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The menopause can be a difficult time for many women, because it marks a time of drastic hormonal change in the body. This brings with it many signs and symptoms which are often unwelcome.
The word ‘menopause’ comes from the Greek, and literally means ‘end of monthly cycle’. It is defined as a permanent cessation (over 12 months) of the menstrual period and occurs as part of the natural ageing process in a woman.
It happens on average at age 51, but any time between 45 and 55 is normal.
Menopause between the ages of 40 and 45 is called ‘early’ menopause. Menopause before the age of 40 is called ‘premature’ menopause, which will be discussed later in this article.
Menopause occurs naturally when the ovaries can no longer produce sufficient oestrogen to maintain regular ovulation and menstruation. This happens when the number of oocytes (egg cells) and the follicles (small fluid-filled sacs) that contain them declines to very low levels. With fewer follicles, the ovaries make less oestrogen and inhibin (a hormone made by the follicles that feeds back to the pituitary gland). This removes the negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, the hormone link between the brain and the ovaries (see our article on the menstrual cycle for details).
This lack of follicles means that the ovaries respond less well to the hormones released from the pituitary gland called follicle stimulating hormone (FSH) and luteinising hormone (LH). With less oestrogen and inhibin, there is less negative feedback, so the pituitary gland produces more and more FSH and LH. A high FSH level can therefore suggest that menopause is approaching. However, FSH levels can swing up and down from day to day during this time, so a single result is not reliable (see later in this article).
It is the low oestrogen that causes most of the unwanted menopausal symptoms in women.
There are 4 main stages of the menopause:
Pre-menopause is the stage before the menopausal transition begins. Periods are usually still regular and the ovaries still release eggs, so a woman can still get pregnant. The unpredictable ovulation and irregular periods that mark the start of the transition belong to peri-menopause (see below). Some women notice the first menopausal symptoms, such as hot flushes, before their periods change.
FSH rises because the ovaries make less inhibin and oestrogen, which reduces the negative feedback on the HPG axis, as mentioned earlier. However, FSH is not a reliable test for menopause, because levels can change a lot from day to day. In the UK, women aged 45 or over with typical symptoms are diagnosed clinically (from their symptoms and periods), without blood tests. An FSH test may be considered in women aged 40 to 45 with symptoms, and in women under 40 when premature menopause is suspected.
This is the ‘transition period’ into the menopause. The menstrual cycle and ovulation become unpredictable. Cycles may shorten to 2 to 3 weeks or lengthen to many months. Infrequent periods are called oligomenorrhoea. This is usually when the symptoms of menopause, such as hot flushes, start. Perimenopause typically lasts a few years and ends 12 months after the last period.
Ovulation still happens some of the time, so a woman can still get pregnant. She should use contraception if she does not want to conceive. Contraception is advised until 2 years after the last period in women aged 40 to 49, and until 1 year after it in women aged 50 or over.
The menopause is defined as when the woman has not experienced a menstrual period for 12 months, reflecting a marked depletion of the ovarian follicles. This is the end point of reproductive ageing. Strictly, the menopause is the final period itself, but it can only be confirmed looking back, after 12 months with no periods.
Pregnancy is still possible for a while, so contraception is still needed for a time (see above). Having no periods (amenorrhoea) does not mean the menopausal symptoms have stopped. They usually last 7 to 9 years in total, and about 1 in 5 women have them for up to 15 years.
This is the stage that follows the menopause: the rest of life after 12 months with no periods. The large hormone swings of the perimenopause settle, and for most women symptoms such as hot flushes gradually ease. However, oestrogen stays low, so some changes, such as vaginal dryness, tend to get worse with time. The risk of longer term conditions such as osteoporosis also rises (see below).
Most of these symptoms and signs can be attributed to the lack of oestrogen present in menopause.
Pre-menopausal and Peri-menopausal
- Hot flushes and sweating
- Insomnia (difficulty sleeping), often made worse by night sweats
- Mood swings, anxiety, low mood and depression
- Problems with memory and concentration
- Irregular menstruation, including changes in length of cycle, length of period or heaviness of bleeding
Peri-menopausal and Menopausal
- Changes in the urethral and bladder lining leading to more frequent UTIs and stress incontinence (leaking urine when coughing, laughing or sneezing)
- Ovarian atrophy
- Loss of vaginal rugae (the folds of the vaginal wall) and increased vaginal dryness, leading to pain or discomfort during sex. These vaginal and urinary changes are now called genitourinary syndrome of menopause.
- Reduced sex drive (low libido)
- Joint and muscle aches, headaches and tiredness
- Increased fat storage
- Breast tissue change
- Reduced skin elasticity
- Weight gain, often around the stomach and upper body
- Urinary incontinence due to reduced pelvic floor tone (the pelvic floor is the layer of muscles that supports the bladder, uterus and bowel)
- Osteoporosis - oestrogen usually inhibits osteoclasts (cells that break down bone). Now that there is less oestrogen, these cells can become more active, leading to an increase in bone resorption (bone being broken down faster than it is rebuilt). Bones become weaker, so fragility fractures (breaks from a minor fall or knock) become more common than in women who have not gone through the menopause.
- Atherosclerosis - again, lower oestrogen affects the lipid profile (the levels of fats such as cholesterol in the blood) of post-menopausal women. This increases the formation of atherosclerotic plaques (fatty deposits in the artery walls), so the risk of heart attack or stroke is higher than in pre-menopausal women.
Non-Pharmacological Treatment Options
The menopause can cause a lot of symptoms which can be very difficult to live with. There are many options to ease the symptoms or to help women cope with them. The menopause itself cannot be prevented, because it is a natural part of ageing.
It is well known that increasing exercise and improving diet can improve general health. They may also help with some menopausal symptoms, although the evidence for this is limited. Regular exercise can help to prevent weight gain and may ease hot flushes. Exercise coupled with a healthy diet can also help improve mood. Weight-bearing exercise, which builds strength, also helps protect against weakening bones. Smoking cessation is also a key part in improving general health and wellbeing, and smoking can make menopause symptoms worse.
Cognitive Behavioural Therapy (CBT)
Cognitive behavioural therapy (CBT) is a talking therapy that can be used to support women through the changes and help them to cope better. It can help with anxiety, low mood, sleep problems and hot flushes. It works by helping women to reframe their thoughts about their symptoms and health. NICE recommends considering menopause-specific CBT for hot flushes and night sweats.
Some women are able to combat the main symptoms of the menopause with alterations to how they live. For example, wearing several thin layers, or sleeping under a few thin blankets rather than one thick one, can help with hot flushes. Layers can be removed and replaced quickly when symptoms occur. Keeping the bedroom cool, using a fan, and avoiding triggers such as spicy food, caffeine and alcohol may also help.
Pharmacological Treatment Options
Hormone replacement therapy (HRT) is the main drug treatment offered to menopausal women to reduce the symptoms of menopause. NICE recommends offering HRT for hot flushes and night sweats. If HRT is unsuitable, a newer once-daily tablet called fezolinetant can be used for moderate to severe hot flushes and night sweats. Fezolinetant has been linked to serious liver injury, so liver function tests (blood tests that show how well the liver is working) are needed before starting it, every month for the first 3 months, and periodically after that. Selective serotonin reuptake inhibitors (SSRIs, a type of antidepressant) should not routinely be offered first for these symptoms alone.
HRT replaces the oestrogen that the ovaries no longer make. It treats the symptoms but does not stop the menopause itself. When HRT is stopped, the natural lack of oestrogen remains, so symptoms may return. If they do, treatment can be restarted.
Reducing HRT gradually may limit the return of symptoms in the short term. In the longer term, it makes no difference to symptoms whether HRT is reduced gradually or stopped straight away.
HRT exists to replace the oestrogen that is lacking in the body. However, in a woman with a uterus, giving oestrogen alone can be dangerous. Unopposed oestrogen (oestrogen given without a progestogen) makes the endometrium (the lining of the uterus) grow, which raises the risk of endometrial cancer. To counter this, combined HRT also contains a progestogen. This is a progesterone-like hormone, either synthetic or identical to the body's own progesterone. It helps to control this overgrowth of the endometrium and so reduces the risk of cancer.
This means that the type of HRT prescribed depends on whether the woman still has a uterus. Women who have had a total hysterectomy (removal of the uterus) are usually offered oestrogen-only HRT. The exception is women who have had endometriosis, a condition where endometrial tissue grows outside the uterus. This tissue could still be stimulated by unopposed oestrogen, so these women are offered combined HRT.
There are three main types of HRT. They are classified on whether they contain a progestogen, and whether any regularly scheduled vaginal bleeding occurs.
- Oestrogen only HRT - this preparation contains only oestrogen as the name suggests, and is indicated in women who no longer have endometrial tissue (commonly achieved by a hysterectomy).
- Cyclical or Sequential HRT - this type of HRT contains both oestrogen and a progestogen to protect the endometrium. It is used in women who are peri-menopausal, meaning they have menopausal symptoms but are still having periods, even if these are irregular. It is taken in a cycle: oestrogen every day, with a progestogen added for 12 to 14 days of each cycle. This leads to a regular withdrawal bleed (a period-like bleed towards the end of the progestogen days).
- Continuous HRT - this type also combines oestrogen and a progestogen, but both are taken every day. It is usually recommended for women with menopausal symptoms who have not had a period for 12 months. It protects the endometrium better than sequential HRT. There is no regular bleed, although irregular bleeding is common at first and should stop within about 6 months.
One other option to taking combined HRT in a woman with a uterus is to use two different forms of hormonal supplementation. This can include one form that supplies oestrogen, like a patch or a gel (see later), and another form that supplies a progestogen. An example is the 52 mg levonorgestrel intrauterine system, a hormonal coil placed in the uterus that releases a progestogen called levonorgestrel. It protects the endometrium and also works as contraception.
HRT comes in many different forms, and it helps to know the main features of each one. These preparations can come in oestrogen only, sequential or continuous forms. The choice of which form is best should be a joint decision between the prescriber and the patient.
- Tablets - all forms of HRT are available as a tablet.
- Advantages - easy to take, easy to stop, discreet to carry, easy to adjust dose.
- Disadvantages - needs to be taken every day.
- Patches - skin patches deliver the hormones (oestrogen only or combined) directly into the bloodstream.
- Advantages - no need to take tablets, easy to stop, lower risk of venous thromboembolism (e.g. deep vein thrombosis) than with oral oestrogen.
- Disadvantages - could cause skin irritation, fall off or be visible; need to remember when to change (e.g. twice a week).
- Gel - an oestrogen gel can be applied onto the skin to supply oestrogen into the bloodstream.
- Advantages - delivers oestrogen directly into the bloodstream, easy to use and to stop.
- Disadvantages - could be messy, difficult to apply the correct amount.
- Spray - an oestrogen-only spray is used once a day on the inner arm or inner thigh. It supplies oestrogen into the bloodstream through the skin.
- Advantages - useful if tablets cannot be taken, easy to stop, does not increase the risk of blood clots.
- Disadvantages - it must dry for about 2 minutes before dressing. Skin contact with other people, especially children, should be avoided, and the area should not be washed for at least 1 hour.
- Local HRT - vaginal oestrogen comes as creams, gels, tablets, pessaries (small soft inserts that dissolve in the vagina) and rings. It relieves vaginal dryness and the other symptoms of genitourinary syndrome of menopause (previously called atrophic vaginitis: a thin, dry and sore vaginal lining caused by low oestrogen). Very little is absorbed into the blood, so no progestogen is needed, even in women with a uterus. It can also be used alongside other HRT. This form of HRT does not combat other symptoms like hot flushes or osteoporosis.
- Advantages - easy to stop, very little absorbed into the body.
- Disadvantages - suitable only for vaginal and urinary symptoms, needs to be inserted into the vagina.
Diagram - The options for HRT prescriptions and when each is indicated
SimpleMed original by Dr. Maddie Swannack
HRT can be started as soon as menopausal symptoms begin even if periods are still mostly regular at this point.
HRT can be stopped at any point. There is no fixed limit on how long it can be taken for symptoms. Treatment should be individualised, using the lowest effective dose, with a review 3 months after starting and then once a year. HRT also lowers the risk of fragility fractures while it is being taken, but this benefit fades once it stops. For bone protection, HRT is generally limited to younger postmenopausal women (usually aged 60 or under) at high risk of fracture who also have menopausal symptoms. In older women the risks usually outweigh the benefits.
- Endometrial Cancer - the risk of endometrial cancer (cancer of the lining of the uterus) increases with oestrogen only HRT in women with a uterus. The risk decreases with continuous combined HRT. It may slightly increase with sequential combined HRT, and the increase may be greater with longer use, fewer days of progestogen in each cycle or a higher oestrogen dose. (Source: V Beral et al., The Lancet, PubMed ID 15866308).
- Breast Cancer - the risk of breast cancer increases with combined HRT. The increase rises with the length of use and declines after stopping, but it can persist for at least 10 years. NICE and the BNF report very little or no increase in risk with oestrogen-only HRT, although a large 2019 analysis found a smaller increase with oestrogen-only HRT than with combined HRT. (Source: The Lancet, PubMed ID 31474332) HRT can still be considered in women who carry a BRCA gene mutation (BRCA1 or BRCA2, an inherited change that raises the risk of breast and ovarian cancer), but the decision is individualised and often made with specialist input.
- Venous Thromboembolism - the risk of venous thromboembolism is increased with oral HRT (taken by mouth), and the size of the increase depends on the type of hormone used. However, this risk is not increased by transdermal oestrogen (given through the skin, such as patches, gels and sprays) at standard doses. (Source: Y. Vinogradova et al., BMJ (British Medical Journal), PubMed ID 30626577).
- Stroke and Heart Disease - the risk of stroke increases with HRT containing oral oestrogen, more so with higher doses. It is unlikely to increase with transdermal oestrogen. HRT does not increase the risk of coronary heart disease. However, it should not be used to prevent cardiovascular disease (disease of the heart and blood vessels).
- Side Effects
- Bleeding - unscheduled (unexpected) vaginal bleeding is common in the first 6 months of taking HRT, and within 3 months of changing the dose or type. It often settles. Unscheduled bleeding after these times should be checked promptly.
- Fluid Retention and Other Effects - oestrogen in HRT can cause fluid retention, bloating, breast tenderness, nausea, headaches and leg cramps.
Weight gain concerns many patients. Weight gain is common around the menopause and with age, whether or not HRT is taken. The British National Formulary (BNF, the UK prescribing reference) also lists weight changes, without saying whether gain or loss, as a common side effect of estradiol (the main oestrogen used in HRT) taken by mouth or through the skin. A woman who is worried about her weight on HRT should raise it at her review.
Premature ovarian insufficiency (POI), often referred to in older texts as premature menopause, occurs when ovarian function declines before the age of 40 years. Ovarian activity can be intermittent and is not always permanent. It can be a devastating diagnosis. POI greatly reduces the chance of getting pregnant naturally, although pregnancy is still sometimes possible. This can be very hard for women who have not yet completed their families.
A diagnosis of premature menopause is made in women under 40 from their symptoms, including no periods or infrequent periods, together with blood tests:
- FSH - while FSH levels are not reliable when predicting physiological menopause, they can be helpful in premature menopause. Two tests need to be taken 4 to 6 weeks apart, and they must both be raised to support a diagnosis of premature ovarian insufficiency. A single test is not enough.
- Thyroid Function and Prolactin - prolactin is a hormone from the pituitary gland that stimulates milk production. Both thyroid function and prolactin should be measured when premature menopause is suspected, because abnormalities in either can temporarily disrupt ovarian function.
There are many possible causes of premature menopause.
Oophorectomy - surgical removal of both ovaries (bilateral oophorectomy) will induce menopause straight away. Before the age of 40, this is a cause of premature menopause. The resulting symptoms can be more severe than in a natural menopause, because oestrogen levels drop suddenly rather than gradually.
Spontaneous POI (previously called premature ovarian failure, POF) - the ovaries stop working normally without surgery or cancer treatment. In many women no cause is found. Known causes include:
- Autoimmune conditions, where the immune system damages the ovaries. This may happen alongside other autoimmune diseases such as thyroid disease, type 1 diabetes and Addison's disease (failure of the adrenal glands).
- Chromosomal Abnormalities - Turner syndrome, a condition where one of the two X chromosomes is missing or partly missing. The ovaries are underdeveloped, which can cause infertility.
- Infections such as mumps and tuberculosis can sometimes cause POI. After mumps, ovarian function usually returns.
- A family history of POI can predispose to development of POI, suggesting a genetic link. Therefore a full family history of medical conditions is helpful.
Cancer Treatments - chemotherapy and radiotherapy can cause ovarian failure on a temporary or permanent basis. The chances of this depend on the type and dose of chemotherapy, where the radiotherapy is aimed, and age at treatment. Younger women are less likely than older women to develop ovarian failure after the same treatment. Women should be offered the chance to discuss their fertility before and after treatment.
Treatments for Premature Menopause
It is important that premature menopause is properly treated, as a longer time without oestrogen raises the risk of osteoporosis and cardiovascular disease. Without HRT, POI is linked with a shorter life expectancy, mainly because of cardiovascular disease.
Women with premature ovarian insufficiency should be offered a choice of hormone replacement therapy (HRT) or a combined hormonal contraceptive, such as the combined oral contraceptive pill. Both protect the bones. HRT may have a better effect on blood pressure, but it is not a contraceptive. In spontaneous POI the ovaries can start working again without warning, so a woman may still get pregnant. The combined pill may suit women who also need contraception. Treatment should continue until at least the usual age of natural menopause (about 51). The combined pill is not usually continued after the age of 50, because its risks then generally outweigh its benefits.
Women with premature menopause should also be offered supportive therapy (such as psychological support), because the changes to hormone levels and the possible loss of fertility can be very difficult.
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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