Menopause

UPDATE Clinical chemistanddruggist.co.uk/update-plus

Module 1794

June: Women’s health

Menopause

Clinical: ● Pregnancy loss

From this module you will learn:

●●The key hormone changes that occur as a woman transitions from the perimenopause to the menopause ●●The variety of symptoms experienced throughout menopause

● Thrush and cystitis ● Menopause

4 June* 11 June 25 June

*Online only for Update Plus subscribers

●●Available treatments, including hormonal, non-hormonal and non-pharmacological options ●●Risks and benefits associated with hormone replacement therapy

Naimah Callachand Pharmacist and medical writer

Menopause is the stage in a woman’s life signified by a loss of ovarian follicular activity and permanent cessation of menstruation. Menopause occurs after the final period and is clinically diagnosed after 12 months of absent periods. It occurs as part of the natural ageing process.

Premature menopause Menopause typically begins between 45-55 years of age. The average age at which women in the UK reach menopause is 51, although some women may experience premature menopause before the age of 40. The cause of premature menopause is often unknown, but genetic, autoimmune and iatrogenic causes have been identified in some women. A strong maternal family history of premature menopause, galactosaemia (a rare genetic metabolic disorder that affects an individual’s ability to metabolise sugar galactose properly) and chromosomal abnormalities are possible genetic causes that have been linked to premature menopause. Underlying autoimmune diseases – such as Addison’s disease, type 1 diabetes or thyroid disorders – play a role in premature menopause. Women predisposed to autoimmune conditions caused by underlying conditions, such as Down’s syndrome, may develop autoimmune premature menopause. There are other causes that can result in premature menopause, including: ●●surgery to remove the ovaries ●●some breast cancer treatments, eg chemotherapy or radiotherapy ●●infections such as mumps, tuberculosis, malaria, varicella and shingles.

Perimenopause The period before menopause, where the natural transition towards menopause occurs, is known as the perimenopause. In this transitional phase, the clinical features of the approaching menopause commence. During this period, irregular cycles of ovulation and menstruation occur and follicular activity begins to fail. For some, this period only lasts a few months, 12 CHEMIST+DRUGGIST 25.06.2016

Vasomotor symptoms occur in 75% of postmenopausal women and may include night sweats and hot flushes

but for many it can last several years. The perimenopause typically ceases 12 months after the final menstrual period – this is when menopause begins.

Symptoms of menopause It is very common for women to experience symptoms as a result of the transition to the menopause. The severity and duration of symptoms will vary, but they often begin during the perimenopause phase and can persist for around four years following the final period. It is thought that one in 10 women may experience symptoms for up to 12 years. Vasomotor symptoms – those related to blood vessels – are the most commonly reported symptoms and occur in approximately 75% of postmenopausal women, with as many as 25% of this group being severely affected. Common vasomotor symptoms include night sweats and hot flushes. These may last several minutes and can involve sweating, palpitations and anxiety. These symptoms can frequently be very distressing and can cause sleep disturbances. They are typically most debilitating during the first two years of menopause.

Chronic sleep disturbance can cause irritability and difficulties with short-term memory and concentration. Other symptoms of menopause include mood changes, such as anxiety or depression. Urogenital symptoms, such as vaginal dryness and recurrent urinary tract infections, can also occur during menopause. This dryness tends to increase in severity over time, and may lead to pain during intercourse, which in turn can cause a reduced libido. Another cause of a lowered sex drive is decreased oestrogen levels, following the cessation of follicular development during the ovarian cycle. Musculoskeletal symptoms can occur during menopause – such as joint stiffness, aches and pains. These symptoms are thought to be associated with the lack of ovarian hormone production. In addition, there is an increased likelihood of developing osteoporosis, because oestrogen is required to maintain bone strength and density. Cardiovascular disease (CVD) is a longterm risk factor of menopause. This is because oestrogen depletion has a detrimental effect on cardiovascular function and metabolism.

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Treatment The main treatment to alleviate menopausal symptoms is currently hormone replacement therapy (HRT). Before initiating treatment, a patient’s specific symptoms and their severity should be taken into consideration. Nonhormonal pharmacological treatments may include the use of antidepressants to treat symptoms such as mood changes, depression and anxiety. Non-pharmacological treatments may take the form of cognitive behavioural therapy or relaxation techniques.

Types of HRT There are two main types of HRT available. Combined HRT contains oestrogen and progestogen, and should be used in women with a uterus. Women without a uterus – for example those who have undergone a hysterectomy – should use oestrogen-only HRT. This is because oestrogen taken alone can increase the risk of increased endometrial cell reproduction and womb cancer. However, when given in combination with progestogen, the risk is reduced. The minimum effective dose of HRT should be used for the shortest period of time, with treatment reviewed annually and alternative treatments considered if the patient suffers from osteoporosis – a condition commonly found in menopause. HRT is available in various forms and the choice of formulation depends on a patient’s preference. Oral HRT undergoes first-pass metabolism, which significantly reduces drug concentration. Therefore, these doses tend to be higher compared to other routes of administration. A subcutaneous HRT implant delivers the drug over four to eight months, achieving high oestrogen levels that persist for a long period of time after the last implant is inserted. These implants come in the form of pellets, which are placed beneath the skin under local anaesthetic. Transdermal patches deliver lower doses of oestrogen. These patches are often used when oral treatment has failed to control the symptoms or have resulted in gastrointestinal problems. HRT gels are available and can be applied to arms, shoulders or thighs, then allowed to

dry for five minutes before dressing. Patients should be advised not to apply topical treatments to their breasts or vaginal area. Some manufacturers also recommend avoiding skin contact with another person – especially if they are male. Certain gels are designed for application to the vaginal route. They are used to deliver short-term low-dose oestrogen for the treatment of urogenital symptoms, such as vaginal atrophy. Intravaginal routes – such as creams, vaginal rings and pessaries – may be difficult to use and therefore this route is not always favoured by patients. In addition, there is also a risk of systemic side effects (see Box 1) when using the vaginal route. Intrauterine devices, such as the Mirena coil, can be prescribed as an alternative route for the delivery of progestogen to protect the endometrium – which undergoes rapid cell proliferation under the action of oestrogen alone – with oestrogen given orally in addition.

HRT side effects Although HRT is effective at relieving symptoms of menopause, there are many side effects associated with treatment. Oestrogen or progesterone-related side effects can occur continuously or randomly throughout treatment (see Box 1). These effects tend to occur in a cyclical pattern during the progestogen phase of treatment. Unscheduled vaginal bleeding within the first three months of beginning HRT treatment is a common side effect in those with a uterus. However, it should be reported to the patient’s GP if it occurs any later. Other side effects often resolve later on, so women should be encouraged to persist with treatment.

What is in HRT? HRT consists of both natural and synthetic oestrogens. Natural oestrogens such as estradiol, estrone and estriol are most suitable for systemic use. On the other hand, some synthetic oestrogens – such as ethinylestradiol and mestranol – are generally not considered for HRT, except in women with early ovarian failure. Progestogens used in combined HRT tablets are almost all synthetic and include

Box 1: Side effects of HRT Oestrogen-related side effects

Progesterone-related side effects

fluid retention

fluid retention

breast tenderness or enlargement

breast tenderness

headaches

headaches or migraine

nausea

mood swings

bloating

depression

leg cramps

acne

dyspepsia

pain in the lower abdomen and back

dydrogesterone, medroxyprogesterone, norethisterone, levonorgestrel and drospirenone. Tibolone is an oral synthetic steroid – having both oestrogen and progesterone characteristics, while possessing only weak male hormone activity. This is licensed for the treatment of oestrogen deficiency symptoms in postmenopausal women, no more than one year after menopause. Tibolone may also be useful in reducing side effects caused by progestogen use.

Why different regimes? In women without a uterus, oestrogen is usually taken continuously with no breaks in therapy. However, for women with a uterus, it is necessary to take progestogen for 10-14 days in each cycle, and this will induce a withdrawal bleed. It is preferable for this to be given in one combined form, as the adverse effects of progestogen may lead to poor compliance if given separately. You should counsel patients on the circumstances in which HRT should be stopped immediately. These include: ●●sudden, severe chest pain ●●sudden breathlessness ●●severe abdominal pain ●●unexplained swelling or severe calf pain in one leg ●●development of serious neurological effects, such as severe, prolonged headache ●●hepatitis, jaundice or liver enlargement ●●high blood pressure.

Long-term risks There has been some uncertainty in patients regarding the use of HRT because there is an increased risk of developing breast, ovarian and endometrial cancer. However, new guidelines from the National Institute for Health and Care Excellence (Nice) state that HRT is effective and should be offered to women with menopausal symptoms following discussions of the risks and benefits. It should be explained that the baseline risk of developing breast cancer for women around menopausal age varies from one woman to another, depending on the presence of underlying risk factors. All HRT treatments increase the risk of breast cancer within one to two years of initiating treatment, with the risk often linked to duration of treatment – this decreases within five years of stopping HRT treatment. For those at high risk of breast cancer, treatment options should be discussed with their GP and referral to a specialist is often necessary. The risk of endometrial cancer can be reduced in women with a uterus by using a combined therapy of oestrogen and progestogen. Longterm use of combined or oestrogen-only HRT is associated with a small increased risk of ovarian cancer, which decreases within a few years of stopping treatment. While taking HRT, the risk of a fragility 25.06.2016 CHEMIST+DRUGGIST 13

UPDATE Clinical chemistanddruggist.co.uk

fracture – due to the presence of osteoporosis – drops, and this benefit is maintained throughout treatment. However, this benefit often decreases when treatment is stopped as the positive effect of oestrogen is lost. HRT is also associated with an increased risk of a venous thromboembolism. Therefore, if a woman has predisposing risk factors then the benefits of using HRT should be assessed before commencing treatment. In addition, both combined HRT and oestrogen-only HRT slightly increase the risk of stroke. Although oestrogen has been shown to be cardio-protective, HRT has not been proven to prevent coronary heart disease, and therefore should not be prescribed for this indication. An increase in incidence of coronary heart disease in women has been found in those who have started combined HRT more than 10 years after menopause.

MENOPAUSE QUIZ

Patient counselling

6. Oestrogen-related side effects include fluid retention, bloating, breast tenderness or

It is important to counsel patients on the possible adverse effects of HRT, as well as the benefits and duration of treatment. You should consider advising patients about bone health to prevent osteoporosis (for more advice, see module 1788 at tinyurl.com/CDosteoporosis), especially for women that have been diagnosed with premature menopause. It is also important to advise women to attend the NHS breast screening programme, which is offered every three years to women aged 50 and above. Cervical screening is also recommended every three years to women aged 25-49, then every five years up until the age of 65.

Pregnancy in menopause Although pregnancy is less likely to occur around the age of menopause, you should advise patients that following the final menstrual period, a woman is considered potentially fertile for a further two years if she is younger than 50, or for one year if she is over 50. For women over 40, contraception may still be necessary – HRT does not provide protection against pregnancy.

Alternative treatments Herbal remedies, such as black cohosh and isoflavones (plant-based phytoestrogens), are available to buy for the treatment of menopausal symptoms. You should advise patients to exercise caution when using complementary therapies, as there is limited evidence on their effectiveness. Nice has also advised that if a woman wants to try complementary therapies, the quality, purity and constituents of the product may be unknown. The Medicines and Healthcare products Regulatory Agency has warned that although medicines are herbal, they are not necessarily safe. It is important to counsel patients on the potential side effects of herbal remedies and make them aware of the potentially serious drug interactions that could occur. 14 CHEMIST+DRUGGIST 25.06.2016

1. Premature menopause occurs before the age of 40 years. True or false? 2. One in 10 women may experience menopause symptoms for up to 12 years. True or false? 3. Vasomotor symptoms occur in more than 85% of postmenopausal women. True or false? 4. Postmenopausal women have an increased risk of osteoporosis. True or false? 5. Oestrogen-only HRT should only be used for women without a uterus. True or false?

enlargement, nausea and headaches. True or false? 7. Synthetic oestrogens, such as ethinylestradiol and mestranol, are more suitable than natural oestrogens for use in HRT. True or false? 8. HRT has been shown to reduce the risk of ovarian cancer. True or false? 9. Long-term use of combined or oestrogen-only HRT is associated with a small increased risk of endometrial cancer. True or false? 10. HRT has been shown to provide some protection against coronary heart disease in women. True or false?

Menopause CPD Reflect What are the most common symptoms associated with menopause? How long do menopause symptoms persist for? What are the side effects and long-term risks of HRT?

Plan This article contains information about menopause including the hormone changes and symptoms that occur and the hormonal, non-hormonal and non-pharmacological treatments that are available.

Find out more about menopause symptoms from the Menopause Matters website at tinyurl.com/menopause21 Read the advice about coping with hot flushes on the NHS Choices website at tinyurl.com/menopause22 Find out more about menopause and bone loss on the NHS Choices website at tinyurl.com/menopause23

The risks and benefits associated with hormone replacement therapy are also discussed.

Revise your knowledge of the hormonal treatments available for menopause from the BNF section 6.4.1.1 Oestrogens and HRT

Act Read more about menopause on the

Evaluate Are you now confident in your knowledge of menopause symptoms and treatments? Could you give advice to patients about the risks and benefits of HRT?

Patient website at tinyurl.com/menopause20