Menopause, also referred to as ‘the change’, happens when your periods stop permanently — signaling the end of reproductive function. Natural menopause usually happens when you reach your 50s (the average age is 51 in the United Kingdom). But some women may experience menopause much earlier (10% have early menopause between 40-45 and 1-2% have premature menopause before 40). Some women experience abrupt menopause due to medical interventions such as chemotherapy, radiotherapy, or surgical removal of ovaries as part of medical treatments.
Natural menopause is a phase of physiological transition in midlife. Sometimes this change can be associated with distressing symptoms, and they may last for few months or sometimes several years. Treatment options for menopausal symptoms include lifestyle changes, alternative therapies, non-hormonal medications, and hormone replacement therapy (HRT). You can decide whether to take HRT or not after considering its benefits versus risks in your unique situation.
What changes or symptoms happen in the menopause and when is HRT needed?
As you approach menopause, the functioning of your ovaries reduces, and your body makes less of two hormones called ‘oestrogen’ and ‘progesterone’. Among other things, these hormones are responsible for bringing on your periods. You may notice your periods become less regular. They might be heavier or lighter and last for more or fewer days than usual. Your periods will become less frequent with time and eventually stop. Levels of another hormone ‘testosterone’ also start declining from the fourth decade of your life.
Perimenopause is the phase when first changes to hormones, periods and symptoms start appearing – this can last for few years or sometimes up to 8-10 years.
You may notice ‘hot flushes’ as you go through menopause (where you suddenly feel hot and go red in the face). This may be associated with bouts of sweating during the day as well as at night. It is also common to find that your vagina feels dry and uncomfortable, which can make sex painful.
You may also experience one or more of the following:
Tiredness
Irritability
Brain fog
Headaches
Joint aches
Trouble sleeping
Heightened anxiety
Depression
Weight gain
Skin/hair/nail changes
Less interest in sex
These symptoms may be attributable to the changes in your hormones or to the changes in your life around the time of menopause. Not everyone experiences distressing menopausal symptoms and needs treatment. Some individuals find the symptoms do not bother them much, while others find them very distressing, and they can negatively affect their quality of life. For most, the symptoms will pass within three to five years, although vaginal dryness is likely to get worse if not treated. For others, symptoms will persist for 15 years or longer.
If you are worried about your symptoms, talk to your health professional about the treatment options available. HRT will help if you have unpleasant menopausal symptoms which cannot be addressed by lifestyle or non-hormonal therapies alone.
What is HRT?
HRT stands for hormone replacement therapy. It is also abbreviated as MHT for menopausal hormone therapy. It consists of the hormone oestrogen either alone or combined with the other hormone progesterone. The aim is to replace some of the oestrogen that your body stops making when you reach menopause. Some women are also prescribed testosterone in addition depending on their symptoms.
What are the types of HRT?
Combined HRT (oestrogen and progesterone) is prescribed if you still have your womb. Taking oestrogen alone can increase your chance of getting cancer of the womb lining (endometrial cancer). Adding progesterone to oestrogen reduces the chance of getting this kind of cancer.
Oestrogen only (no progesterone) is prescribed when you have had a hysterectomy. This is because you do not need progesterone to protect the lining of the womb (there are few exceptions such as severe endometriosis, endometrial cancer, or symptoms specifically responsive to progesterone). You can take oestrogen-only HRT as there is no chance of getting endometrial cancer.
HRT can be administered in two ways:
Continuous combined HRT — oestrogen and progesterone, taken together daily for 28 days. This means that there will be no monthly withdrawal bleeds.
Sequential HRT — oestrogen only for the first 14-16 days then both hormones for the second 12-14 days. This usually results in monthly withdrawal bleeds as it tries to copy your natural cycle and give you a period.
Cyclical HRT is often prescribed for women who have menopausal symptoms but are still having periods or for those who stopped their periods less than one year ago. Continuous HRT (without bleeds) is more suitable if you have not had periods for more than one year.
HRT is available for prescription in several different forms. You can take it as:
Skin patches
Oral tablets
Capsules
Gel
Spray
Implant under the skin
Vaginal ring
Progestogen-releasing uterine coil
Vaginal cream or pessaries
Some types work best for certain symptoms. As transdermal oestrogen (patch/gel/spray) is associated with a lower risk of blood clotting than oral HRT, a transdermal route may be preferable for some individuals. This route is advantageous for those with diabetes, high blood pressure, high BMI, migraines, and other cardiovascular risk factors, especially above the age of 60.
Progesterone types can vary in HRT. Body-identical or body-similar versions such as micronised natural progesterone or dydrogesterone appear to be safer than synthetic versions. Vaginal oestrogen creams or pessaries do not carry the same risks associated with oral or transdermal HRT. As the dose of oestrogen is low, they do not require the protective effect of progesterone.
Talk to your health professional to decide which product is likely to suit you most.
What are the benefits of HRT and how long after starting HRT do you feel a difference in symptoms?
For most symptomatic women, benefits of use of HRT outweigh the risks.
Benefits include:
Reduction in vasomotor symptoms such as hot flushes and night sweats — HRT is the most effective medical treatment for reducing vasomotor symptoms. These usually improve within three to four weeks of starting treatment and maximal benefit is gained by about three to six months.
Improvement in quality of life — HRT may improve sleep, muscle aches/pains and your overall quality of life. Many individuals experience improved mood, less brain fog, better libido, and less depressive symptoms.
Improvement of urogenital symptoms — HRT significantly improves vaginal dryness and pain during sex. HRT is also effective in improving stress incontinence (leaking urine when you cough or sneeze). It can relieve the symptoms of urinary frequency and prevent frequent urinary tract infections, as it has some effect on the urinary bladder and urethral tissues. Vaginal oestrogen creams or pessaries are the preparations of choice for urogenital symptoms.
Reduction in osteoporosis (brittle bones) risk — HRT is effective in preserving bone mineral density. Women taking HRT have a significantly decreased incidence of fractures with long-term use. Although bone density declines after discontinuation of HRT, some studies have demonstrated that women who take HRT for a few years around the time of menopause may have a long-term bone protective effect for many years after stopping HRT.
Reduction in cardiovascular disease — The effect of HRT on cardiovascular disease depends on the timing and duration of HRT as well as pre-existing cardiovascular disease. HRT reduces the incidence of coronary heart disease if it is started within ten years of menopause.
Other benefits
HRT has a protective effect against connective tissue loss in tissues such as skin, bones, joints, and mucous membranes. Some studies have shown that HRT has benefits for metabolic health and it may reduce the risk of diabetes for some women. There may be a possible reduction in the long-term risk of cognitive decline in specific groups of women who take HRT (for example those with certain genetic markers). There is a need for further robust research to confirm these findings. Studies have demonstrated a reduction in the risk of colorectal cancer with use of combined HRT.
What are the risks associated with HRT?
Like other medications, there are side effects and risks associated with taking HRT. For most individuals, the increased risks are very small, but you will need to talk to your doctor to weigh up the risks and benefits for you as an individual.
Doctors are advised that women should take the lowest effective dose of HRT that controls their symptoms effectively. There is limited data on the use of HRT in women after 70.
The main risks of HRT are:
Thromboembolic disease (blood clots in veins and lungs)
Stroke
Breast cancer
Endometrial cancer
Cardiovascular event
Gallbladder disease
Large studies such as the Women’s Health Initiative (WHI) and the Million Women Study (MWS) caused concerns and controversy over the long-term use of HRT when their findings were published 20 years ago.
However, reanalysis of some of that data and findings from recent studies over the past decade have shown that in women who need treatment of menopausal symptoms — initiating HRT during perimenopause or early menopause will provide a favourable benefit-to-risk ratio.
Venous thromboembolism
Oral HRT (combined oestrogen and progesterone or oestrogen only) slightly increases the risk of venous thromboembolism (VTE) or venous blood clots), pulmonary embolism (blood clot in lungs) and stroke. The risk of VTE is increased two to three times with oral HRT. In one big study, over five years, less than 1 in 100 women taking oral HRT got a blood clot in their lungs. But this was about twice the number of women who were not taking HRT. If you’ve had blood clots before, you should let your doctor know and talk about whether oral HRT is suitable for you.
Overall, the risk of blood clotting with oral HRT is a lot lower than taking the contraceptive pill or risk during pregnancy. The risk increases with age (mainly over 60) and with other risk factors such as obesity, previous thromboembolic disease, smoking, and immobility. In healthy women below 60, the absolute risk of VTE is low and mortality risks from VTE are low. The type, dose and delivery system of both oestrogen and progesterone influence the risk of thromboembolic disease. The VTE risk appears to be higher among users of oestrogen plus synthetic forms of progesterone than among users of oestrogen alone. The risk is increased especially during the first year of treatment. Previous users of HRT have a similar risk as never users.
Transdermal oestrogen or progesterone (delivered through skin) and oral natural micronised progesterone or Mirena intrauterine coil are safer concerning thrombotic risk as they do not seem to increase the risk of blood clotting above the background risk in women without history of blood clots.
Stroke
The risk of stroke appears to be slightly increased when taking oral oestrogen-only or combined HRT although the absolute risk is very small below the age of 60. Transdermal oestrogen again seems to be safer. The effects of HRT on stroke may be dose-related and so the lowest effective dose is usually prescribed in women who have significant risk factors for stroke.
Breast cancer
Data regarding the true effect of HRT on the incidence of breast cancer are still contentious. Combined HRT slightly increases the risk of breast cancer. The risk is a little higher for women who take HRT over the age of 60. The risk goes up slowly in the first five years you use HRT, then more quickly if you continue using it afterwards. However, the absolute risk is small at around one extra case of breast cancer per 1,000 women per year.
Lifestyle factors such as smoking, excess alcohol intake and obesity have a similar or greater impact on breast cancer risk as compared to HRT. Mortality from breast cancer is not significantly increased in HRT users. Breast cancers found in women who take HRT are easier to treat than those in women not on HRT.
The risk of breast cancer with oestrogen-only HRT is far less than with combined HRT. Most studies do not demonstrate an increased risk of breast cancer in women taking oestrogen-only HRT and some studies have shown a reduced risk. It is also important to understand that the small increased risk of breast cancer with combined HRT does not apply to women who only use vaginal oestrogen and women who take HRT for early or premature menopause until the age of 51 years.
Endometrial cancer
Oestrogen-only HRT substantially increases the risk of endometrial cancer in women with a womb (uterus). The use of continuous combined HRT (both oestrogen + progesterone) or cyclical progesterone for at least twelve days every month almost eliminates this risk. If higher than recommended (unlicensed) doses of oestrogen doses are used as part of HRT, these need to be balanced adequately with more progesterone dose.
Heart disease
Women who are over 60, start HRT more than 10 years after menopause and have cardiovascular risk factors may have an increased risk of heart disease. But the risk is small and overall, no increase in serious morbidity or mortality attributable to heart disease is noted when transdermal and body-identical HRT preparations are offered. The data are limited and the decision to start HRT after 60 should be based on individual benefits versus risks assessment. Starting HRT within 10 years of onset of menopause is associated with reduced risk of future heart disease.
Other risks
There is a chance that taking HRT for a year or more could increase your risk of gallbladder disease (gallstones). Current data on HRT and the risk of ovarian cancer are conflicting. Some observational research suggests that HRT may slightly increase your chance of getting some types of ovarian tumours, although the risk seems to disappear when you stop using HRT.
What are the common side effects of HRT and how can they be minimised?
Women react differently to HRT, so there is no one preparation that is better than any of the others.
Some of the common side effects which you may experience on HRT include:
Oestrogen-related — breast tenderness, leg cramps, skin irritation, bloating, indigestion, nausea, and headaches.
Progesterone-related — premenstrual syndrome-like symptoms, fluid retention, acne, oily skin, breast tenderness, backache, depression, bloating, constipation, mood swings and pelvic pain.
Nausea can be reduced by taking the HRT tablet at night with food instead of in the morning or by changing from tablets to another type of HRT.
Many of these common side effects simply go away when you have been on HRT for a while. Sometimes a change of product helps. Monthly sequential preparations should produce regular, predictable, and acceptable period-like bleeds. Erratic breakthrough bleeding is common in the first 3-6 months of continuous combined and long-cycle HRT regimens (with no regular period-like bleeds). If bleeding tends to be heavy or irregular on sequential combined HRT, then the dose of progesterone can be doubled or increased in duration to 21 days. If there is persistent irregular vaginal bleeding after six months of starting HRT, you will need to have further investigations and possibly a change of progesterone type or dose. If you experience predominantly progesterone-induced side effects, you can change the progesterone type, dose, or frequency. If you experience significant nausea or migraine headaches with oral preparations, patches can often be a better option. Avoiding cyclical bleeds may also help with migraines. Progesterone-related side effects can sometimes be minimised if the Mirena coil is used as the progesterone arm of HRT.
Does HRT cause weight gain?
There is no evidence of weight gain with HRT. Researchers have found that, although women may put on some weight when they first start to take HRT (mainly due to fluid retention), after a while their weight is the same as it was before treatment.
Some women tend to gain weight during the menopause, so any weight gain may not be a result of HRT. The body’s fat distribution changes, with an increase in fat around the waist and less around the hips and buttocks.
When should HRT not be taken?
HRT is usually not prescribed or prescribed with caution in certain conditions such as:
Pregnancy and breast-feeding
Undiagnosed abnormal vaginal bleeding
Active venous thromboembolic disease
Active heart disease
Current or past breast cancer
Current or past endometrial cancer
Other oestrogen-dependent cancers
Active liver disease
Uncontrolled high blood pressure
Women who would like to consider HRT but have one of these conditions should seek specialist advice and they may be able to have HRT after input from relevant specialists alongside medications to treat the underlying conditions.
What tests are needed before or after starting HRT?
When you start HRT, the doctor or nurse will discuss your age, symptoms, and medical conditions before looking at the risks and benefits of HRT which are specific to you. These can change and will be discussed in your yearly reviews. Tests are usually not necessary before starting HRT unless there is a sudden change in menstrual pattern such as persistent heavy/irregular periods, bleeding between periods or after intercourse and postmenopausal bleeding. In these situations, you will be asked to have a pelvic ultrasound scan to assess the lining of the womb and a biopsy of the womb lining may be performed.
If there is a personal or family history of VTE, a thrombophilia screen (blood test to look for a tendency to develop blood clots easily) may be helpful. If there is a high risk of breast cancer, you will be asked to consider a mammography or MRI scan and referred to familial breast cancer services depending on the level of your risk. A blood test for lipid and glucose profile will be requested if you have risk factors associated with cardiovascular disease.
How to decide on the right type of HRT preparation (cyclical or bleed-free)?
The choice of delivery route and type of HRT depends on your preference but there are advantages to certain delivery routes. It is recommended that you are prescribed sequential combined HRT (giving monthly periods) if your last menstrual period was less than one year ago. You can be prescribed continuous combined HRT (without periods) if you have received sequential combined HRT for at least one year, or if it has been at least one year since your last menstrual period. Local preparations such as vaginal creams and pessaries are highly effective for symptoms of vaginal dryness, painful sex, and urinary frequency. Around 10% to 20% of women still have persistent symptoms with local oestrogen so they will require systemic HRT in addition.
How long can you take HRT?
There is no maximum duration of time you can take HRT. For women who continue to have symptoms, their benefits from HRT usually outweigh any risks. As long as women have an annual review of HRT with their healthcare professional and the benefits outweigh the risks — they can continue with HRT. Most women aim to stop taking HRT after their menopausal symptoms diminish, which is usually three to five years after they start. However, for many, symptoms may continue longer for 10 years or beyond. If a decision is made to stop, gradually decreasing your HRT dose is usually recommended — rather than stopping abruptly. You may have a relapse of menopausal symptoms after you stop HRT, but these should pass within a few weeks or months.
If you have symptoms that persist for several months after you stop HRT, or if you have particularly severe symptoms, HRT may need to be restarted, usually at a lower dose. After you have stopped HRT, you may need additional treatment for vaginal dryness and prevention of osteoporosis.
Is HRT a contraceptive?
HRT is not a contraceptive. You may be potentially fertile for up to two years after your last menstrual period if you are under 50 years of age and for one year if you are over 50 years. You should therefore use appropriate contraception during this time to avoid pregnancy. A progesterone-only pill alongside combined HRT or Mirena coil with oestrogen are common ways of having both HRT and contraception.
What are the signs that HRT is not working?
Getting the right dose and combination of hormones to work for menopausal symptoms can take time. If your symptoms do not improve or persist despite taking HRT for more than 2-3 months or if you experience significant side effects, a change of dose or type of HRT is needed. This is because the absorption of hormones from different HRT preparations may vary between individuals. Sometimes, your doctor may consider a blood test for oestrogen level to assess this.
What is the role of testosterone in HRT?
Testosterone levels drop gradually during natural menopausal transition (it is produced by both ovaries and adrenal glands in the body). Some women experience a persistent lack of libido despite taking HRT containing oestrogen. Testosterone can help in this situation. Some women notice improved energy levels, better mood and less brain fogging on testosterone however more research is needed to confirm these benefits. Testosterone is used in small doses and usually does not cause side effects. Excessive use can cause oily skin, excess body hair, scalp hair loss and deepening of voice and is therefore not recommended.
What is bio-identical or body-identical HRT?
Most commercially available combined HRT preparations contain progestogens — compounds which have progesterone-like actions but are synthetic. Micronised progesterone is natural progesterone devoid of any androgenic as well as glucocorticoid activities and is considered safer than synthetic progestogens. This combined with 17-beta oestradiol oestrogen is regulated and recommended body-identical HRT.
Bio-identical HRT refers to compounded HRT preparations which are combinations of plant oestrogens and progesterone-like compounds created by independent pharmacies or clinics. These are currently not recommended in the UK by the British Menopause Society as long-term safety data is lacking for many of these.
What are the alternatives to HRT?
Whether you take HRT or decide not to take it, a healthy diet, good sleep hygiene, regular exercise in some form and stress reduction activities are key for good long-term health. If you are unable to have HRT, other medications or treatments may be prescribed to help control unpleasant menopausal symptoms. For vaginal dryness and painful sex, vaginal lubricants and moisturisers are often effective.
For hot flushes and night sweats, antidepressants or selective noradrenaline and serotonin reuptake inhibitors such as Venlafaxine, Gabapentin and Clonidine (blood pressure lowering agent) are oral medications which can be prescribed. They can be effective for some but do have side effects such as dizziness, dry mouth, low libido, and constipation. CBT (cognitive behavioural therapy) can be effective for vasomotor, sleep and mood-related symptoms. Recently, NK3 receptor antagonists (a new class of oral medications) have been approved in the UK as a non-hormonal treatment for hot flushes.
Alternative therapies including homeopathy, hypnotherapy and acupuncture are also offered at specialist clinics although the evidence base for these remains weak. If you wish to consider any of these alternatives, you should talk to your doctor in detail about the risks versus benefits of these treatment options and make an informed choice.
Is follow-up needed after starting HRT?
You will generally be asked to come for a follow-up consultation after starting HRT in about three months. Most symptoms are likely to have responded to oestrogen at this time, and any residual symptoms may require adjustment of treatment. If the chosen HRT suits you and appears effective, you may wish to see your GP or the specialist clinic once or twice every year to review the ongoing need for and safety of continuing HRT. Regular blood pressure monitoring is recommended at follow-up visits. Both mammograms and cervical screening as per national guidelines are recommended in postmenopausal women on HRT.
Useful links for further information –
Menopause Research and Education Fund: https://mref.uk
The Daisy Network: https://www.daisynetwork.org
Menopause and Cancer: https://menopauseandcancer.org
Mr Vikram Talaulikar
Specialist in Reproductive Medicine
He graduated in medicine in India in 2003 and completed postgraduate degree in obstetrics and gynaecology in 2007.
He is a fellow of the Royal College of Obstetricians and Gynaecologists and completed PhD degree at St. George’s University of London in 2016.
His clinical interests include reproductive endocrinology, polycystic ovary syndrome, recurrent miscarriage, premature ovarian insufficiency, and menopause.
He is a certified ‘menopause specialist’ by the British Menopause Society.
He has published widely in Reproductive Medicine and Menopause. He is a member of the British Fertility Society, European Society of Human Reproduction and Embryology, British Menopause Society, and International Menopause Society.
He runs a busy menopause and PCOS clinic at UCLH and Menopause Clinic London on Harley Street. He is a Principal trainer for FSRH Menopause SS module and a trainer for BMS principles and practice of menopause care programme.
