What the hormones really change in the menopause

Part 2 of 12 · All topics on the menopause

More than a single “female hormone”

When people talk about the menopause years, the word oestrogen almost always comes up first. It is often described as a kind of universal regulator: less oestrogen, so the simple story goes, leads to sleep problems, weight gain, poor skin, depression and all the other symptoms. The body, however, works in a more complex way.

Oestrogens are a group of hormones with effects on, among other things, the womb lining, bones, brain, blood vessels and mucous membranes. Progesterone plays a role especially in connection with the cycle and the womb lining. Both hormone systems form a control loop with the brain and the ovaries. Another hormone, FSH – follicle-stimulating hormone – stimulates the maturing of the follicles in the ovaries.

In the course of reproductive ageing, this control loop changes. The number and responsiveness of the follicles decrease. Ovulation no longer takes place as usual in every cycle. As a result, the course of the hormones becomes more irregular. Sometimes oestrogen levels are quite high, at other times lower. Later, after the last period, the body’s own oestrogen production is on average clearly lower than in the years of regular cycles. [1] [2]

It helps to picture not a steadily falling level but rather a changeable flow. This metaphor does not replace a medical description, but it explains why a single blood test in the perimenopause often does not reliably sum up the situation.

What happens in the brain – and what we do not know

Hot flushes are one of the best-studied phenomena of the menopause years. Research describes changes in central temperature regulation; neuroendocrine signalling pathways, among others, play a part. The clinical effectiveness of medicines that block certain neurokinin receptors supports the importance of this system. However, that does not mean that every sensation of heat can be reduced to a single messenger substance. [3] [4]

Oestrogens also act on neural systems linked to mood and cognition. It cannot be concluded directly from this, however, that hormone therapy improves memory in general. A systematic analysis of 34 randomised trials found no general positive effect of hormone therapy on the areas of cognitive performance examined. Individual subgroups and treatment situations were assessed differently, but the evidence is not enough for a blanket recommendation for “brain protection”. [5]

This distinction is central: a biologically plausible mechanism is not yet proof of an effective treatment. Conversely, symptoms that cause real distress should be taken seriously even if research cannot yet fully explain their mechanism.

Why sleep problems can reinforce each other

Many women report that night-time hot flushes are what first make them sleep badly, and that they are more irritable or exhausted the next day. That is understandable. But not every sleep disorder during the menopause years begins with night sweats. Sleep quality is also influenced by physical illnesses, psychological strain, habits, medicines and changes in sleep with age.

For this very reason there is not just one treatment answer. In a randomised trial of 106 women with insomnia and vasomotor symptoms, telephone-based cognitive behavioural therapy for insomnia improved sleep without reducing the frequency of the hot flushes themselves. The symptoms can therefore be connected and still be treatable separately. [6]

For these pages, that means: the page Hot flushes and sleep looks at hot flushes and sleep together, but it does not mix up their causes and treatments. An effective approach to sleep does not necessarily have to be hormone treatment. Equally, hormone treatment is not automatically the right answer to every form of exhaustion.

Hormones and bones: a well-supported link

Oestrogens influence bone metabolism. After the menopause, bone loss can increase. This is one of the well-supported reasons why bone health belongs in health advice in midlife. The assessment of an individual’s fracture risk, however, takes into account not only menopausal status but also other factors such as age, existing fractures, family history, certain medicines and illnesses. [7] [8]

It would still be wrong to conclude from this mechanism that every woman must take hormones as a preventive measure. A treatment is decided on the basis of individual risk, other indications, possible contraindications and personal preferences. The basics of bone metabolism are therefore explained only briefly here, while practical questions about osteoporosis, exercise and risk assessment follow on the pages Weight, muscles, bones and heart and What you can influence yourself.

Hormones, weight and metabolism: not a simple equation

With increasing age, body composition can change. In some women fat mass increases while muscle mass or muscle strength decreases. The menopause can influence fat distribution, but at the same time physical activity, diet, sleep, illnesses, medicines and general ageing processes are also at work. A single hormone does not explain the whole picture.

Particularly problematic is the blanket statement: “From the menopause onwards, oestrogen deficiency automatically makes you fat.” It links a common everyday experience with an impermissibly simple cause. Promises that a particular diet or supplement can “reset” the body “hormonally” make just as little sense.

These pages will therefore distinguish between relieving symptoms and long-term health prevention. Strength training can make sense for muscle health regardless of any direct effect on hot flushes. Exercise can contribute to cardiometabolic health, even though the scientific evidence that a particular form of training specifically reduces vasomotor symptoms is limited. [9]

What research means by “associated”

In medical studies you often read: “Symptom X is associated with the menopause.” At first, this means only that there is a statistical link. It does not yet answer the question of whether the menopause causes the symptom.

For example, a large systematic review found that muscle and joint complaints were reported more often in the perimenopause than before the transition. The data came mainly from observational studies, often with a cross-sectional design. Factors such as age, state of health, exercise and measuring methods cannot always be separated sufficiently. It would be overstating things to read the result as proof that altered hormones alone cause the pain. [10]

Randomised controlled trials answer different questions. In them, groups are assigned to different treatments at random. This often allows treatment effects to be examined more reliably. Such studies also have limits: the participants may not match everyone who is treated later; the period of observation can be short; rare side effects sometimes appear only after approval.

One example is the new medicines for hot flushes. The SKYLIGHT and OASIS trials provide important randomised data on effectiveness. For fezolinetant, however, relevant liver safety risks later became known, which led to additional monitoring recommendations. [3] [4] [11]

Why you do not need “perfect hormone levels”

Some offers on the internet promise to decode individual symptoms precisely using comprehensive hormone profiles, saliva tests or finely tuned “balance programmes”. Such promises seem attractive: they appear to turn a confusing stage of life into a measurable problem with a clear solution.

For the typical clinical perimenopause from the age of 45, guidelines specifically do not recommend routinely using a broad range of hormone measurements. The changes are assessed primarily from age, the course of the cycle and symptoms. In certain situations, especially at a younger age, laboratory tests can make sense. [8] [12]

A measurement can be scientifically precise and still help little with the specific clinical question. That is not a contradiction. A good test must not only deliver a value but improve a decision. The page Bleeding and diagnosis shows when this is the case.

Why hormones are not simple on-off switches

The word “hormone” often sounds like a single force that controls feelings, weight, sleep and sexuality all at once. In reality, hormones act within complex systems. They are released, bind to receptors, are converted in tissues and are regulated through feedback. Not every effect is the same in all organs. When the ovaries’ oestrogen production becomes more irregular during the transition, this therefore does not mean that on a particular day every cell in the body experiences the same change.

Oestradiol, an important oestrogen during the reproductive years, influences, among other things, the regulation of body temperature, bone remodelling, mucous membranes and many other tissues. Progesterone is produced after ovulation mainly by the corpus luteum and is closely tied to the cycle. FSH and LH are signals from the brain to the ovaries, not simply “good” or “bad” hormones. The FSH value can rise because the ovaries no longer respond to the signal as they used to. This change is part of the biology, but it is not a verdict in itself on health or on the need for treatment.

It is also important that oestrogen does not disappear completely from one day to the next. The relative contributions of different sources and forms change. After the menopause a certain amount of oestrogens is still produced outside the ovaries, among other routes through conversion processes in fatty tissue. It cannot be concluded from this, however, that more body fat would be a sensible “hormone therapy”, nor that every slim woman must automatically have a particularly severe course. The regulation is complex, and health relationships should not be reduced to a single measured value.

What the cycle reveals about hormones – and what it does not

The menstrual cycle is the result of finely tuned signals. In many reproductive cycles an egg matures, ovulation takes place and the luteal phase follows. With increasing reproductive age, ovulation can become more irregular. Some bleeds occur after ovulation, others without it. The mere presence of a monthly period therefore cannot reliably show that every hormonal phase was “normal”. Conversely, a missed period does not immediately show that a natural pregnancy has become impossible.

It is tempting to read a fixed hormonal pattern from a few symptoms: irritability must be “progesterone deficiency”, weight gain always “oestrogen dominance”, tiredness necessarily “adrenal fatigue”. Such labels sound catchy but are often too imprecise or not scientifically established for an individual diagnosis. Sound medicine asks about the course, checks other causes where appropriate and chooses a treatment according to the specific problem. It does not necessarily need an oversimplified hormone story for this.

One example is breast tenderness, cycle fluctuations and mood swings. They can go along with hormonal changes, but can also occur independently of them. The symptoms you notice are real. Only the conclusion about one particular hormone value should not be drawn from it automatically.

The brain as intermediary

Why can falling or fluctuating oestrogen signals make some women suddenly feel too warm? The brain contains networks that control heat production and heat loss. In recent years science has described more precisely how neuroendocrine signals, including through the neurokinin system, contribute to the development of hot flushes. This is relevant because it explains new medicines that do not simply replace oestrogen but act specifically on this signalling pathway. [3] [4]

The finding does not prove that all symptoms arise in the brain or can be reduced to the same mechanism. Sleep disorders, for example, can be triggered by night sweats, but also by pain, brooding, medicines or sleep apnoea. A patient can therefore have a genuine hormonally influenced disturbance of heat regulation and, at the same time, insomnia in its own right. If both are recognised separately, additional treatment options open up.

For memory and concentration the picture is even more layered. Oestrogen receptors are found in the nervous system, but this biological fact does not mean that additional oestrogen improves every woman’s thinking. For such statements, randomised trials are more decisive than the mere plausibility of a mechanism. A meta-analysis of 34 controlled trials found no convincing general cognitive benefit of menopausal hormone therapy. [5]

Bones react differently from skin

Bones are living tissue. They are constantly being built up and broken down. Oestrogen signals influence this balance; after the menopause, bone loss can temporarily proceed faster. Bone health, avoiding falls, diet and, where appropriate, targeted osteoporosis testing are therefore important topics in midlife. How to assess the risk and which measures can help is explained on the pages Weight, muscles, bones and heart and What you can influence yourself.

The mucous membranes of the vagina and urinary tract also react to changed hormone signals. Unlike hot flushes, which ease over time in some women, genitourinary symptoms can persist or increase without treatment. Here, local therapy often has to be judged differently from systemic treatment for hot flushes. This is a good example of why the statement “hormones help” is too imprecise: what matters is the region of the body, the form of treatment, the condition and the aim.

Skin and hair can also change somewhat in midlife. But ageing, predisposition, thyroid function, diet and illnesses all play a part. Hair loss that suddenly becomes noticeable cannot be explained by a hormonal label alone. Sometimes a different investigation is more important than any supposed “hormone balancing”.

What a hormone measurement actually measures

Laboratory values show concentrations at one point in time. For many hormones that is useful and medically necessary. In the perimenopause, however, the information value of single values is limited, because production can vary over the course of a day, between cycles and depending on medicines. The British NICE guideline generally advises against various hormone tests to identify the perimenopause in otherwise healthy people aged 45 and over with typical symptoms; for people aged 40 to 45, and where premature ovarian insufficiency is suspected, the situation can be different. [8]

Some commercial offers present detailed saliva or urine profiles with traffic-light colours and apparently exact treatment recommendations. The graphic presentation can look more precise than the clinical meaning really is. A result should always answer the question that led to the test. If that question is not clear, even an extensive test is not automatically helpful.

Conversely, there are situations in which laboratory values do make sense: someone who is severely exhausted and bleeds very often could, for example, have an iron deficiency. Someone who has a racing heart and weight loss may need a thyroid check. These are concrete medical questions, not a general search for a perfect “hormone balance”.

Why “natural” is not a safety category

Oestradiol is a molecule the body makes itself. When it is used as a medicine, its effect nonetheless depends on dose, absorption, accompanying active substances, personal risk and duration of use. The same applies to progesterone and other hormonal products. The claim that a substance is harmless in principle because it is familiar to the human body is not tenable. The body’s own mechanisms can also promote illnesses, and body-identical medicines can have side effects or contraindications.

The distinction between an approved, standardised medicine and an individually compounded “bioidentical” mixture that has not been tested accordingly is therefore more important than an advertising label. Approved products have checked quality and defined amounts of active substance. With individually compounded preparations, dosage and the available data can be harder to assess. The page Supplements and myths deals with such promises in more detail, without lumping the different forms of therapy together.

A picture that makes the connections easier

Imagine an orchestra whose individual instruments play now louder, now softer. The music changes, but not every instrument is responsible for every passage. The hormonal changes are one part of the orchestra. Sleep, chronic illnesses, medicines, exercise, mood and living circumstances play along as well. Anyone who looks at only a single instrument will struggle to explain the sound.

This picture is not a medical theory but a reminder of a good principle of thinking: complex symptoms should be looked at in a differentiated way. The menopause years are an important biological reality, but not a universal diagnosis. This prevents both the playing down of typical symptoms and the wrong attribution of other illnesses.

What the ovaries, the brain and the womb have to do with each other

The cycle is the result of several interlinked processes. In the brain, signals are released that influence the ovaries; the ovaries produce, among other things, oestrogens and, after ovulation, progesterone; the womb lining responds to the hormonal changes. Many women know mainly the visible result, the bleed. In the menopausal transition, however, the whole interplay changes. The number and function of the remaining egg follicles change, and the feedback between the ovaries and the brain becomes more irregular.

This is one of the reasons why the perimenopause cannot be understood as a tank from which a constant amount of oestrogen slowly leaks out. On some days the oestradiol level can be comparatively high, on others low. Ovulation may still take place or may not. The bleed shows only a section of these processes. A one-off blood test therefore cannot capture the whole dynamic. [1]

The body is not “wrongly controlled” as a result. Rather, reproductive function changes, and the regulation has to adapt. Some consequences are well supported, such as the effects on bone remodelling and temperature regulation. On other topics the research is considerably more complex. Mood and concentration, for example, are also linked to sleep and many individual factors.

Why a high FSH value does not automatically mean illness

FSH is often called the “menopause value”. In fact it is a signalling hormone that, among other things, stimulates ovarian function. When the feedback from the ovaries becomes weaker, FSH values can rise. In the transition phase, however, they fluctuate. A high value on one day therefore does not predict exactly when the last period will come. Equally, a different value does not reliably rule out a perimenopause.

Context matters. For a 49-year-old with typical hot flushes and marked cycle fluctuations, guidelines generally do not recommend routine hormonal laboratory testing to establish the perimenopause. For a 41-year-old whose periods have stopped and who may have an early menopause, the assessment can be different. Medicines and hormonal contraception also change how much a result can tell you. [8]

This does not mean that laboratory medicine is pointless in the menopause years. Depending on the symptom, it can be useful, for example, to check for a thyroid disorder, anaemia or other possible causes. But the test should answer a specific question, rather than produce as complete a “hormone profile” as possible whose results are then interpreted without clear consequences.

The great importance of small receptors

Hormones act by binding to matching receptors in tissues. In this way the same messenger substance can have different effects in different organs. Oestrogens influence the womb lining, bone remodelling, mucous membranes and other systems. Which effect ends up dominating depends on the tissue, the distribution of receptors, the concentration and other signals involved. A model in which a single hormone controls the whole body like a central volume control is therefore too crude.

Hormone therapy with medicines is also more than simply “topping up” a deficiency. Different active substances, doses and routes of use do not affect the body in exactly the same way. Anyone who wants to make medical decisions should therefore ask about the specific treatment regimen. This is explained in detail on the page Hormone therapy; here it is enough to know that chemical structure, target tissue and dose play a role.

The hypothalamus and sensitivity to heat

Body temperature is regulated through complex networks in the brain. During the menopause, signals linked to oestrogen and neurokinin messenger substances change. As a result, the threshold at which the body triggers sweating or other forms of heat loss can become more sensitive. This helps to explain why hot flushes can be triggered even by only a slight change in body temperature.

The development of new neurokinin receptor antagonists has made this field of research especially visible. If a medicine acts specifically on one part of the signalling pathway and reduces hot flushes in randomised trials, this supports the biological importance of that pathway. It does not mean, however, that the whole menopausal process would thereby be explained. A mechanism can be relevant for one symptom without being the sole explanation for weight, skin, mood and sexuality. [3] [4]

Why bones behave differently from sleep

For bones, the long-term effect of hormonal changes is relatively well studied. Changes in the balance between bone formation and bone loss can influence bone density over the years. This often happens without any noticeable sign. For sleep the situation is different. A bad night can arise from night sweats, pain, brooding, sleep apnoea or entirely different factors. The same stage of life therefore does not provide the same kind of medical evidence for both topics.

On these pages this distinction is central. On bone health we can speak comparatively clearly about biological effects and long-term risks. With subjective symptoms we have to take individual experiences seriously and at the same time be careful about claims of cause. That is not a devaluation but a precise application of scientific knowledge.

Hormones are not the whole story of ageing either

A body changes in many dimensions between 40 and 60. Muscle mass, sleep habits, activity level and chronic illnesses do not develop only along the lines of the menopause. Ageing, social environment and medical care also influence health. The question “What causes oestrogen deficiency?” is therefore only one part of the bigger question “What is changing in this stage of life?”.

These pages separate these aspects, because otherwise promises of treatment could arise that go too far scientifically. An effective treatment for hot flushes is not automatically a remedy for all signs of ageing. Conversely, good treatment of blood pressure is important even if it does not take away a single hot flush. A differentiated view protects against false expectations – and opens up more sensible courses of action.