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Next Lesson - Malignancies of the Reproductive Tract
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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 aging process in a woman.
It happens on average at age 51, but any time between 45 and 55 is normal.
Menopause that occurs before this time is defined as ‘premature’, which will be discussed later in this article.
Menopause occurs naturally when the ovaries become unable to produce oestrogen. This happens when the number of oocytes (egg cells/follicles) in the ovaries declines to very low levels. As a result less oestrogen and inhibin is produced by the ovaries due to lack of follicles which removes the negative inhibition of the HPG axis (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). This lack of response to FSH and LH causes the pituitary gland to produce more and more of these hormones, meaning that a high FSH level can indicate that menopause has begun (but this is not always reliable – see later in article).
It is the low oestrogen that causes most of the unwanted menopausal symptoms in women.
There are 4 main stages of the menopause:
In pre-menopause, ovulation becomes unpredictable and fertility is reduced. Ovulation now occurs early in the cycle or is absent entirely, therefore conception in this period is very difficult to achieve despite seemingly regular menstrual periods. This lack of ovulation lowers oestrogen, beginning to cause the menopausal symptoms listed below.
The low oestrogen causes the removal of negative feedback on the HPG axis as mentioned earlier, which increases FSH levels in the body, meaning that FSH could be used to indicate the beginning of menopause. However, this is not a very reliable test because ovulation and the hormonal release during this stage are very unpredictable, meaning that blood tests should not be used to define the beginning of the menopause.
This is the ‘transition period’ into the menopause. It is when the menstrual cycle and ovulation become even more unpredictable (oligomenorrhoea), and is when the symptoms of menopause are noticed.
Although ovulation is not common in this phase, it is possible, meaning that a woman is still technically fertile in this time and should use contraception when having sex if she does not want to conceive.
The menopause is defined as when the woman has not experienced a menstrual period in 12 months and therefore the number of ovarian follicles has reached 0. This is the end point of reproductive aging and the woman is no longer fertile.
The menopause includes the time from this cessation of periods (amenorrhoea) to when the menopausal symptoms begin to ease and disappear. In a sense this is a ‘second puberty’: when going through puberty, it takes time for the body to adapt to the new levels of hormones that are in the body; this is also true of the menopause.
This is the stage that follows the calming of the menopausal symptoms. As the drastic hormonal shifts settle, the body settles back into a natural rhythm and most of the symptoms of menopause become more manageable. To continue the analogy, this stage of the menopause is similar to the calming of the difficulties of puberty as adulthood is reached.
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
- Mood swings and depression
- Irregular menstruation, including changes in length of cycle, length of period or heaviness of bleeding
- Changes in the urethral and bladder lining leading to more frequent UTIs and stress incontinence
- Ovarian atrophy
- Loss of vaginal rugae and increased vaginal dryness leading to difficulty in sex
- Bloating and constipation
- Increased fat storage
- Breast tissue change
- Reduced skin elasticity
- Weight gain (often due to changes in appetite)
- Urinary incontinence due to reduced pelvic floor tone
- Osteoporosis – oestrogen usually inhibits osteoclasts (cells that break down bone) so now there is less oestrogen, these cells can become more active leading to an increase in bone reabsorption. This leads to an increase in fragility fractures compared to women who have not gone through the menopause.
- Atherosclerosis – again, lower oestrogen affects the lipid profile of post-menopausal women, increasing the formation of atherosclerotic plaques, which increases the risk of heart attack or stroke compared to pre-menopausal women.
Non-Pharmacological Treatment Options
The menopause can cause a lot of symptoms which can be very difficult to live with. This means that there are lots of options used to treat the symptoms or improve coping mechanisms, but there are no ways to prevent menopause entirely as it is a natural process of aging.
It is well known that increasing exercise and improving diet can improve general health, but can also improve the symptoms of menopause. Regular exercise can help to prevent weight gain and improve hot flushes. Exercise coupled with a healthy diet can also help improve mood. Smoking cessation is also a key part in improving general health and wellbeing.
Cognitive Behavioural Therapy (CBT)
Cognitive behavioural therapy can be used in to support women through the changes and help them to cope better. CBT can be used to remedy the anxiety, low mood, sleep and physical symptoms such as hot flushes, encouraging women to reframe their thoughts about their health.
Some women are able to combat the main symptoms of the menopause with alterations to how they live. For example, wearing many thin layers can help with hot flushes or sleeping with a number of thinner blankets rather than one thick one, as a layers can be removed and replaced quickly when symptoms occur.
Pharmacological Treatment Options
Hormone replacement therapy (HRT) is the most common pharmacological therapy offered to menopausal woman to reduce the symptoms of menopause.
HRT replaces the oestrogen that has been lost with the cessation of ovulation. This does not prevent menopausal symptoms forever, because once the HRT is stopped (for the reasons explained later), there will still be the natural lack of oestrogen, which can cause the symptoms.
However, for some women this delay can be convenient, because the woman might be at a different stage in life where she can better cope with the symptoms, and in other women, a short prescription of HRT can cover the period where the symptoms would have occurred, meaning when ceasing HRT, they experience a lessened effect of the lack of oestrogen.
HRT exists to replace the oestrogen that is lacking in the body. However, giving oestrogen alone can be dangerous as unopposed oestrogen can predispose to endometrial cancer due to increased proliferation of the endometrium. To counter the risk of endometrial cancer, some forms of HRT contain progesterone as well, which helps to control this overgrowth of the endometrium and prevent cancer.
This means that the type of HRT prescribed depends on whether the patient has any endometrial tissue left, i.e. women who have had a hysterectomy (provided they did not suffer with endometriosis, a condition where endometrial tissue can occur outside the uterus. This extra endometrial tissue could still become cancerous if oestrogen-only preparations are used).
There are three main types of HRT. They are classified on whether they contain progesterone, 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 progesterone to protect the endometrium. It is commonly indicated in women who are pre-menopausal or peri-menopausal, meaning they suffer the menopausal symptoms but are still having periods. It is taken in a cycle with a portion without taking the HRT, meaning that ‘periods’ occur in the break.
- Continuous HRT – this is another example of HRT that combines oestrogen and progesterone but is recommended in women who have not had a period in over 12 months, suffering with the symptoms of menopause. Because this type of HRT is taken continuously, no ‘periods’ occur.
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 progesterone, like a progesterone-containing contraceptive intrauterine system (also called a coil).
HRT comes in many different forms, and it is important that a little is known about each form. These preparations can come in oestrogen only, sequential or continuous forms, and the choice of which form is best should be made as a joint decision with 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.
- Implants – less commonly prescribed. A pellet of oestrogen is inserted under the skin under local anaesthetic, lasting up to six months.
- Advantages – long lasting, a fit-and-forget form of HRT.
- Disadvantages – involves a surgical procedure and anaesthetic, not easy to stop or reverse.
- Local HRT – creams, tablets and pessaries which are inserted into the vagina to deliver local oestrogen to relieve specifically vaginal dryness and atrophic vaginitis. This form of HRT does not combat other symptoms like hot flushes or osteoporosis.
- Advantages – easy to stop.
- Disadvantages – suitable only for vaginal dryness and atrophic vaginitis, needs to be inserted into the vagina.
Diagram - The options for HRT prescriptions and when each is indicated
SimpleMed original by 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, and if it is being taken to control the symptoms of menopause, it is often only needed to be taken for a short time. It can be taken for long periods though, there is no recommended limit to the prescription. If HRT is taken as a protective factor for osteoporosis (which is only used as a last line treatment), it might be taken on a more long term basis.
- Endometrial Cancer – the risks of endometrial cancer increase with oestrogen only HRT but decrease with combined HRT preparations. (Source: V Beral et al. The lancet PMID 15866308).
- Breast Cancer – the risks of breast cancer do increase with HRT use. (Source: The Lancet, PMID 31474332) However, there is no contraindication for women who carry the BRCA gene mutation.
- Venous Thromboembolism – the risks of venous thromboembolism are increased with the use of oral HRT, and this risk is proportional to the amount of oestrogen contained. However, this risk is not increased by transdermal oestrogen, like patches. (Source: Y. Vinogradova et al. BMJ, PMID 30626577).
- Side Effects
- Bleeding – this is quite common in the initial period of starting HRT, but often resolves. If it occurs after 3 months of taking HRT, it should be investigated.
- Fluid Retention – this can be aggravated by HRT.
Weight gain, while concerning to many patients, has been shown to be unrelated to HRT use, and is instead related to menopause.
Premature menopause is a condition that occurs when the menopause occurs in a woman who is younger than 40 years old. It can be a devastating diagnosis for the patient as it marks the end of the naturally fertile period of a woman, so can drastically change the lives of women who have not yet competed their families.
A diagnosis of premature menopause can be made based on a number of 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 4-6 days apart, and they must both be elevated to diagnose premature menopause.
- Thyroid Function and Prolactin – it is important that these are measured when suspecting premature menopause as abnormalities in these can temporarily disrupt ovarian function.
There are many possible causes of premature menopause.
Oophorectomy – surgical oophorectomy (or the removal of the ovaries) will induce premature menopause. This can often be very severe, as there will be a sudden and very drastic drop in oestrogen levels.
Primary Ovarian Failure (POF) – primary/premature ovarian failure occurs when the ovaries stop working. This does have some known causes but can occur without a known cause.
- Autoimmune conditions such as systemic lupus erythematosus, where antibodies damage the ovaries.
- Chromosomal Abnormalities – Turner’s Syndrome, a condition where a woman has only one X chromosome instead of the normal two.
- A family history of POF can predispose to development of POF 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 occurring depend on the type of chemotherapy used, where the radiotherapy is focussed, and age at treatment (younger women can tolerate higher doses with less issues).
Treatments for Premature Menopause
It is important that premature menopause is properly treated, as the extended period of time without oestrogen in the life can lead to more severe osteoporosis and atherosclerosis.
The mainstays of treatment for premature menopause are HRT and the combined oral contraceptive pill, depending on whether the woman wishes to become pregnant or not. POF with unknown cause can be unpredictable in ovulation, so a woman may still be fertile. It is often suggested that these therapies be extended to between 50 and 55 to offer the best cover in bone and cardiovascular protection.
It is also recommended that supportive therapy options be provided to women who go through premature menopause, as the changes to hormone levels and possible loss of fertility can be very difficult.
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell
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