ovarian insufficiency, but not necessarily sterility, is based on the CoSRH clinical guideline.
  • The BMS document [Marsden, 2022] recommends diagnosing menopause in women with breast cancer with an elevated FSH level (more than 30 IU/L) on two blood samples taken 4–6 weeks apart. It also states that FSH levels can be unreliable in the presence of tamoxifen. Discussion with the woman’s breast team is recommended as accurate determination of menopausal status may affect choice of adjuvant breast cancer therapy.

Seeking advice

• The recommendation to seek specialist advice if unsure about diagnosis is based on the BMS standards [BMS, 2022a] and what CKS considers to be good practice.

Basis for recommendation

The recommendations on suspecting premature ovarian insufficiency (POI) are based largely on the National Institute for Health and Care Excellence (NICE) guideline Menopause: identification and management [NICE, 2024a], the European Society of Human Reproduction and Embryology (ESHRE) Guideline on premature ovarian insufficiency [ESHRE, 2024], a care pathway Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society [Lambrinoudaki, 2022], the College of Sexual and Reproductive Healthcare (CoSRH) clinical guideline Contraception for women aged over 40 years [CoSRH, 2023], and the Endocrine Society clinical practice guideline Treatment of symptoms of the menopause [Stuenkel, 2015], and the British Menopause Society consensus statement Premature ovarian insufficiency [Hamoda, 2024a].

When to suspect premature ovarian insufficiency (POI)

• The recommendation on when to suspect a diagnosis of POI is largely based on the NICE clinical guideline [NICE, 2024a].
  • The NICE clinical guideline states that the presence of menopausal symptoms and elevated follicle-stimulating hormone (FSH) levels on two blood samples in a woman younger than 40 years indicates a diagnosis of POI.
  • NICE reviewed the evidence from three studies (low- to very low-quality evidence) of women at high risk of POI, to determine the diagnostic accuracy of cycle irregularity, vasomotor symptoms, FSH level, anti-Müllerian hormone (AMH), antral follicle count (AFC), inhibin B, inhibin A, oestrogen, and ovarian volume. These indexes were considered either individually or in combination.
    • Limited evidence showed that FSH levels more than 30 mIU/mL can be a useful diagnostic tool for women at high risk of POI who have already started hormone replacement therapy (HRT).
    • Evidence on the other diagnostic tools, such as inhibin B, oestradiol, and AFC (and the combination of tests), found that these tests may not be useful in the diagnosis of POI.
    • The NICE guideline development group discussed the clinical relevance of the results and the limitations of the interpretation of FSH levels (which tend to fluctuate widely over time) and recommended the repeat of FSH measurements in two blood tests between 4–6 weeks apart. This time interval was based on the group's expertise and clinical experience.
    • NICE noted that some women present for a diagnosis of POI to be confirmed whilst on HRT, when there may have been some doubt about the pre-treatment diagnosis, but treatment was started because of symptoms. NICE states if despite HRT, FSH levels are still elevated in these women, it is very likely they have POI.
• This approach is supported by the EMAS care pathway [Lambrinoudaki, 2022].
  • EMAS noted that there is a discordance between national and international societies regarding the appropriate threshold in FSH concentrations to diagnose POI. ESHRE guideline suggests a threshold of greater than 25 IU/L, while NICE suggest FSH concentrations greater than 30 IU/L. The EMAS guideline states that FSH concentrations greater than 40 IU/L, measured on at least two occasions (4–6 weeks apart), are diagnostic of POI.
• The ESHRE guideline[ESHRE, 2024] recommends that diagnosis of POI is based on history of disordered menstrual cycles (spontaneous amenorrhea or irregular menstrual cycles) for at least 4 months, and elevated FSH concentration greater than 25 IU/l.
  • ESHRE states that a second FSH test may be required (after 4-6 weeks) if the first set of results are inconclusive, and the index of clinical suspicion is high. The guideline notes that given the sometimes-fluctuant nature of POI, menses may return, and FSH/estradiol levels normalize. As such, a second test may paradoxically confuse the situation and is not needed if the first test is diagnostic.
  • ESHRE do not recommend diagnosing POI based on serum estradiol concentrations. However, a low estradiol concentration indicates hypoestrogenism, and in combination with an elevated FSH concentration provides additional confirmation of the POI diagnosis.
• The recommendation to not use serum AMH levels routinely to diagnose POI is largely based on the NICE clinical guideline [NICE, 2024a].
  • It noted that AMH does not fluctuate significantly within or between menstrual cycles, but it is an expensive test that is not widely available in primary care, results may be inconsistent depending on the AMH assay used, and results may be affected by the use of combined hormonal contraceptives and HRT. The NICE guideline development group concluded that this test should not be used in isolation to diagnose women with POI.
  • The ESHRE guideline [ESHRE, 2024] recommends that AMH should not be used as the primary diagnostic test for POI.
  • The EMAS care pathway states that although AMH levels may be helpful in assessment of ovarian reserve and prediction of reproduction outcomes, it has no clinical use in predicting age at menopause onset [Lambrinoudaki, 2022].
• The recommendation that FSH levels should not be used to identify menopause in people using combined oestrogen and progestogen contraception or high dose progestogen is based on the NICE clinical guideline, which notes that the diagnostic accuracy of FSH levels may be affected by women taking hormonal treatment [NICE, 2024a]. In addition, it is extrapolated from the CoSRH clinical guideline, which notes that women using combined hormonal contraception have very suppressed levels of estradiol, FSH, and luteinizing hormone (LH) even if measured during the hormone-free interval, so these investigations cannot be used to assess menopausal status [CoSRH, 2023].

Specialist advice/referral

• The recommendation on when to consider seeking specialist advice or referral is extrapolated from the BMS consensus statement [Hamoda, 2024a] and the ESHRE guideline[ESHRE, 2024]. 

Basis for recommendation

The information on other causes for menopausal symptoms is based on the National Institute for Health and Care Excellence (NICE) clinical guideline Menopause [NICE, 2024a], the care pathway from the European Menopause and Andropause Society Menopause, wellbeing and health [Lambrinoudaki, 2022], the Endocrine Society clinical practice guideline Treatment of symptoms of the menopause [Stuenkel, 2015], the American Association of Clinical Endocrinologists (AACE) consensus publication Medical guidelines for clinical practice for the diagnosis and treatment of menopause [Goodman, 2011], and expert opinion in review articles [Watt, 2018; Santoro, 2021]. It is also pragmatic, based on what CKS considers to be good clinical practice.

What information and advice should I give a person who has symptoms associated with menopause or is approaching menopause?

• Provide evidence-based information about menopause and treatment options to help the person make informed, individualized decisions about management. Discuss:
  • What menopause is, including that it is a life transition, which:
    • Usually takes place in mid-life or, 
    • Can happen earlier because of surgery or medical treatment, an inherited condition, or an unknown cause — support and information about menopause and fertility should be provided to people who are likely to experience menopause as a result of medical or surgical treatment before and after they have their treatment.
  • Short and long-term health implications and commonly associated symptoms:
    • Explain that symptoms associated with menopause may vary from minor to severe and be experienced over short or long time periods.
  • Management options and the risks and benefits associated with each of these:
    • Lifestyle measures (see below).
    • Non-hormonal treatments.
    • Hormonal drug treatments.
  • Sources of information, advice, and support, such as:
    • The NHS leaflet Menopause.
    • Women's Health Concern (the patient arm of the British Menopause Society), which has a range of factsheets and an email advice service.
    • The Royal College of Obstetricians and Gynaecologists, which provides various patient leaflets in the section on Menopause and later life.
    • Menopause Matters, which provides information on menopause, menopausal symptoms, and treatment options.
    • Rock My Menopause, which has a variety of factsheets and podcasts on various aspects of menopause.
    • The Daisy Network, which is a nationwide support group for women diagnosed with premature ovarian insufficiency or premature menopause.
• Give information and advice on lifestyle measures to improve menopause symptoms: 
  • Advise the person that:
    • Implementing or maintaining a healthy lifestyle can improve menopause symptoms, prevent chronic disease and improve wellbeing.
  • Provide information on:
    • Healthy diet (low in saturated fat and salt and rich in calcium and vitamin D).
    • Stopping smoking.
    • Reducing alcohol intake.
    • Regular physical activity.
  • For hot flushes and night sweats, advise the person that:
    • Regular exercise, weight loss (if applicable), wearing lighter clothing/layers of clothing, turning down central heating, sleeping in a cooler room, using fans, reducing stress, and avoiding possible triggers (such as spicy foods, caffeine, smoking, and alcohol) may be helpful — see the CKS topics on Obesity, Smoking cessation, and Alcohol - problem drinking for more information.
  • For sleep disturbances, advise the person that:
    • Avoiding exercise late in the day and implementing sleep hygiene measures may help — see the CKS topic on Insomnia for more information.
  • For low mood and anxiety, advise the person that:
    • Adequate sleep, regular physical activity, and relaxation techniques may help.
  • For cognitive symptoms, advise the person that:
    • Regular physical activity and good sleep hygiene may help.
• Give information and advice on interventions, or changes the person can make to support their health and wellbeing.
  • If support is needed in the workplace:
    • Advise the person to talk to their line manager, supervisor or designated person (or where available seek occupational health advice).
  • If the person has, or is at risk of, cardiovascular disease (CVD):
    • Advise on measures to manage CVD risk factors — see the CKS topic on CVD risk assessment and management for information on assessment of CVD risk and ways to reduce the risk.
    • Do not offer combined or oestrogen-only HRT for primary or secondary prevention of cardiovascular disease (CVD).
  • Encourage engagement with national screening programmes (if appropriate):
    • See the CKS topics on Cervical screening, Breast screening, and Bowel screening  for more information.
  • Advise on bone health:
    • See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.
  • Explain the importance of maintaining muscle mass and strength through physical activity.
• Discuss the need for contraception:
  • Advise that:
    • A woman is potentially fertile for 2 years after her last menstrual period if she is between 40 and 50 years of age, and for 1 year if she is over 50 years of age.
    • In general, all women can stop contraception at the age of 55 years.
    • Hormone replacement therapy (HRT) does not provide contraception.
  • Be aware that:
    • All progestogen-only methods of contraception are safe to use as contraception alongside sequential HRT.
    • Combined hormonal contraception (CHC) can be used in eligible women under 50 years of age as an alternative to HRT for relief of menopausal symptoms and prevention of loss of bone mineral density. Women should be advised to switch to a non-injectable progestogen-only contraception or a non-hormonal method at 50 years of age as the risks of CHC generally outweigh the contraceptive benefits.
  • See the CKS topics on Contraception - assessment, Contraception - combined hormonal methods and Contraception - progestogen-only methods for more information.

How should I manage menopausal symptoms with hormone replacement therapy?

If a person wishes to consider the use of hormone replacement therapy (HRT) for the management of menopausal symptoms:

• Provide information on lifestyle measures for relief of menopause associated symptoms and to improve health and wellbeing. 
  • See the section on  Information and lifestyle advice for more information.
• Discuss HRT as a possible treatment for menopause-associated symptoms:
  • Tailor this information to the person’s age, medical history (including both personal history and family history, for example, of breast cancer), co-morbidities, and contraindications.
  • Talk about the adverse effects, benefits, and risks associated with:
    • Different types and routes of administration of HRT.
    • Duration and dose of HRT.
  • NICE has produced a variety of publications to support healthcare professionals in the communication of benefits and risks of HRT.
• Consider seeking specialist advice/refer to a healthcare professional with expertise in menopause if:
  • The person has a condition that may be affected by HRT.
  • The person has symptoms associated with menopause and contraindications to HRT or, 
  • There is uncertainty about the most suitable management options for symptoms.
• If the person chooses to take HRT:
  • Offer an appropriate individualised choice of HRT preparation based on co-morbidities, contraindications, medical history, and symptoms.
  • Discuss the possible duration of treatment at the outset.
  • Prescribe the lowest effective dose.
  • Explain the need for regular review (see below).
  • See the section on Prescribing information for further information on choosing a route of administration, choice of hormone, and recommended regimes.
• For people with a uterus, offer combined HRT:
  • Discuss different combined HRT options to identify the one that best balances benefits and risks for the person — a discussion aid on HRT and the likelihood of certain medical conditions is available from NICE.
    • People with a uterus require progestogen (administered for 12–14 days a cycle in a sequential regimen in perimenopause and daily in a continuous combined regimen in menopause) to minimize the risk of endometrial hyperplasia and endometrial cancer associated with unopposed oestrogen exposure.
    • Sequential regimens can be delivered through oral and transdermal preparations. Continuous combined regimens can be delivered through oral and transdermal preparations — the progesterone component can also be delivered through a 52 mg levonorgestrel releasing intrauterine system.
    • The dose of the progestogen should be proportionate to the dose of oestrogen — if higher doses of oestrogen are required, the person should consider increasing the progestogen dose to ensure adequate endometrial protection.
  • Explain to people with a uterus that vaginal bleeding is a common side effect of systemic HRT within the first 3 months of treatment — advise them to seek medical help promptly if they experience vaginal bleeding after 3 months.
    • For more information, see the section on Management of unscheduled bleeding on HRT.
• For people who have had a total hysterectomy offer oestrogen-only HRT.
  • Discuss the different oestrogen-only HRT options to identify the one that best balances benefits and risks for the person — a discussion aid on HRT and the likelihood of certain medical conditions is available from NICE.
• For people who have had a total hysterectomy and a diagnosis of endometriosis offer combined HRT. 
  • Continued combined oestrogen and progestogen HRT is advised following hysterectomy in women who have widespread endometriosis to reduce the risk of stimulation and malignant transformation of endometrial deposits. 
  • Changing to oestrogen only at a later date due to a better safety profile can be considered but must be balanced with the risk of reactivating endometriosis and potential malignant transformation of endometrial deposits. 
  • HRT medication should be reviewed and suspended if symptoms recur.
• For vasomotor symptoms:
  • In people with a uterus, offer an oral or transdermal combined (oestrogen plus progestogen) preparation.
  • In people without a uterus, offer an oral or transdermal oestrogen-only preparation.
  • In eligible people under 50 years of age, offer a choice of HRT or a combined hormonal contraceptive as an alternative option, if there are no contraindications.
    • See the CKS topic on Contraception - assessment for more information.
  • Consider non-hormonal treatments (such as menopause-specific CBT) in addition to HRT or for people in whom HRT is contraindicated or for those who prefer not to take HRT.
    • See the section on Non-hormonal treatments for more information.
• For mood disorders:
  • Consider HRT to alleviate depressive symptoms (not meeting the criteria for diagnosis of depression) with onset around the same time as other symptoms associated with menopause.
  • Consider non-hormonal treatments (such as CBT) in addition to HRT or instead of HRT.
  • For more information on management of mood disorders, see the CKS topics on Depression and Generalized anxiety disorder.
• For genitourinary symptoms associated with menopause:
  • Offer low dose vaginal oestrogen to people with genitourinary symptoms associated with menopause — some people taking systemic HRT may benefit from additional low-dose vaginal oestrogen.
  • Make a shared decision with the person about whether to use an oestrogen cream, gel, tablet, pessary, or ring.
  • Advise the person that:
    • Vaginal oestrogen can be used on its own or in combination with non-hormonal vaginal moisturizers and lubricants.
    • They should attend for regular review of symptoms and treatment.
    • Symptoms often return when vaginal oestrogen is stopped but treatment can be restarted if necessary.
  • If vaginal oestrogen preparations are contraindicated, for example, in people with a history of breast cancer:
    • Offer non-hormonal moisturisers or lubricants.
    • Seek specialist advice on the use of vaginal oestrogen if genitourinary symptoms continue despite trying non-hormonal treatments (off-label indication).
  • Consider vaginal prasterone for genitourinary symptoms if vaginal oestrogen, or non-hormonal moisturisers or lubricants have been ineffective or are not tolerated.
  • Consider ospemifene as an oral treatment for genitourinary symptoms, if the use of locally applied treatments is impractical, for example, because of disability.
    • Ospemifene should not be prescribed to women with breast cancer who are being treated with anti-estrogenic therapy.  
  • A visual summary on the management of genitourinary symptoms is available from NICE.
• For low sexual desire (hypo-active sexual desire disorder [HSDD]) associated with menopause:
  • Consider testosterone supplementation if HRT alone is not effective and other causes of low sexual desire have been excluded — be aware that evidence is limited and this is an off-label indication.
    
    • If the person is using an oral HRT preparation, consider switching from oral to transdermal oestrogen as this can increase the proportion of circulating free testosterone without requiring exogenous testosterone.
  • If the person wishes to consider testosterone supplementation, advise them:
    • That monitoring of testosterone levels is required.
    • On the adverse effects – the commonest are excess hair growth, acne and weight gain, which are usually reversible with reduction in dosage or discontinuation. Alopecia, deepening of voice, and clitoral enlargement may occur, but are rare if testosterone levels remain within the normal female physiological range.
    • That long-term safety data are limited.
    • That it may take 3–6 months to evaluate efficacy.
    • That regular review including assessment of clinical response and adverse effects and discussion on the risks and benefits of long term use is needed.
  • Prescribe topical testosterone therapy in line with local guidance:
    • Before starting testosterone therapy check total testosterone levels to establish a baseline for future monitoring and to ensure that levels are not in the upper range before starting treatment.
    • Recheck levels 3–6 weeks after starting treatment and thereafter every 6–12 months to ensure levels remain within the female physiological range.
  • Ensure that genitourinary symptoms associated with menopause are treated adequately for example, through use of vaginal oestrogen, to avoid dyspareunia.
• Do not recommend the use of bioidentical hormone replacement therapy.
• Stop systemic HRT in people who are diagnosed with breast cancer.
• Ensure review is arranged after 3 months if HRT has been started or changed, then at least annually thereafter — review earlier if clinically indicated (for example treatment ineffectiveness or adverse effects). At each review:
  • Reinforce lifestyle advice and carry out basic health checks including measuring weight and blood pressure.
  • Assess the efficacy and tolerability of treatment(s) and rediscuss the benefits and risks of continuing treatment.
    • Women taking sequential HRT over the age of 45 years should be offered, after five years of use or by 54 years of age (whichever comes first), a change to continuous combined HRT.
    • If not doing so already, advise women who continue HRT over the age of 60 years to have estradiol administered transdermally.
  • Assess for bothersome adverse effects (such as breast tenderness, mood swings, fluid retention, or irregular bleeding) or persistent symptoms, and offer to adjust the HRT dose or preparation if appropriate. Options include: 
    • Adjusting the dose of oestrogen.
    • Changing the dose or type of progestogen for example endometrial protection can be achieved with the use of a levonorgestrel-containing intra-uterine device, which will also provide contraception in the perimenopause.
    • Alter the route of administration, for example switch from oral to transdermal.
  • If there is a sudden change in menstrual pattern, intermenstrual bleeding, postcoital bleeding, or postmenopausal bleeding:
    • Assess appropriately and arrange an urgent 2-week referral if a gynaecological cancer is suspected.
    • See the section on Management of unscheduled bleeding on HRT and the CKS topic on  Gynaecological cancers - recognition and referral for more information.
  • If treatments do not improve symptoms or there are ongoing side effects, consider:
    • An alternative cause for symptoms.
    • Referral to a healthcare professional with expertise in menopause.
  • Support the person to make an individual decision on when and how to stop HRT. Advise that:
    • HRT should be continued for as long as benefits of symptom control and improved quality of life outweigh any risks — there is no arbitrary limit for duration of HRT use.
    • HRT may be gradually reduced over 3–6 months, or stopped suddenly, depending on the person's preferences.
      • Explain that gradually reducing HRT may limit recurrence of symptoms in the short term; gradually reducing or immediately stopping HRT makes no difference to symptoms in the longer term.
      • If troublesome symptoms recur, options include restarting HRT at a low dose, or considering alternative non-hormonal treatments.
      • Vaginal oestrogen preparations may be required long term, but regular attempts to stop treatment, such as annually, can be made.

How should I manage unscheduled bleeding on HRT

If a woman presents with unscheduled bleeding on HRT:

• Take a detailed history asking about bleeding patterns, HRT preparations taken, and individual risk factors for cancer and endometrial hyperplasia. 
  • Major risk factors for endometrial cancer include:
    • Body mass index (BMI) of 40 or higher.
    • Genetic predisposition (such as Lynch or Cowden syndrome).
    • Oestrogen-only HRT for more than 6 months in women with a uterus.
    • Tricycling HRT (quarterly progestogen) for more than 12 months.
    • Prolonged sequential HRT regimen: use for more than 5 years when started in women aged 45 years or older.
    • 12 months or more of using norethisterone or medroxyprogesterone acetate for less than 10 days per month or micronised progesterone for less than 12 days per month, as part of a sequential regimen.
  • Minor risk factors for endometrial cancer include:
    • BMI of 30–39.
    • Unopposed oestrogen for more than 3 months, but less than 6 months.
    • Tricycling HRT (quarterly progestogen) for more than 6, but less than 12 months.
    • More than 6 months, but less than 12 months of using norethisterone or medroxyprogesterone acetate for less than 10 days per month or micronised progesterone for less than 12 days per month, as part of a sequential regimen.
    • Progestogen dose out of proportion to oestrogen dose for more than 12 months (including expired 52 mg levonorgestrel intrauterine device [LNG-IUD]).
    • Anovulatory cycles, such as in Polycystic ovarian syndrome.
    • Diabetes.
  • Optimisation of modifiable factors can, in themselves, reduce episodes of unscheduled bleeding on HRT and endometrial cancer risk.
• Offer examination (abdominal and pelvic) and where relevant initial investigations, for example cervical screening, lower genital tract swabs, and body mass index.
• Refer, using an urgent suspected cancer pathway (for an appointment within 2 weeks) for endometrial cancer if:
  • One major risk factor or three minor risk factors for endometrial cancer are identified, irrespective of bleeding type or interval since starting or changing HRT preparations. Adjustments to the progestogen, or stopping HRT, should be offered whilst awaiting assessment.
• Refer for an urgent (within 6 weeks) transvaginal ultrasound scan (TVS) if:
  • There is any heavy or prolonged bleeding or two minor cancer risk factors are identified, irrespective of interval since starting or changing HRT or,
  • The first presentation with bleeding occurs more than six months after starting HRT or more than 3 months after a change in dose or preparation.
• In the absence of risk factors for endometrial cancer:
  • Offer adjustments in the progestogen or HRT preparation (see below), for 6 months in total, if unscheduled bleeding:
    • Occurs within 6 months of starting HRT or,
    • Is persisting 3 months after a change in HRT dose or preparation.
  • If unscheduled bleeding continues in low-risk women, after 6 months of adjustments:
    • Discuss the options of an urgent ultrasound (within six weeks) versus weaning off HRT and consideration of non-hormonal alternatives (to avoid invasive investigations).
  • For women who elect to stop HRT:
    • If the bleeding has settled at a 4-week follow-up, and continued cessation of HRT is acceptable, no further investigations are required. 
    • If the bleeding has settled at a 4-week follow-up and there is a preference to restart HRT, offer adjustments in HRT for 6 months and then an urgent ultrasound if bleeding is heavy and/or persistent during the 6 months or, is continuing after this interval.
• If TVS has been requested for unscheduled bleeding on HRT:
  • Refer, using an urgent suspected cancer pathway (for an appointment within 2 weeks) for endometrial cancer if the endometrium is thickened (more than 4 mm for continuous combined HRT or more than 7 mm for sequential HRT).
  • Reassure women with a uniform endometrium that is fully visualised, and measures 4 mm or less with continuous combined HRT or 7 mm or less with sequential HRT, that the risk of endometrial cancer is low. 
    • Offer HRT adjustments for 6 months and then offer endometrial assessment, on an urgent suspected cancer pathway, if bleeding increases during the 6 months or, is continuing after this interval.
• In the absence of any clinical features requiring further investigation or referral, consider adjustments to HRT to reduce unscheduled bleeding episodes:
  • Assess adherence and understanding of how to use the prescribed preparation including dose and duration of progestogen – for example, a combined patch or pill may reduce administration errors compared to separate oestrogen and progestogen components.
  • Offer all women a 52 mg LNG-IUD as this preparation reduces episodes of unscheduled bleeding compared to all other preparations.
  • Consider offering oral preparations (if there are no risk factors for thrombosis) as a first-line therapy, or to women with recurrent unscheduled bleeding on transdermal preparations as these provide higher rates of amenorrhoea compared to transdermal preparations.
  • Offer vaginal oestrogens if there are atrophic findings on examination.
• For clinicians:
  • A flowchart detailing the investigation and management of unscheduled bleeding on HRT is available is available from the British Menopause Society (BMS).
• For patients:
  • A patient factsheet Management of unscheduled bleeding on hormone replacement therapy (HRT) is available from Women’s Health Concern (the patient arm of the BMS).

What non-hormonal treatments can I offer?

If a person chooses not to take hormone replacement therapy (HRT), or it is not tolerated or is contraindicated:

• Advise on lifestyle measures for menopause symptom relief. See the section on Information and lifestyle advice for more information.
• If lifestyle measures are insufficient, advise on non-hormonal treatments and non-drug treatment options for symptom relief, including risks and benefits.
• For vasomotor symptoms:
  • Consider Fezolinetant as an option to treat moderate to severe vasomotor symptoms associated with menopause when hormone replacement therapy is unsuitable.
  • Consider menopause-specific cognitive behavioural therapy (CBT).
  • Do not routinely offer selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or clonidine as first-line treatment for vasomotor symptoms alone.
• For mood disorders:
  • Consider CBT as an option for people who have depressive symptoms (not meeting the criteria for a diagnosis of depression) in association with vasomotor symptoms: 
    • In addition to other management options or,
    • For people for whom other options are contraindicated or,
    • For those who prefer not to try other options.
  • For information on the management of depression and anxiety, see the CKS topics on Depression and Generalized anxiety disorder.
• For sleep problems associated with menopause:
  • Consider menopause-specific CBT as an option for people who have sleep problems (such as night-time awakening) in association with vasomotor symptoms: 
    • In addition to other management options or,
    • For people for whom other options are contraindicated or,
    • For people who prefer not to try other options.
  • Consider underlying factors other than menopause that may lead to sleep problems and manage appropriately – for more information, see the CKS topic on Insomnia.
• For urogenital symptoms (genitourinary syndrome of menopause):
  • In people with genitourinary symptoms in whom vaginal oestrogen preparations are contraindicated, or for people who prefer not to use vaginal oestrogen:
    • Consider non-hormonal vaginal lubricants and moisturisers:
      • Moisturisers should be used at least twice weekly, irrespective of sexual activity.
      • Lubricants are primarily used for short term relief of vaginal dryness and should be used at the time of sexual activity to reduce discomfort — oil based preparations can weaken condoms.
    • Be aware that these preparations may be used alone or, if appropriate, in addition to vaginal oestrogen preparations. See the section on Hormone replacement therapy (HRT) for more information.
• For people considering unregulated preparations or complementary therapies to manage menopause-associated symptoms, explain that: 
  • The efficacy and safety of unregulated hormone preparations are unknown.
  • There is some evidence that isoflavones and black cohosh may relieve vasomotor symptoms, but the quality, purity, constituents, and safety of these products may be unknown, and different preparations may vary.
• Arrange review:
  • After 3 months, then at least annually thereafter, unless there are clinical indications for an earlier review (such as treatment ineffectiveness or adverse effects). At each review:
    • Reinforce information and lifestyle advice.
    • Assess the efficacy and tolerability of treatment(s).
    • Advise that the use of vaginal moisturizers and lubricants may be continued for as long as needed.
• Offer to refer the person to a healthcare professional with expertise in menopause, if treatments do not improve menopausal symptoms.
  • See the section on Referral for more information.

How should I manage women with comorbidities?

For women with co-morbidities, offer hormonal, non-hormonal, or non-drug treatment options depending on the risks, benefits, adverse effects, and contraindications. If there is any uncertainty about appropriate management, seek specialist advice from a healthcare professional with expertise in menopause or refer to the relevant specialist team.

• Women with, or at high risk of, breast cancer:
  • Stop systemic hormone replacement therapy (HRT) in women who are diagnosed with breast cancer.
    • See the CKS topic on Breast cancer - recognition and referral for more information.
  • Offer referral to a healthcare professional with expertise in menopause.
  • Do not offer HRT routinely to women with menopausal symptoms and a history of breast cancer.
  • Advise on lifestyle measures, non-hormonal, and non-drug treatment options for symptom relief.
    • Selective serotonin reuptake inhibitor (SSRI) antidepressants (off-label use) may be considered for women with breast cancer for relieving menopausal symptoms (particularly hot flushes), but not for those taking tamoxifen. Fluoxetine and paroxetine should be avoided as they may inhibit the effect of tamoxifen.
    • Do not recommend the use of isoflavones, red clover, black cohosh, vitamin E, or magnetic devices to treat menopausal symptoms in women with breast cancer.
    • Advise that the herbal preparation St John's wort may interact with other drugs such as tamoxifen, anticoagulants, and anticonvulsants. In addition, there is uncertainty about the appropriate dose and possible variation in potency of over-the-counter preparations.
• Women with increased risk of venous thromboembolism (VTE):
  • Consider the use of transdermal rather than oral HRT for people at increased risk of VTE, including women with a BMI over 30 kg/m².
  • Consider referring people at high risk of VTE (for example, with a strong family history of VTE or a hereditary thrombophilia) to a haematologist for assessment before considering the use of HRT.
• Women with increased risk of coronary heart disease or stroke:
  • For people with a personal history of coronary heart disease or stroke, ensure that combined or oestrogen-only HRT is discussed with and offered, if appropriate, by a healthcare professional with expertise in menopause.
    • At the time of update, use of combined or oestrogen-only HRT in people with active or recent arterial thromboembolic disease was off-label.
  • For people with cardiovascular risk factors, assess and manage optimally before considering the use of HRT. 
    • See the CKS topics on CVD risk assessment and management, Lipid modification - CVD prevention, Hypertension, Non-alcoholic fatty liver disease (NAFLD), and Obesity for more information.
  • Consider the use of transdermal rather than oral HRT for women at increased risk of cardiovascular disease.
• Women with type 2 diabetes:
  • Consider the use of HRT after taking any other co-morbidities into account and seeking specialist advice if needed.
    • Advise that HRT is not associated with an adverse effect on blood glucose control.
    • See the CKS topic on Diabetes - type 2 for more information.
• Women with hypothyroidism:
  • Advise that thyroid-stimulating hormone (TSH) levels should be monitored regularly (for example, 6–12 weeks after starting oral HRT), to ensure that levels remain in the acceptable range — dose of levothyroxine (LT4) may need to be increased.
    • See the CKS topic on Hypothyroidism for more information.

When should I refer a woman with menopausal symptoms?

• Refer to a healthcare professional with expertise in menopause if:
  • Symptoms associated with menopause are ongoing and lifestyle measures, hormonal, or non-hormonal, or non-drug treatments are ineffective.
  • There are ongoing adverse effects from treatment.
  • There is uncertainty about the most suitable treatment option, for example, if the person has co-morbidities and/or contraindications to treatment.
  • There is uncertainty about diagnosing premature ovarian insufficiency or early menopause, or specialist advice is needed to manage the condition. 
    • For more information, see the section on premature ovarian insufficiency. 
    • Referral to reproductive medicine and/or specialist psychology services may also be indicated.
  • Symptoms associated with menopause develop in trans men or non-binary people registered female at birth who have taken gender-affirming hormone therapy in the past.
    • Be aware that menopause-specific cognitive behaviour therapy may be considered for vasomotor symptoms, difficulties with sleep or depressive symptoms associated with menopause:
      • In addition to other management options or,
      • If other options are contraindicated or, 
      • For those who prefer not to try other options.
• Consider referral for psychosexual counselling, depending on the person's wishes:
  • If there is persistent altered sexual function and hormonal and/or non-hormonal, or non-drug treatments are ineffective.
• If there is a sudden change in bleeding pattern, intermenstrual bleeding, postcoital bleeding, or postmenopausal bleeding:
  • Assess appropriately and arrange an urgent 2-week referral if a gynaecological cancer is suspected — see the section on Management of unscheduled bleeding on HRT and the CKS topic on Gynaecological cancers - recognition and referral for more information.
• Ensure that all people who are likely to experience menopause as a result of medical or surgical treatment have been offered:
  • The opportunity to discuss fertility, both before and after they have their treatment, with a healthcare professional with expertise in fertility.
  • The opportunity to discuss menopause, both before and after they have their treatment, with a healthcare professional with expertise in menopause.

How should I manage a person with premature ovarian insufficiency?

• Refer the person to a specialist with expertise in menopause or reproductive medicine:
  • If there is uncertainty about diagnosing premature ovarian insufficiency.
  • For further investigation to identify an underlying cause (where possible).
  • To help them manage all aspects of physical and psychosocial health related to their condition, including subfertility.
• Provide information on premature ovarian insufficiency and menopause, including the importance of:
  • Starting individualised hormonal treatment:
    • This can be with hormone replacement therapy (HRT) or a combined hormonal contraceptive, and treatment should be continued until at least the age of natural menopause (unless contraindicated).
      • Younger people may require higher doses of oestrogen than those used in older people — seek specialist advice if unsure.
    • For more information, see the section on Hormone replacement therapy (HRT).
  • Lifestyle measures such as:
    • Healthy diet (including adequate intake of calcium and vitamin D).
    • Regular physical activity (aerobic and weight-bearing).
    • Avoidance of smoking
    • Moderation of alcohol intake.
    • For more information, see the section on Information and lifestyle advice.
  • Regular review to monitor treatment efficacy, adverse effects, complications, cardiovascular risk factors and bone health.
    • For more information, see the sections on Information and lifestyle advice and Hormone replacement therapy (HRT).
• Explain to people with POI starting hormonal treatment that: 
  • The baseline population risk of diseases such as breast cancer and cardiovascular disease increases with age and is very low in people under the age of 40 years.
  • HRT may have a beneficial effect on blood pressure when compared with a combined oral contraceptive.
  • Both HRT and combined oral contraceptives offer bone protection. 
  • HRT is not a contraceptive — spontaneous pregnancy may occur in about 1.5–10% of women with POI.
  • For more information, see the section on Information and lifestyle advice.
• Ensure that people with premature ovarian insufficiency and contraindications to hormonal treatments are given advice on bone and cardiovascular health, and on symptom management.
  • For more information, see the sections on  Information and lifestyle advice and Non-hormonal treatments.

Contraindications and cautions

• Do not prescribe hormone replacement therapy (HRT) in women with:
  • Current, past, or suspected breast cancer.
  • Known or suspected oestrogen-dependent cancer.
  • Undiagnosed vaginal bleeding.
  • Untreated endometrial hyperplasia.
  • Previous idiopathic or current venous thromboembolism (deep vein thrombosis or pulmonary embolism).
  • Active or recent arterial thromboembolic disease (for example, angina or myocardial infarction).
  • Acute or active liver disease.
  • Pregnancy.
  • Thrombophilic disorder.
• Prescribe HRT with caution in women with:
  • Acute porphyrias.
  • Diabetes mellitus (increased risk of heart disease).
  • Factors predisposing to venous thromboembolism.
  • History of breast nodules or fibrocystic disease — closely monitor breast status (risk of breast cancer).
  • History of endometrial hyperplasia.
  • Hypophyseal tumours.
  • Increased risk of gallbladder disease.
  • Migraine or migraine-like headaches.
  • Increased risk of breast cancer — see the CKS topic on Breast cancer - managing FH for more information.
  • Endometriosis — seek specialist advice due to the potential risk of disease reactivation and malignant transformation.
  • Uterine fibroids — may increase in size.
• For further information on risks of HRT see the section on Risks of HRT.

[Stuenkel, 2015; NAMS, 2022; Malhas, 2022; BNF, 2025]

Route of administration

• Hormone replacement therapy (HRT) is available as oral or transdermal preparations, depending on the person's preferences.
  • Oestrogen-only preparations are given to people without a uterus, and combined oestrogen and progestogen preparations are given to people with an intact uterus.
• Transdermal preparations:
  • Transdermal preparations are available as a gel (oestrogen only), patch (oestrogen only or combined oestrogen and progestogen), or spray (oestrogen only). 
  • Transdermal preparations may be appropriate if the person has:
    • Persistent, troublesome symptoms with oral treatment.
    • Troublesome adverse effects with oral treatment.
    • A history of, or increased risk of, venous thromboembolism. 
    • Cardiovascular risk factors, such as obesity, hypertension, or hypertriglyceridaemia. See the CKS topic on CVD risk assessment and management for more information. 
    • Concomitant hepatic enzyme-inducing drug treatment (for example carbamazepine).
    • A gastrointestinal disorder that may affect the absorption of oral treatment.
    • A history of migraine or gallbladder disease.
    • Lactose sensitivity (many HRT oral preparations contain lactose).
  • People who continue HRT intake over the age of 60 should be advised to have estradiol administered transdermally.
• Levonorgestrel-releasing intrauterine system:
  • If the person is using combined HRT, the progestogen component may also be given separately as an oral tablet or as a levonorgestrel-releasing intrauterine system (such as Mirena®).
• Low-dose vaginal oestrogen:
  • Low dose vaginal oestrogen is available as a vaginal tablet (Vagifem®), creams (Ovestrin® or Gynest®), gel (Blissel®), pessary (Imvaggis®), and vaginal ring (Estring®), depending on the person's preferences.
  • A progestogen for endometrial protection is not needed as systemic absorption of vaginal oestrogen is minimal.
  • Some people taking systemic HRT may require vaginal oestrogen in addition to achieve symptom control. 
• The British Menopause Society (BMS) has published several guides to support clinicians in appropriate prescription of HRT — BMS Tools for Clinicians.

[Stuenkel, 2015; Anagnostis, 2020; Ayres, 2022; BMS, 2022a; Lambrinoudaki, 2022]  [NAMS, 2022; NICE, 2024a]

Choice of hormone

• Choice of systemic oestrogen
  • 'Natural' oestrogens (such as estradiol [oestradiol], estrone [oestrone], and estriol [oestriol]) are found in normal physiology (may be manufactured chemically, or extracted from a plant or animal source) and are generally used in systemic hormone replacement therapy (HRT) preparations.
  • 'Synthetic' oestrogens (such as mestranol or ethinylestradiol) are generally not used in HRT due to their greater metabolic impact.
• Choice of progestogen
  • A progestogen is a synthetic hormone virtually identical to progesterone, with similar biological effects.
  • Several different progestogens (such as dydrogesterone, medroxyprogesterone, norethisterone, levonorgestrel and micronized progesterone) are administered alongside oestrogen in HRT in women with a uterus. 
    • Combined HRT patches only contain norethisterone or levonorgestrel.
    • Micronised progesterone is structurally identical to the progesterone produced by the corpus luteum — it is typically administered orally as it has variable transdermal absorption, which is unlikely to protect the endometrium.
    • Micronized progesterone or dydrogesterone may be preferred in women with hypertriglyceridaemia due to their neutral effect on lipid profile.
    • Dydrogesterone is contraindicated in people with, or a history of, meningioma, a rare adverse effect. 
  • Women vary in their tolerance to progestogens, and changing the progestogen component of combined HRT may be needed if progestogenic adverse effects occur.
    • Medroxyprogesterone and dydrogesterone may be better tolerated than norethisterone or levonorgestrel, because they are less androgenic.
    • The levonorgestrel intrauterine system (LNG-IUS) is an alternative route of delivery of progestogen, which provides endometrial protection locally, resulting in low systemic levels of levonorgestrel. 
      • A 52mg LNG-IUS may be used with oestrogen for up to 5 years for endometrial protection as part of an HRT regimen.
      • The device must be changed every 5 years. 
      • Mirena® is currently the only LNG-IUS licensed for endometrial protection as part of an HRT regimen (licensed for 4 years but may be used for up to 5 years off-label) however the College of Sexual and Reproductive Healthcare (CoSRH) supports use of any 52mg LNG-IUS for up to 5 years (outside product license) for this purpose.
    • The LNG-IUS may be useful in women:
      • With persistent progestogenic adverse effects from systemic HRT.
      • With troublesome or heavy withdrawal bleeds taking cyclical HRT (where endometrial pathology has been excluded).
      • If contraception is needed along with HRT. See the section on Information and lifestyle advice for more information. 

[Rees, 2009; Hill, 2016; Anagnostis, 2020; Ayres, 2022; Hamoda, 2022b; Lambrinoudaki, 2022]  [NAMS, 2022; Stephens, 2022; CoSRH, 2023; Hamoda, 2024b; EMC, 2024; ESHRE, 2024; BNF, 2025]

Regimen

• The hormone replacement therapy (HRT) regimen used depends on the person’s wishes, whether they are perimenopausal or postmenopausal and the route of administration.
  • If a person chooses to take HRT, use the lowest effective dosage.
• Combined HRT can be prescribed as a monthly sequential/cyclical regimen or a continuous combined regimen:
  • Monthly sequential/cyclical regimen:
    • Oestrogen is taken daily, and progestogen is given at the end of the cycle for 12–14 days, depending on the type of progestogen. 
      • A monthly progestogen dose, in proportion to the estrogen dose, is recommended in women with a uterus. 
      • More than 6 months of unopposed oestrogen or 12 months of tricycling (oestrogen daily with a progestogen course every 3 months), are major risk factors for endometrial cancer.
    • Options for the progestogen component in low-dose sequential regimens include:
      • Norethisterone — 5 mg/day for 12 days a month (no smaller [1-2mg] dose stand-alone norethisterone preparations are available in the UK).
      • Oral micronised progesterone — 200 mg/day for 12 days a month.
      • Medroxyprogesterone acetate — 10 mg/day for 12 days a month.
      • Dydrogesterone — 10 mg/day for 12-14 days a month.
    • Women who require higher dose oestrogen should consider having their progestogen dose increased to ensure adequate endometrial protection, for example micronised progesterone 300 mg for 12 days a month instead of 200 mg in cyclical HRT regimens.
      • Advise women that there are limited data relating to the optimal progestogen dose needed to provide endometrial protection in women taking high-dose oestrogen (particularly in perimenopausal women taking sequential HRT).
    • Guidance from the British Menopause Society (in partnership with the British Society of Gynaecological Endoscopy, British Gynaecological Cancer Society, Faculty of Sexual & Reproductive Healthcare, Getting It Right First Time (GIRFT), Royal College of General Practitioners and the Royal College of Obstetricians & Gynaecologists) recommends that:
      • Women taking sequential HRT over the age of 45 should be offered, after five years of use or by age 54 (whichever comes first), a change to continuous combined HRT.
    • Note: the absence of bleeding whilst taking a cyclical regimen reflects an atrophic endometrium.
      • Exclude pregnancy in perimenopausal women or women with premature ovarian insufficiency.
      • Check compliance with therapy if the progestogen component is taken separately.
  • Continuous combined regimen:
    • Both oestrogen and progestogen are taken daily.
    • Continuous combined HRT provides more effective endometrial protection than sequential HRT and is usually recommended for women who have had amenorrhoea for 12 months before starting HRT (including women on contraception or post-ablation).
    • Women are expected to be amenorrhoeic on this preparation 6 months after initiation.
    • Continuous combined HRT is associated with less unscheduled bleeding than sequential HRT in postmenopausal women but if given to perimenopausal women who still have menstrual cycles, endogenous follicular activity can lead to irregular bleeding.
    • The suggested dose of progestogen given in a continuous combined HRT regimen is:
      • A minimum of 0.5 mg/day of norethisterone or,
      • A minimum of 2.5 mg/day of medroxyprogesterone acetate.
    • The dose of the progestogen should be proportionate to the dose of oestrogen.
      • Women who require high dose oestrogen intake should consider having their progestogen dose increased to ensure adequate endometrial protection for example:
        • Micronised progesterone 200 mg daily on a continuous basis instead of 100 mg in continuous combined HRT regimens.
      • Advise women that there are limited data relating to the optimal progestogen dose needed to provide endometrial protection in women taking high-dose oestrogen.
  • For information on assessment and management of unscheduled bleeding on HRT, see the section on Management of unscheduled bleeding on HRT.
• Vaginal oestrogen therapy:
  • Topical oestrogens are used to treat the symptoms of vaginal atrophy related to oestrogen deficiency in postmenopausal women. 
    • If vaginal and/or bladder symptoms of urogenital atrophy predominate, vaginal oestrogen alone can be used.
    • Vaginal oestrogen may also be required in addition for some women taking systemic HRT. 
    • Systemic effects of oestrogen are minimised by using the lowest effective dose to control symptoms; the dose may be increased on the advice of a healthcare professional with expertise in menopause if there is inadequate symptom control.
  • Options for topical oestrogens include:
    • Estradiol – available as vaginal tablet (such as Vagifem®10) or ring (Estring®).
      • Estring® should be inserted into upper third of vagina and worn continuously. It should be replaced after 3 months — the maximum duration of continuous treatment is 2 years.
    • Estriol — available as:
      • Creams (for example Ovestin® (0.1%) and Gynest® (0.01%) creams),
      • Pessaries (for example Imvaggis® pessary 0.03mg) and,
      • Gels (for example Blissel® 50 micrograms vaginal gel). 
  • Vaginal tablets and creams should be used nightly for 2 weeks (3 weeks for pessary and gel) and then twice weekly. 
    • Twice weekly maintenance doses can be continued long-term.
    • Symptoms frequently recur on cessation of therapy. 
• The British Menopause Society (BMS) has published several guides to support clinicians in appropriate prescription of HRT — BMS Tools for Clinicians. 

[Rees, 2009; Ayres, 2022; Hamoda, 2022b; Stephens, 2022; BMS, 2024; NICE, 2024a; BNF, 2025]

Adverse effects

Hormone replacement therapy (HRT) may cause a variety of adverse effects.

• Oestrogen-related adverse effects include:
  • Fluid retention, bloating, breast tenderness or enlargement, nausea, headaches, leg cramps, and dyspepsia.
  • Exogenous oestrogens may induce or exacerbate symptoms of hereditary and acquired angioedema.
• Progestogen-related adverse effects include:
  • Fluid retention, breast tenderness, headaches or migraine, mood swings, premenstrual syndrome-like symptoms, depression, acne vulgaris, lower abdominal pain, and back pain. They tend to occur in a cyclical pattern during the progestogen phase of cyclical HRT.
• Vaginal bleeding problems:
  • Unscheduled vaginal bleeding is a common adverse effect of systemic HRT, within the first 6 months of treatment or within 3 months of changing the dose or preparation.
  • Monthly cyclical regimens should produce regular withdrawal bleeding towards the end of the progestogen phase.
  • For more information on assessment and management of unscheduled bleeding on HRT, see the section on Management of unscheduled bleeding on HRT.

[Stuenkel, 2015; Stephens, 2022; BMS, 2024; NICE, 2024a] 

Regimen

Fezolinetant is licensed as an oral medication to be taken as a 45 mg tablet once per day. 

[BNF, 2026; EMC, 2026]

Contraindications and cautions

Important safety information for fezolinetant

MHRA/CHM advice: Fezolinetant (Veoza®): risk of liver injury; new recommendations to minimise risk (April 2025)

An EU-wide review of safety data found serious drug-induced liver injury associated with fezolinetant. Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels exceeding 10 times the upper limit of normal (ULN) with concurrent elevations in bilirubin and/or alkaline phosphatase (ALP) have been reported, including signs and symptoms suggestive of liver injury in some cases. These were generally reversible on stopping fezolinetant.

Healthcare professionals are advised that liver-function tests (LFTs) must be performed before treatment initiation, then monthly for the first 3 months and periodically thereafter, as clinically indicated, during treatment. LFTs must also be performed when signs or symptoms suggestive of liver injury occur. Monitoring should continue until LFTs normalise.

Treatment with fezolinetant:

• Should be avoided in patients with known, or at higher risk of, liver disease.
• Must not be started if ALT or AST, or total bilirubin is 2 times the ULN or more.

Treatment must be discontinued if serum transaminases are:

• Exceeding 5 times the ULN.
• Three times ULN or more and either total bilirubin exceeds 2 times the ULN, or symptoms of liver injury develop.

Patients or their carers should be advised to seek immediate medical attention if signs or symptoms of liver injury occur.

[BNF, 2026; EMC, 2026]

Adverse effects

Common or very common

• Abdominal pain
• Diarrhoea
• Insomnia

Frequency not known

• Drug-induced liver injury
• Endometrial adenocarcinoma

[BNF, 2026; EMC, 2026]

Drug Interactions

Medications that are predicted to increase exposure to Fezolinetant. Manufacturers advise avoiding.

• Ciprofloxacin 
• Combined hormonal contraceptives 
• Fluvoxamine
• Givosiran 
• Mexiletine 
• Osilodrostat
• Rucaparib 
• Vemurafenib 

[BNF, 2026; EMC, 2026]