Menopause, properly explained

Why the ovaries wind down

You are born with all the eggs you will ever have. As the supply runs low in your forties, the ovaries respond less to FSH, the signal from the pituitary gland in the brain. They make less oestradiol, and less of a hormone called inhibin that normally keeps FSH in check, so FSH rises. Cycles become irregular, and often no egg is released.

When no egg is released, very little progesterone is made, so progesterone usually falls first. Oestrogen swings widely, sometimes higher than before, and then falls. After menopause the main oestrogen is oestrone, made in body fat at much lower levels.

How oestrogen works

Oestradiol is a steroid hormone made from cholesterol. It passes into cells and binds to oestrogen receptors, known as alpha and beta. The pair then moves to the DNA and changes which genes are switched on, which is why its effects build over days and weeks. Some receptors sit on the cell surface and act within minutes, for example in the walls of blood vessels.

Different tissues carry different mixes of receptors. Alpha receptors dominate in the womb, breast, liver and bone. Beta receptors are more common in the brain, bladder, gut and blood vessels. That is why falling oestrogen can be felt in so many places at once.

What progesterone does

Progesterone is made after an egg is released. In the womb it stops the lining overgrowing, and when it falls the lining sheds as a period. In the brain it is turned into allopregnanolone, which acts on the calming GABA system and helps sleep. With fewer cycles releasing an egg, perimenopause often brings heavier or erratic periods, breast tenderness and poorer sleep. It is also why anyone with a womb who takes oestrogen needs a progestogen alongside it.

Hot flushes

Your body keeps its core temperature inside a narrow comfort zone, set by the hypothalamus in the brain. A group of nerve cells there, known as KNDy neurons, is normally held in check by oestrogen. When oestrogen falls they become overactive and signal through a messenger called neurokinin B. The comfort zone narrows, so a tiny rise in temperature sets off the full cooling response: blood vessels in the skin open, the heart speeds up and you sweat, often followed by a chill. Fezolinetant, a newer non hormonal tablet, works by blocking this same signal.

Brain fog

Oestrogen receptors are dense in the parts of the brain that handle memory and attention. Oestrogen helps brain cells use glucose for energy and supports the messengers serotonin, dopamine and acetylcholine. During perimenopause the brain is adjusting to swinging levels, and broken sleep, flushes and low mood add to the load. In the large SWAN study, the dip in learning seen during perimenopause recovered after menopause. Memory problems that are severe, getting steadily worse or affecting daily life should be checked in their own right.

Aches and pains

Oestrogen receptors are found in cartilage, the joint lining, tendons, ligaments and muscle. Oestrogen dampens inflammation and supports collagen and muscle repair. As it falls, joint pain and stiffness become more common, tendons stiffen and muscle strength drops faster. Researchers have named this the musculoskeletal syndrome of menopause. Resistance training and enough protein make the biggest difference. Hot, swollen joints, or pain that keeps getting worse, still need a proper assessment.

Vaginal and bladder changes

The vagina, vulva, urethra and base of the bladder are rich in oestrogen receptors. Oestrogen keeps the lining thick and elastic, supports blood flow and natural lubrication, and feeds the friendly bacteria that keep the area acidic and protected. Without it the lining thins and those bacteria fall, leading to dryness, soreness, pain during sex, urgency and repeated urine infections. Doctors call this genitourinary syndrome of menopause. Unlike flushes, it tends to get worse over time. Low dose vaginal oestrogen works locally and can be used long term.

Bones

Bone is rebuilt all the time. One set of cells, osteoclasts, breaks down old bone while another, osteoblasts, lays down new bone. Oestrogen acts as a brake on the breakdown cells. When it falls, breakdown outpaces building, and bone is lost fastest in the years around your last period. Weight bearing and resistance exercise, calcium, vitamin D and protein all help. HRT reduces the risk of fractures while you take it.

The heart

Oestrogen helps the lining of your blood vessels make nitric oxide, which keeps arteries relaxed, and it helps the liver keep LDL cholesterol down. After menopause LDL cholesterol rises, arteries stiffen, blood pressure tends to climb and fat moves to the waist, so heart risk catches up over the following decade. It is worth knowing your blood pressure, cholesterol and blood sugar (HbA1c). HRT is not prescribed to prevent heart disease, but NICE says it does not increase heart disease risk when started under 60.

Diagnosis

NICE advises that women over 45 with typical symptoms are diagnosed on their symptoms, without an FSH blood test, because hormone levels swing from day to day in perimenopause. Blood tests can help under 45, and are needed if periods stop before 40.

How HRT is put together

Oestrogen relieves the symptoms. Through the skin, as a patch, gel or spray, it does not raise the risk of blood clots the way tablets do. If you have a womb you also need a progestogen to protect its lining, such as micronised progesterone capsules or a hormone coil. While you still have periods it is usually taken for part of each month. Once periods have stopped for long enough, it can be taken every day so there is no monthly bleed.

Vaginal oestrogen is very low dose. It can be used alongside HRT or on its own, and it is fine to use long term.

Testosterone

NICE says testosterone can be considered for low sexual desire when HRT alone has not helped. It is a small daily dose of gel or cream, with a blood test before starting and checks during treatment to keep levels within the normal female range. The most common side effects are acne and extra hair growth. Studies have not shown that it helps energy, mood or memory.

Contraception

HRT does not reliably prevent pregnancy, and pregnancy is still possible in perimenopause. Contraception is needed for two years after your last period if it happens before 50, and for one year if it happens after 50. Everyone can stop at 55. The 52 mg hormone coil can provide contraception and the progestogen part of HRT at the same time.

The 1,000 women

These figures come from the UK medicines regulator, the MHRA, in 2019. Of 1,000 women aged 50 who never use HRT, about 63 will be diagnosed with breast cancer by the age of 69. Five years of HRT from 50 adds about 5 cases with oestrogen only HRT, 14 with sequential combined HRT (with a monthly bleed) and 20 with continuous combined HRT (no bleed).

The comparison bars

These come from the British Menopause Society, which uses a different study base and a five year window, so its HRT figure is not the same. Its figures are under review following the 2024 NICE update, but the point holds: weight, alcohol and exercise move breast cancer risk at least as much as HRT does.

Time and type

Less than a year of HRT adds little or no risk, while ten years roughly doubles the extra cases. Some of the extra risk lasts for more than ten years after stopping. Low dose vaginal oestrogen has not been shown to raise breast cancer risk.

Womb cancer

Oestrogen on its own thickens the womb lining, which is why a progestogen is always added if you have a womb. NICE found continuous combined HRT does not increase womb cancer risk. Any unexpected bleeding on HRT should be checked.

The 100 squares

Cancer Research UK estimates how many UK breast cancers are caused by each risk factor. Around 23 in every 100 are linked to causes that can be prevented. The rest come down to age, genes, chance and factors we cannot yet change.

Working out your risk

A family history clinic estimates your personal lifetime risk of breast cancer. Under 17% is close to average. Moderate risk is 17 to 30%, and high risk is 30% or more, which includes women who carry a known gene such as BRCA1 or BRCA2. If your chance of carrying a gene is 10% or more, you will usually be offered genetic testing, ideally starting with a relative who has had cancer.

What changes

Women at higher risk may be offered earlier or extra breast screening. If you are at moderate or high risk and considering HRT, NICE advises the lowest dose for the shortest time, oestrogen only HRT where possible (which applies if you have had a hysterectomy), and generally only up to the age of 50. HRT is not automatically ruled out. It becomes a decision you make with the specialist team.

Other cancers in the family

Ovarian cancer in the family can point to a BRCA gene. Bowel or womb cancer at a young age can point to Lynch syndrome. Mention both to your GP.

About the bars

The bars are an illustration, not anyone's measured risk. They show why the same medicine gives a bigger number when the starting point is higher. Real estimates follow the same pattern. One UK study estimated that between the ages of 50 and 80, five years of combined HRT from 50 raises breast cancer risk from about 9.8% to 11.0% with an average family history, and from about 19.6% to 22.4% with a strong family history. Example 3, Helen, walks through how this plays out.

When to take extra care

HRT is usually avoided if you have or have had breast cancer, especially if it was hormone sensitive, and decisions sit with your breast team. A previous blood clot or clotting disorder needs specialist advice first. Oestrogen through the skin does not carry the extra clot risk of tablets. Migraine, including migraine with aura, does not rule HRT out, and patches or gels at the lowest effective dose are preferred. Unexplained vaginal bleeding should be investigated before starting. Liver disease that has not settled, a recent heart attack or stroke, and high blood pressure that is not controlled also need care.

The alternatives

Cognitive behavioural therapy designed for menopause can reduce the impact of flushes, night sweats, low mood and sleep problems, with or without HRT. Fezolinetant is a once daily non hormonal tablet for moderate to severe flushes when HRT is not suitable, and it needs liver blood tests before and during treatment. Vaginal moisturisers and lubricants help with dryness. Vaginal oestrogen after breast cancer is a conversation to have with your breast team.

Herbal remedies and supplements vary widely in quality and can interact with other medicines, so tell your prescriber about anything you take.