Menopause and its management

What is the menopause?

As women move towards the menopause, menstruation becomes erratic and eventually stops. There are a number of secondary effects described as 'menopausal symptoms' - see 'Presentation' section, below.

The climacteric, menopausal transition stage, or perimenopause, is the period of change leading up to the last period. The menopause itself is a retrospective diagnosis of the time when menstruation permanently ceases. It can only be defined with certainty after twelve months' spontaneous amenorrhoea.

Premature ovarian insufficiency (POI) is when the menopause occurs under the age of 40 years and is a syndrome consisting of amenorrhoea, elevated gonadotrophins and oestrogen deficiency. It occurs in around 1% of women. The term early menopause is used for those women who go through their menopause between 40-44 years.

Epidemiology

Population studies identify smoking and low socio-economic factors as being associated with premature menopause. Other factors which can affect the age at which women have their final period include age at menarche, parity, previous oral contraceptive history (as some methods will cause amenorrhoea), BMI, ethnicity and family history.^{1 2}

Many women do not seek medical advice for menopausal symptoms. Variations in consultation patterns for menopause may depend on many factors, including access to healthcare, cultural and educational differences, psychosocial difficulties and variation in symptom severity.

Aetiology

The menopause is a natural phenomenon which occurs in all women when their finite number of ovarian follicles becomes depleted. As a result, oestrogen and progesterone hormone levels fall, and luteinising hormone (LH) and follicle-stimulating hormone (FSH) increase in response.

The menopause can be induced by surgical removal of the ovaries or by iatrogenic ablation of ovarian function by chemotherapy, radiotherapy or by treatment with gonadotrophin-releasing hormone (GnRH) analogues.

Menopause symptoms

Menopausal symptoms are attributed to tissue sensitivity for lower oestrogen levels. This primarily affects the oestrogen receptors in the brain. The experience of women varies widely; some are debilitated and others are unaffected by their symptoms. Some women experience symptoms while still menstruating and others not until a year or more after their last period.

The menopausal transition stage usually begins when women are in their mid-to-late 40s. The final menstrual period usually occurs between the ages of 45 and 55. The average age of the menopause in women in the UK is 51 years.

Around 80% of women going through their menopause experience symptoms, and around a quarter have severe symptoms. Symptoms of the menopause last far longer than most women anticipate; frequent menopausal vasomotor symptoms (VMS), including night sweats and hot flushes, persist in more than half of women for more than seven years. ²³

Menstrual irregularity

• The majority of women notice irregularities to the menstrual cycle, which may last for up to four years.

• The cycle may lengthen to many months or shorten to 2-3 weeks.

• Approximately 10% of women have an abrupt cessation of periods.

Hot flushes and sweats (also known as vasomotor symptoms, VMS)

• These are hallmark symptoms which occur in about 80% of women.²

• Hot flushes commonly affect the face, head, neck and chest and last for a few minutes.

• They are caused by a loss of homeostasis by the central thermoregulatory centre.

Urinary and vaginal symptoms

• Urogenital symptoms arise directly from loss of the trophic effect of oestrogen.

• These may include dyspareunia, vaginal discomfort and dryness, recurrent lower urinary tract infection and urinary incontinence.

• Urinary symptoms may not manifest until 5-10 years after the menopause.

Sleep disturbance⁴

• This is a common symptom reported by women.

• Symptoms may be secondary to VMS, are affected by psychosocial factors and may contribute to depression, irritability and poor concentration.

Mood changes ⁵

• These may include anxiety, nervousness, irritability, memory loss and difficulty concentrating.

• Perimenopause is accompanied by an increased risk of new and recurrent depression.

Loss of libido

• This can be caused by a number of hormonal factors; oestrogen, progesterone and testosterone have all been implicated.

• Vaginal dryness, loss of self-image and other psychosocial factors also play a part.

• Relationship factors and life stresses may also be relevant; women of menopausal age often have demanding jobs, childcare responsibilities and sometimes also caring responsibilities for elderly parents. A feeling that the mental load of handling all these facets of life is not being shared equitably can cause tensions in a relationship and lead to a loss of the desire to have intercourse.

Other changes

These may include brittle nails, thinning of the skin, hair loss and generalised aches and pains. These are due to falling oestrogen levels.

Differential diagnosis

The diagnosis will usually be obvious from the clinical picture but may be harder to make in younger women in the early stages of the menopause.

Other causes of secondary amenorrhoea, such as pregnancy and hypogonadotrophic hypogonadism, may need to be considered.

Diagnosing the menopause (investigations)⁶

The diagnosis of the menopause in the majority of women is a clinical one and investigations are usually not recommended.

Laboratory tests are not required in the following otherwise healthy women aged over 45 years with menopausal symptoms:

• Perimenopause based on VMS and irregular periods.

• Menopause in women who have not had a period for at least 12 months and are not using hormonal contraception.

• Menopause based on symptoms in women without a uterus.

FSH levels may be useful in women who are taking hormonal contraception which has rendered them amenorrhoeic. As they cannot use the cessation of periods to know when to stop their contraception, a single FSH at the age of 50 can be done. If in the menopausal range, contraception can be stopped one year later. It is also recommended in those aged under 45 in whom the menopause is suspected. ⁷

A single raised FSH is not diagnostic for the menopause. A high level will just indicate a lack of ovarian response at a point in time. Similarly, an FSH result in the pre-menopausal range does not rule out that the woman is peri-menopausal and may benefit from hormone replacement therapy (HRT).

Other tests that may be relevant

• Cardiovascular risk factor screen - the NHS offers a health check for all those over the age of 40, so if not done already then it would be appropriate to offer a blood pressure check and blood tests for lipids, HbA1c, renal and liver function.

• Cervical screening and mammograms - ensure the woman is up to date with her cervical screening and also mammograms (if she has reached the age for NHS screening).

Tests which are usually unhelpful

• LH (although it is often automatically done with an FSH by the lab)

• Oestradiol.

• Progesterone.

The following tests should not be used to diagnose perimenopause or menopause in women aged over 45 years:

• Anti-Müllerian hormone.

• Inhibin A or B.

• Estradiol.

• Antral follicle count.

• Ovarian volume.

Associated diseases

The relationship between the menopause and the development of associated conditions is sometimes difficult to differentiate from age-related morbidity but is easiest to demonstrate in cases of premature primary and secondary ovarian failure.

• Cardiovascular disease: including coronary artery disease, stroke and peripheral arterial disease. These all increase significantly after the menopause.

• Osteoporosis: the link between osteoporosis and oestrogen deficiency is well documented. Menopause and the accompanying loss of ovarian oestrogens is associated with reduced bone mineral density (BMD).⁸

• Urogenital atrophy. ⁹

• Redistribution of body fat: fat tends to be redistributed around the abdomen with age. This is recognised as being an independent risk factor for cardiovascular disease and diabetes.

• Dementia: An early menopause is associated with an increased risk of dementia, and dementia is more common in women than in men. However, there may be confounding factors for this latter fact, including the fact that women live longer, and men are more likely to die of a cardiovascular cause at a younger age. ^{10 11}

Menopause treatment and management⁶¹²

An individualised approach should be undertaken at all stages of diagnosis, investigation and management of menopause. Women should receive adequate information about the symptoms and treatment of the menopause, including benefits and risks of treatment. In addition, women who are likely to go through the menopause as a result of surgical or medical treatment should be given information about menopause and fertility before their treatment. The 2024 update of the National Institute for Health and Care Excellence (NICE) guidance was accompanied by a discussion aid, giving detailed figures on some of the risks and benefits of HRT - it would be useful to send women a link to this, so that they can read it in their own time.

Healthy lifestyle

Encourage a healthy lifestyle. Stopping smoking, losing weight and limiting alcohol are all beneficial to a woman going through the menopause. Women should also be encouraged to take regular aerobic exercise and to ensure they have adequate calcium intake (around 700 mg/day). Avoidance or reduction of caffeine may help.

HRT

HRT is the most effective treatment to relieve the symptoms caused by the menopause completely, although it may not be suitable for everyone. HRT is particularly effective in treating:

• VMS (hot flushes/night sweats).

• Mood swings.

• Vaginal and bladder symptoms.

VMS are usually improved within four weeks of starting treatment and maximal benefits will be gained by three months. They may persist for many years (the average is just over seven years) and therefore treatment may need to be continued. Regular assessment of the benefits versus the risks of ongoing treatment should be undertaken at least annually and are covered in detail in the Hormone Replacement Therapy leaflet.

Vaginal symptoms tend to be slower to respond to treatment and to recur if treatment is stopped. There is good evidence for the efficacy of topical HRT in the short-term treatment of menopausal atrophic vaginitis.^{2 9}Vaginal symptoms are improved, vaginal atrophy and pH decrease and there is improved epithelial maturation with topical oestrogen preparations compared to placebo or non-hormonal gels. Vaginal lubricants can also be effective to use as non-hormonal alternatives, especially if the main symptoms are pain on intercourse due to dryness. This is discussed in more detail in the leaflet on HRT - topical vaginal, including NICE advice about the use of topical HRT in women who have had breast cancer.

Cognitive behavioural therapy (CBT)^{6 13}

• HRT can often help to alleviate low mood which arises as a result of the menopause.

• Menopause-specific cognitive behavioural therapy (CBT) can also be beneficial, used with HRT, or alone for women who do not want HRT, or for whom it is contraindicated. There is evidence that it can be beneficial for VMS, low mood and insomnia.

• There is no good evidence that antidepressants improve the low mood that is associated with the menopause, but they may be useful where there is co-existing depression.

See also the separate Hormone replacement therapy (including benefits and risks) article.

Alternatives to HRT

Alternatives to HRT are available and may be useful for women with contra-indications to hormonal treatment (such as hormone-dependent tumours) or for those who perceive the risks of HRT to be too great.

Prescribable alternatives ^{261415 16}

There is marginal evidence for the use of clonidine in the management of VMS, and a significant amount of evidence for the use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, although the benefits can sometimes be limited by the side-effect of nausea. Of these options, only clonidine has a UK licence to treat VMS and the others are used on an unlicensed basis. There is also some evidence for gabapentinoids (such as gabapentin), and oxybutynin, both of which are also unlicenced for this indication.

In 2023, the MHRA approved fezolinetant for the management of VMS in the UK. It is a neurokinin 3 receptor antagonist, which acts on the hypothalamic-pituitary-ovarian axis. NICE did not include this drug in the November 2024 update of their menopause guideline and it is therefore currently only available privately. A NICE technical appraisal is in process, with an expected publication date of May 2025.

Over the counter alternatives ^{1617 18}

There are a variety of preparations available over the counter, including black cohosh, soy and red clover. These all contain phyto-oestrogens (a natural form of oestrogen) and also carry a significant placebo effect. There is some evidence for effectiveness of black cohosh for treating VMS, but the evidence for isoflavones and soy is of poor quality. Foods containing soy may also improve symptoms. Women who have had breast cancer should be strongly advised against using anything bought over the counter for the menopause, as there is limited safety data and some evidence of harm; for example, black cohosh reduces the effectiveness of tamoxifen and isoflavones, including red clover, have oestrogenic activity and so should not be used in women with a history of breast cancer. There is also limited evidence regarding their safety with regard to venous thromboembolism,

A particular issue with herbal remedies bought over the counter is that it is often impossible to know if one brand has the same amount of the active ingredient as another; they are not regulated in the same way that prescribed medicines are. A small number of herbal products have the Traditional Herbal Registration Certification Mark, which includes a logo with the initials THR and a picture of a leaf. This indicates that the herbal medicine has been registered with the Medicines and Healthcare products Regulatory Authority (MHRA) and meets its quality standards. Patients who want to use herbal medication should be advised that we can make no promises about safety or efficacy, but that the safest way to do this would be to stick to THR marked products, of which there are a few for the menopause.

Management of premature ovarian insufficiency (POI) and early menopause ¹⁹

Early menopause is defined as a menopause between the ages of 40 and 45 years. This occurs in up to 20% of women. POI is defined as a menopause below the age of 40, and occurs in around 1% of women.

All women with an early menopause have an increased risk of osteoporosis, cardiovascular disease and dementia if they are not given HRT appropriately.

In essence, the principles of oestrogen replacement are the same as for women experiencing menopausal symptoms and problems at any age. However, the symptoms may be more severe in premature menopause, particularly after surgical menopause, often requiring higher doses of oestrogen than those needed following spontaneous menopause at a later age. In addition, the aetiology of the premature or early menopause needs to be considered, as this may change the treatment offered (eg, if it were following surgery for an oestrogen-sensitive cancer).

Women with an early menopause should be offered HRT unless contra-indicated - the balance of risks and benefits is different for this group of women, with the benefits being more clear-cut, as they are only being given the hormones that most women would have naturally. It is normally continued until they reach at least 51 years. There is no evidence that there is any increased risk of breast cancer compared with normally menstruating women of the same age. They may need larger doses of HRT to control vasomotor symptoms. Caution should only apply in women who have had breast cancer, in which case a written discussion with their oncologist would be sensible. When unsure, referral to a specialist menopause clinic is also useful, although availability of these on the NHS varies by area.

Refer to the Premature ovarian insufficiency article for more detailed information about that condition.

Current controversies in HRT

Bioidentical HRT²⁰

Bioidentical hormones are ones which are exact copies of hormones found naturally, such as progesterone, estradiol and estriol. The word progesterone is used to describe the naturally occurring hormone, whereas the term progestogen describes a synthetic hormone of this type.

The British Menopause Society (BMA) differentiates two types of bioidentical HRT:

• Regulated bioidentical HRT (rBHRT) is prescribed by doctors - examples include micronised progesterone and oestradiol. It is thought that some of these products have benefits over synthetic alternatives, for example that micronised progesterone carries a lower risk of breast cancer than some progestogens, although more data is needed. These products are all MHRA approved.

• Compounded bioidentical HRT (cBHRT) are manufactured by specialist pharmacies, which may be based in the UK or abroad. They have not been evaluated by the MHRA and are sometimes prescribed by healthcare professionals with no qualifications in menopause. Tests to evaluate hormone levels from blood or saliva are often recommended alongside cBHRT, often at large cost, and with no clear evidence. The BMS advise against the use of cBHRT - this view is shared by the International Menopause Society, and the Advertising Standards Association has also ruled against misleading promotion of cBHRT.

The BMS statement on the updated NICE menopause guidance ²¹

The NICE guidance on menopause was updated in November 2024; on the same day, the BMS produced a statement expressing concern about some of the evidence used in the guideline, the scope of the guideline, and some of the figures given. For more detail about this, see the leaflet Hormone replacement therapy.

Interactions between the NHS and the private sector; use of high-dose HRT ^{22 23}

Patients may choose to see a clinician in the private sector and will sometimes then ask the GP to continue the prescription which has been started privately. Recently, there have been concerns raised about high doses of HRT prescribed in some private clinics. As with any medication, the medicolegal liability lies entirely with the clinician that signs the prescription. If the private prescription is something that the GP would have prescribed anyway, then it is perfectly reasonable to prescribe it on the NHS. However, if the GP does not feel that they are safely able to prescribe and/or monitor, then the patient should be told that they must continue to get their prescription privately, or have a new assessment with the GP who will then prescribe something that they feel more comfortable with. This is discussed in more detail in the leaflet Hormone replacement therapy.